Zhang Zhang

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neuroinflammatory conditions characterized by widespread brain alterations. However, how cortical hierarchical organization is altered across these disorders and how such alterations relate to underlying molecular architecture remain unclear. Methods: We applied the Morphometric INverse Divergence (MIND) framework to structural MRI data from 62 MS patients, 53 NMOSD patients, and 74 healthy controls. Cortical gradients were constructed based on MIND features to represent the hierarchical organization across the cortex. The derived MIND‐gradient metrics were integrated with multiscale analyses, including clinical and neuropsychological assessments, neurotransmitter system mapping, and transcriptomic profiling coupled with enrichment analyses, to link macroscale structural organization with molecular and functional substrates. Results: MIND‐gradient analyses showed alterations in cortical hierarchical organization in MS and NMOSD, mainly involving frontal and parietal regions. The primary MIND gradient was significantly associated with the spatial distributions of multiple neurotransmitter receptors and transporters. Transcriptomic analyses identified 1978 gradient‐associated genes in MS and 2485 in NMOSD. These genes were enriched in immune‐related, synaptic, and transport‐related biological processes in both disorders, with shared and non‐overlapping enriched terms. Cellular enrichment analysis further highlighted enrichment for myelinating oligodendrocytes, and developmental enrichment analysis suggested different temporal enrichment patterns in MS and NMOSD. Conclusions: These findings provide insights into cortical hierarchical alterations in MS and NMOSD and highlight potential molecular correlates that warrant further investigation in longitudinal studies.

Background: Alzheimer’s disease (AD) and multiple sclerosis (MS) share neuroimmune mechanisms that drive neurodegeneration. Current clinical interventions are largely confined to a single-disease approach, owing to the absence of trans-disease diagnostic markers and common therapeutic targets. Objective: To map common and disease-specific grey matter (GM) atrophy patterns in AD and MS and identify their genetic correlations. Methods: We performed a trans-disease meta-analysis in large-sample neuroimaging data from 2001 to 2024 (2,070 MS versus 1,625 healthy control, and 1,624 AD versus 1,607 healthy control) to map GM atrophy regions. The cross-sample partial least squares regression was applied to integrate gene expression profiles from the Allen Human Brain Atlas with region-specific GM atrophy patterns, achieving cross-scale analysis of identify neurodegeneration-associated genes. Results: MS-specific atrophy localized to the bilateral dorsomedial thalamic nucleus and precentral gyrus, whereas AD-specific atrophy centered on bilateral hippocampus-amygdala complex in age-unadjusted comparisons. The common atrophy patterns were found in the bilateral superior temporal gyrus, insulae, posterior cingulate cortex, amygdalae, and striatal components. We identified 834 genes whose spatial expression patterns were associated with the common GM atrophy pattern in AD and MS, including PLS2 + and PLS2- subsets, which encompass biological processes such as immunological homeostasis imbalance, cellular stress response, and neurometabolic/functional regulation. Conclusion: Findings establish shared cortical–limbic-striatal atrophy as pivotal neurodegeneration nexus in AD and MS. The identified gene-imaging signatures provide insights into potential pathway-specific mechanisms and may inform future therapeutic target discovery for dual-disease intervention.

Background: The combination of photodynamic therapy (PDT) and immunotherapy has been explored as an innovative approach to enhance efficacy against tumors. However, PDT shows limited effectiveness in treating deep-seated tumors, as light and lasers do not sufficiently penetrate tissue. Methods: Herein, we introduced a nanocarrier (NP_VR) via self-assembly, using an amphiphilic copolymer to co-deliver the hydrophobic photosensitizer verteporfin (VP) and the immunoadjuvant imiquimod (R837). Results: Our X-ray-induced photodynamic therapy (X-PDT) mechanism induced NP_VR to generate a large amount of cytotoxic reactive oxygen species (ROS), which directly killed cancer cells. Moreover, the released R837 facilitated immunogenic cell death following the X-PDT process and promoted the maturation of dendritic cells (DCs), thereby eliciting immune responses against malignant triple-negative breast cancer (TNBC). In animal experiments, the combined therapy using NP_VR showed a tumor growth inhibition rate of ~70%. Conclusions: This novel strategy opens new avenues to designing next-generation nanomedicines for use in immunotherapy and other combination therapies.

