CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice.

Podocyte lipotoxicity mediated by impaired cellular cholesterol efflux plays a crucial role in the development of diabetic kidney disease (DKD), and the identification of potential therapeutic targets that regulate podocyte cholesterol homeostasis has clinical significance. Coiled-coil domain containing 92 (CCDC92) is a novel molecule related to metabolic disorders and insulin resistance. However, whether the expression level of CCDC92 is changed in kidney parenchymal cells and the role of CCDC92 in podocytes remain unclear. In this study, we found that Ccdc92 was significantly induced in glomeruli from type 2 diabetic mice, especially in podocytes. Importantly, upregulation of Ccdc92 in glomeruli was positively correlated with an increased urine albumin-to-creatinine ratio (UACR) and podocyte loss. Functionally, podocyte-specific deletion of Ccdc92 attenuated proteinuria, glomerular expansion and podocyte injury in mice with DKD. We further demonstrated that Ccdc92 contributed to lipid accumulation by inhibiting cholesterol efflux, finally promoting podocyte injury. Mechanistically, Ccdc92 promoted the degradation of ABCA1 by regulating PA28α-mediated proteasome activity and then reduced cholesterol efflux. Thus, our studies indicate that Ccdc92 contributes to podocyte injury by regulating the PA28α/ABCA1/cholesterol efflux axis in DKD.

Prediction of delayed graft function by early salivary microbiota following kidney transplantation.

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.

A Stepwise Interventional Strategy for the Removal of Adherent Totally Implanted Central Venous Access Port Catheters.

BACKGROUND: To evaluate the safety and effectiveness of a stepwise interventional strategy for the removal of adherent totally implanted central venous access port catheters, consisting of a guidewire support, antegrade coaxial separation, and retrograde coaxial separation with increasing technical complexity. METHODS: This study has a retrospective design. Thirty-two patients who had failed routine removal of the port catheter and were then transferred to interventional radiology between November 2017 and December 2023 were reviewed. The technical success and complication rates were recorded. RESULTS: All adherent catheters were successfully removed without catheter fragmentation, using guidewire support (n = 21), antegrade coaxial separation (n = 5), and retrograde coaxial separation (n = 6). The technical success rate was 100%, and no complications occurred. CONCLUSIONS: The proposed stepwise interventional strategy successfully removed adherent port catheters, with good safety and high effectiveness. It appeared to reduce the incidence of catheter fracture during the removal of adherent totally implantable central venous access port catheters.

Transcriptome Analysis Reveals Cross-Talk between the Flagellar Transcriptional Hierarchy and Secretion System in Plesiomonas shigelloides.

Plesiomonas shigelloides, a Gram-negative bacillus, is the only member of the Enterobacteriaceae family able to produce polar and lateral flagella and cause gastrointestinal and extraintestinal illnesses in humans. The flagellar transcriptional hierarchy of P. shigelloides is currently unknown. In this study, we identified FlaK, FlaM, FliA, and FliAL as the four regulators responsible for polar and lateral flagellar regulation in P. shigelloides. To determine the flagellar transcription hierarchy of P. shigelloides, the transcriptomes of the WT and ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were carried out for comparison in this study. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and luminescence screening assays were used to validate the RNA-seq results, and the Electrophoretic Mobility Shift Assay (EMSA) results revealed that FlaK can directly bind to the promoters of fliK, fliE, flhA, and cheY, while the FlaM protein can bind directly to the promoters of flgO, flgT, and flgA. Meanwhile, we also observed type VI secretion system (T6SS) and type II secretion system 2 (T2SS-2) genes downregulated in the transcriptome profiles, and the killing assay revealed lower killing abilities for ΔflaK, ΔflaM, ΔfliA, and ΔfliAL compared to the WT, indicating that there was a cross-talk between the flagellar hierarchy system and bacterial secretion system. Invasion assays also showed that ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were less effective in infecting Caco-2 cells than the WT. Additionally, we also found that the loss of flagellar regulators causes the differential expression of some of the physiological metabolic genes of P. shigelloides. Overall, this study aims to reveal the transcriptional hierarchy that controls flagellar gene expression in P. shigelloides, as well as the cross-talk between motility, virulence, and physiological and metabolic activity, laying the groundwork for future research into P. shigelloides' coordinated survival in the natural environment and the mechanisms that infect the host.

