In the setting of periprosthetic humeral fractures, the humeral stem of the implant represents a substantial challenge to the optimal method of proximal fixation. This study aimed to compare the ...initial biomechanical stability provided by cerclage cables with a locking plate insert versus bicortical locking screws (i.e., the gold standard for fixation) in fresh cadaveric humeri.
After calculating the sample size, we utilized 10 sets of cadaveric specimens and created a 5-mm osteotomy gap 120 mm distal to the tip of the greater tuberosity, simulating a Wright and Cofield type-B periprosthetic humeral fracture on each specimen. Using 3 locking screws for distal fragment fixation, identical in all specimens, the specimens were assigned to Group A (3 cerclage cables with a plate insert) or Group B (3 locking bicortical screws) for proximal fragment fixation. Biomechanical tests included stiffness in varus and valgus bending, torsion, and axial compression, and a single load to failure.
No significant differences were observed in the biomechanical metrics between the 2 groups.
Our study revealed that fixation with use of cerclage cables with a plate insert demonstrated biomechanical stability comparable with that of bicortical locking screw fixation when addressing the proximal fragment in Wright and Cofield type-B periprosthetic humeral fractures.
For proximal fragment fixation of periprosthetic humeral fractures, cerclage cables with a plate insert can be utilized as an effective fixation method that offers initial fixation strength that is comparable to the use of 3 locking bicortical screws.
The composite cathode of an all-solid-state battery composed of various solid-state components requires a dense microstructure and a highly percolated solid-state interface different from that of a ...conventional liquid-electrolyte-based Li-ion battery. Indeed, the preparation of such a system is particularly challenging. In this study, quantitative analyses of composite cathodes by three-dimensional reconstruction analysis were performed beyond the existing qualitative analysis, and their microstructures and reaction interfaces were successfully analyzed. Interestingly, various quantitative values of structure properties (such as the volume ratio, connectivity, tortuosity, and pore formation) associated with material optimization and process development were predicted, and they were found to result in limited electrochemical charge/discharge performances. We also verified that the effective two-phase boundaries were significantly suppressed to ∼23% of the total volume because of component dispersion and packing issues.
Neural crest (NC) generates diverse lineages including peripheral neurons, glia, melanocytes, and mesenchymal derivatives. Isolating multipotent human NC has proven challenging, limiting our ability ...to understand NC development and model NC-associated disorders. Here, we report direct reprogramming of human fibroblasts into induced neural crest (iNC) cells by overexpression of a single transcription factor, SOX10, in combination with environmental cues including WNT activation. iNC cells possess extensive capacity for migration in vivo, and single iNC clones can differentiate into the four main NC lineages. We further identified a cell surface marker for prospective isolation of iNCs, which was used to generate and purify iNCs from familial dysautonomia (FD) patient fibroblasts. FD-iNC cells displayed defects in cellular migration and alternative mRNA splicing, providing insights into FD pathogenesis. Thus, this study provides an accessible platform for studying NC biology and disease through rapid and efficient reprogramming of human postnatal fibroblasts.
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•Postnatal human fibroblasts can be reprogrammed into induced neural crest (iNC)•iNC can be generated by overexpression of SOX10 in combination with WNT activation•iNC cells exhibit capacity for multilineage differentiation and migration in vivo•Patient-derived iNC cells allow cellular modeling of neural crest diseases
Overexpression of SOX10, in combination with appropriate extracellular cues, is sufficient to directly reprogram human fibroblasts into induced neural crest cells, which can generate the four main neural crest lineages.
Chiral perovskites have garnered significant attention, owing to their chiroptical properties and emerging applications. Current fabrication methods often involve complex chemical synthesis routes. ...Herein, an alternative approach for introducing chirality into nonchiral hybrid organic–inorganic perovskites (HOIPs) using nanotemplates composed of cholesteric polymeric networks is proposed. This method eliminates the need for additional molecular design. In this process, HOIP precursors are incorporated into a porous cholesteric polymer film, and two-dimensional (2D) HOIPs grow inside the nanopores. Circularly polarized light emission (CPLE) was observed even though the selective reflection band of the cholesteric polymer films containing a representative HOIP deviated from the emission wavelength of the 2D HOIP. This effect was confirmed by the induced circular dichroism (CD) observed in the absorbance band of the HOIP. The observed CPLE and CD are attributed to the chirality induced by the template in the originally nonchiral 2D HOIP. Additionally, the developed 2D HOIP exhibited a long exciton lifetime and good stability under harsh conditions. These findings provide valuable insights into the development and design of innovative optoelectronic materials.
Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key ...molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.
