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Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

In this paper, the self-diffusion coefficients (SDC) of CH4/CO2/H2O in coal molecules under different ensemble conditions and the effects of temperature and pressure are calculated by grand canonical Monte Carlo and molecular dynamics (MD) methods. Results indicated that the self-diffusion coefficients of CH4 and CO2 gradually increase with the increasing temperature under the NPT ensemble. The SDC of H2O increases undulatory and it is higher than that of CH4 and CO2 at each temperature, where the diffusion activation energy followed the order of \begin{document}$E({{\mathrm{H}}_2{\mathrm{O}}})

Abundance sensitivity is an important technical index of magnetic mass spectrometer, which describes the extent to which the tailing of intense ion peaks at a mass number in its neighborhood affects the weak ion peaks during isotope ratio measurement. It is particularly important in the measurement of isotope ratios containing low abundance nuclides, such as 234U/238U, 236U/238U, and 230Th/232Th. However, the abundance sensitivity of magnetic mass spectrometer is only of the order of 10−6 without taking additional technical measures. To further improve the abundance sensitivity, the techniques of tandem mass spectrometer, such as magnetic-electric, magnetic-magnetic and magnetic-electric-quadrupole tandem mass spectrometer, and retarding filter can be adopted. In fact, while various tandem mass spectrometer techniques can effectively improve the abundance sensitivity of an instrument, they also significantly increase the size, complexity, and cost of instrument, and therefore are not widely used. In contrast, due to its simple structure, small size, and excellent performance, the retarding filter has become a key component for commercial magnetic mass spectrometers to improve abundance sensitivity. Based on the basic principles of ion optics, a retarding filter consisting of five electrodes with a compact structure of only (40×50×50) mm3 was developed by utilizing the ion optics simulation software SIMION8.1. In addition to the function of energy retarding, the retarding filter also has the function of direction retarding, which greatly enhances the filtering capability to scatter ions. To test the ion transmission efficiency and the abundance sensitivity under different voltages, the retarding filter was installed on a domestic double-focusing thermal ionization mass spectrometer (TIMS). The instrument mainly consists of a thermal ionization source, a double focusing mass analyzer consisting of an electrostatic analyzer and a magnetic mass analyzer, a zoom lens, and a multi-collector detector, which can be configured with up to 16 faraday cups, 4 electron multipliers, and 2 retarding filters. The results showed that the abundance sensitivity of the mass spectrometer is successfully improved from

The occurrence of geological hazards and the instability of geotechnical engineering structures are closely related to the time-dependent behavior of rock. However, the idealization boundary condition for constant stress in creep or constant strain in relaxation is not usually attained in natural geological systems. Therefore, generalized relaxation tests that explore the simultaneous changes of stress and strain with time under different stress levels with constant pore-water pressure are conducted in this study. The results show that in area I, area II, and area III, the stress and strain both change synchronously with time and show similar evolutionary laws as the strain-time curve for creep or the stress-time curve for relaxation. When the applied stress level surpasses the σci or σcd threshold, the variations in stress and strain and their respective rates of change exhibit a significant increase. The radial deformation and its rate of change exhibit greater sensitivity in response to stress levels. The apparent strain deforms homogeneously at the primary stage, and subsequently, gradually localizes due to the microcrack development at the secondary stage. Ultimately, interconnection of the microcracks causes the formation of a shear-localization zone at the tertiary stage. The strain-time responses inside and outside the localization zone are characterized by local strain accumulation and inelastic unloading during the secondary and tertiary stages, respectively. The width of the shear-localization zone is found to range from 4.43 mm to 7.08 mm and increased with a longer time-to-failure. Scanning electron microscopy (SEM) reveals a dominant coalescence of intergranular cracks on the fracture surface, and the degree of physiochemical deterioration caused by water-rock interaction is more severe under a longer lifetime. The brittle sandstone's time-dependent deformation is essentially controlled by microcrack development during generalized relaxation, and its expectancy-life is determined by its initial microstructural state and the rheological path.

