Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report.

BACKGROUND: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. CASE SUMMARY: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 µg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 µg/L. The patient's clinical symptoms demonstrated a notable improvement. CONCLUSION: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

Modified Nishida Procedure Combined with Lateral Rectus Disabling for Duane Retraction Syndrome.

Duane retraction syndrome (DRS) is a complex congenital cranial dysinnervation disorder. The choice of surgical procedure in esotropic-DRS depends upon several factors that include: the amount of esotropia in the primary position, the presence and severity of palpebral fissure narrowing, globe retraction, presence of medial rectus muscle (MR) contracture, the likelihood of improving abduction, age of the patient, and the presence of binocularity and stereopsis. In the presence of MR contracture, MR recession is performed either alone (unilaterally or bilaterally) or in conjunction with Y splitting plus recession of the lateral rectus muscle (LR) for reducing globe retraction. MR recession, with or without adjustable sutures, may be simultaneously combined with partial thickness vertical rectus muscle transposition (VRT) or with superior rectus muscle transposition (SRT). We describe a novel combination of surgical procedures in the management of esotropic-DRS in two patients. In our first patient, following an initial MR recession combined with LR disinsertion and periosteal fixation (LRDAPF), a modified Nishida procedure was performed. In our second patient following a prior simultaneous MR recession and LR Y splitting with recession, we combined periosteal fixation of the LR with a modified Nishida procedure of the vertical rectus muscles.

Silver nanoparticles selectively induce human oncogenic γ-herpesvirus-related cancer cell death through reactivating viral lytic replication.

Silver nanoparticle (nAg), which is one of the most common manufactured nanomaterials, has a wide range of biomedical applications. The human oncogenic γ-herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV), are etiologically linked to many malignancies. Currently, there are no efficient or specific treatments for these types of tumors, and most patients die because of resistance to conventional cytotoxic chemotherapy. Despite nAg having antitumor and antiviral activities, its effects on oncogenic herpesvirus-related cancer cells remain largely unknown. Here, we reveal that nAg presents higher cytotoxicity against KSHV- or EBV-latently infected cells via reactivating viral lytic replication, which relies on the induction of reactive oxygen species (ROS) generation and autophagy. Moreover, nAg blocks KSHV primary infection by directly destroying virion particles, as well as effectively inhibits colony formation and moderately represses the growth of KSHV-associated tumors in xenograft mouse model. Taken together, these results demonstrate the therapeutic potential of nAg for use in the antiviral infection and treatment of oncogenic herpesvirus-related cancers.

Enhanced microwave-absorption with carbon-encapsulated Fe-Co particles on reduced graphene oxide nanosheets with nanoscale-holes in the basal plane.

In this study, an Fe-Co alloy is coated with carbon and decorated on a holey reduced graphene oxide nanosheet (FeCo@C/HRGO) composite. The structure is synthesized using liquid-phase reduction and hydrothermal processes followed by high-temperature calcination. The FeCo@C/HRGO composite is identified and characterized using XRD, XPS, Raman spectroscopy, TEM, and SEM. This novel composite exhibits excellent electromagnetic-wave absorption properties. The maximum reflection loss for FeCo@C/HRGO reaches -76.6 dB at 16.64 GHz with a thickness of 1.7 mm. The RL below -10 dB reaches 14.32 GHz for a thickness of 1.7-5.0 mm. This confirms that microwave absorption of FeCo@C can be substantially improved upon decoration with HRGO nanosheets.

Recovery of Lost Color and Depth Frames in Multiview Videos.

