Ischemic Microenvironment-Targeted Bioinspired Lipoprotein Sequentially Penetrates Cerebral Ischemic Lesions to Rescue Ischemic Stroke.

Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Pretreatment can alleviate programmed cell death in mesenchymal stem cells.

In this editorial, we delved into the article titled "Cellular preconditioning and mesenchymal stem cell ferroptosis." This groundbreaking study underscores a pivotal discovery: Ferroptosis, a type of programmed cell death, drastically reduces the viability of donor mesenchymal stem cells (MSCs) after engraftment, thereby undermining the therapeutic value of cell-based therapies. Furthermore, the article proposes that by manipulating ferroptosis mechanisms through preconditioning, we can potentially enhance the survival rate and functionality of MSCs, ultimately amplifying their therapeutic potential. Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs, we deem it imperative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.

Histological and transcriptomic insights into the interaction between grapevine and Colletotrichum viniferum.

Introduction: Grape is of high economic value. Colletotrichum viniferum, a pathogen causing grape ripe rot and leaf spot, threatens grape production and quality. Methods: This study investigates the interplay between C. viniferum by Cytological study and transcriptome sequencing. Results: Different grapevine germplasms, V. vinifera cv. Thompson Seedless (TS), V. labrusca accession Beaumont (B) and V. piasezkii Liuba-8 (LB-8) were classified as highly sensitive, moderate resistant and resistant to C. viniferum, respectively. Cytological study analysis reveals distinct differences between susceptible and resistant grapes post-inoculation, including faster pathogen development, longer germination tubes, normal appressoria of C. viniferum and absence of white secretions in the susceptible host grapevine. To understand the pathogenic mechanisms of C. viniferum, transcriptome sequencing was performed on the susceptible grapevine "TS" identifying 236 differentially expressed C. viniferum genes. These included 56 effectors, 36 carbohydrate genes, 5 P450 genes, and 10 genes involved in secondary metabolism. Fungal effectors are known as pivotal pathogenic factors that modulate plant immunity and affect disease development. Agrobacterium-mediated transient transformation in Nicotiana benthamiana screened 10 effectors (CvA13877, CvA01508, CvA05621, CvA00229, CvA07043, CvA05569, CvA12648, CvA02698, CvA14071 and CvA10999) that inhibited INF1 (infestans 1, P. infestans PAMP elicitor) induced cell death and 2 effectors (CvA02641 and CvA11478) that induced cell death. Additionally, transcriptome analysis of "TS" in response to C. viniferum identified differentially expressed grape genes related to plant hormone signaling (TGA, PR1, ETR, and ERF1/2), resveratrol biosynthesis genes (STS), phenylpropanoid biosynthesis genes (PAL and COMT), photosynthetic antenna proteins (Lhca and Lhcb), transcription factors (WRKY, NAC, MYB, ERF, GATA, bHLH and SBP), ROS (reactive oxygen species) clearance genes (CAT, GSH, POD and SOD), and disease-related genes (LRR, RPS2 and GST). Discussion: This study highlights the potential functional diversity of C. viniferum effectors. Our findings lay a foundation for further research of infection mechanisms in Colletotrichum and identification of disease response targets in grape.

Cocrystal of Lutein with Improved Stability and Bioavailability.

Lutein (LT) is a natural carotenoid and is widely used for its vision protection and antioxidant activity. However, the long-chain polyene structure makes lutein sensitive to light and oxygen and poses many difficulties in the production, processing, and storage. In addition, the special chemical structure of LT leads to low solubility and bioavailability. In this study, we propose an efficient solution to address these issues. A cocrystal of LT with adipic acid (LT-APC) was obtained for the first time. The cocrystals were fully characterized. After cocrystallization, the melting point of marketed LT was increased. The chemical stability of LT was significantly improved, and the influence of impurities on stability was limited. Dissolution experiments were performed in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and the cocrystal generated a much higher apparent solubility. To deepen insight into the mechanisms underlying the cocrystal's improved solubility, wettability tests were performed by contact angle determination and film flotation methods. The cocrystal presented better wettability than the marketed LT. Finally, pharmacokinetic studies of marketed LT and its cocrystal were conducted in rats. The results showed that the cocrystal exhibited 3.4 times higher C max and 2.2 times higher AUC at a single dose compared with marketed LT.

