Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Objective To analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

Objective To analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.