Effects of different routes of heparin on instant blood-mediated inflammatory reaction after portal vein islet transplantation. / ä¸åŒè·¯å¾„è‚ç´ å¯¹é—¨é™è„‰èƒ°å²›ç§»æ¤æœ¯åŽç«‹å³ç»è¡€æ¶²ä»‹å¯¼ç‚Žç—‡ååº”çš„å½±å“.

OBJECTIVES: Heparin is mainly used as an anticoagulant in clinic, and it also has a certain anti-inflammatory effect. At present, after portal vein islet transplantation in diabetic patients, heparin is mainly infused through the peripheral veins of the limbs to achieve the purpose of anticoagulation and protection of the graft, rather than through the portal vein. In this study, animal experiments were conducted to investigate the effect of heparin infusion via the portal vein and marginal ear vein on the instant blood-mediated inflammatory reaction (IBMIR) after portal vein islet transplantation, which is the choice of anticoagulation methods for clinical islet transplantation to provide a basis for decision-making. METHODS: A total of 50 neonatal pigs (Xeno-1 type, 3-5 days) were selected. Islets were isolated and purified from the pancreas of neonatal pigs. Ten non-diabetic Landrace pigs (1.5-2.0 months) served as recipients, and 12 000 IEQ/kg neonatal porcine islets were transplanted into the liver through the portal vein. All recipients received bolus injection of 50 U/kg of heparin 10 minutes before transplantation. After the bolus injection of heparin, the experimental group received heparin via the portal vein [10 U/(kg·h), 5 recipients], and the control group received heparin via the marginal ear vein [10 U/(kg·h), 5 recipients]. The superior vena cava blood was collected from the 2 groups pre-operation at 1, 3, 24 h post-operation of the transplantation. The portal vein blood was collected from the experimental group at 1 and 3 h after the transplantation as well. The levels of complement C3a, C5a, thrombin-antithrombin complex (TAT), ß-thromboglobulin (ß-TG), and D-dimer as well as activated partial thromboplastin time (APTT) in superior vena cava blood from 1 and 3 h post-transplantation were detected in the 2 groups, and the levels of anti-Xa and anti-IIa in the portal vein and superior vena cava blood from 1 and 3 h post-transplantation in the experimental group were detected. Twenty four hours after the transplantation, the liver tissues in the 2 groups were collected for pathological examination to observe the inflammatory cell infiltration and peripheral thrombosis around the islets graft in liver. RESULTS: Before transplantation, there was no statistically significant difference in C3a, C5a, TAT, ß-TG, D-dimer levels and APTT between the 2 groups (all P>0.05). At 1 and 3 h after transplantation, the C3a, TAT, and D-dimer levels in the experimental group were significant decreased than those in the control groups (all P<0.05), and at 3 h after transplantation the C5a was significant decreased than that in the control group (P<0.05). At 1 and 3 h after transplantation, the anti-Xa and anti-IIa levels in the portal vein blood were significantly increased than those in the superior vena cava blood in the experimental group (all P<0.05). Pathological results showed the presence of islet cell clusters in the liver blood vessels. The thrombus formation and neutrophil infiltration around islet graft was not obvious in the experimental group, while massive thrombus formation and neutrophil infiltration in the control group. CONCLUSIONS: Compared with marginal ear vein infusion of heparin, the direct infusion of heparin in the portal vein has a certain inhibitory effect on complement system, coagulation system activation and inflammatory cell infiltration in portal vein islet transplantation, which may attenuate the occurrence of IBMIR.

Protective effect of necrostatin-1 on the damage of pancreas islet cells induced by TNF-α. / Necrostatin-1对TNF-α诱导的胰岛细胞损伤的保护作用.

OBJECTIVES: To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α. METHODS: After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells. RESULTS: The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all P<0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all P<0.05). CONCLUSIONS: TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.

[Application of intravoxel incoherent motion diffusion weighted imaging for assessment of early chronic allograft nephropathy].

