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Recent therapeutic strategies for hemophilia include long-term therapeutic gene expression using adeno-associated virus (AAV) and rebalancing therapy via the downregulation of anticoagulant pathways. However, these approaches have limitations in immune responses or insufficiency to control acute bleeding. Thus, we developed a therapeutic strategy for hemophilia B by a combined rebalancing and human factor 9 (hF9) gene knockin (KI) using a lipid nanoparticle (LNP) and AAV. Antithrombin (AT; Serpin Family C Member 1 [Serpinc1]) was selected as the target anticoagulation pathway for the gene KI. First, the combined use of LNP-clustered regularly interspaced short palindromic repeats (CRISPR) and AAV donor resulted in 20% insertions or deletions (indels) in Serpinc1 and 67% reduction of blood mouse AT concentration. Second, hF9 coding sequences were integrated into approximately 3% of the target locus. hF9 KI yielded approximately 1,000 ng/mL human factor IX (hFIX) and restored coagulation activity to a normal level. LNP-CRISPR injection caused sustained AT downregulation and hFIX production up to 63 weeks. AT inhibition and hFIX protein-production ability could be maintained by the proliferation of genetically edited hepatocytes in the case of partial hepatectomy. The co-administration of AAV and LNP showed no severe side effects except random integrations. Our results demonstrate hemophilia B therapy by a combination of rebalancing and hF9 KI using LNP and AAV.

The cations in the solution spontaneously exchange with the constituent atoms in metal nanoparticles, forming single-atom alloys (SAAs) catalysts. The prepared PdRu SAA catalyst exhibited superior activity than commercial Pt for methanol oxidation reaction.

Quantitative determination and in situ monitoring of molecular chirality at extremely low concentrations is still challenging with simple optics because of the molecular-scale mismatch with the incident light wavelength. Advances in spectroscopy

Objective: Effects of direct-fed Enterococcus faecium plus bacteriophages (EF-BP) were investigated as potential substitutes for pharmacological ZnO for weanling pigs.Methods: Dietary treatments were supplementations to a basal diet with none (NC), 3,000- ppm ZnO (PC), 1×1010 colony-forming units of E. faecium plus 1×108 plaque-forming units (PFU) of anti-Salmonella typhimurium bacteriophages (ST) or 1×106 PFU of each of anti-enterotoxigenic Escherichia coli K88 (F4)-, K99 (F5)-, and F18-type bacteriophages (EC) per kg diet. In Exp 1, twenty-eight 21-day-old crossbred weanling pigs were individually fed one of the experimental diets for 14 days and euthanized for histological examination on intestinal mucosal morphology. In Exp 2, 128 crossbred weanling pigs aged 24 days were group-fed the same experimental diets in 16 pens of 8 piglets on a farm with a high incidence of post-weaning diarrhea.Results: None of the diarrheal score or fecal consistency score (FCS), average daily gain (ADG), gain: feed ratio, structural variables of the intestinal villus, and goblet cell density, differed between the EF-BP (ST+EC) and NC groups, between EF-BP and PC, or between ST and EC, with the exception of greater gain: feed for EF-BP than for PC (p

Chiral plasmonic nanostructures have facilitated a promising method for manipulating the polarization state of light. While a precise structural modification at the nanometer-scale-level could offer chiroptic responses at various wavelength ranges, a system that allows fast response control of a given structure has been required. In this study, we constructed uniformly arranged chiral gold helicoids with cobalt thin-film deposition that exhibited a strong chiroptic response with magnetic controllability. Tunable circular dichroism (CD) values from 0.9° to 1.5° at 550 nm wavelength were achieved by reversing the magnetic field direction. In addition, a magnetic circular dichroism (MCD) study revealed that the gap structure and size-related surface plasmon resonance induced MCD peaks. We demonstrated the transmitted color modulation, where the color dynamically changed from green-to-red, by controlling the field strength and polarizer axis. We believe current work broadens our understanding of magnetoplasmonic nanostructure and expands its potential applicability in optoelectronics or optical-communications.

Cerebral air embolism (CAE), an entry of air into cerebrovascular circulation, is a rare complication which occurs during various in-hospital techniques. CAE has symptoms similar to acute cerebral infarction and causes serious neurological damage. Proper treatment must be done through rapid diagnosis. We present a case of CAE that showed on susceptibility weighted magnetic resonance imaging following self removal of central venous catheter.

Background: Osteolysis is one of the most common problems that occurs after total hip and knee arthroplasty and has recently become a significant problem after total ankle arthroplasty (TAA). In this study, we investigated the role of LIM homeobox transcription factor 1-β (Lmx1b) in osteoclast differentiation. By evaluating the expression profiles associated with osteolysis following TAA treatment, Lmx1b was found to be differentially expressed in patients with osteolysis after TAA.Methods: To identify the important genes associated with osteolysis after TAA, RNA sequencing was performed by analyzing 8 patient samples: 5 primary TAA samples (control group) and 3 TAA samples revised for flexion instability (osteolysis group). By analyzing the differentially expressed genes and gene ontologies, Lmx1b expression was found to be upregulated in the osteolysis group compared to that in the control group. Focusing on the role of Lmx1b in bone cells, Lmx1b was overexpressed by a retrovirus in osteoclast precursor cells. The cultured cells were stained with tartrate-resistant acid phosphatase, and the expression of osteoclast-related genes was analyzed using real-time polymerase chain reaction.Results: Lmx1b overexpression in osteoclast precursors suppresses osteoclast formation and resorptive activity. The expression of osteoclast marker genes was significantly reduced during osteoclast differentiation by Lmx1b overexpression. Furthermore, Lmx1b is associated with nuclear factor of activated T cells 1 (NFATc1) and inhibited NFATc1 translocation into the nucleus.Conclusions: These results provide novel insights into the anti-bone resorptive effect of Lmx1b on osteolysis after TAA and may lead to the development of effective preventative and therapeutic strategies for peri-implant osteolysis.

Objective: Patients with spinal cord injury (SCI) are often unstable and require intensive care unit (ICU) treatment in the acute phase. This study assists in the prognosis and treatment direction of SCI patients by retrospectively examining and analyzing the clinical characteristics of SCI patients admitted to the ICU.Methods: In this study, a total of 102 SCI patients were admitted to the ICU of our hospital from February 2013 to March 2019. Based on the medical records, the patient's gender, age, mechanism of injuries, day of hospitalization, surgery timing, tracheostomy, ventilator use, steroid use, underlying disease, and hypotension were investigated. To assess the clinical outcome, the american spinal injury association (ASIA) impairment scale and limb motor grade three weeks and six months after injury was evaluated.Results: Of the 102 patients, 76 (74.51%) were male, and the average age was 57.57 years. Of these, 87 (85.29%) had spinal surgery, while 30 (34.48%) had surgery within 36 h after injury. High doses of steroids were administered in 15 patients (14.85%). As for the ASIA impairment scale, Grade A at the initial stage of injury reached 15% of all patients but decreased to 5.1% after three weeks and 1.9% after six months.Conclusion: Early surgery was advantageous in improving the lower extremity motor grade at three weeks of injury. Although steroid use has no significant effect compared to the risk of complications in several previous studies, in this study, it was observed that the ASIA scale improved six months after injury in patients receiving high-dose steroids.

Despite the Pt-catalyzed alkaline hydrogen evolution reaction (HER) progressing via oxophilic metal-hydroxide surface hybridization, maximizing Pt reactivity alongside operational stability is still unsatisfactory due to the lack of well-designed and optimized interface structures. Producing atomically flat two-dimensional Pt nanodendrites (