Follistatin N terminus differentially regulates muscle size and fat in vivo

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminus-deleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy

Association between prophylactic hydration volume and risk of contrast-induced nephropathy after emergent percutaneous coronary intervention

Background: Intravenous hydration during percutaneous coronary intervention (PCI) significantly reduces the risk of contrast-induced nephropathy (CIN), but there are no well-defined protocols regard¬ing the optimal hydration volume (HV) required to prevent CIN following emergent PCI. Therefore, this study investigates the association between the intravenous HV and CIN after emergent PCI. Methods: 711 patients were prospectively recruited who had underwent emergent PCI with hydration at routine speed and the relationship was investigated between HV or HV to weight ratio (HV/W) and the CIN risk, which was defined as a ≥ 25% or ≥ 0.5 mg/dL increase in serum creatinine levels from baseline within 48–72 h of exposure to the contrast. Results: The overall CIN incidence was 24.7%. Patients in the higher HV quartiles had elevated CIN rates. Multivariate analysis showed that higher HV/W ratios were not associated with a decreased risk (using the HV) of CIN, but they were associated with an increased risk (using the HV/W) of CIN (Q4 vs. Q1: adjusted odds ratio 1.99; 95% confidence interval 1.05–3.74; p = 0.034). A higher HV/W ratio was not significantly associated with a reduced risk of long-term death (all p > 0.05). Conclusions: The data suggests that a higher total HV is not associated with a decreased CIN risk or beneficial long-term prognoses, and that excessive HV may increase the risk of CIN after emergent PCI

Research on Bi-level Cooperative Robust Planning of Distributed Renewable Energy in Incremental Distribution Network Considering Demand Response

The paper constructs a two-level collaborative planning model for incremental distribution network considering demand response and distributed renewable energy access. In the upper model, the goal is to minimize the investment cost of the distribution network, and the lower model takes the system's operating cost optimally, fully considers the uncertainty of renewable energy output, and introduces robust optimization to solve it. It can be seen from the simulation results that the consideration of demand response in the distribution network planning is conducive to delaying investment costs, enhancing power user load flexibility, and effectively avoiding load shedding and other problems. The research results lay the foundation for the feasibility of demand response resources participating in power grid plannin

Estimation of mechanics parameters of rock in consideration of confining pressure using monitoring while drilling data

During the drilling process, high-strength rock can lead to various issues such as drilling suppression, bit wear, and increased operational costs. To ensure safe and efficient drilling operations, it is crucial to accurately predict the strength parameters of the rock and recommend modifications to operational procedures. This paper proposes a low-cost and fast measurement method for predicting the strength parameters of rock in the field. To evaluate the effectiveness of this method, a drilling process monitoring experiment was conducted on sandstone, limestone, and granite. The experiment studied the effect of confining pressure on the response of cutting with an impregnated diamond bit. By analyzing the relationship between the thrust force, torque force, and penetration depth under different confining pressures, the researchers developed an analytical model for drilling that considers confining pressure, compressed crushed zone, and bit geometry. The results show that the confining pressure has a significant effect on the cutting response. As the confining pressure increases, the thrust force, torque force, and penetration depth at the cutting point also increase. Furthermore, a new measurement method was proposed to determine the strength parameters, such as cohesion, internal friction angle, and unconfined compressive strength. The estimated strength parameters for the three rock types using the drilling method were in good agreement with those of the standard laboratory test, with an error range of 10%. This method of estimating rock strength parameters is a practical tool for engineers. It can continuously and quickly obtain the drilling parameters of in-situ rocks