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Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy.

Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in suckling piglets, leading to severe economic losses worldwide. There is an urgent need to find new therapeutic methods to prevent and control PEDV. Not only is there a shortage of commercial anti-PEDV drugs, but available commercial vaccines fail to protect against highly virulent PEDV variants. We screened an FDA-approved library of 911 natural products and found that tomatidine, a steroidal alkaloid extracted from the skin and leaves of tomatoes, demonstrates significant inhibition of PEDV replication in Vero and IPEC-J2 cells in vitro. Molecular docking and molecular dynamics analysis predicted interactions between tomatidine and the active pocket of PEDV 3CL protease, which were confirmed by fluorescence spectroscopy and isothermal titration calorimetry (ITC). The inhibiting effect of tomatidine on 3CL protease was determined using cleavage visualization and FRET assay. Tomatidine-mediated blocking of 3CL protease activity in PEDV-infected cells was examined by western blot detection of the viral polyprotein in PEDV-infected cells. It indicates that tomatidine inhibits PEDV replication mainly by targeting 3CL protease. In addition, tomatidine also has antiviral activity against transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), encephalo myocarditis virus (EMCV) and seneca virus A (SVA) in vitro. These results may be helpful in developing a new prophylactic and therapeutic strategy against PEDV and other swine disease infections.

The amyloid-beta (Aβ) hypothesis that dyshomeostasis between Aβ production and clearance is a very early, key molecular factor in the etiology of Alzheimer’s disease (AD) has been proposed and examined in the AD research field. Scientists have focused on seeking natural products or drugs to influence the dynamic equilibrium of Aβ, targeting production and clearance of Aβ. There is emerging evidence that resveratrol (Res), a naturally occurring polyphenol mainly found in grapes and red wine, acts on AD in numerous in vivo and in vitro models. Res decreases the amyloidogenic cleavage of the amyloid precursor protein (APP), enhances clearance of amyloid beta-peptides, and reduces Aβ aggregation. Moreover, Res also protects neuronal functions through its antioxidant properties. This review discusses the action of Res on Aβ production, clearance and aggregation and multiple potential mechanisms, providing evidence of the useful of Res for AD treatment.

The Taishan Antineutrino Observatory (TAO) is a liquid-scintillator satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO) to measure the reference reactor neutrino spectrum with unprecedented energy resolution. We use inhomogeneous Poisson process and Tweedie generalized linear model (GLM) to characterize the detector response and the charge distribution of a SiPM. We develop a pure probabilistic model for time and charge of SiPMs from first principles to reconstruct point-like events in the TAO central detector. Thanks to our precise model and the high photo-coverage and quantum efficiency of the SiPM tiles at TAO, we achieve vertex position resolution better than 20 mm , energy resolution of about 2 % at 1 MeV and < 0.5 % non-uniformity, marking the world’s best performance of liquid scintillator detectors. With such resolution, we perceive MeV events to exhibit track effects. It opens up an exciting possibility of computed tracking calorimeter for unsegmented liquid scintillator detector like TAO. Our methodology is applicable to other experiments that utilize PMTs for time and charge readouts.

To address the challenge of achieving precise real-time monitoring of significant deformation in deep roadway surrounding rock, a quasi-distributed strain-sensing cable (SSC), which has a spatial resolution of 1 m, was developed based on the principle of Identical Weak Fiber Bragg Gratings. The performance of SSC has been evaluated through a series of calibration tests, revealing a range of 0%-3%, an accuracy level of 0.5%, a strain sensitivity measuring at 1.23 pm/µε, and a temperature sensitivity recorded as 10.78 pm/°C. Furthermore, a real-time deformation monitoring system has been established to monitor rock deformation, consisting of SSC, supporting installation equipment, demodulation equipment, and monitoring software. Moreover, the proposed methodology was applied in the deep roadway of Guqiao coal mine. The results showed that the maximum surface displacement of the roadway is 103.47 mm, while the lateral contrast error stands at 5%. The maximum strain value of the surrounding rock measures 27,095 µε. The depth of rock rupture zone is about 3 m, while the boundary of rock damage zone extends up to 6 m. This information serves as the foundation for determining the parameters of the roadway reinforcement support design.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2–HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.

Gas hydrate saturation is an important index for evaluating gas hydrate reservoirs, and well logs are an effective method for estimating gas hydrate saturation. To use well logs better to estimate gas hydrate saturation, and to establish the deep internal connections and laws of the data, we propose a method of using deep learning technology to estimate gas hydrate saturation from well logs. Considering that well logs have sequential characteristics, we used the long short-term memory (LSTM) recurrent neural network to predict the gas hydrate saturation from the well logs of two sites in the Shenhu area, South China Sea. By constructing an LSTM recurrent layer and two fully connected layers at one site, we used resistivity and acoustic velocity logs that were sensitive to gas hydrate as input. We used the gas hydrate saturation calculated by the chloride concentration of the pore water as output to train the LSTM network. We achieved a good training result. Applying the trained LSTM recurrent neural network to another site in the same area achieved good prediction of gas hydrate saturation, showing the unique advantages of deep learning technology in gas hydrate saturation estimation.

Water injection, as a widely used technique to prevent coal burst, can restrain the fractured coal seam and released the energy storage. In this study, laboratory tests were firstly carried out on standard coal specimens with five different water contents (i.e., 0%, 0.6%, 1.08%, 1.5%, 2.0%, and 2.3%). The failure mode, fragment size, and energy distribution characteristics of coal specimens were investigated. Experimental results show that strength, elastic strain energy, dissipated energy, brittleness index, as well as impact energy index decrease with increasing water content. Besides, the failure mode transitions gradually from splitting ejection to tensile-shear mixed failure mode as water content increases, and average fragment size shows positively related to water content. Moreover, scanning electron microscope tests results indicate that water in coal sample mainly causes the mineral softening and defects increase. Furthermore, a numerical model containing roadway excavation was established considering the water on coal burst prevention. Modelling results revealed that water injection can reduce degree of coal burst and ejection velocity of coal blocks, while it will raise up the depth of crack zone and surface displacement of roadway. Combined with laboratory tests and numerical results, the micro mechanism, energy mechanism, and engineering significance of water injection on coal burst prevention were finally analyzed.

Coal burst is a type of dynamic geological hazard in coal mine. In this study, a modified bursting energy index, which is defined as the ratio of elastic strain energy at the peak strength to the released strain energy density at the post-peak stage, was proposed to evaluate the coal burst proneness. The calculation method for this index was also introduced. Two coal mines (PJ and TJH coal mines) located in Ordos coalfield were used to verify the validity of the proposed method. The tests results indicate that modified bursting energy index increases linearly with increasing uniaxial compressive strength. The parameter A, which is used to fit relation between total input and elastic strain energy density, has a significant effect on the modified bursting energy index. A large value of parameter A means more elastic strain energy before the peak strength while a small value indicates most of input energy was dissipated. Finally, the coal burst proneness of these two coal mines was evaluated with the modified index. The results of modified index are consistent with that of laboratory tests, and more reasonable than that from original bursting energy index because it removed the dissipated strain energy from the total input strain energy density.