IncX3 plasmid-mediated spread of blaNDM gene in Enterobacteriaceae among children in China.

BACKGROUND: blaNDM gene was prevalent among children, and became the predominant cause of severe infection in infants and children. This study aimed to investigate the epidemiology and molecular characteristics of blaNDM in Enterobacteriaceae among children in China. METHODS: Carbapenem-resistant Enterobacteriaceae (CRE) were collected in the Children's Hospital of Fudan University from January 2016 to December 2022. Five carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) were screened by PCR method. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. blaNDM-carrying plasmids were typed by PCR-based Incompatibility (Inc) typing method. Moreover, plasmid comparison was performed with 213 publicly available IncX3 plasmids. RESULTS: A total of 330 CRE strains were enrolled, 96.4% of which carried carbapenemase genes. blaNDM gene accounted for 64.8% (214 strains) and included four variants, including blaNDM-1 (59.8%), blaNDM-5 (39.3%), blaNDM-7 (0.5%) and blaNDM-9 (0.5%). There were no predominant MLST lineages of blaNDM carrying strains. IncX3 was the major plasmid carrying blaNDM-1 (68.0%) and blaNDM-5 (72.6%), and was dominant in blaNDM-K. penumoniae (79.8%), blaNDM-E. coli (58.2%) and blaNDM-E. cloacae (61.0%), respectively. Majority (79.0%) of clinical IncX3 plasmids in the world carried blaNDM, and the prevalence of blaNDM in IncX3 plasmids was more common in China (95.8%) than other countries (58.1%, p<0.01). CONCLUSION: blaNDM is highly prevalent in CREs among children in China. The spread of blaNDM was mainly mediated by IncX3 plasmids. Surveillance and infection control on the spread of blaNDM among children are important.

Loss of an extensive ciliary connectome induces proteostasis and cell fate switching in a severe motile ciliopathy.

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in CCDC39 and CCDC40 cause severe disease not explained by loss of motility. Using human cells with pathological variants in these genes, Chlamydomonas genetics, cryo-electron microscopy, single cell RNA transcriptomics, and proteomics, we identified perturbations in multiple cilia-independent pathways. Absence of the axonemal CCDC39/CCDC40 heterodimer results in loss of a connectome of over 90 proteins. The undocked connectome activates cell quality control pathways, switches multiciliated cell fate, impairs microtubule architecture, and creates a defective periciliary barrier. Both cilia-dependent and independent defects are likely responsible for the disease severity. Our findings provide a foundation for reconsidering the broad cellular impact of pathologic variants in ciliopathies and suggest new directions for therapies.

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Ablation of Brg1 in fibroblast/myofibroblast lineages attenuates renal fibrosis in mice with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is one of the most common complications of diabetes and represents a prototypical form of chronic kidney disease (CKD). Interstitial fibrosis is a key pathological feature of DN. During DN-associated renal fibrosis, resident fibroblasts trans-differentiate into myofibroblasts to remodel the extracellular matrix, the underlying epigenetic mechanism of which is not entirely clear. METHODS: Diabetic nephropathy was induced in C57B6/j mice by a single injection with streptozotocin (STZ). Gene expression was examined by quantitative PCR and Western blotting. Renal fibrosis was evaluated by PicroSirius Red staining. RESULTS: We report that expression of Brg1, a chromatin remodeling protein, in renal fibroblasts was up-regulated during DN pathogenesis as assessed by single-cell RNA-seq. Treatment with high glucose similarly augmented Brg1 expression in primary renal fibroblasts in vitro. Importantly, Brg1 ablation in quiescent renal fibroblasts or in mature myofibroblasts equivalently attenuated renal fibrosis in the context of diabetic nephropathy in mice. Additionally, administration with a small-molecule Brg1 inhibitor PFI-3 ameliorated renal fibrosis and improved renal function in mice induced to develop DN. SIGNIFICANCE: In conclusion, our data provide novel genetic evidence that links Brg1 to fibroblast-myofibroblast transition and renewed rationale for targeting Brg1 in the intervention of DN-associated renal fibrosis.

ß-catenin inhibition disrupts the homeostasis of osteogenic/adipogenic differentiation leading to the development of glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased ß-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting ß-catenin signaling in glucocorticoid-induced GONFH rats. Col2+ lineage largely contributes to BMSCs and was found an osteogenic commitment in the femoral head through 9 mo of lineage trace. Specific deletion of ß-catenin gene (Ctnnb1) in Col2+ cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that ß-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH and identify an ideal genetic-modified mouse model of GONFH.

