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: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Objective To investigate the effects of laparoscopic sleeve gastrectomy(LSG)on the cardiac structure and function in obese patients with heart failure(HF)and compare the efficacy of LSG across obese patients with different HF types.Methods This study included 33 obese patients with HF who underwent LSG.The clinical indicators were compared between before operation and 12 months after operation.Repeated measures analysis of variance was employed to evaluate the changes in echocardiographic parameters before operation and 3,6,and 12 months after operation.Patients were allocated into a HF with preserved ejection fraction group(n=17),a HF with mildly reduced ejection fraction group(n=5)and a HF with reduced ejection fraction(HFrEF)group(n=11)based on left ventricular ejection fraction(LVEF)before operation for subgroup analyses of the effects of LSG on the cardiac structure and function of obese patients with HF.The paired samples t-test was conducted to assess the degree of cardiac structural and functional alterations after LSG.Results The 33 patients included 69.7% males,with an average age of(35.3±9.9)years,and a body mass index(BMI)of(51.2±9.8)kg/m².The median follow-up was 9.0(5.0,13.3)months.Compared with the preoperative values,the postoperative BMI(P=0.002),body surface area(BSA)(P=0.009),waist circumference(P=0.010),hip circumference(P=0.031),body fat content(P=0.007),and percentage of patients with cardiac function grades Ⅲ-IV(P<0.001)decreased.At the 12-month follow-up left atrial diameter(P=0.006),right atrial long-axis inner diameter(RAD1)(P<0.001),right atrial short-axis inner diameter(RAD2)(P<0.001),right ventricular inner diameter(P=0.002),interventricular septal thickness at end-diastolic(P=0.002),and left ventricular end-diastolic volumes(P=0.004)and left ventricular end-systolic volumes(P=0.003) all significantly reduced compared with preoperative values.Additionally,left ventricular fractional shortening and LVEF improved(both P<0.001).Subgroup analyses revealed that cardiac structural parameters significantly decreased in the HF with preserved ejection fraction,HF with mildly reduced ejection fraction,and HFrEF subgroups compared with preoperative values.Notably,the HFrEF group demonstrated the best performance in terms of left atrial diameter(P=0.003),left ventricular inner diameter at end-diastole(P=0.008),RAD1(P<0.001),RAD2(P=0.004),right ventricular inner diameter(P=0.019),left ventricular end-diastolic volume(P=0.004)and left ventricular end-systolic volume(P=0.001),cardiac output(P=0.006),tricuspid regurgitation velocity(P=0.002),and pulmonary artery systolic pressure(P=0.001) compared to preoperatively.Postoperative left ventricular fractional shortening(P<0.001,P=0.003,P<0.001)and LVEF(P<0.001,P=0.011,P=0.001)became higher in all the three subgroups than the preoperative values.Conclusions LSG decreased the body weight,BMI,and BSA,improved the cardiac function grade,reversed the enlargement of the left atrium and left ventricle,reduced the right atrium and right ventricle,and enhanced the left ventricular systolic function.It was effective across obese patients with different HF types.Particularly,LSG demonstrates the best performance in improving the structures of both atria and ventricles in obese patients with HFrEF.
Humans ; Male ; Female ; Gastrectomy/methods* ; Heart Failure/complications* ; Adult ; Obesity/physiopathology* ; Laparoscopy ; Middle Aged ; Heart/physiopathology* ; Stroke Volume

Objective To investigate the internalized weight bias and weight control beliefs regarding the current status,influencing factors,and impacts on eating behaviors of women losing weight. Methods A convenient sampling method was used to select the females who underwent physical examination in the Peking Union Medical College Hospital from August to December 2023.The general information questionnaire,Weight Bias Internalization Scale,Weight Control Belief Questionnaire,and Chinese version of Three-Factor Eating Questionnaire were utilized for investigation.Latent class analysis was conducted to explore the potential categories based on the characteristics of internalized weight bias and weight control beliefs.Univariate analysis and multiple-factor linear regression analysis were performed to explore influencing factors of potential categories and their effects on eating behaviors. Results A total of 518 subjects were included in this study.The internalized weight bias and weight control beliefs could be classified into three potential categories: low weight bias tolerance type(53.7%),medium weight bias persistence type(29.5%),and high weight bias overcritical type(16.8%).Logistic regression analysis showed that body mass index,unmarriage,and divorce were the influencing factors of the high weight bias overcritical type.The scores of non-control eating and emotional eating in medium weight bias persistence type and high weight bias overcritical type were higher than those in low weight bias tolerance type(all P<0.001). Conclusions The attitudes of Chinese women towards body weight can be categorized into low weight bias tolerance type,medium weight bias persistence type,and high weight bias overcritical type.The high weight bias overcritical type is characterized by high weight bias and high personal responsibility attribution,and it is closely associated with negative eating behaviors.A high body mass index,unmarriage,and divorce are high-risk factors for developing the high weight bias overcritical type.
Humans ; Female ; Feeding Behavior/psychology* ; Surveys and Questionnaires ; Adult ; Body Mass Index ; Weight Loss ; Body Weight ; Body Image ; Middle Aged ; Weight Prejudice

This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

AIM To investigate the in vivo pharmacokinetics of chlorogenic acid,isoquercetin,ferulic acid,isorhamnetin and shionone in Asteris Radix et Rhizoma in rats.METHODS Twelve rats were randomly assigned into 2 groups and given intragastric administration of conventional dose(0.63 g/kg)and large dose(3.3 g/kg)of Asteris Radix et Rhizoma extracts,respectively,after which blood collection was made at 0.083,0.167,0.33,0.5,0.75,1,1.5,2,4,6,8,12,24 h,UPLC-MS/MS was adopted in the plasma concentration determination of various effective constituents,and main pharmacokinetic parameters were calculated.RESULTS Various effective constituents in the large dose group demonstrated prolonged t1/2,MRT0-∞ as compared with those in the conventional dose group(P＜0.05).After dose correction,Cmax of chlorogenic acid,isoquercetin,shionone in the large dose group displayed no obvious changes(P＞0.05),while Cmax of ferulic acid,isorhamnetin,and AUC0-t,AUC0-∞ of various effective constituents were higher than those in the conventional dose group(P＜0.05).CONCLUSION Various effective constituents in the high dose of Asteris Radix et Rhizoma can maintain high-concentration and long-time effects on rat bladder tissue.

AIM To evaluate the quality consistency of Tongmai Granules,Tongmai Tablets,Tongmai Capsules and Tongmai Oral Liquid.METHODS The HPLC fingerprints were established,after which the contents of danshensu,protocatechuic aldehyde,3'-hydroxy puerarin,puerarin,puerarin apioside,daidzin,ferulic acid,salvianolic acid B and salvianolic acid A were determined,and cluster analysis and principal component analysis were adopted in the quality analysis from the perspective of daily intake.RESULTS There were 21 common peaks in the fingerprints for 39 batches of samples with the similarities of 0.765-0.997.Various batches of samples were clustered into 5 categories,2 principal components demonstrated the accumulative variance contribution rate of 83.53％ .The daily intakes of various constituents in different dosage forms exhibited obvious differences,especially for that of salvianolic acid B,which were low in tablets and capsules,and their heterogeneities existed among the same dosage forms.CONCLUSION This simple and accurate method can provide a reference for the quality evaluation of Tongmai preparations from different manufacturers.