OBJECTIVE: To investigate the feasibility and clinical application of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) technique in non-invasive assessment for early chronic allograft nephropathy (CAN).
 Methods: A total of 23 renal allograft recipients were recruited from inpatients or outpatients according to the inclusion and exclusion criteria for this study. Recipients were divided into a CAN group (n=12, pathologically confirmed early CAN patients) and a control group (n=11, volunteers with long-term stable renal function). Abdominal MRI was performed on patients of renal allograft with a multi-b value DWI sequence. IVIM2b-new software was used for obtaining the IVIM-DWI quantitative parameter pseudo-color maps and the values of IVIM-DWI of renal parenchyma, including the pure diffusion coefficient (D), perfusion correlation diffusion coefficient (D*) and perfusion fraction (f). The IVIM quantitative parameters between the two groups were compared using independent sample t test. ROC analysis was performed when the differences in parameter were statistically significant and the area under curve (AUC) was calculated.
 Results: In IVIM bi-exponential analysis, The D value was significantly decreased in the CAN group compared with the control group (P<0.05), whereas there are no significantly difference in value of D* and f between the two groups (all P>0.05). The AUC of D value for distinguishing the early CAN from the control were 0.784 with sensitivity and specificity at 58.3% and 90.9%, respectively.
 Conclusion: The IVIM-DWI quantitative parameter D can non-invasively assess early CAN to some extent. IVIM-DWI technique is expected to be an effective, easy and non-invasive method to detect early CAN, and assist early diagnose as well as dynamically monitor CAN.

Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway.

Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation. Moreover, we revealed that resveratrol impaired glucose metabolism by mainly inhibiting expression of HK2 mediated by the Akt signaling pathway, and exogenous overexpression of constitutively activated Akt1 in NSCLC cells substantially rescued resveratrol-induced glycolysis suppression. The in vivo data indicated that resveratrol obviously suppressed tumor growth in a xenograft mouse model. Our results suggest targeting HK2 or metabolic enzymes appears to be a new approach for clinical NSCLC prevention or treatment.

Proton Magnetic Resonance Spectroscopy-Detected Changes of Marrow Fat Content in a Rabbit Model of Osteoporosis Treated With Epigallocatechin-3-Gallate.

OBJECTIVE: The aim of this study was to longitudinally evaluate the changes in marrow fat content of ovariectomized (OVX) rabbits treated with epigallocatechin-3-gallate (EGCG) using proton magnetic resonance spectroscopy (H-MRS). METHODS: Thirty-six female New Zealand rabbits were equally divided into sham operation, OVX controls, and OVX treated with EGCG (intraperitoneally, 1.8 mg/kg) for 5 months. Marrow fat fraction by H-MRS and bone density by peripheral quantitative computed tomography were determined at 0, 3, and 5 months. Serum biomarkers and marrow adipocytes were determined at the end of experiment. RESULTS: Estrogen deficiency increased marrow fat content in a time-dependent manner, with a variation of marrow fat fraction (FF) (+25.3%) at month 3 from baseline, and it was maintained until month 5 (+66.6%, all P < 0.001). In comparison with the sham-operated controls, adipocytes density, size, and percentage of adipocytes area in the OVX controls increased by 62.9%, 44.4%, and 178%, respectively (all P < 0.05). These OVX-induced pathological changes were partly reversed by EGCG treatment. In addition, EGCG treatment reduced bone turnover and increased bone density of OVX rabbits. CONCLUSIONS: Epigallocatechin-3-gallate exhibits an anabolic effect on osteoporotic bone by concomitantly rescuing bone mass and mitigating marrow adiposity. H-MRS appears to be a useful tool for monitoring osteoporosis-related treatments.

Effects and mechanisms of action of SARI on androgen-independent prostate cancer (DU145) cells.