Suv39h1 contributes to activation of hepatic stellate cells in non-alcoholic fatty liver disease by enabling anaerobic glycolysis.

AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic. Excessive fibrogenesis, characterized by activation of hepatic stellate cells (HSCs), is a hallmark event in late stages of NAFLD. HSC activation is metabolically programmed by anaerobic glycolysis. In the present study we investigated the involvement of suppressor of variegation 3-9 homolog 1 (Suv39h1), a lysine methyltransferase, in NAFLD-associated liver fibrosis. METHODS AND MATERIALS: Liver fibrosis was induced by feeding the mice with a methionine-and-choline deficient (MCD) diet for 8 weeks. RESULTS: We report that germline deletion of Suv39h1 attenuated liver fibrosis in mice fed an MCD diet. In addition, HSC conditional deletion of Suv39h1 similarly ameliorated liver fibrosis in the NAFLD mice. Interestingly, co-culturing with hepatocytes exposed to palmitate promoted glycolysis in wild type HSCs but not in Suv39h1 deficient HSCs. Mechanistically, Suv39h1 facilitated the recruitment of hypoxia induced factor (HIF-1α) to stimulate the transcription of hexokinase 2 (HK2) in HSCs thereby enhancing glycolysis. Importantly, a positive correlation between Suv39h1, HK2, and myofibroblast markers was identified in liver specimens from NAFLD patients. SIGNIFICANCE: In conclusion, our data identify a novel pathway that contributes to the liver fibrosis and points to the possibility of targeting Suv39h1 for the intervention of liver fibrosis in NAFLD.

The prospective associations among time management tendency, negative emotions, and problematic smartphone use in Chinese nursing students: enlightenment from COVID-19.

Purpose: The regularity of epidemic prevention and control measures in China has meant that nursing students have been exposed to more electronic devices, while problematic smartphone use has increased. The purpose of this study is to determine the prospective associations among time management tendency, negative emotions, and problematic smartphone use in nursing students during the COVID-19 pandemic. Methods: A longitudinal study was conducted between November 2021 and May 2022. A total of 989 nursing students participated. The convenience sampling method was adopted and the following tools were used: the Adolescence Time Management Disposition Scale, the Depression Anxiety Stress Scales - 21, and the Mobile Phone Addiction Index. Multiple parallel mediation models were used by Mplus. Results: Time management tendency had a significantly negative effect on problematic smartphone use (p < 0.05). Further tests using mediation models showed that stress as a negative emotion mediated the relationship between time management tendency and problematic smartphone use (p < 0.05) over time. Conclusion: Nursing educators need to strengthen the stress resistance and time management ability of nursing students.

Sleep health and associated factors among undergraduates during the COVID-19 in China: A two-wave network analysis.

Using network analysis, the current study investigated the pathways that underlie selected components of sleep health and their changes over time. Undergraduates (N = 1423; 80.60% female) completed a two-wave survey, sleep health (i.e. chronotypologies (CTs), sleep procrastination (SP), sleep quality (SQ)), psychological distress (PD), emotion regulation (ER), self-control (SC), problematic smartphone use (PSU) were measured. CTs, SP, and SQ formed a spatially contiguous pattern that remained unchanged in both waves. ER and PD node increased its strength, betweenness, and closeness in the network, while the link between the two was strengthened at T2. PSU was connected to SP, but not to CTs and SQ during both waves. In the context of the network approach, SP had the highest strength, and its associations with other dimensions of individual sleep may represent key factors in understanding the influence of exposure to the COVID-19 outbreak on sleep health.

Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study.

OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.

Ultrabright NIR-II Nanoprobe for Image-Guided Accurate Resection of Tiny Metastatic Lesions.

Fluorescence imaging is a vital way to delineate the tumor boundaries. Here, we achieve a NIR-II aggregation-induced emission luminogen (AIEgen) with a fluorescence quantum yield (QY) of 12.6% in water through straightforward alkyl side chain modification. After loading of NIR-II AIEgen into polystyrene (PS) nanospheres, the thermal deactivation pathway is extremely limited, thereby concentrating absorption excitation on fluorescence emission. The fluorescence intensity is further enhanced by 5.4 times, the QY increases to 21.1%, and the NIR-II imaging signal is accordingly enhanced by 8.7 times, surpassing conventional DSPE-PEG carriers. The NIR-II@PS nanoprobe showcases superior resolution and tissue penetration depth compared to indocyanine green (ICG) and short-range near-infrared AIEgens. In vivo investigations underscore its tumor-to-normal tissue ratio (3.9) at 24 h post intravenous injection, enabling complete resection of ≤1 mm metastases under NIR-II bioimaging guidance. Additionally, the PS carrier-nanoparticles exhibit low toxicity in vivo, laying a promising foundation for the future design of medical nanomaterials.