Macroautophagy allows for bulk degradation of cytosolic components in lysosomes. Overexpression of GFP/RFP‐LC3/GABARAP is commonly used to monitor autophagosomes, a hallmark of autophagy, despite ...artifacts related to their overexpression. Here, we developed new sensors that detect endogenous LC3/GABARAP proteins at the autophagosome using an LC3‐interacting region (LIR) and a short hydrophobic domain (HyD). Among HyD‐LIR‐GFP sensors harboring LIR motifs of 34 known LC3‐binding proteins, HyD‐LIR(TP)‐GFP using the LIR motif from TP53INP2 allowed detection of all LC3/GABARAPs‐positive autophagosomes. However, HyD‐LIR(TP)‐GFP preferentially localized to GABARAP/GABARAPL1‐positive autophagosomes in a LIR‐dependent manner. In contrast, HyD‐LIR(Fy)‐GFP using the LIR motif from FYCO1 specifically detected LC3A/B‐positive autophagosomes. HyD‐LIR(TP)‐GFP and HyD‐LIR(Fy)‐GFP efficiently localized to autophagosomes in the presence of endogenous LC3/GABARAP levels and without affecting autophagic flux. Both sensors also efficiently localized to MitoTracker‐positive damaged mitochondria upon mitophagy induction. HyD‐LIR(TP)‐GFP allowed live‐imaging of dynamic autophagosomes upon autophagy induction. These novel autophagosome sensors can thus be widely used in autophagy research.
Synopsis
Overexpression of fluorescently tagged Atg8/LC3 proteins to visualize autophagosomes can lead to artifacts; new peptide sensors have been developed that allow live‐imaging of endogenous LC3/GABARAP proteins at autophagosomes and at depolarized mitochondria.
HyD‐LIR(TP)‐GFP detects all LC3/GABARAP‐positive autophagosomes, but gives the strongest signal for GABARAPL1‐positive autophagosomes.
HyD‐LIR(TP)‐GFP allows live‐imaging of dynamic autophagosomes.
HyD‐LIR(Fy)‐GFP specifically localizes to LC3A/B‐positive autophagosomes without affecting autophagic flux.
HyD‐LIR(TP)‐GFP or HyD‐LIR(Fy)‐GFP efficiently colocalize with MitoTracker‐positive damaged mitochondria upon mitophagy induction.
Overexpression of fluorescently tagged Atg8/LC3 proteins to visualize autophagosomes can lead to artifacts; new peptide sensors have been developed that allow live‐imaging of endogenous LC3/GABARAP proteins at autophagosomes and at depolarized mitochondria.
Transient elastography (TE), a non-invasive tool that measures liver stiffness, has been evaluated in meta-analyses for effectiveness in assessing liver fibrosis in European populations with chronic ...hepatitis C (CHC). However, these data cannot be extrapolated to populations in Asian countries, where chronic hepatitis B (CHB) is more prevalent. In this study, we performed a meta-analysis to assess the overall performance of TE for assessing liver fibrosis in patients with CHB.
Studies from the literature and international conference abstracts which enrolled only patients with CHB or performed a subgroup analysis of such patients were enrolled. Combined effects were calculated using area under the receiver operating characteristic curves (AUROC) and diagnostic accuracy values of each study.
A total of 18 studies comprising 2,772 patients were analyzed. The mean AUROCs for the diagnosis of significant fibrosis (F2), severe fibrosis (F3), and cirrhosis (F4) were 0.859 (95% confidence interval CI, 0.857-0.860), 0.887 (95% CI, 0.886-0.887), and 0.929 (95% CI, 0.928-0.929), respectively. The estimated cutoff for F2 was 7.9 (range, 6.1-11.8) kPa, with a sensitivity of 74.3% and specificity of 78.3%. For F3, the cutoff value was determined to be 8.8 (range, 8.1-9.7) kPa, with a sensitivity of 74.0% and specificity of 63.8%. The cutoff value for F4 was 11.7 (range, 7.3-17.5) kPa, with a sensitivity of 84.6% and specificity of 81.5%.
TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB.
NF-E2-related factor 2 (Nrf2) has been demonstrated to be a key transcription factor regulating the anti-inflammatory genes including heme oxygenase-1 (HO-1) in experimental sepsis models. Based on ...the fact that 3,4,5-trihydorxycinnamic acid (THC) has been reported to possess anti-inflammatory properties in BV2 microglial cells, the possible effects of THC and its underlying mechanism was examined against lipopolysaccharide (LPS)-induced RAW 264.7 cell culture and septic mouse models. Pretreatment of RAW 264.7 cells with THC significantly attenuated LPS-induced NO, PGE
2
production, and expression of iNOS and COX-2. THC also significantly suppressed LPS-induced release of pro-inflammatory cytokines and degradation of IκB-α. Increased phosphorylation of Nrf2 and nuclear translocation of Nrf2 were observed with THC treatment with consequent expression of HO-1. The data demonstrated that multiple signaling pathways including Akt, p38, and PKC are involved in the THC-induced activation of Nrf2/HO-1 pathway. Treatment of THC resulted in significantly increased survival of LPS-induced septic mice. THC also significantly ameliorated LPS-induced septic features such as hypothermia and increased vascular leakage. In accordance with the data from cell culture model, THC exhibited increased expression of HO-1 in kidney and decreased serum level of pro-inflammatory mediators such as TNF-α, IL-1β, and NO. Taken together, the present study for the first time demonstrates that THC inhibits inflammation in LPS-induced RAW264.7 cells by Nrf2 activation and improves survival of mice in LPS-induced endotoxemia model.
We recently observed the emergence of fluconazole-resistant Candida parapsilosis bloodstream isolates harboring a Y132F substitution in Erg11p in South Korea. These Y132F isolates had a higher ...propensity to cause clonal transmission than other fluconazole-resistant isolates and persisted within hospitals for several years, as revealed by microsatellite typing.
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