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.

Objective To investigate the effect of naringenin(Nar)on hippocampal neuronal injury in neonatal mice with bilirubin encephalopathy,focusing on the Nrf2/GPX4-mediated ferroptosis pathway.Methods Neonatal mice were randomly divided into Control group,Model group,Nar low(Nar-L),high dose group(Nar-H)and high dose naringenin combined with Nrf2 inhibitor ML385 group(Nar-H+ML385),with 15 mice in each group.With the exception of the Control group,mice in the other groups were injected with bilirubin solution(20 μg/g)through the cerebellar bulbar cisterna to establish neonatal mouse bilirubin encephalopathy model.After the establishment of the model,intraperitoneal injection of naringin(25 or 100 mg/kg)or ML385(30 mg/kg)was administered once daily for a consecutive period of 7 days.After intervention,the neurobehavioral changes of each group of mice were observed.The water maze experiment was conducted to assess the long-term learning and memory abilities of the mice in each group.Nissl staining was performed to observe hippocampal neuron damage in mice.Chemical methods were used to measure the levels of malondialdehyde(MDA),4-hydroxynonenal(4-HNE),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in the hippocampal tissue of mice.Colorimetric analysis was employed to determine the content of Fe2+in hippocampal tissue.Western blotting was utilized to detect protein expression levels of nuclear associated factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)protein in the hippocampal tissue of mice.Results Compared with the Control group,the Model group showed different degrees of abnormal neural behavior,and the long-term learning and memory ability were significantly reduced(P<0.05),at the same time,the hippocampal nerve was seriously damaged,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly increased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly decreased(P<0.05).Compared with the Model group,the Nar-L and Nar-H groups had less abnormal behavior,and the long-term learning and memory ability were significantly enhanced(P<0.05),at the same time,the hippocampal nerve injury was significantly improved,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly decreased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly increased(P<0.05).However,the combined intervention of ML385 significantly attenuates the beneficial effects of Nar on hippocampal neuron damage in neonatal mice with bilirubin encephalopathy.Conclusion This study suggested that Nar can ameliorate neuronal damage in hippocampus of neonatal mice with bilirubin encephalopathy,possibly through the regulation of iron death mediated by Nrf2/GPX4 axis.

Objective To investigate the effect and mechanism of benserazide on bleomycin-induced pulmonary fibrosis in mice.Methods Male C57BL/6 mice were randomly divided into normal control group,model control group,pirfenidone group(50 mg·kg-1),and low-dose and high-dose benserazide groups(300 and 600 mg·kg-1),with 6 mice in each group.Except for normal control group,the other groups were given bleomycin(3.5 mg·kg-1)by non-invasive tracheal instillation to establish a mouse model of pulmonary fibrosis.Seven days after modeling,pirfenidone group and low-dose and high-dose benserazide groups were intragastrically administered the corresponding doses of drugs for 14 consecutive days.After the drug administration,the mice in each group were sacrificed.The pathological morphology of the lung tissue in each group was observed by hematoxylin-eosin(HE)staining and Masson staining.The content of hydroxyproline(HYP)in the lung tissue of mice,the content of lactic acid in the lung tissue and serum,and the activity of hexokinase(HK)in the lung tissue were detected by using kits.The expression levels of Collagen I and Fibronectin in the lung tissue of mice in each group were detected by immunohistochemistry.The expression levels of α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins in the lung tissue of mice in each group were detected by Western blotting.Results Compared with normal control group,the lung tissue structure of model control group mice was damaged,with thickened alveolar septa and fibrotic changes such as collagen accumulation.The content of HYP and lactic acid and the activity of HK in the lung tissue increased significantly,and the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α,and IL-6 proteins were significantly increased.Compared with model control group,treatment with benserazide significantly alleviated the pathological damage of lung tissue in mice,significantly reduced the content of HYP,lactic acid and HK activity in lung tissue,and significantly decreased the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins.Conclusion Benserazide ameliorates bleomycin-induced pulmonary fibrosis in mice by modulating the HK2-mediated glycolysis pathway.