Histone methyltransferase Suv39h1 regulates hepatic stellate cell activation and is targetable in liver fibrosis.

OBJECTIVE: Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. DESIGN: HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat-Cre mice or the Postn-CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. RESULTS: We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice. More importantly, Suv39h1 inhibition by a small-molecule compound chaetocin dampened HSC-myofibroblast transition in cell culture and mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed HMOX1 transcription. HMOX1 depletion blunted the effects of Suv39h1 inhibition on HSC-myofibroblast transition in vitro and liver fibrosis in vivo. Transcriptomic analysis revealed that HMOX1 might contribute to HSC-myofibroblast transition by modulating retinol homeostasis. Finally, myofibroblast-specific HMOX1 overexpression attenuated liver fibrosis in both a preventive scheme and a therapeutic scheme. CONCLUSIONS: Our data demonstrate a previously unrecognised role for Suv39h1 in liver fibrosis and offer proof-of-concept of its targetability in the intervention of cirrhosis.

Transcriptional expression of PHR2 is positively controlled by the calcium signaling transcription factor Crz1 through its binding motif in the promoter.

IMPORTANCE: The fungal cell wall consists of glucans, mannoproteins, and chitin and is essential for cell viability, morphogenesis, and pathogenesis. The enzymes of the GH72 family are responsible for ß-(1,3)-glucan elongation and branching, which is crucial for the formation of the glucan-chitin polymer at the bud neck of yeast cells. In the human fungal pathogen Candida albicans, there are five GH72 enzyme-encoding genes: PHR1, PHR2, PHR3, PGA4, and PGA5. It is known that expression of PHR1 and PHR2 is controlled by the pH-responsive Rim101 pathway through the transcription factor Rim101. In this study, we have demonstrated that the transcription expression of PHR2 is also controlled by the transcription factor Crz1 through its binding motif in the promoter. Therefore, we have uncovered a dual-control mechanism by which PHR2 expression is negatively regulated via CaRim101 through the pH-responsive pathway and positively modulated by CaCrz1 through the calcium/calcineurin signaling pathway.

Are "night owls" or "morning larks" more likely to delay sleep due to problematic smartphone use? a cross-lagged study among undergraduates.

Sleep is an important physiological process, but staying up late has become a worldwide problem, particularly among university students. Sleep procrastination has been found to associated with sleep biorhythms and problematic smartphone use ("PSU") in previous studies. This two-wave study examines the longitudinal reciprocal relationship between PSU and sleep procrastination, together with the moderating role of sleep biorhythms. Participants comprised 1,423 Chinese university students. The results revealed that PSU and sleep procrastination are reciprocally related. Additionally, sleep biorhythms moderated this relationship, as PSU at T1 significantly predicted sleep procrastination at T2 for the morning larks group but not the night owls group. Accordingly, both PSU and sleep biorhythms should be considered when developing interventions for sleep procrastination.

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). AIM OF STUDY: The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. MATERIALS AND METHODS: Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. RESULTS: Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. CONCLUSION: In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.

A bibliometric and visualized analysis of nanoparticles in musculoskeletal diseases (from 2013 to 2023).

As the pace of research on nanomedicine for musculoskeletal (MSK) diseases accelerates, there remains a lack of comprehensive analysis regarding the development trajectory, primary authors, and research focal points in this domain. Additionally, there's a need of detailed elucidation of potential research hotspots. The study gathered articles and reviews focusing on the utilization of nanoparticles (NPs) for MSK diseases published between 2013 and 2023, extracted from the Web of Science database. Bibliometric and visualization analyses were conducted using various tools such as VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package. China, the USA, and India emerged as the key drivers in this research domain. Among the numerous institutions involved, Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University exhibited the highest productivity levels. Vallet-Regi Maria emerged as the most prolific author in this field. International Journal of Nanomedicine accounted for the largest number of publications in this area. The top five disorders of utmost significance in this field include osteosarcoma, cartilage diseases, bone fractures, bone neoplasms, and joint diseases. These findings are instrumental in providing researchers with a comprehensive understanding of this domain and offer valuable perspectives for future investigations.

