Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome ...editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond.
Hydrotalcite-like-compound-derived Ni-Fe/Mg/Al catalyst, which is known to have high catalytic performance on reforming when activated by pre-reduction with H2, was combined with small amount of ...noble metal to obtain self-activation ability (startability) in toluene reforming with model exhaust gas of gasoline engine of automobiles. Rh is found to be the most effective noble metal from the viewpoints of the inherent reforming activity, good promotion of reduction of NiFe, and stability. Physical mixing of Rh/CeO2 and Ni-Fe/Mg/Al powders before shaping to granules gave higher activity in the startability test (reaction without pre-reduction) than other combination methods of Rh/CeO2 + Ni-Fe/Mg/Al, although the activity increase from Rh/CeO2 was much smaller than the potential activity of Ni-Fe/Mg/Al catalyst induced by pre-reduction with H2. Direct addition of Rh to Ni-Fe/Mg/Al by impregnation gave inferior performance to the mixture catalyst, because of the lower activity of Rh on hydrotalcite-derived oxide support than that of Rh on CeO2 support. The characterization with XRD, TEM-EDX and XAS showed that the reduction degrees of Ni, Fe and even Rh were small during the startability test. The Ni and Fe species only located near Rh species were probably reduced by reforming products from toluene formed over Rh.
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•Non-reduced catalysts were used for reforming of toluene as startability test.•Rh was added to Ni-Fe/Mg/Al catalyst with various methods to improve startability.•Mixing of Rh/CeO2 and Ni-Fe/Mg/Al powders before shaping gave the best performance.•The activity of the mixture catalyst was more due to Rh/CeO2 than NiFe species.•The small contribution of NiFe to the activity is due to the low reduction degree.
Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. ...Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Crude oil contains heavy waxes and asphaltenes, which eventually accumulate at the bottom of crude oil tanks as sludge. Therefore, it is necessary to remove sludge periodically to restore the ...original storage capacity of crude oil tanks or for tank inspection and overhaul. Conventionally, crude oil washing (COW) has been used to remove sludge from tanks. However, sludge is disposed of as industrial waste, resulting in significant costs. To solve this problem, sludge volume reduction technology (SVR) was developed as a new technology. The key point of this technology is to recover reusable oil from sludge using a centrifuge and mix it with crude oil without re-sludging. From the results of the study, it was found that re-sludge generation can be suppressed by mixing the recovered oil with the original crude oil under turbulent flow conditions while heating the oil when mixing it with the crude oil. Furthermore, the demonstration test of this technology was conducted in the UAE, and it was confirmed that about 5200 kL of recovered oil could be obtained from about 9000 kL of sludge accumulated in a crude oil tank, and that the technology was effective in reducing sludge by more than 50 %.
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► Chloride-free Ru/MnCO3 was synthesized as catalysts for Fischer–Tropsch synthesis (FTS). ► Ru/MnCO3 shows high activity under low pressure conditions below 1MPa. ►Metallic Ru ...particle sizes remained constant after 120h-FTS reaction. ► The origin of catalyst deactivation was explained in terms of the extent of hydrocarbon deposition.
The catalytic activities and different behaviors for catalyst deactivation by forming surface hydrocarbon deposits were investigated on the Cl-free Ru/MnCO3 Fischer–Tropsch synthesis (FTS) catalysts in a low pressure fixed-bed reactor. Catalytic activity of LT-Ru(NO) was found to be a little higher than that of Ru(NO). The differences seem to stem mainly from ruthenium particle sizes and reduction behavior of adsorbed CO on the catalysts, which would be consistent with the results of CH4 formation from temperature-programmed reduction (TPR) of pre-adsorbed CO, as well as Ru particle sizes, as ascertained by H2 and CO adsorptions and TEM measurements. The Ru particle sizes of used catalysts obtained after 120h-reaction were approximately close to those of fresh catalysts and no ruthenium aggregation occurred. The origin of catalyst deactivation was investigated in terms of the extent of hydrocarbon deposition. The adsorbed atomic carbon at the peak temperature around 250–350°C was eliminated by H2 treatment, but the more heavy hydrocarbons at peak temperature over 400°C such as polymeric and graphitic carbons were not removed by any treatment. The nature of hydrocarbon deposition would be suggested by measuring the deposited carbon with the help of the characterizations, such as thermo-gravimetric analysis, temperature-programmed reduction and diffuse reflectance infrared Fourier transform (FT-IR) measurements.