Abstract To explore the static pressure dynamic disaster mechanism of coal-and-gas outburst (CGO) fluid, the self-developed multi-field coupling large-scale physical simulation test system of coal mine dynamic disaster was used to carry out gas outburst and CGO physical simulation tests in straight, L-shaped and T-shaped roadways. The influence of roadway shape on the evolution of static pressure was explored, and the role of pulverized coal in the process of static pressure dynamic disaster was clarified. The results indicated that the static pressure showed a fluctuating downward trend during the outburst process. When gas outburst, the middle and front parts of the roadway in the straight section roadway were the most serious areas of static pressure disasters in the three shapes of roadways. The duration and range of high static pressure disaster in L-shaped roadway were larger than those in T-shaped and straight roadways in turn. When CGO, the most serious area of static pressure disaster in L-shaped and T-shaped roadways moved backward to the middle of the straight section roadway, and there was a rebound phenomenon in the process of static pressure fluctuation decline, which showed the pulse characteristics of CGO. During the outburst, the static pressure dynamic disaster hazard of L-shaped roadway was higher than that of T-shaped roadway, and the static pressure at the bifurcation structure decayed faster than that at the turning structure, which indicated that T-shaped roadway was more conducive to the release of static pressure in roadway, thus reduced the risk of static pressure disaster. When gas outburst, the static pressure attenuation of the fluid in the roadway before and after the turning and bifurcation structure was greater than that of CGO. The peak static pressure and impulse of the fluid during gas outburst were 2 times and 4–5 times that of CGO respectively. The presence of pulverized coal reduced the attenuation of static pressure and the hazard of dynamic disaster, prolonged the release time of energy, and led to the change of the maximum static pressure disaster area.

Physical simulation test is an effective method of occurrence mechanism and prevention and control of coal mine gas disasters. At present, the mechanical strength and permeability of briquette materials used in coal mine gas disasters physical simulation test are very different from that of raw coal. How improve the compressive strength and permeability of the briquette coal（BC） is the key problem in the briquette forming process. Based on this, several secondary carbonized briquettes with different holding time were made by a hot pressing method in this paper, and SEM, NMR, XRD, FTIR, MTS-815 rock mechanics test system and gas-containing coal thermal-fluid-solid coupling triaxial servo seepage test device were used to test and analyze secondary carbonized briquettes with different holding times. The effects of different holding times on microcrystalline structural parameters, basic structural units of aromatic hydrocarbons, alkyl side chains and various functional groups, surface morphology, T2 spectral morphology, and porosity evolution were analyzed, the mechanical and seepage characteristics of secondary carbonized briquet under different holding times were clarified. and the optimal holding time was determined. The results show that the surface roughness and pore diameter of the secondary carbonized briquette gradually increase with the increases of holding time, and cracks appear on the surface of BC after increasing to 6.7 h. The longer holding time, the more obvious cracks are. BC cumulative porosity and mesoporous porosity increased gradually, while microporous porosity decreased gradually. The aromatic layer spacing (d002) decreased first and then increased, while the microcrystalline diameter (La) and microcrystalline height (Lc) increased first and then decreased. The length of fatty chain decreased, and the degree of condensation of aromatic ring (Aar/Aal) increased first and then decreased. The uniaxial compressive strength increases first and then decreases, and the permeability decreases first and then increases. When the holding time is 5.3 h, the optimal holding time is obtained. In this case, the uniaxial compressive strength and elastic modulus of hot pressing BC are the largest, Poisson's ratio and permeability are the smallest, and its mechanical strength, permeability and density are 9.85 MPa, 1.49 × 10−15 m2, and 1.127 g/cm3, respectively. This study has important practical guiding significance for improving the real reducibility of the occurrence mechanism and prevention and control basic test of coal mine gas disaster and effectively preventing and controlling coal mine gas disaster accidents.