This study aimed to characterize the role and mechanisms of action of suppressor of AP-1, regulated by IFN (SARI) in androgen-independent prostate cancer cells using the DU145 cell line. Prostate cancer cell lines were transfected to permit both the overexpression and inhibition of SARI. MTT assays and Transwell assays were performed to detect the effects of SARI overexpression and inhibition on the proliferation activity, invasiveness, and metastatic ability of DU145 cells. Expression of vascular endothelial growth factor (VEGF) and tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was monitored in the experimental groups using a qPCR assay and western blot analysis. Additionally, DU145 cells were separately treated with 5, 50, and 100 µmol/L AG490 for 48 h and SARI expression was detected using the qPCR assay and western blot analysis. We also monitored the effects of AG490 treatment (100 µmol/L for 48 h) on both the SARI-SiRNA DU145 cells and empty vector DU145 (DU145-V) cells using the MTT assay and a Transwell migration assay. SARI overexpression and SARI-SiRNA DU145 prostate cancer cell lines were successfully established. The proliferation activity and the invasion and migration abilities of DU145-SARI cells were significantly lower compared with the DU145-V group (P < 0.05). Conversely, the proliferation activity and the invasion and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). VEGF and p-STAT3 expression levels were lower in the SARI overexpression group compared with the DU145-V group and the control group (P < 0.05). In contrast, VEGF and p-STAT3 expression levels were higher in the SARI-SiRNA group compared with both the DU145-V group and the control group (P < 0.05). In comparison with the control group, SARI expression levels were higher in DU145 cells treated with 50 and 100 µmol/L AG490. Upon treatment with 100 µmol/L AG490 for 48 h, the proliferation activity and invasiveness and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). SARI significantly affects the proliferation, invasion, and metastasis of DU145 cells. It is possible that SARI inhibits the proliferation, invasion, and migration of androgen-independent prostate cancer cells by regulating downstream genes through the SARI/STAT3/VEGF pathways.

Development of a Water-Soluble Fluorescent Probe Based on Natural Flavylium for Mercury(II) Ion Detection and Clinical Antidote Evaluation.

The health hazard posed by Hg2+ makes it imperative to develop a fast and convenient means for detecting Hg2+ in water samples and living objects. While fluorescence sensing technology is considered a promising candidate, the poor water solubility and fluorescence quenching in aqueous solutions of most existing probes limit their practical application. To overcome this, we developed a natural flavylium-inspired fluorescent probe with excellent water solubility. Our probe demonstrated outstanding performance of high sensitivity (LOD = 0.47 nM), fast response (<10 min), and great selectivity for Hg2+. Notably, we validated its applicability in real water, urine samples, and living cells. Furthermore, the probe was successfully applied to evaluate the effectiveness of antidotes for clinical Hg2+ poisoning.

Ratiometric and discriminative visualization of autophagic processes with a novel dual-responded lysosome-specific fluorescent probe.

BACKGROUND: Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy. METHODS: Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury. RESULTS: We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event. CONCLUSIONS: In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.

Superselective Prostate Artery Embolization for Treatment of Severe Haematuria Secondary to Rapid Progression of Treatment-Induced Neuroendocrine Prostate Cancer: A Case Report.