Deep learning-based detection of irreversible pulpitis in primary molars.

BACKGROUND: Changes in healthy and inflamed pulp on periapical radiographs are traditionally so subtle that they may be imperceptible to human experts, limiting its potential use as an adjunct clinical diagnostic feature. AIM: This study aimed to investigate the feasibility of an image-analysis technique based on the convolutional neural network (CNN) to detect irreversible pulpitis in primary molars on periapical radiographs (PRs). DESIGN: This retrospective study was performed in two health centres. Patients who received indirect pulp therapy at Peking University Hospital for Stomatology were retrospectively identified and randomly divided into training and validation sets (8:2). Using PRs as input to an EfficientNet CNN, the model was trained to categorise cases into either the success or failure group and externally tested on patients who presented to our affiliate institution. Model performance was evaluated using sensitivity, specificity, accuracy and F1 score. RESULTS: A total of 348 PRs with deep caries were enrolled from the two centres. The deep learning model achieved the highest accuracy of 0.90 (95% confidence interval: 0.79-0.96) in the internal validation set, with an overall accuracy of 0.85 in the external test set. The mean greyscale value was higher in the failure group than in the success group (p = .013). CONCLUSION: The deep learning-based model could detect irreversible pulpitis in primary molars with deep caries on PRs. Moreover, this study provides a convenient and complementary method for assessing pulp status.

[Ethical considerations for medical applications of implantable brain-computer interfaces].

Implantable brain-computer interfaces (BCIs) have potentially important clinical applications due to the high spatial resolution and signal-to-noise ratio of electrodes that are closer to or implanted in the cerebral cortex. However, the surgery and electrodes of implantable BCIs carry safety risks of brain tissue damage, and their medical applications face ethical challenges, with little literature to date systematically considering ethical norms for the medical applications of implantable BCIs. In order to promote the clinical translation of this type of BCI, we considered the ethics of practice for the medical application of implantable BCIs, including: reducing the risk of brain tissue damage from implantable BCI surgery and electrodes, providing patients with customized and personalized implantable BCI treatments, ensuring multidisciplinary collaboration in the clinical application of implantable BCIs, and the responsible use of implantable BCIs, among others. It is expected that this article will provide thoughts and references for the research and development of ethics of the medical application of implantable BCI.

P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model.

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.

Synthesis of zwitterionic polyelectrolyte nanogels via electrostatic-templated polymerization.

Zwitterionic polyelectrolyte nanogels are prospective nanocarriers due to their soft loading pocket and regulated charges. We here report a facile strategy, namely, electrostatic-templated polymerization (ETP) for synthesizing zwitterionic nanogels with controlled size and properties. Specifically, with anionic-neutral diblock polymers as the template, zwitterionic monomers such as carboxybetaine methacrylate (CBMA) or carboxybetaine acrylamide (CBAA) are polymerized together with a cross-linker at pH 2 where the monomers exhibit only positive charge due to the protonation of the carboxyl group. The obtained polyelectrolyte complex micelles dissociate upon introducing a concentrated salt. The subsequent separation yields the released template and zwitterionic nanogels with regulated size and swelling ability, achieved by tuning the salt concentration and cross-linker fraction during polymerization. The obtained PCBMA nanogels exhibit charges depending on the pH, which enables not only the selective loading of different dye molecules, but also encapsulation and intracellular delivery of cytochrome c protein. Our study develops a facile and robust way for fabricating zwitterionic nanogels and validates their potential applications as promising nanocarriers for load and delivery of functional charged cargos.

PGAM4 silencing inhibited glycolysis and chemoresistance to temozolomide in glioma cells.