Comparison of Injury Severity Score (ISS) and New Injury Severity Score (NISS) in the Evaluation of Thoracic Trauma Patients: A Retrospective Cohort Study.

Objective: To explore the value of the injury severity score (ISS) and the new injury severity score (NISS) for evaluating injuries and predicting complications (pneumonia and respiratory failure) and poor prognoses (in-hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death) in patients with thoracic trauma. Methods: The data of consecutive patients with thoracic trauma who were admitted to the department of cardiothoracic surgery of a tertiary hospital between January 2018 and December 2021 were retrospectively collected. ISS and NISS were calculated for each patient. The study outcomes were complications and poor prognoses. The differences in ISS and NISS between patients with complications and poor prognoses and patients without the abovementioned conditions were compared using the Mann‒Whitney U test. Discrimination and calibration of ISS and NISS in predicting outcomes were compared using the area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer‒Lemeshow (H-L) statistic. Results: A total of 310 patients were included. ISS and NISS of patients with complications and poor prognoses were greater than those of patients without complications and poor prognoses, respectively. The discrimination of ISS in predicting pneumonia, respiratory failure, in-hospital tracheal intubation, extended length of hospital stay, ICU admission, prolonged ICU stay, and death (AUCs: 0.609, 0.721, 0.848, 0.784, 0.763, 0.716, and 0.804, respectively) was not statistically significantly different from that of NISS in predicting the corresponding outcomes (AUCs: 0.628, 0.712, 0.795, 0.767, 0.750, 0.750, and 0.818, respectively). ISS showed better calibration than NISS for predicting pneumonia, respiratory failure, in-hospital tracheal intubation, extended length of hospital stay, and ICU admission but worse calibration for predicting prolonged ICU stay and death. Conclusion: ISS and NISS are both suitable for injury evaluation. There was no statistically significant difference in discrimination between ISS and NISS, but they had different calibrations when predicting different outcomes.

Multifocal Epstein-Barr Virus-Positive Mucocutaneous Ulcers in a Patient With Crohn's Disease.

Epstein-Barr Virus-positive mucocutaneous ulcer (EBVMCU) is a rare and new category of mature B-cell neoplasms commonly linked to immunosuppression. It often has a benign course and regresses spontaneously after discontinuation or dose reduction of immunosuppressive agents. We report the case of a 48-year-old woman on long-term azathioprine therapy for rectosigmoid Crohn's disease. In contrast to the prevalent sites typically associated with EBVMCU, such as the oral mucosa and skin, this patient was found to have locations in the gastrointestinal tract and upper neck. These areas tested positive for histopathology consistent with EBVMCU and were excised due to bowel perforation and concern for malignancy.

Profiling of Phakopsora pachyrhizi transcriptome revealed co-expressed virulence effectors as prospective RNA interference targets for soybean rust management.

Soybean rust (SBR), caused by an obligate biotrophic pathogen Phakopsora pachyrhizi, is a devastating disease of soybean worldwide. However, the mechanisms underlying plant invasion by P. pachyrhizi are poorly understood, which hinders the development of effective control strategies for SBR. Here we performed detailed histological characterization on the infection cycle of P. pachyrhizi in soybean and conducted a high-resolution transcriptional dissection of P. pachyrhizi during infection. This revealed P. pachyrhizi infection leads to significant changes in gene expression with 10 co-expressed gene modules, representing dramatic transcriptional shifts in metabolism and signal transduction during different stages throughout the infection cycle. Numerous genes encoding secreted protein are biphasic expressed, and are capable of inhibiting programmed cell death triggered by microbial effectors. Notably, three co-expressed P. pachyrhizi apoplastic effectors (PpAE1, PpAE2, and PpAE3) were found to suppress plant immune responses and were essential for P. pachyrhizi infection. Double-stranded RNA coupled with nanomaterials significantly inhibited SBR infection by targeting PpAE1, PpAE2, and PpAE3, and provided long-lasting protection to soybean against P. pachyrhizi. Together, this study revealed prominent changes in gene expression associated with SBR and identified P. pachyrhizi virulence effectors as promising targets of RNA interference-based soybean protection strategy against SBR.

Can digital technology innovation contribute to firms' market value?

