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We report Raman scattering from wurtzite single-crystalline InGaAs nanowires (NWs) to probe optical phonon behaviors associated with spatial grading in alloy composition along the NW length. Polarized Raman spectra revealed several optical phonons and their scattering symmetries: (i) InAs-like A1(LO) and A1(TO) phonons and (ii) GaAs-like A1(LO), A1(TO), and E2(high) phonons. In addition, strong anisotropic behavior was observed in the Raman tensor elements of the A1(TO) phonon mode. Interestingly, a spatial mapping of the GaAs-like A1(TO) phonon along the NW length direction showed a systematic increase in energy from the NW top (~255 cm−1) to the midpoint (~263 cm−1), indicating an increase in the Ga mole fraction from about 0.5 to about 0.8. Further toward the NW bottom, the GaAs-like A1(TO) phonon energy saturated to the peak value at about 264 cm−1. In the upper half of the NW, the phonon linewidths broadened significantly due to the spatial grading in In/Ga composition along the NW length. When the composition grading was negligible in the bottom half of the NW, the spectral widths were considerably narrowed. The GaAs-like E2(high) phonon showed similar variations in both energy and spectral width along the NW length. [ABSTRACT FROM AUTHOR]

The antiviral role of the tripartite motif-containing (TRIM) protein family , a member of the E3-ubiquitin ligase family, has recently been actively studied. Hepatitis B virus (HBV) infection is a major contributor to liver diseases; however, the host factors regulated by cytokine-inducible TRIM21 to suppress HBV remain unclear. In this study, we showed the antiviral efficacy of TRIM21 against HBV in hepatoma cell lines, primary human hepatocytes isolated from patient liver tissues, and mouse model. Using TRIM21 knock-out cells, we confirmed that the antiviral effects of interferon-gamma, which suppress HBV replication, are diminished when TRIM21 is deficient. Northern blot analysis confirmed a reduction of HBV RNA levels by TRIM21. Using Luciferase reporter assay, we also discovered that TRIM21 decreases the activity of HBV enhancers, which play a crucial role in covalently closed circular DNA transcription. The participation of the RING domain and PRY-SPRY domain in the anti-HBV effect of TRIM21 was demonstrated through experiments using deletion mutants. We identified a novel interaction between TRIM21 and hepatocyte nuclear factor 4α (HNF4α) through co-immunoprecipitation assay. More specifically, ubiquitination assay revealed that TRIM21 promotes ubiquitin-mediated proteasomal degradation of HNF4α. HNF1α transcription is down-regulated as a result of the degradation of HNF4α, an activator for the HNF1α promoter. Therefore, the reduction of key HBV enhancer activators, HNF4α and HNF1α, by TRIM21 resulted in a decline in HBV transcription, ultimately leading to the inhibition of HBV replication.IMPORTANCEDespite extensive research efforts, a definitive cure for chronic hepatitis B remains elusive, emphasizing the persistent importance of this viral infection as a substantial public health concern. Although the risks associated with hepatitis B virus (HBV) infection are well known, host factors capable of suppressing HBV are largely uncharacterized. This study elucidates that tripartite motif-containing protein 21 (TRIM21) suppresses HBV transcription and consequently inhibits HBV replication by downregulating the hepatocyte nuclear factors, which are host factors associated with the HBV enhancers. Our findings demonstrate a novel anti-HBV mechanism of TRIM21 in interferon-gamma-induced anti-HBV activity. These findings may contribute to new strategies to block HBV., Competing Interests: The authors declare no conflict of interest.