Background: Coronary computed tomography angiography (CCTA) can be used to investigate the relationship between white adipose tissue (WAT) and brown adipose tissue (BAT) in pericardial fat (PF) and high-risk plaques (HRP) in patients with coronary artery disease (CAD). This study aimed to explore the association between specific components of PF and HRP/culprit ischemic plaques, as well as their mediating role in overall metabolic status, providing new imaging evidence for predicting adverse events in CAD. Methods: The clinical risk factors and imaging images of 107 CAD patients were retrospectively analyzed. Quantification of coronary artery calcium scores (CACS), PF, WAT, BAT, and pericardial fat attenuation (PFatt) were performed on non-contrast CT images. CCTA was used to evaluate myocardial ischemia and the presence of HRP. Fractional flow reserve derived from CCTA (CT-FFR) was performed in three major coronary arteries, with a threshold of ≤0.80 considered indicative of the presence of lesion-specific ischemia. HRP was defined as the presence of at least two of the four HRP features including positive remodeling (PR), low attenuation, napkin-ring sign (NRS), and spotty calcification. Mediator analysis was performed using Hayes (2018) Model-4. Results: A total of 107 CAD patients aged 65±8 years were included in this study. There were 49 patients (45.79%) with HRP and 57 patients (53.27%) with lesion-specific ischemia (CT-FFR ≤0.80). PF including WAT and BAT in the HRP group was significantly higher than that in the non-HRP group (PF: 241.28 vs. 204.94 cm³, P=0.005, WAT: 91.78 vs. 78.40 cm³, P=0.002, BAT: 56.25 vs. 46.71 cm³, P=0.008). Adding WAT to meaningful clinical risk factors and CACS increases the area under the curve (AUC) for HRP prediction {AUC [95% confidence interval (95% CI)]: 0.789 (0.692–0.887) vs. 0.655 (0.535–0.775), Pvs. 0.796 (0.696–0.897), PConclusions: PF is associated with HRP, and clinical risk factors increase the risk of plaque rupture by promoting PF volume accumulation, especially WAT, which may be a potential predictor of HRP.

Objectives: Pulmonary hypertension (PH) in patients with right ventricular systolic dysfunction (RVSD) is associated with a poor prognosis. This study assessed the characteristics of right atrial (RA) function using cardiac magnetic resonance feature tracking (CMR-FT) before RVSD onset and evaluated the long-term prognostic significance of these characteristics. Materials and methods: A total of 96 PH patients, including 36 without RVSD (PH-nonRVSD) and 60 with RVSD (PH-RVSD), were compared to 20 healthy controls (HCs). The RA reservoir, conduit, booster pump functions, and the right ventricular global longitudinal strain (RVGLS) were evaluated. Ventricular morphological and functional parameters of the RA and right ventricle (RV) were also acquired. Results: Compared with HCs, both RA reservoir and conduit functions were significantly reduced ( p _s < 0.05) in the PH-nonRVSD, without significant morphological changes in either the RA or RV ( p _s > 0.05). The RA reservoir and conduit function were significantly correlated with the right ventricular ejection fraction (RVEF), RVGLS, pulmonary vascular resistance, brain natriuretic peptide, cardiac index, and 6-min walk distance. Receiver operating characteristic analysis demonstrated that RA conduit function outperformed RVGLS and RVEF in differentiating PH-nonRVSD and HCs. However, a reduction in RA booster pump function was observed only in the PH-RVSD group ( p < 0.001). During a median follow-up period of 97 (80–106) months, 45% of the included patients died. RA reservoir function was an independent predictor of all-cause mortality (HR = 0.963, 95% CI: 0.935–0.992, p = 0.014). Conclusions: RA function can detect right heart dysfunction prior to RVSD and monitor disease progression in patients with PH. Moreover, RA reservoir function independently predicts long-term prognosis. Critical relevance statement: Impairment of right atrial (RA) function, assessed by cardiac magnetic resonance feature tracking (CMR-FT), in pulmonary hypertension (PH) patients is sensitive in detecting right-sided heart dysfunction before right ventricular systolic dysfunction and can be utilized to monitor disease progression and long-term prognosis. Key Points: RA function is sensitive in detecting early right heart dysfunction in PH patients. The disease progression of PH can be monitored by assessing RA function. RA function can serve as a tool for predicting long-term prognosis. Graphical