With the rapid development of digital technology, digital technology innovation has become a core driver of China's economic development. Thus, this study uses A-share listed companies from 2003 to 2021 as the research sample. The digital patents of firms are identified to portray the level of digital technology innovation by matching the digital economy industry classification code, national economy industry classification code, and IPC number. Considers the economic effect of digital technology innovation from the perspective of firm market value. It is found that digital technology innovation significantly contributes to the increase in firm market value, and this finding still holds when robustness tests are performed. Mechanistic tests have shown that digital technology innovation affects firm market value by driving digital transformation, promoting productivity, and enhancing market profitability. Further analysis reveals that digital technology innovation has a more significant effect on increasing firm market value for large, non-state, capital-intensive, technology-intensive and low internal control costs firms. This study verifies the enabling effect of digital technology innovation on the development of the real economy at the micro level, and provides insights for the optimization of China's digital technology innovation policies and the formulation of firms' digital development strategies.

Plasma proteomic signature of neonates in the context of placental histological chorioamnionitis.

BACKGROUND: Placental histological chorioamnionitis (HCA) is recognised as a significant risk factor for various adverse neonatal outcomes. This study aims to explore if the inflammatory protein levels in neonates were associated with HCA. METHODS: All women with singleton births from February 2020 to November 2022 were selected and divided into three groups based on maternal placental pathology results: the HCA-stage 1 group (n=24), the HCA-stage 2 group (n=16) and the control group (n=17). Olink Target 96 Inflammation Panel was used to detect the levels of 92 inflammation-related proteins in the plasma of newborns from all three groups within 24 hours after birth. We compared the protein profiles through differential protein expression analysis. RESULTS: A total of six inflammation-related proteins exhibited significant differences between the HCA-stage 1 and the control group. Specifically, TRANCE and CST5 were significantly upregulated (p=0.006, p=0.025, respectively), whereas the expression of IFN-gamma, CXCL9, CXCL10 and CCL19 was significantly downregulated (p=0.040, p=0.046, p=0.007, p=0.006, respectively). HCA-stage 2 newborns had significantly elevated levels of CD5 and CD6 and decreased IFN-gamma, CXCL10 and CCL19 in comparison to controls. These differential proteins were significantly enriched in positive regulation of cytokine activity, leucocyte chemotaxis and positive regulation of T-cell activation pathway-related Gene Ontology terms. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that viral protein interaction with cytokine and cytokine receptor, interleukin-17/NF-kappa B/toll-like receptor/chemokine signalling pathway, and cytokine-cytokine receptor interaction exhibited significant differences. Spearman analysis demonstrated a significant positive connection between the levels of CD6 and CD5 proteins, not only in neonatal leucocytes but also in maternal leucocytes. Additionally, CD6 was found to be associated with neonatal birth weight. CONCLUSIONS: In conclusion, placental histological changes associated with chorioamnionitis appear to influence the expression of inflammatory proteins in offspring. Notably, CD6 and CD5 proteins may potentially contribute to the pathogenesis of HCA-related neonatal diseases.

Transformable 3D curved high-density liquid metal coils - an integrated unit for general soft actuation, sensing and communication.

Rigid solenoid coils have long been indispensable in modern intelligent devices. However, their sparse structure and challenging preparation of flexible coils for soft robots impose limitations. Here, a transformable 3D curved high-density liquid metal coil (HD-LMC) is introduced that surpasses the structural density level of enameled wire. The fabrication technique employed for high-density channels in elastomers is universally applicable. Such HD-LMCs demonstrated excellent performance in pressure, temperature, non-contact distance sensors, and near-field communication. Soft electromagnetic actuators thus achieved significantly improved the electromagnetic force and power density. Moreover, precise control of swinging tail motion enables a bionic pufferfish to swim. Finally, HD-LMC is further utilized to successfully implement a soft rotary robot with integrated sensing and actuation capabilities. This groundbreaking research provides a theoretical and experimental basis for expanding the applications of liquid metal-based multi-dimensional complex flexible electronics and is expected to be widely used in liquid metal-integrated robotic systems.

Association of the weight-adjusted waist index with hypertension in the context of predictive, preventive, and personalized medicine.