The cycle usage test of Ni/MgO catalyst for the steam reforming of naphthalene/benzene as model tar compounds of biomass gasification were conducted. Both calcined and reduced Ni/MgO catalysts showed ...same catalytic activities regardless with H
2 pretreatment. The carbon species on used catalyst could be completely oxidized by 10% O
2/Ar mixture at 873
K for 40
min. This catalyst showed stable activity (carbon based conversion: av. 55%) at 1073
K for 10
h. However, the catalyst lost its activity during cycle usage tests (steam reforming
→
oxidation
→
steam reforming).
Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," ...characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer.BACKGROUNDExcessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer.This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined.METHODSThis retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined.AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016).RESULTSAL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016).The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.CONCLUSIONSThe presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.
Reforming of toluene with model exhaust gas was carried out as Reformed EGR of gasoline engine mainly at 773 K with Ni-M/Mg/Al (Ni 12 wt%, M = Fe, Co, Cu) prepared from corresponding ...hydrotalcite-like compounds. Ni-Fe/Mg/Al (Fe/Ni = 0.1–0.5) showed clearly higher performance than Ni/Mg/Al in terms of activity, coke-deposition resistance and stability. In contrast, Ni-M/Mg/Al (M/Ni = 0.25, M = Co, Cu) showed similar behaviors to Ni/Mg/Al. The optimum Fe/Ni ratio was 0.25 from toluene conversion and the suppression of benzene formation. Ni-Fe/Mg/Al (Fe/Ni = 0.25) showed high coke-deposition resistance at any position of the catalyst bed, indicating that both substrate decomposition and CO disproportionation were suppressed. The coke amount was not increased even at low temperature (773 K) or higher toluene partial pressure (toluene/H2O/N2/CO2 = 0.5–1.2/11.8/71.2/11.8, molar ratio), but the activity gradually decreased under such conditions. The Ni-Fe alloy nanoparticles in the reduced Ni-Fe/Mg/Al were almost unchanged during the reaction. The deactivated catalyst was regenerated successfully by the treatment under N2 at 873 K, catalytic use at 973 K or re-reduction. These results suggest that the deactivation was caused by carbonaceous species which can be removed easily even by N2 treatment, rather than by graphite-like coke that is difficult to be eliminated via such simple treatment.
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•Ni/Mg/Al derived from hydrotalcite-like-compound was modified with Fe, Co or Cu.•Modified Ni/Mg/Al catalysts were applied to reforming of toluene with model exhaust gas.•Ni-Fe/Mg/Al showed higher performance than Ni/Mg/Al and Ni-M/Mg/Al (M = Co, Cu).•Ni-Fe alloy nanoparticles were unchanged during the reforming of toluene at 773 K.•Regeneration of deactivated Ni-Fe/Mg/Al catalyst is possible by simple treatments.
The influence of support on the catalytic performances of Pt and Ni based catalysts for the steam reforming of naphthalene/benzene as model tar compounds of biomass gasification was investigated. ...Pt/Al2O3 catalyst showed relatively high and stable activity in steam reforming for 30h at 1023K and 1073K with steam/carbon (S/C) molar ratio of 3. However, this catalyst remarkably lost its activity after 1st step of oxidation treatment during cycle test of steam reforming-oxidation treatment. On the other hand, when hydrogen treatment was conducted as a regeneration method, Pt/Al2O3 catalyst showed stable performance for 5 cycles. Ni/Al2O3 and Pt/Al2O3 catalysts showed similar catalytic behaviors for steam reforming and cycle test. Pt/MgO catalyst exhibited stable activity at 1073K for the steam reforming under steady state and cycle utilization test of steam reforming-oxidation treatment. However, when the reaction temperature was reduced to 1023K, Pt/MgO catalyst lost its activity for both cases. It is concluded from the above results that Al2O3 supported catalysts were excellent catalysts for the steam reforming of naphthalene/benzene to produce H2.
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