BACKGROUND: Treatment-induced neuroendocrine prostate cancer (t-NEPC) represents a highly aggressive subtype of castration-resistant prostate cancer that commonly arises from prostate adenocarcinoma (AdPC) after continuous androgen deprivation therapy (ADT). However, current treatments for t-NEPC are limited and far from satisfactory. According to our limited knowledge, report regarding the management of t-NEPC related hemorrhage is rare. Here, we report a case of t-NEPC formation after chronic hormonal therapy accompanying with severe bleeding in primary tumor and share our experiences to deal with the severe hematuria resulting from the progression of t-NEPC tumor. CASE PRESENTATION: An 80-year-old man with a significantly high prostate-specific antigen was diagnosed via pathology as advanced AdPC due to multiple bone metastases. He then received ADT including bicalutamide and goserelin. After 20 months of stable disease, the cancer rapidly progressed and presented with severe gross hematuria caused by bleeding of the primary tumor. The histopathologic analysis of a secondary biopsy of the primary tumor confirmed neuroendocrine prostate cancer, and subsequent genetic testing revealed germ-line mutations in the RB1 and FOXA1. To control the bleeding and relieve symptoms, the patient was treated with superselective prostate artery embolization (PAE). After the left internal pudendal artery and the right prostatic artery were embolized, hematuria was quickly alleviated and disappeared. However, the patient was not a suitable candidate to platinum-based chemotherapy due to weak constitution. Goserelin was continuously applied to maintain castration level of serum testosterone. Meanwhile, palliative radiotherapy to the prostate tumor, high-risk lymph node drainage areas (including iliac and para-aortic lymph nodes, internal iliac lymph nodes, presacral lymph nodes and obturator nerve lymph nodes) and bone metastases (right sacroiliac joint and thoracic vertebra) was performed and relieved the pain. Unfortunately, this patient eventually died of cachexia and multiple organ failure nearly 27 months after initial diagnosis. CONCLUSION: To treat severe hematuria caused by progression of t-NEPC, superselective PAE may be a rapid and efficient way to stop bleeding.

Suppressor of activator protein-1 regulated by interferon expression in prostate cancer tissues and cells.

PURPOSE: The aim of this study was to investigate the role of the suppressor of activator protein-1 regulated by interferon (SARI), in the development and progression of prostate cancer. METHODS: Sixty-seven prostate cancer tissue specimens and 20 benign prostatic hyperplasia specimens were used to investigate the correlation between SARI expression and clinicopathologic parameters. Immunohistochemistry was used to detect the SARI and E-cadherin protein expression in the prostate cancer and benign prostatic hyperplasia specimens, and their correlation was established. Quantitative PCR (qPCR) was used to determine the SARI mRNA expression in a normal prostate cell line (RWPE-1) and prostate cancer cell lines (LNCaP and PC3). Western blotting was used to detect the SARI protein expression in the RWPE-1, LNCaP, and PC3 cell lines. RESULTS: SARI protein expression did not correlate with the prostate cancer patients' age or serum Prostate-Specific Antigen value but did show a correlation with the tumor stage of prostate cancer and Gleason score. SARI and E-cadherin expression in the prostate cancer tissue was significantly lower than in the benign prostatic hyperplasia specimens, suggesting a positive correlation between the SARI and E-cadherin expression. SARI mRNA and protein were highly expressed in RWPE-1, the normal prostate cell line, but SARI mRNA and protein expression were reduced in the prostate cancer cell lines, LNCaP and PC3. Significant differences in the expression were found between the prostate cancer cell lines and the normal prostate cell line. CONCLUSION: In this study, high SARI expression was found to be negatively correlated with the development and progression of prostate cancer.

Comparing the Efficacy and Safety of High-Intensity Focused Ultrasound and Uterine Artery Embolization in Caesarean Scar Pregnancy: A Meta-analysis.

INTRODUCTION: High-intensity focused ultrasound (HIFU) followed by curettage and uterine artery embolization (UAE) followed by curettage are two methods of treatment for caesarean scar pregnancy (CSP). There is currently no consistent evidence concerning any difference in efficacy and safety between UAE and HIFU. Therefore, a meta-analysis was performed to compare the efficacy and safety of HIFU and UAE in the treatment of CSP. METHODS: Studies published in PubMed, Cochrane, Embase, Web of Science, Chinese BioMedical Literature Service System, and Chinese National Knowledge Infrastructure databases were searched and the main outcomes in the studies were extracted. RESULTS: Of 8 studies and 715 patients included in this study, 388 and 327 patients were in the HIFU group and UAE groups, respectively. Compared with the UAE group, patients in the HIFU group had less blood loss [weighted mean difference (WMD) = - 22.58 ml; 95% confidence interval (CI) - 44.45 to - 0.70; p < 0.05), lower incidence of adverse events [odds ratio (OR) = 0.17; 95% CI 0.06-0.46; p < 0.05); shorter duration of hospital stay (WMD = - 0.96 days; 95% CI - 1.88 to - 0.03; p < 0.05); and a longer ß-human chorionic gonadotropin normalisation time (WMD = 9.59 days; 95% CI 1.66-17.52; p < 0.05). CONCLUSION: Patients in the HIFU group appeared to have better outcomes than those in the UAE group; thus, HIFU may be a priority option for the early management of CSP. However, this needs to be confirmed by multi-centre, large-scale randomised controlled trials.