Aucubin Alleviates Intervertebral Disc Degeneration by Repressing NF-κB-NLRP3 Inflammasome Activation in Endplate Chondrocytes.

Background: Intervertebral disc degeneration (IDD) is a prevalent degenerative disease and often recognized as the primary cause of lower back pain (LBP). Aucubin (Au) is a natural compound with anti-inflammatory properties in various diseases. The present study aimed to confirm the therapeutic effect of Au on IDD and explore its potential mechanism in vivo and in vitro. Methods: The process of IDD was simulated using the lumbar spine instability (LSI) model. In vivo, the therapeutic effect of Au on LSI-induced mice was evaluated by micro-CT and histomorphometry. Additionally, immunohistochemistry was applied to detect the cartilage metabolism and inflammasome activation in endplate. In vitro, the cytotoxicity of Au on ATDC5 cells was detected by Cell Counting Kit-8 (CCK-8), and the biological effects of Au were evaluated by Quantitative Real-time PCR (qRT-PCR) and Western blotting. Results: Micro-CT analysis showed that Au administration significantly alleviated LSI-induced disc volume narrowing and endplate cartilage degeneration, which was further supported by Alcian Blue Hematoxylin/Orange G (ABH/OG) staining. Immunohistochemistry results verified that Au could increase the expression of Col2α1 and Aggrecan, reduce the expression of Mmp-13, and attenuate the degradation of the endplate extracellular matrix (ECM). Mechanistically, we found that Au treatment, both in vivo and in vitro, significantly inhibited NF-κB-NLRP3 inflammasome activation in chondrocytes as determined by the decreased expression of p-P65, NLRP3, and Caspase-1. Discussion: Taken together, our findings have demonstrated for the first time that Au treatment ameliorated the degeneration of cartilage endplates in IDD may by inhibiting NF-κB-NLRP3 inflammasome activation in chondrocytes and provided a potential candidate for the treatment of IDD.

Polystyrene-Based Matrix to Enhance the Fluorescence of Aggregation-Induced Emission Luminogen for Fluorescence-Guided Surgery.

Achieving ultrabright fluorogens is a key issue for fluorescence-guided surgery (FGS). Fluorogens with aggregation-induced emission (AIEgens) are potential agents for FGS on the benefit of the bright fluorescence in physiological conditions. Herein, the fluorescence brightness of AIEgen is further improved by preparing the nanoparticle using a polystyrene-based matrix and utilizing it for tumor FGS with a high signal-to-background ratio. After encapsulating AIEgen into polystyrene-poly (ethylene glycol) (PS-PEG), the fluorescence intensity of the prepared AIE@PS-PEG nanoparticles is multiple times that of nanoparticles in 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol) (DSPE-PEG), a commonly used polymer matrix for nanoparticle preparation. Molecular dynamics simulations suggest that higher free energy is required for the outer rings of AIEgen to rotate in polystyrene than in the DSPE, indicating that the benzene rings in polystyrene can restrict the intramolecular motions of AIEgen better than the alkyl chain in DSPE-PEG. Fluorescence correlation microscopy detections suggest that the triplet excited state of AIEgens is less in PS-PEG than in DSPE-PEG. The restricted intramolecular motions and suppressed triplet excited state result in ultrabright AIE@PS-PEG nanoparticles, which are more conducive to illuminating tumor tissues in the intestine for FGS. The illumination of metastatic tumors in lungs by AIE@PS-PEG nanoparticles is also tried.

Magnetic susceptibility and R2*-based texture analysis for evaluating liver fibrosis in chronic liver disease.