Objective: Hypertension (HTN) is a prevalent global health concern. From the standpoint of preventive and personalized medicine (PPPM/3PM), early detection of HTN offers a crucial opportunity for targeted prevention and personalized treatment. This study aimed to evaluate the association between the weight-adjusted waist index (WWI) and HTN risk. Methods: A case-control study using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was conducted. Logistic regression models assessed the association between WWI and HTN. Subgroup analyses explored differences in age, sex, ethnicity, and diabetes status. Restricted cubic spline (RCS) analyses examined potential nonlinear relationships. Results: A total of 32,116 participants, with an average age of 49.28 ± 17.56 years, were included in the study. A significant positive association between WWI and the risk of HTN was identified (odds ratio [OR], 2.49; 95% CI, 2.39-2.59; P < 0.001). When WWI was categorized into quartiles (Q1-Q4), the highest quartile (Q4) exhibited a stronger association compared to Q1 (OR, 2.94; 95% CI, 2.65-3.27; P < 0.001). Subgroup analyses indicated that WWI was a risk factor for HTN across different populations, although variations in the magnitude of effect were observed. Furthermore, the findings from the RCS elucidated a nonlinear positive correlation between WWI and HTN. Conclusion: WWI is independently associated with HTN risk, highlighting its potential as a risk assessment tool in clinical practice. Incorporating WWI into early detection strategies enhances targeted prevention and personalized management of HTN. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00375-3.

[Population structure and fruiting ability of Rosa persica]. / 单叶蔷薇种群结构与结实能力.

We analyzed age structure and dynamics, spatial distribution patterns, and reproductive capabilities of four Rosa persica populations in Xinjiang, to evaluate the survival status of the species and explore the reasons behind its endangerment. The results showed that the populations had fewer individuals in the youngest (Ⅰ) and oldest (Ⅵ-Ⅷ) age classes, with a predominance of middle-aged individuals, resulting in an irregular pyramid-shaped distribution, described as "high in the middle, low on both sides". The populations were generally growing, but were susceptible to external environmental disturbances (Vpi'＞0, Pmax＞0). The mortality rate (qx) and vanish rate (Kx) peaked at age Ⅴ, leading to a sharp decline in plant abundance. The life expectancy (ex) decreased progressively with the increases of age class, reaching its lowest at age Ⅷ, which indicated minimal vitality at this stage. A time sequence analysis predicted a future dominance of individuals at age Ⅴ-Ⅷ, suggesting an aging trend. Spatially, the four populations were predominantly clumped, with the intensity of clumping ranked from highest to lowest as P4, P3, P1, and P2. P3 and P4 exhibited better reproductive capabilities than P1 and P2. There was a significant positive correlation between hundred-fruit weight and plant height and crown width, and between total seed number and crown width and hundred-fruit weight.

Integrating artificial intelligence (S-Detect software) and contrast-enhanced ultrasound for enhanced diagnosis of thyroid nodules: A comprehensive evaluation study.

PURPOSE: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K-TIRADS), S-Detect software and contrast-enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules. METHODS: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K-TIRADS. S-Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast-enhanced features. RESULTS: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K-TIRADS alone, S-Detect software alone, CEUS alone, the combined application of K-TIRADS and CEUS, the combined application of S-Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S-Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above. CONCLUSION: The utilization of S-Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S-Detect software with CEUS demonstrates superior diagnostic performance compared to employing K-TIRADS, S-Detect software, CEUS used individually, as well as the combined application of K-TIRADS with CEUS.

Lens Power and Associated Factors in Nonhuman Primate Subjects: A Cross-sectional Study.

Purpose: We aimed to examine the normative profile of crystalline lens power (LP) and its associations with ocular biometric parameters including age, axial length (AL), spherical equivalent refraction (SE), corneal radius (CR), lens thickness, anterior chamber depth, and AL/CR ratio among a cynomolgus monkey colony. Methods: This population-based cross-sectional Non-human Primate Eye Study recruited middle-aged subjects in South China. All included macaques underwent a detailed ophthalmic examination. LP was calculated using the modified Bennett's formula, with biometry data from an autorefractometer and A-scan. SPSS version 25.0 was used for statistical analysis. Results: A total of 301 macaques with an average age of 18.75 ± 2.95 years were collected in this study. The mean LP was 25.40 ± 2.96 D. Greater LP was independently associated with younger age, longer AL, and lower SE (P = 0.028, P = 0.025, and P = 0.034, respectively). LP showed a positive correlation with age, SE, CR, AL, lens thickness, and anterior chamber depth, whereas no correlation was observed between LP and AL/CR ratio. Conclusions: Our results suggested the LP distribution in the nonhuman primate colony and indicated that AL and SE strongly influenced the rate of LP. Therefore, this study contributed to a deeper understanding of the relative significance of the LP on the optics of the crystalline lens study.