Cancer Therapy Based on Smart Drug Delivery with Advanced Nanoparticles.

BACKGROUND: Cancer, as one of the most dangerous disease, causes millions of deaths every year. The main reason is the absence of an effective and thorough treatment. Drug delivery systems have significantly reduced the side-effect of chemotherapy. Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems. METHODS: In this article, we will describe in detail the different kinds of nanoparticles and their mechanisms emphasizing the triggering factors in drug delivery. Besides, the application of smart drug delivery systems in imaging will be introduced. RESULTS: Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems. CONCLUSION: Despite considerable progress in nanoparticle research over the past decade, such as smart drug delivery systems for the treatment of cancer, molecular imaging probes and the like. The range of nanoparticles used in multifunction systems for imaging and drug delivery continues to grow and we expect this dilatation to continue. But to make nanoparticles truly a series of clinical products to complement and replace current tools, constant exploration efforts and time are required. Overall, the future looks really bright.

Intravoxel incoherent motion derived liver perfusion/diffusion readouts can be reliable biomarker for the detection of viral hepatitis B induced liver fibrosis.

BACKGROUND: Recent two studies reported that intravoxel incoherent motion (IVIM) analysis can separate healthy livers and viral hepatitis B (VHB) induced liver fibrosis. However, in these two studies the starting b value for bi-exponential decay analysis was b =10 and 15 s/mm2 respectively. The current study has two primary aims. The first is to further confirm the diagnostic value of IVIM in detecting liver fibrosis. The second is to test whether by sampling very low b value densely, then b =0 s/mm2 image could be included to improve IVIM's diagnostic performance. METHODS: This was a prospective study with data acquired at the Third Xiangya Hospital of Central South University, Changsha, China. Healthy volunteers and patients suspected of VHB induced liver fibrosis with liver biopsy performed, as well as hepatocellular carcinoma patients scheduled for surgery, were recruited. All the hepatocellular carcinoma patients had liver fibrosis. After exclusions based on pre-defined criteria for image data quality, for IVIM analysis this study included 20 healthy volunteers; 4 chronic VHB patients with biopsy showing no liver fibrosis; 11 stage-1 liver fibrosis patients, 10 stage-2 liver fibrosis patients, 2 stage-3 liver fibrosis patients, and 5 stage-4 liver fibrosis patients. In the liver fibrosis patients, 1, 19, and 8 cases had inflammation grade-0, grade-1, and grade-2 respectively. The reference IVIM bi-exponential decay curve fitting analysis was segmented fitting performed with b =2 s/mm2 image as the starting point and a threshold-b of 60 s/mm2. This reference fitting method was compared with threshold-b of 40 s/mm2, full fitting, fitting starting from b =0, 5, and 10 s/mm2 respectively. The potential correlation between IVIM readouts and liver function was assessed for the liver fibrosis patients. RESULTS: Based on the smaller coefficient of variation (CoV) for the volunteer group and the smaller patient/volunteer ratios [= (mean measurement for patient groups)/(mean measurement for healthy volunteers)], the comparison of fitting methods favored the reference approach starting from b =2 s/mm2 with a threshold-b of 60 s/mm2. The IVIM measures of four patients without liver fibrosis resembled those of healthy subjects. PF offered the best diagnostic value for separating healthy livers and fibrotic livers, and a threshold of PF =0.1406 separated all fibrotic livers and healthy livers with an exception of one hepatocellular carcinoma patient (fibrosis grade-2/inflammation grade-2). The correlation between fibrosis grading and inflammation grading was weakly positive; while compared with fibrotic livers with inflammation grade-1, fibrotic livers with inflammation grade-2 showed a trend of higher Dfast. A weak correlation is shown with lower PF and lower Dfast associated with lower total protein, lower albumin; higher alanine transaminase, higher aspartate transaminase; higher total bilirubin, and higher direct bilirubin. CONCLUSIONS: Segmented-fitting with threshold-b =60 s/mm2 and starting from non-zero very low b value outperforms other methods. IVIM has high sensitivity in detecting liver fibrosis, and PF and Dfast have potential correlation with serum liver function biomarkers. IVIM measures and liver fibrosis grading are not in a linear relationship.