PURPOSE: To explore potential feasibility of texture features in magnetic susceptibility and R2* maps for evaluating liver fibrosis. METHODS: Thirty-one patients (median age 46 years; 22 male) with chronic liver disease were prospectively recruited and underwent magnetic resonance imaging (MRI), blood tests, and liver biopsy. Susceptibility and R2* maps were obtained using a 3-dimensional volumetric interpolated breath-hold examination sequence with a 3T MRI scanner. Texture features, including histogram, gray-level co-occurrence matrix (GLCM), gray-level dependence matrix (GLDM), gray-level run length matrix (GLRLM), gray-level size zone matrix (GLSZM), and neighboring gray tone difference matrix (NGTDM) features, were extracted. Texture features and blood test results of non-significant (Ishak-F < 3) and significant fibrosis patients (Ishak-F ≥ 3) were compared, and correlations with Ishak-F stages were analyzed. Areas under the curve (AUCs) were calculated to determine the efficacy for evaluating liver fibrosis. RESULTS: Nine texture features of susceptibility maps and 19 features of R2* maps were significantly different between non-significant and significant fibrosis groups (all P < 0.05). Large dependence high gray-level emphasis (LDHGLE) of GLDM and long run high gray-level emphasis (LRHGLE) of GLRLM in R2* maps showed significantly negative and good correlations with Ishak-F stages (r = -0.616, P < 0.001; r = -0.637, P < 0.001). Busyness (NGTDM) in susceptibility maps, LDHGLE of GLDM and LRHGLE of GLRLM in R2* maps yield the highest AUCs (AUC = 0.786, P = 0.007; AUC = 0.807, P = 0.004; AUC = 0.819, P = 0.003). CONCLUSION: Texture characteristics of susceptibility and R2* maps revealed possible staging values for liver fibrosis. Susceptibility and R2*-based texture analysis may be a useful and noninvasive method for staging liver fibrosis.

Quantitative dynamic contrast-enhance MRI parameters for rectal carcinoma characterization: correlation with tumor tissue composition.

OBJECTIVE: To investigate the relationship between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) measurements and the potential composition of rectal carcinoma. METHODS: Twenty-four patients provided informed consent for this study. DCE-MRI was performed before total mesorectal excision. Quantitative parameters were calculated based on a modified Tofts model. Whole-mount immunohistochemistry and Masson staining sections were generated and digitized at histological resolution. The percentage of tissue components area was measured. Pearson correlation analysis was used to evaluate the correlations between pathological parameters and DCE-MRI parameters. RESULTS: On the World Health Organization (WHO) grading scale, there were significant differences in extracellular extravascular space (Ktrans) (F = 9.890, P = 0.001), mean transit time (MTT) (F = 9.890, P = 0.038), CDX-2 (F = 4.935, P = 0.018), and Ki-67 (F = 4.131, P = 0.031) among G1, G2, and G3. ECV showed significant differences in extramural venous invasion (t = - 2.113, P = 0.046). Ktrans was strongly positively correlated with CD34 (r = 0.708, P = 0.000) and moderately positively correlated with vimentin (r = 0.450, P = 0.027). Interstitial volume (Ve) was moderately positively correlated with Masson's (r = 0.548, P = 0.006) and vimentin (r = 0.417, P = 0.043). There was a moderate negative correlation between Ve and CDX-2 (r = - 0.441, P = 0.031). The rate constant from extracellular extravascular space to blood plasma (Kep) showed a strong positive correlation with CD34 expression (r = 0.622, P = 0.001). ECV showed a moderate negative correlation with CDX-2 (r = - 0.472, P = 0.020) and a moderate positive correlation with collagen fibers (r = 0.558, P = 0.005). CONCLUSION: The dynamic contrast-enhanced MRI-derived parameters measured in rectal cancer were significantly correlated with the proportion of histological components. This may serve as an optimal imaging biomarker to identify tumor tissue components.

A glycosylated Phr1 protein is induced by calcium stress and its expression is positively controlled by the calcium/calcineurin signaling transcription factor Crz1 in Candida albicans.

As one of the most important human fungal pathogens, Candida albicans senses and adapts to host niches with different pH values through the pH-responsive Rim101 pathway. Its transcription factor Rim101 activates the expression of alkaline pH-induced genes including PHR1 that encodes a glycosylphosphatidylinsitol-anchored ß(1,3)-glucanosyltransferase critical for hyphal wall formation. The calcium/calcineurin signaling pathway is mediated by the transcription factor Crz1 in yeasts and other lower eukaryotes. Here we report that deletion of PHR1 leads to calcium sensitivity of C. albicans cells. In addition, expression of Phr1 is induced by calcium stress and under the control of Crz1 in C. albicans. EMSA assay demonstrates that Crz1 binds to one CDRE element in the PHR1 promoter. Alkaline treatment induces two species of glycosylated Phr1 proteins with different degrees of glycosylation, which is independent of Crz1. In contrast, only one species of Phr1 protein with a low degree of glycosylation is induced by calcium stress in a Crz1-dependent fashion. Therefore, we have provided an evidence that regulation of cell wall remodeling is integrated through differential degrees of Phr1 glycosylation by both the pH-regulated Rim101 pathway and the calcium/calcineurin signaling pathway in C. albicans. Video Abstract.