Gliomas account for about 80% of malignant brain tumors. The incidence of a new brain tumor is 6.4 per 100,000 persons per year with an overall 5-year survival rate of 33.4%. Regardless of the great advances that have been made in recent years, the causes and pathogenesis of glioma remain unclear. Here we study how phosphoglycerate mutase 4 (PGAM4) contributes to glioma. Using a variety of methods to examine glioma cell viability, proliferation, apoptosis, glycolysis, as well as ChIP coanalysis with modified histone H3, we showed that PGAM4 was significantly upregulated in patients with glioma and associated with poor survival. Silencing PGAM4 attenuated cell viability, proliferation, and glycolysis in T98G cells and suppressed tumor growth in vivo, while overexpressing PGAM4 promoted cell viability, proliferation, and glycolysis in U251 cells via regulating glycolysis pathway. Study also revealed that PGAM4 was regulated by EP300-mediated modifications of H3K27ac. PGAM4 silencing inhibited cell viability and proliferation, suppressed tumor growth, and decreased chemoresistance to temozolomide in glioma cells through suppressing glycolysis.

GRg1 inhibits the TLR4/NF-kB signaling pathway by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR.

BACKGROUND: Diabetic retinopathy (DR) is a common diabetic neurodegenerative disease that affects vision in severe cases. Current therapeutic drugs are ineffective for some patients with severe side effects, and ginsenoside-Rg1 (GRg1) has been shown to protect against DR and may serve as a new potential drug for DR. This study aimed to confirm the protective effect of GRg1 against DR and its molecular mechanism. METHODS: Human retinal microvascular endothelial cells (hRMECs) and rats were used to construct DR models in vitro and in vivo. Cell proliferation was detected by BrdU assays, the cell cycle was detected by flow cytometry, and TNF-α, IL-6 and IL-1ß levels were detected by ELISA. qRT‒PCR, Western blotting and immunohistochemistry were used to detect the expression of related genes and proteins, and angiogenesis assays were used to assess angiogenesis. RIP and RNA pull down assays were used to determine the relationship between miR-216a-5p and TLR4; retinal structure and changes were observed by HE staining and retinal digestive spread assays. RESULTS: GRg1 effectively inhibited HG-induced hRMEC proliferation, cell cycle progression and angiogenesis and reduced the levels of intracellular inflammatory cytokines and growth factors. HG downregulated the expression of miR-216a-5p and upregulated the expression of TLR4/NF-kB signaling pathway-related proteins. Importantly, GRg1 inhibited TLR4/NF-kB signaling pathway activation by upregulating miR-216a-5p, thereby inhibiting HG-induced cell proliferation, cell cycle progression, angiogenesis, and the production of inflammatory cytokines and growth factors. In addition, animal experiments confirmed the results of the cell experiments. CONCLUSIONS: GRg1 inhibits TLR4/NF-kB signaling by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR, providing a potential therapeutic strategy for DR.

Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. METHODS: Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. RESULTS: Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1ß, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1ß, IL-18, HMGB1 and the cleaved form of GSDMD. CONCLUSIONS: Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

Bayesian causal inference: a critical review.

This paper provides a critical review of the Bayesian perspective of causal inference based on the potential outcomes framework. We review the causal estimands, assignment mechanism, the general structure of Bayesian inference of causal effects and sensitivity analysis. We highlight issues that are unique to Bayesian causal inference, including the role of the propensity score, the definition of identifiability, the choice of priors in both low- and high-dimensional regimes. We point out the central role of covariate overlap and more generally the design stage in Bayesian causal inference. We extend the discussion to two complex assignment mechanisms: instrumental variable and time-varying treatments. We identify the strengths and weaknesses of the Bayesian approach to causal inference. Throughout, we illustrate the key concepts via examples. This article is part of the theme issue 'Bayesian inference: challenges, perspectives, and prospects'.

Is Convolutional Neural Network Accurate for Automatic Detection of Zygomatic Fractures on Computed Tomography?