A Missense Variant p.Ala117Ser in the Transthyretin Gene of a Han Chinese Family with Familial Amyloid Polyneuropathy.

Familial amyloid polyneuropathy (FAP) is a dominantly inherited disorder. This study aims to explore the genetic features of a Han Chinese family with FAP, characterized by bloating, alternating diarrhea and constipation, and weakness in his feet. Amyloid presented histologically in the vessel walls of hepatic portal area and nerves of the surgically excised liver specimens from the proband by hematoxylin and eosin staining. Amyloid deposition was further confirmed with Congo red treatment. A c.349G>T transversion (p.Ala117Ser) in TTR gene exon 4 was identified in the proband with typical autonomic neuropathy and peripheral motor neuropathy, as well as in his asymptomatic son. The variant was not detected in 200 normal ethnically matched controls. These findings provide new insights into FAP cause and diagnosis and have implications for genetic counseling.

Novel Self-assembled Organic Nanoprobe for Molecular Imaging and Treatment of Gram-positive Bacterial Infection.

Background: Increasing bacterial infections as well as a rise in bacterial resistance call for the development of novel and safe antimicrobial agents without inducing bacterial resistance. Nanoparticles (NPs) present some advantages in treating bacterial infections and provide an alternative strategy to discover new antibiotics. Here, we report the development of novel self-assembled fluorescent organic nanoparticles (FONs) with excellent antibacterial efficacy and good biocompatibility. Methods: Self-assembly of 1-(12-(pyridin-1-ium-1-yl)dodecyl)-4-(1,4,5-triphenyl-1H-imidazol-2-yl)pyridin-1-ium (TPIP) in aqueous solution was investigated using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The bacteria were imaged under a laser scanning confocal microscope. We evaluated the antibacterial efficacy of TPIP-FONsin vitro using sugar plate test. The antimicrobial mechanism was explored by SEM. The biocompatibility of the nanoparticles was examined using cytotoxicity test, hemolysis assay, and histological staining. We further tested the antibacterial efficacy of TPIP-FONsin vivo using the S. aureus-infected rats. Results: In aqueous solution, TPIP could self-assemble into nanoparticles (TPIP-FONs) with characteristic aggregation-induced emission (AIE). TPIP-FONs could simultaneously image gram-positive bacteria without the washing process. In vitro antimicrobial activity suggested that TPIP-FONs had excellent antibacterial activity against S. aureus (MIC = 2.0 µg mL-1). Furthermore, TPIP-FONs exhibited intrinsic biocompatibility with mammalian cells, in particular, red blood cells. In vivo studies further demonstrated that TPIP-FONs had excellent antibacterial efficacy and significantly reduced bacterial load in the infectious sites. Conclusion: The integrated design of bacterial imaging and antibacterial functions in the self-assembled small molecules provides a promising strategy for the development of novel antimicrobial nanomaterials.