This study prepared magnetron-sputtering deposition film on a large-scale curved workpiece with a favorable thickness uniformity using a rectangular target cathode. For a substrate rotation structure with eccentric rotation/revolution composite motion, the geometrical model of the thickness distribution of the coating film on a large substrate was established in combination with the principle of rectangular cathode magnetron sputtering. The integral formula of the film thickness was derived, and various film thickness distribution patterns under different parameters were simulated. According to the present research results, the film thickness distribution can be optimized by adjusting the revolution-to-rotation radius and eccentric ratios. At an eccentric distance of 400 mm and a radius ratio of 2.78, the most favorable uniformity degree of 0.87 was obtained, which was controlled by the motion path of the fixed point on the substrate. The proposed approach helps to obtain large-scale films with favorable uniformity on the substrate.

This paper presents an investigation that aims to: (1) explore the relations between core symptoms of adult Attention Deficit and Hyperactivity Disorder (ADHD) and several typical Internet activities, and (2) compare the predictive power of two core symptoms of ADHD- inattention and hyperactivity/impulsivity- in predicting Internet addiction. Methods: A total of 2016 Chinese college students participated in this study. The ADHD symptoms were assessed using Conners self-rating scales and DSM-5 semistructured interviews. Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (SCID-5) was used to exclude other psychiatric disorders. Chen's Internet addiction scale (CIAS) was used to evaluate Internet addiction. Information about Internet activities (e.g., online gaming) was collected through a self-constructed questionnaire. Results: The ratio of Internet addiction problems among individuals with ADHD symptoms is significantly higher than in ordinary individuals (48.9% vs. 14.3%). Further, each core ADHD symptom has unique relations with different types of Internet activities. Specifically, both core ADHD symptoms are negatively associated with information downloading and online learning, and positively associated with online gaming, while online shopping is only associated with hyperactivity/impulsivity. Furthermore, both core ADHD symptoms are significant predictors of Internet addiction, especially inattention. Conclusion: College students with ADHD symptoms are at a higher risk of having Internet addiction than peers without ADHD symptoms. For individuals with ADHD symptoms and excessive online gaming and/or online shopping behaviors, the probability of having Internet addiction is even higher. These findings have important implications for identifying risk factors of Internet addiction and preventing Internet addiction in Higher Education settings.

In response to the problems of low strength and high permeability of coal materials in the current physical simulation test of coal mine gas dynamics, a set of experimental research methods for optimizing the molding conditions of hot-pressed briquette. Firstly, a hot-pressed briquette test system was independently established and the advantages and future improvement directions of the test system were summarized. At the same time, based on the Horsfield dense stacking theory, the optimal preparation plan for coal briquette materials was formulated. Finally, a molding condition optimization method was developed that combines the Markov distance measurement method and the golden section method. To verify the effectiveness of the experimental method, the secondary carbonization experiments of briquette were conducted under different molding pressure conditions by controlling the molding temperature to 311.8 ℃, heating rate to 5 ℃/min, and holding time to 5.3 h. The response characteristics of the microstructure, physical and mechanical properties, and permeability characteristics of the hot-pressed briquette under different molding pressure conditions were studied. The results show that with the increase of molding pressure, the total porosity gradually decreases, and the uniaxial compressive strength shows a trend of first increasing and then decreasing. The main forms of failure are block spalling and longitudinal fracture. The initial permeability shows a trend of first decreasing and then increasing, while the minimum permeability shows a trend of first decreasing, then increasing and then decreasing. Using the specific values of each molding condition as the test points, and the key parameters of hot-pressed coal and raw coal as the evaluation parameters, a sample matrix was constructed to calculate the Mahalanobis distance between hot-pressed briquette and raw coal under each molding condition, and then optimize the experimental interval using the golden section method. The optimized final molding pressure is 80 MPa. Under these molding conditions, the density, uniaxial compressive strength, and initial permeability of the hot-pressed briquette produced are 1.137 g/cm3, 12.21 MPa, and 1.32 × 10−15 m2, respectively. They are highly similar to the 1.132 g/cm3, 12.83 MPa, and 1.08 × 10−15 m2 of the raw coal, achieving the goal of improving the strength of the briquette and reducing the permeability of the briquette.