In this paper, we consider an integrated error concealment system for lost color frames and lost depth frames in multiview videos with depths. We first proposed a pixel-based color error-concealment method with the use of depth information. Instead of assuming that the same moving object in consecutive frames has minimal depth difference, as is done in a state-of-the-art method, a more realistic situation in which the same moving object in consecutive frames can be in different depths is considered. In the derived motion vector candidate set, we consider all the candidate motion vectors in the set, and weight the reference pixels by the depth differences to obtain the final recovered pixel. Compared with the two state-of-the-art methods, the proposed method has average peak signal-to-noise ratio gains of up to 8.73 and 3.98 dB, respectively. Second, we proposed an iterative depth frame error-concealment method. The initial recovered depth frame is obtained by depth-image-based rendering from another available view. The holes in the recovered depth frame are then filled in the proposed priority order. Preprocessing methods (depth difference compensation and inconsistent pixel removal) are performed to improve the performance. Compared with a method that uses the available motion vector in a color frame to recover the lost depth pixels, the hybrid motion vector extrapolation method, the inpainting method and the proposed method have gains of up to 4.31, 10.29, and 6.04 dB, respectively. Finally, for the situation in which the color and the depth frames are lost at the same time, our two methods jointly perform better with a gain of up to 7.79 dB.

The synergy in cytokine production through MyD88-TRIF pathways is co-ordinated with ERK phosphorylation in macrophages.

Although specific single Toll-like receptor (TLR) ligands are known to drive the development of Th1 or Th2 immunity, the outcome of different combinations of TLR ligands on innate immunity is not well defined. Spatiotemporal dynamics are critical in determining the specificity of the immune response, but the mechanisms underlying combinatorial TLR stimulation remain unclear. Here, we tested pairwise combinations of TLR ligands separated by different time intervals for their effect on cytokine production in macrophages. We observed that stimulation via a combination of MyD88- and TRIF-utilizing adaptors leads to a highly synergistic cytokine response. On a timescale of 4-24 h, macrophages pretreated with poly(I:C) (TLR3 ligand) are cross-primed to a second stimulation with R848 (TLR7 ligand) and vice versa, and each condition exhibits different optimal time windows of synergistic response for each cytokine. We show that the synergy resulting from combinatorial stimuli (poly(I:C) and R848 is also regulated by the order and dosage of the TLR agonists. Secondary response genes, which depend on new protein synthesis for transcription, show greater synergy than primary response genes, and such enhancement is abolished when new protein synthesis is inhibited. Synergistic cytokine production appears concordant with sustained ERK phosphorylation, suggesting that the de novo factors act via inhibition of ERK dephosphorylation, for example, by the downregulation of dual specificity phosphatase 6. Taken together, our findings illustrate a checkpoint in the innate immune system, where the synchronization of timing of both MyD88 and TRIF pathways is required for a maximal cytokine response and potential memory effect in macrophages.

SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to human.

Sterile-alpha and Armadillo motif containing protein (SARM) was recently identified as the fifth member of the Toll-like receptor (TLR) adaptor family. Whilst the Caenorhabditis elegans SARM homologue, TIR-1, is crucial for efficient immune responses against bacterial infections, human SARM was demonstrated to function as a specific inhibitor of TRIF-dependent TLR signaling. The opposing role of SARM in C. elegans and human is intriguing, prompting us to seek clarification on the enigmatic function of SARM in an ancient species which relies solely on innate immunity for survival. Here, we report the discovery of a primitive but functional SARM (CrSARM) in the immune defense of a "living fossil", the horseshoe crab, Carcinoscorpius rotundicauda. CrSARM shares numerous signature motifs and displays significant homology with vertebrate and invertebrate SARM homologues. CrSARM downregulates TRIF-dependent TLR signaling suggesting the conservation of SARM function from horseshoe crab to human. During infection by Pseudomonas aeruginosa, CrSARM is rapidly upregulated within 3h and strongly repressed at 6h, coinciding with the timing of bacterial clearance, thus demonstrating its dynamic role in innate immunity. Furthermore, yeast-two-hybrid screening revealed several potential interaction partners of CrSARM implying the role of SARM in downregulating TLR signaling events. Altogether, our study shows that, although C. elegans SARM upregulates immune signaling, its disparate role as a suppressor of TLR signaling, specifically via TRIF and not MyD88, is well-conserved from horseshoe crab to human.