Currently,acquired immune deficiency syndrome(AIDS)has emerged as a global public health crisis that profoundly compromises human immune defenses.By systematically dismantling the im-mune system,human immunodeficiency virus(HIV)renders individuals vulnerable to opportunistic in-fections and malignancies,ultimately culminating in AIDS progression.It is urgent to eradicate the latent HIV virus and achieve a functional cure,thus limiting the development of AIDS and improving the quality of patients.Epigenetics investigates heritable alterations in gene expression that occur independently of DNA sequence.The intricate regulation of HIV gene expression is orchestrated through multifaceted epi-genetic mechanisms involving both viral and host factors.Understanding the epigenetic mechanisms asso-ciated with HIV infection is crucial for clearing latent viruses and achieving control and treatment of AIDS in the future.Therefore,we will discuss the epigenetic regulatory patterns and mechanisms involved in HIV infection,particularly emphasize on four principal mechanisms:DNA methylation,histone modifica-tion,non-coding RNA regulation and RNA modification.We comprehensively analyze how these regula-tory factors influence the viral life cycle,particularly regarding latency establishment,reactivation dy-namics,and persistent infection maintenance.Furthermore,we delineate the interplay between epigenet-ic regulators and key cellular signaling pathways during HIV pathogenesis.The review culminates in a critical appraisal of recent breakthroughs and persistent challenges in epigenetics-based therapeutic strate-gies,while highlighting innovative approaches for functional cure development.By elucidating the pivotal role of epigenetic regulation in HIV latency,this review aims to establish a novel theoretical foundation and innovative research directions for next-generation AIDS therapeutics rooted in epigenetic modifica-tion.

Objective To investigate the effect and mechanism of benserazide on bleomycin-induced pulmonary fibrosis in mice.Methods Male C57BL/6 mice were randomly divided into normal control group,model control group,pirfenidone group(50 mg·kg-1),and low-dose and high-dose benserazide groups(300 and 600 mg·kg-1),with 6 mice in each group.Except for normal control group,the other groups were given bleomycin(3.5 mg·kg-1)by non-invasive tracheal instillation to establish a mouse model of pulmonary fibrosis.Seven days after modeling,pirfenidone group and low-dose and high-dose benserazide groups were intragastrically administered the corresponding doses of drugs for 14 consecutive days.After the drug administration,the mice in each group were sacrificed.The pathological morphology of the lung tissue in each group was observed by hematoxylin-eosin(HE)staining and Masson staining.The content of hydroxyproline(HYP)in the lung tissue of mice,the content of lactic acid in the lung tissue and serum,and the activity of hexokinase(HK)in the lung tissue were detected by using kits.The expression levels of Collagen I and Fibronectin in the lung tissue of mice in each group were detected by immunohistochemistry.The expression levels of α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins in the lung tissue of mice in each group were detected by Western blotting.Results Compared with normal control group,the lung tissue structure of model control group mice was damaged,with thickened alveolar septa and fibrotic changes such as collagen accumulation.The content of HYP and lactic acid and the activity of HK in the lung tissue increased significantly,and the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α,and IL-6 proteins were significantly increased.Compared with model control group,treatment with benserazide significantly alleviated the pathological damage of lung tissue in mice,significantly reduced the content of HYP,lactic acid and HK activity in lung tissue,and significantly decreased the expression levels of Collagen I,Fibronectin,α-SMA,TGF-β1,Smad2,p-Smad2,TNF-α and IL-6 proteins.Conclusion Benserazide ameliorates bleomycin-induced pulmonary fibrosis in mice by modulating the HK2-mediated glycolysis pathway.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

BACKGROUND:Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus.Most of the existing studies have analyzed the gait parameters of patients during straight-line walking,but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE:To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS:Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery,Huadong Hospital Affiliated to Fudan University,Shanghai,China,from September 2022 to February 2023 were selected as the patient group,and 18 healthy accompanying family members were selected as the healthy control group.The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test,Multi-Directional Reach Test,Berg Balance Scale,and Static Balance Function Test(reaction time,speed of movement,directional control,maximum offset distance,and endpoint travel). RESULTS AND CONCLUSION:The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group(P＜0.05).The results of the stretching test in the four directions of anterior,posterior,leftand right were significantly lower in the patient group than in the healthy control group(P＜0.05).The Berg Balance Scale scores in the patient group were lower than those in the healthy control group(P＜0.05).In the Static Balance Function Test,the results of reaction,movement speed,directional control,maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group(P＜0.05).To conclude,patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits,and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources,resulting in postural instability and increasing the risk of falls.