Abstract To further investigate the weakening effect of pore water pressure on intact rock mechanics properties and characteristics of fracture surface after failure, direct shear tests of sandstone were conducted under different pore pressure. A 3D scanner was employed to digitize the morphology of the post-shear fracture surface. The variogram function was applied to quantify the anisotropic characteristics of post-shear fracture surface. The relationship between deformation during shear failure of intact rock and quantitative parameters of fracture surface after shear failure was initially established. It can be found that amplitudes of the sinusoidal surface determine the maximum value of variogram, and period affect lag distance that reach the maximum value of variogram. Test results revealed that the increase of pore pressure has obvious weakening effect on shear strength and deformation of rock. Moreover, the increase of pore pressure makes the shear fracture surface flatter. It can be obtained that both Sill max and Range max are positively related to shear strain, but negatively related to normal strain.

Abstract Background The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult. Results We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography. Conclusions Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.

Abstract Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it’s hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.

Blockchain technology is a key technology in the current information field and has been widely used in various industries. Blockchain technology faces significant challenges in privacy protection while ensuring data immutability and transparency, so it is crucial to implement private computing in blockchain. To target the privacy issues in blockchain, we design a secure multi-party computation (SMPC) protocol DHSMPC based on homomorphic encryption in this paper. On the one hand, homomorphic encryption technology can directly operate on ciphertext, solving the privacy problem in the blockchain. On the other hand, this paper designs the directed decryption function of DHSMPC to resist malicious opponents in the CRS model, so that authorized users who do not participate in the calculation can also access the decryption results of secure multi-party computation. Analytical and experimental results show that DHSMPC has smaller ciphertext size and stronger performance than existing SMPC protocols. The protocol makes it possible to implement complex calculations in multi-party scenarios and is proven to be resistant to various semi-malicious attacks, ensuring data security and privacy. Finally, this article combines the designed DHSMPC protocol with blockchain and cloud computing, showing how to use this solution to achieve trusted data management in specific scenarios.

Among numerous polluting compounds, the organic dyes and antibiotics are two servious factors causing water pollution. Hence, it is urgent to find a fast and safe way to degrade waste water in a sustainable approach. Here, ferroelectric heterostructure based on 2D Bi2MoO6 nanosheets and Bi2S3 nanorods has been prepared by a two-step solvothermal method for the reduction of organic dyes and antibiotics. Due to the energy band balance between Bi2S3 and Bi2MoO6, the formed type-II heterostructure can populate charge transfer at the junction and effectively inhibit electron-hole recombination. Under ultrasonic stimulation, catalytic active sites of a Bi2MoO6/Bi2S3 heterostructure for pollutant degradation can be generated through rapid charge transfer activation, thus enhancing the catalytic degradation effect of organic dyes and antibiotics. The Bi2MoO6/Bi2S3 heterostructure not only has good degradation effect, but also shows better stability. This work opens up new avenues for designing highly-efficient catalysts, which is of importance for wastewater degradation and energy-saving applications.

In the context of new power systems， the diverse distributed power sources and user-side behavior have introduced instability in bus loads， thus presenting a fresh challenge for short-term load forecasting. In response to this challenge， a noise reduction forecasting method for bus load based on sequence decomposition is proposed. The construction and decomposition rules of the variational mode decomposition （VMD） are applied to the sequence decomposition of bus load. The residual terms following the sequence decomposition are smoothed using locally weighted regression （LWR） to forecast the noise reduction of bus load. Based on the measured active power data of bus load in an area， a recurrent neural network （RNN） is constructed to forecast the bus load after noise reduction. The results indicate that this method effectively eliminates the noise of the bus load sequence， and the sequence tends to be smooth while retaining the characteristics of the original bus load sequence. Moreover， it yields excellent forecasting curves and accurate forecasting results.