PURPOSE: Zygomatic fractures involve complex anatomical structures of the mid-face and the diagnosis can be challenging and labor-consuming. This research aimed to evaluate the performance of an automatic algorithm for the detection of zygomatic fractures based on convolutional neural network (CNN) on spiral computed tomography (CT). MATERIALS AND METHODS: We designed a cross-sectional retrospective diagnostic trial study. Clinical records and CT scans of patients with zygomatic fractures were reviewed. The sample consisted of two types of patients with different zygomatic fractures statuses (positive or negative) in Peking University School of Stomatology from 2013 to 2019. All CT samples were randomly divided into three groups at a ratio of 6:2:2 as training set, validation set, and test set, respectively. All CT scans were viewed and annotated by three experienced maxillofacial surgeons, serving as the gold standard. The algorithm consisted of two modules as follows: (1) segmentation of the zygomatic region of CT based on U-Net, a type of CNN model; (2) detection of fractures based on Deep Residual Network 34(ResNet34). The region segmentation model was used first to detect and extract the zygomatic region, then the detection model was used to detect the fracture status. The Dice coefficient was used to evaluate the performance of the segmentation algorithm. The sensitivity and specificity were used to assess the performance of the detection model. The covariates included age, gender, duration of injury, and the etiology of fractures. RESULTS: A total of 379 patients with an average age of 35.43 ± 12.74 years were included in the study. There were 203 nonfracture patients and 176 fracture patients with 220 sites of zygomatic fractures (44 patients underwent bilateral fractures). The Dice coefficient of zygomatic region detection model and gold standard verified by manual labeling were 0.9337 (coronal plane) and 0.9269 (sagittal plane), respectively. The sensitivity and specificity of the fracture detection model were 100% (p＞.05). CONCLUSION: The performance of the algorithm based on CNNs was not statistically different from the gold standard (manual diagnosis) for zygomatic fracture detection in order for the algorithm to be applied clinically.

Maturation, Morphology, and Function: The Decisive Role of Intestinal Flora on Microglia: A Review.

Recent studies have shown that the gut microbiota regulates intestinal function and maintains intestinal homeostasis, as well as interacting with the central nervous system to affect brain function and human behavior. Microglia are the most common immune cell type in the central nervous system during homeostasis. These cells play an important role in immune surveillance by responding to infections and other pathological conditions. Microglia also play a major role in maintaining brain homeostasis in both developing and adult mice by phagocytosing cell debris and regulating the formation of neural networks. The specific signaling pathways and cytokines that control the maturation and activation of microglia are currently not fully established. However, research on germ-free (GF) mice and specific pathogen-free (SPF) mice indicate that gut microbiota have important interactions with microglia. Here, we review the latest research findings on how gut microbiota can affect the morphology, maturation, phenotype and function of microglia. We also discuss recent advances in the gut microbiota-microglia-disease axis.

Intelligent Health Assessment of Aviation Bearing Based on Deep Transfer Graph Convolutional Networks under Large Speed Fluctuations.

As a critical support and fixed component of aero engines, electro-hydrostatic actuators, and other equipment, the operation of aviation bearings is often subject to high speed, high-temperature rise, large load, and other continuous complex fluctuation conditions, which makes their health assessment tasks more difficult. To solve this problem, an intelligent health assessment method based on a new Deep Transfer Graph Convolutional Network (DTGCN) is proposed for aviation bearings under large speed fluctuation conditions. First, a new DTGCN algorithm is designed, which mainly uses the domain adaptation mechanism to enhance the performance of Graph Convolutional Network (GCN) and the generalization performance of transfer properties. Specifically, order spectrum analysis is employed to resample the vibration signals of aviation bearings and transform them into order spectral signals. Then, the trained 1dGCN is used as the feature extractor, and the designed Dynamic Multiple Kernel Maximum Mean Discrepancy (DMKMMD) is calculated to match the difference in edge distribution. Finally, the aligned features are fed into the softmax classifier for intelligent health assessment. The effectiveness of the proposed diagnostic algorithm and method are validated by using aviation bearing fault data set under large speed fluctuation conditions.

Transcriptome Analysis Reveals the Effect of PdhR in Plesiomonas shigelloides.