Apelin (APLN) is a biomarker contributing to the diagnosis and prognosis of hepatocellular carcinoma.

Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models.

The relationship between physical exercise and sense of social fairness among college students: the chain-mediated role of perceived social support and life satisfaction.

Background: The development of a stable society is closely linked to a prevalent sense of social fairness. Participating in physical activities, which are inherently social, plays a crucial role in fostering mental stability within social contexts. Objective: This study aims to examine how physical exercise influences the sense of social fairness among college students, focusing on the potential mediating effects of perceived social support and life satisfaction. Methods: The study surveyed 496 Chinese college students using several scales: the Physical Activity Rating Scale-3 (PARS-3), Perceived Social Support Scale (PSSS), Satisfaction with Life Scale (SWLS), and Social Justice Scale (SJS). Results: (1) A positive correlation was found between physical exercise and sense of social fairness (r = 0.151, p < 0.01). A significant direct effect of physical exercise on sense of social fairness was also observed (ß = 0.151, t = 3.971, p < 0.01). (2) Physical exercise was a positive predictor of perceived social support (ß = 0.113, t = 4.062, p < 0.01), which in turn positively influenced both life satisfaction (ß = 0.333, t = 18.047, p < 0.01) and sense of social fairness (ß = 0.485, t = 6.931, p < 0.01). Additionally, life satisfaction had a positive effect on sense of social fairness (ß = 0.431, t = 3.247, p < 0.01). (3) Both perceived social support and life satisfaction significantly mediated the relationship between physical exercise and sense of social fairness through two pathways: physical exercise → perceived social support → sense of social fairness (mediating effect: 0.055); and physical exercise → perceived social support → life satisfaction → sense of social fairness (mediating effect: 0.016). Conclusion: (1) Physical exercise enhances both perceived social support and the sense of social fairness among college students, suggesting that it not only directly contributes to an enhanced sense of social fairness but also fosters supportive social relationships. (2) The influence of physical exercise on the sense of social fairness operates both directly and indirectly through the mediating roles of perceived social support and, sequentially, life satisfaction.

Non-invasive diagnosis of liver fibrosis via MRI using targeted gadolinium-based nanoparticles.

INTRODUCTION: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner. RESULTS: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice. CONCLUSIONS: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

2D spatiotemporal passive cavitation imaging and evaluation during ultrasound thrombolysis based on diagnostic ultrasound platform.

Acoustic cavitation plays a critical role in various biomedical applications. However, uncontrolled cavitation can lead to undesired damage to healthy tissues. Therefore, real-time monitoring and quantitative evaluation of cavitation dynamics is essential for understanding underlying mechanisms and optimizing ultrasound treatment efficiency and safety. The current research addressed the limitations of traditionally used cavitation detection methods by developing introduced an adaptive time-division multiplexing passive cavitation imaging (PCI) system integrated into a commercial diagnostic ultrasound platform. This new method combined real-time cavitation monitoring with B-mode imaging, allowing for simultaneous visualization of treatment progress and 2D quantitative evaluation of cavitation dosage within targeted area. An improved delay-and-sum (DAS) algorithm, optimized with a minimum variance (MV) beamformer, is utilized to minimize the side lobe effect and improve the axial resolution typically associated with PCI. In additional to visualize and quantitatively assess the cavitation activities generated under varied acoustic pressures and microbubble concentrations, this system was specifically applied to perform 2D cavitation evaluation for ultrasound thrombolysis mediated by different solutions, e.g., saline, nanodiamond (ND) and nitrogen-annealed nanodiamond (N-AND). This research aims to bridge the gap between laboratory-based research systems and real-time spatiotemporal cavitation evaluation demands in practical uses. Results indicate that this improved 2D cavitation monitoring and evaluation system could offer a useful tool for comprehensive evaluating cavitation-mediated effects (e.g., ultrasound thrombolysis), providing valuable insights into in-depth understanding of cavitation mechanisms and optimization of cavitation applications.