Background: The diagnosis of coronary artery disease (CAD) has traditionally relied on invasive coronary angiography (ICA), a method with inherent risks. As a noninvasive technique, computed tomography-derived fractional flow reserve (CT-FFR) can integrate both anatomical and functional assessments of the coronary arteries, identifying hemodynamically significant stenosis and thereby reducing unnecessary invasive procedures. Although its clinical value has been demonstrated, its widespread clinical adoption is constrained by physician perception. Objective: To quantify the professional attitudes and willingness to adopt CT-FFR for clinical application among cardiologists and radiologists, and to identify the key determinants influencing their positivity. Methods: A cross-sectional survey was conducted from May to June 2023 across five provinces and cities in China. Data were collected from 265 cardiothoracic physicians using a validated, structured questionnaire (Cronbach’s α = 0.884). The questionnaire assessed two core dimensions using a five-point Likert scale: “Attitude” (15 questions) and “Willingness” (eight questions). Higher scores indicated more positive attitudes or willingness. Results: The survey was completed by 265 physicians, with overall attitudes being positive. The median scores for the attitude and willingness dimensions were 51 (interquartile range: 48, 55) and 31 (interquartile range: 29, 32), respectively, with a significant positive correlation between them (r = 0.571, p < 0.001). While over 60% of physicians acknowledged that CT-FFR could prevent unnecessary invasive procedures, 38.1% still expressed concerns about its diagnostic accuracy. Logistic regression analysis showed that physicians working in specialized cardiovascular hospitals held more positive attitudes (OR = 3.085, p = 0.017). Multivariable analysis further confirmed that a positive attitude was the strongest independent predictor driving willingness to adopt (OR = 6.280, p < 0.001). Conclusion: Participants’ belief in the development potential of CT-FFR was positively associated with their willingness to learn, receive training, consider improvements, and participate in clinical research involving CT-FFR.

Myocardial infarction (MI) is characterized by rapid onset and high mortality. Due to the complexity of its pathological process, targeted therapy for MI has been a long-standing challenge. Macrophages, as immune cells, selectively accumulate in the infarct area after MI. This inherent targeting ability, coupled with excellent immune evasion capabilities, makes macrophages an ideal source for targeted delivery to damaged myocardium as a biomimetic delivery carrier. Therefore, in this work, we aimed to develop biomimetic nanoparticles for specific targeted drug delivery to efficiently treat MI. Using cell membrane-coated nanotechnology, we prepared resveratrol-loaded nanoparticles (RESNPs) using poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated the surface of RESNPs with macrophage membranes to prepare biomimetic nanoparticles MM/RESNPs. We then described the physical properties of MM/RESNPs, and their targeting, therapeutic effects, and safety were evaluated in a MI mouse model. The results show that MM/RESNPs exhibited good biocompatibility and could effectively target damaged myocardial sites. MM/RESNPs were found to considerably improve cardiac function and reduce the infarct size in MI mice. Furthermore, MM/RESNPs demonstrated good biosafety after long-term administration. Macrophage membrane-coated biomimetic nanoparticles (MM/RESNPs) exhibit excellent nanoperformance and biosafety, enabling targeted drug delivery and achieving safe and effective treatment for MI.

Background: AD involves deficits in essential brain chemicals. A functional neurocompensatory response in brain regions critical for executive control has been reported for early AD. It is unclear whether such an effect can be detected in brain metabolites and affected by medication treatments. In this study, we used single‐voxel proton magnetic resonance spectroscopy (SV‐1H‐MRS, short as MRS here) to quantify neurochemical changes non‐invasively. Our objectives are to 1) examine differences in key neurometabolites between brain regions either compromised or preserved in early AD and 2) test the potential effect of medication treatment on metabolite levels in the brain regions.Method: Sixteen participants with early AD (76.8±8.0 yrs, 56.2% female) and 20 normal controls (73.6 ± 6.3 yrs, 60% female) had two MRS sessions six months apart. AD patients took cholinesterase inhibitors as part of standard care following the baseline scan. MRS acquisition used 4T MRI with LASER sequence from two voxels (5.12cm³), respectively placed in the posterior cingulate gyri (PCG) and the left dorsolateral prefrontal cortex (DLPFC). Spectra data were fitted using fitMAN and analyzed using ANOVA for main effect and interactions (voxel placement, subject group, scan time).Result: The level of many metabolites was greater in the DLPFC than in the PCG voxels (F_s>4.01, p_s4.09, p_s4.04, p_s6.71, p_s5.08, p_s<0.027).Conclusion: The data showed a lower level of several metabolites essential for maintaining neuronal function and connectivity in early AD than normal aging, especially in brain regions that are compromised early in the disease process. The study suggested a positive impact of clinical management of early AD on enabling neurocompensation for at least six months.