The pyruvate dehydrogenase complex regulator (PdhR) was originally identified as a repressor of the pdhR-aceEF-lpd operon, which encodes the pyruvate dehydrogenase complex (PDHc) and PdhR itself. According to previous reports, PdhR plays a regulatory role in the physiological and metabolic pathways of bacteria. At present, the function of PdhR in Plesiomonas shigelloides is still poorly understood. In this study, RNA sequencing (RNA-Seq) of the wild-type strain and the ΔpdhR mutant strains was performed for comparison to identify the PdhR-controlled pathways, revealing that PdhR regulates ~7.38% of the P. shigelloides transcriptome. We found that the deletion of pdhR resulted in the downregulation of practically all polar and lateral flagella genes in P. shigelloides; meanwhile, motility assay and transmission electron microscopy (TEM) confirmed that the ΔpdhR mutant was non-motile and lacked flagella. Moreover, the results of RNA-seq and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) showed that PdhR positively regulated the expression of the T3SS cluster, and the ΔpdhR mutant significantly reduced the ability of P. shigelloides to infect Caco-2 cells compared with the WT. Consistent with previous research, pyruvate-sensing PdhR directly binds to its promoter and inhibits pdhR-aceEF-lpd operon expression. In addition, we identified two additional downstream genes, metR and nuoA, that are directly negatively regulated by PdhR. Furthermore, we also demonstrated that ArcA was identified as being located upstream of pdhR and lpdA and directly negatively regulating their expression. Overall, we revealed the function and regulatory pathway of PdhR, which will allow for a more in-depth investigation into P. shigelloides pathogenicity as well as the complex regulatory network.

Convolutional neural network models for automatic diagnosis and graduation in skin frostbite.

The study aimed to develop and validate a convolutional neural network (CNN)-based deep learning method for automatic diagnosis and graduation of skin frostbite. A dataset of 71 annotated images was used for the training, the validation, and the testing based on ResNet-50 model. The performances were evaluated with the test set. The diagnosis and graduation performance of our approach was compared with two residents from burns department. The approach correctly identified all the frostbite of IV (18/18, 100%), but with respectively 1 mistake in the diagnosis of degree I (29/30, 96.67%), II (28/29, 96.55%) and III (37/38, 97.37%). The accuracy of the approach on the whole test set was 97.39% (112/115). The accuracy of the two residents were respectively 77.39% and 73.04%. Weighted Kappa of 0.583 indicates good reliability between the two residents (P = .445). Kendall's coefficient of concordance is 0.326 (P = .548), indicating differences in accuracy between the approach and the two residents. Our approach based on CNNs demonstrated an encouraging performance for the automatic diagnosis and graduation of skin frostbite, with higher accuracy and efficiency.

[Ethics considerations on brain-computer interface technology].

The development and potential application of brain-computer interface (BCI) technology is closely related to the human brain, so that the ethical regulation of BCI has become an important issue attracting the consideration of society. Existing literatures have discussed the ethical norms of BCI technology from the perspectives of non-BCI developers and scientific ethics, while few discussions have been launched from the perspective of BCI developers. Therefore, there is a great need to study and discuss the ethical norms of BCI technology from the perspective of BCI developers. In this paper, we present the user-centered and non-harmful BCI technology ethics, and then discuss and look forward on them. This paper argues that human beings can cope with the ethical issues arising from BCI technology, and as BCI technology develops, its ethical norms will be improved continuously. It is expected that this paper can provide thoughts and references for the formulation of ethical norms related to BCI technology.

Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice. / å—æ›¿éº¦è€ƒé šé ¯å‡è½»å››æ°¯åŒ–ç¢³è¯±å¯¼çš„å°é¼ è‚çº¤ç»´åŒ–.

OBJECTIVES: Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism. METHODS: A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-ß1, α-SMA, and COL1 were detected using real-time PCR. RESULTS: Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-ß1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-ß1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF. CONCLUSIONS: MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-ß1. This study is expected to provide a target for the treatment of hepatic fibrosis.

Fluorescent Probes Based on AIEgen-Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity.

Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.