Objective To investigate the effect of naringenin(Nar)on hippocampal neuronal injury in neonatal mice with bilirubin encephalopathy,focusing on the Nrf2/GPX4-mediated ferroptosis pathway.Methods Neonatal mice were randomly divided into Control group,Model group,Nar low(Nar-L),high dose group(Nar-H)and high dose naringenin combined with Nrf2 inhibitor ML385 group(Nar-H+ML385),with 15 mice in each group.With the exception of the Control group,mice in the other groups were injected with bilirubin solution(20 μg/g)through the cerebellar bulbar cisterna to establish neonatal mouse bilirubin encephalopathy model.After the establishment of the model,intraperitoneal injection of naringin(25 or 100 mg/kg)or ML385(30 mg/kg)was administered once daily for a consecutive period of 7 days.After intervention,the neurobehavioral changes of each group of mice were observed.The water maze experiment was conducted to assess the long-term learning and memory abilities of the mice in each group.Nissl staining was performed to observe hippocampal neuron damage in mice.Chemical methods were used to measure the levels of malondialdehyde(MDA),4-hydroxynonenal(4-HNE),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in the hippocampal tissue of mice.Colorimetric analysis was employed to determine the content of Fe2+in hippocampal tissue.Western blotting was utilized to detect protein expression levels of nuclear associated factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)protein in the hippocampal tissue of mice.Results Compared with the Control group,the Model group showed different degrees of abnormal neural behavior,and the long-term learning and memory ability were significantly reduced(P<0.05),at the same time,the hippocampal nerve was seriously damaged,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly increased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly decreased(P<0.05).Compared with the Model group,the Nar-L and Nar-H groups had less abnormal behavior,and the long-term learning and memory ability were significantly enhanced(P<0.05),at the same time,the hippocampal nerve injury was significantly improved,and the contents of MDA,4-HNE and Fe2+in hippocampal tissue were significantly decreased(P<0.05),the activities of SOD and GSH-Px and the protein expression levels of Nrf2,SLC7A11 and GPX4 were significantly increased(P<0.05).However,the combined intervention of ML385 significantly attenuates the beneficial effects of Nar on hippocampal neuron damage in neonatal mice with bilirubin encephalopathy.Conclusion This study suggested that Nar can ameliorate neuronal damage in hippocampus of neonatal mice with bilirubin encephalopathy,possibly through the regulation of iron death mediated by Nrf2/GPX4 axis.

Currently,acquired immune deficiency syndrome(AIDS)has emerged as a global public health crisis that profoundly compromises human immune defenses.By systematically dismantling the im-mune system,human immunodeficiency virus(HIV)renders individuals vulnerable to opportunistic in-fections and malignancies,ultimately culminating in AIDS progression.It is urgent to eradicate the latent HIV virus and achieve a functional cure,thus limiting the development of AIDS and improving the quality of patients.Epigenetics investigates heritable alterations in gene expression that occur independently of DNA sequence.The intricate regulation of HIV gene expression is orchestrated through multifaceted epi-genetic mechanisms involving both viral and host factors.Understanding the epigenetic mechanisms asso-ciated with HIV infection is crucial for clearing latent viruses and achieving control and treatment of AIDS in the future.Therefore,we will discuss the epigenetic regulatory patterns and mechanisms involved in HIV infection,particularly emphasize on four principal mechanisms:DNA methylation,histone modifica-tion,non-coding RNA regulation and RNA modification.We comprehensively analyze how these regula-tory factors influence the viral life cycle,particularly regarding latency establishment,reactivation dy-namics,and persistent infection maintenance.Furthermore,we delineate the interplay between epigenet-ic regulators and key cellular signaling pathways during HIV pathogenesis.The review culminates in a critical appraisal of recent breakthroughs and persistent challenges in epigenetics-based therapeutic strate-gies,while highlighting innovative approaches for functional cure development.By elucidating the pivotal role of epigenetic regulation in HIV latency,this review aims to establish a novel theoretical foundation and innovative research directions for next-generation AIDS therapeutics rooted in epigenetic modifica-tion.