Context.—: Recently, an exchangeable copper (CuEXC) assay has been suggested as a robust and feasible diagnostic tool for Wilson disease (WD). Although WD is a disorder that requires lifelong treatment and monitoring, few data are currently available regarding the status of copper levels in children., Objective.—: To evaluate the performance of copper assays and establish a reference interval for total copper and CuEXC in the pediatric population., Design.—: Serum samples from children aged 1-5 (n = 122), 6-12 (n = 125), and 13-18 years (n = 120) were analyzed. Total copper and CuEXC concentrations were directly measured using inductively coupled plasma mass spectrometry, and relative CuEXC levels were calculated. Total copper reference intervals, CuEXC levels, and relative CuEXC levels were determined based on the 2.5th and 97.5th percentiles of the data with 90% confidence intervals., Results.—: There were significant differences in the median concentrations of total copper and relative CuEXC among the age groups. Reference intervals determined for total copper were 82 to 167, 75 to 139, and 64 to 133 μg/dL for children aged 1 to 5, 6 to 12, and 13 to 18 years, respectively. The reference intervals for CuEXC were 4.29 to 9.79, 4.02 to 9.09, and 3.55 to 8.25 μg/dL for children aged 1 to 5, 6 to 12, and 13 to 18 years, respectively. Among 11 patients with suspected WD, relative CuEXC values were elevated in all 3 diagnosed with WD., Conclusions.—: The pediatric reference intervals derived in this study are expected to be useful for the diagnosis, differential diagnosis, treatment, and monitoring of pediatric patients with WD.

Bisphosphonate drugs such as zoledronic acid (ZOL), used for the treatment of common bone disorders, target the skeleton and inhibit bone resorption by preventing the prenylation of small GTPases in bone-destroying osteoclasts. Increasing evidence indicates that bisphosphonates also have pleiotropic effects outside the skeleton, most likely via cells of the monocyte/macrophage lineage exposed to nanomolar circulating drug concentrations. However, no effects of such low concentrations of ZOL have been reported using existing approaches. We have optimized a highly sensitive in vitro prenylation assay utilizing recombinant geranylgeranyltransferases to enable the detection of subtle effects of ZOL on the prenylation of Rab- and Rho-family GTPases. Using this assay, we found for the first time that concentrations of ZOL as low as 10nM caused inhibition of Rab prenylation in J774 macrophages following prolonged cell culture. By combining the assay with quantitative mass spectrometry we identified an accumulation of 18 different unprenylated Rab proteins in J774 cells after nanomolar ZOL treatment, with a >7-fold increase in the unprenylated form of Rab proteins associated with the endophagosome pathway (Rab1, Rab5, Rab6, Rab7, Rab11, Rab14 and Rab21). Finally, we also detected a clear effect of subcutaneous ZOL administration in vivo on the prenylation of Rab1A, Rab5B, Rab7A and Rab14 in mouse peritoneal macrophages, confirming that systemic treatment with bisphosphonate drug can inhibit prenylation in myeloid cells in vivo outside the skeleton. These observations begin a new era in defining the precise pharmacological actions of bisphosphonate drugs on the prenylation of small GTPases in vivo.

Background and Objectives: Blood group O individuals have been shown to have lower levels of von Willebrand factor (vWF). It is not known if these differences are associated with an increased bleeding risk. We retrospectively assessed estimated blood loss (EBL) in group O and non-group O men undergoing radical prostatectomy., Materials and Methods: All patients undergoing radical retropubic prostatectomy from October 1986 through January 1997 were evaluated for ABO type, EBL in the operating room and red blood cell (RBC) transfusion requirements., Results: Complete data were available for 138 group O and 168 non-group O men. Average intraoperative blood loss was 1996 mLs for all men and there was no significant difference in the EBL or transfusion requirements for group O patients. Substantial blood loss (EBL of at least 3 liters) did occur in 20.3% of group O and 13.1% of non-group O patients (P = 0.12). There were no significant differences between the two groups in the number of autologous, allogeneic or total RBCs transfused either intraoperatively or within 48 hours of surgery., Conclusion: There was no difference in blood loss or RBC transfusion requirements between group O and non-group O patients undergoing radical prostatectomy. The lower levels of vWF that have been found in group O individuals do not appear to put group O men at significant risk for greater operative blood loss or transfusion requirements during radical prostatectomy., Summary: Group O men undergoing radical prostatectomy do not have greater estimated blood loss or transfusion requirements as compared to non-group O men.