Numerical simulation of blasting behavior of rock mass with cavity under high in-situ stress.

With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

Therapeutic SHPRH-146aa encoded by circ-SHPRH dynamically upregulates P21 to inhibit CDKs in neuroblastoma.

Recent research has underscored the significance of circular RNAs (circRNAs) in various cancers, including neuroblastoma (NB). Specifically, circ-SHPRH, a unique circRNA, has been revealed to inhibit tumor growth by sequestering miRNAs or producing the SHPRH-146aa protein. To explore circ-SHPRH's involvement in NB and its potential application in gene therapy, this study examined circ-SHPRH expression in 94 NB tissues and cell lines (SK-N-BE(2), SH-SY5Y) using real-time PCR and fluorescence in situ hybridization (FISH). Functional assays encompassing both overexpression and knockdown experiments in NB cell lines, as well as in vivo investigations, were conducted. RNA-seq analysis revealed a correlation between circ-SHPRH and the pathway of P21 (CDKN1A), a pivotal cell cycle regulator. Validation through PCR and other techniques confirmed that circ-SHPRH upregulated P21 expression. Furthermore, the regulatory role of circ-SHPRH in the P21-CDK pathway was corroborated through SHPRH-146aa expression analysis. Notably, adenovirus-mediated circ-SHPRH overexpression effectively curbed NB tumor growth in NSG mice, while combining circ-SHPRH with everolimus exhibited potential for NB treatment. This study elucidates the remarkable significance of circ-SHPRH in NB and its prospective utility in gene therapy, thereby paving the way for innovative therapeutic approaches.

Dress me an outfit: advanced probiotics hybrid systems for intelligent IBD therapy.

Inflammation bowel disease (IBD) has emerged as a public health challenge worldwide; with high incidence and rapid prevalence, it has troubled billions of people and further induced multitudinous systemic complications. Recent decade has witnessed the vigorous application of food-borne probiotics for IBD therapy; however, the complicated and changeable environments of digestive tract have forced probiotics to face multiple in vivo pressures, consequently causing unsatisfied prophylactic or therapeutic efficacy attributed to off-targeted arrival, damaged viability, insufficient colonization efficiency, etc. Fortunately, arisen hybrid technology has provided versatile breakthroughs for the targeted transplantation of probiotics. By ingeniously modifying probiotics to form probiotics hybrid systems (PHS), the biological behaviors of probiotics in vivo could be mediated, the interactions between probiotics with intestinal components can be facilitated, and diverse advanced probiotic-based therapies for IBD challenge can be developed, which attribute to the intelligent response to microenvironment of PHS, and intelligent design of PHS for multiple functions combination. In this review, various PHS were categorized and their intestinal behaviors were elucidated systematically, their therapeutic effects and intrinsic mechanism were further analyzed. Besides, shortages of present PHS and the corresponding solutions have been discussed, based on which the future perspectives of this field have also been proposed. The undeniable fact is that PHS show an incomparable future to bring the next generation of advanced food science.

Dressing probiotics with versatile outfits would impart them with extended functions, including elevated targeted efficiency to the nidi, controlled in situ release, enhance intestinal colonization, comprehensive microecology regulation, and so on. In this article, we systematically analyzed and categorized PHS for intelligent IBD therapy published in recent decade, and discussed their pros and cons to further raise the future orientation for PHS development.

Engineered probiotic cocktail with two cascade metabolic Escherichia coli for the treatment of hyperlysinemia.

Engineering probiotics have emerged as a potential strategy for the treatment of metabolic diseases. However, due to the exceptional complexity of these metabolic disorders and the intricate relationship between gut microbes, it is difficult to achieve an ideal therapeutic effect in a specific metabolic disorder using only a single engineered strain. In this work, we proposed a probiotic cocktail strategy by engineering two cascade metabolic bacteria to treat hyperlysinemia, an inherited lysine metabolic disorder with loss of α-aminoadipate semialdehyde synthase (AASS) activity. A probiotic E. coli Nissle 1917 strain EcNT (pTLS) with a heterologous enzyme pathway in Saccharomyces cerevisiae was engineered to metabolize the excess lysine. Another one EcNT (pK25) was engineered to consume the products of lysine metabolism. The bacterial cocktail enables the maintenance of a metabolic cascade with AASS-like functional activity to maintain the blood lysine concentrations and downstream metabolites. In vitro experimental results showed that the cocktail bacteria had a better metabolic capacity and metabolites balance at a ratio of EcNT (pTLS) and EcNT (pK25) of 1:2. Feeding of the cocktail bacteria to the mouse model effectively reduced the concentration of lysine and balanced saccharopine in the plasma of hyperlysinemia-like mice. These findings not only provide a promising strategy of probiotic stains for the treatment of hyperlysinemia but also highlight the potential of engineered cascade cocktails to intervene and even cure other inherited metabolic diseases.

Constructing Pd@Layered-CoOx/MFI Bifunctional Catalyst for Efficient Ethyl Acetate Oxidation: Boosted C═O Activation and *O Species Transformation.

Oxygenated volatile organic compounds (OVOCs), emitted in large quantities by the chemical industry, are a major contributor to the formation of ozone and subsequent particulate matter. For the efficient catalytic oxidation of OVOCs, the challenges of molecular activation and intermediate inhibition remain. The construction of bifunctional active sites with specific structures offers a promising way to overcome these problems. Here, the Pd@Layered-CoOx/MFI bifunctional catalyst with core-shell active sites was rationally fabricated though a two-step ligand pyrolysis method, which exhibits a superb oxidation efficiency toward ethyl acetate (EA). Over this, 13.4% of EA (1000 ppm) can be oxidized at just 140 °C with a reaction rate of 13.85 mmol·gPd-1·s-1, around 176.7 times higher than that of the conventional Pd-CoOx/MFI catalyst. The electronic coupling of the Pd-Co pair promotes the electron back-donation from Pd nanoparticles to the layered CoOx shell and facilitates the formation of Pd2+ species, which greatly enhances the adsorption and activation of the electron-rich C═O bond of the EA molecules. In addition, the synergy of these core-shell Pd@Layered-CoOx sites accelerates the activation and transformation of *O species, which inhibit the formation of acetaldehyde and ethanol byproducts, ensuring the rapid total oxidation of EA molecules via the Mars-van Krevelen mechanism. This work established a solid foundation for exploring robust bifunctional catalysts for deep OVOC purification.

Unraveling the Drug Response Heterogeneity with Single-Cell Vibrational Phenomics.

Drug responses heterogeneity is often highlighted to justify the need for precision medicine. However, due to the highly complex nature of cell phenotypes in many diseases, one of key challenges is how to obtain the high content features in a cellular population. Here we present a single-cell vibrational phenomics approach, integrating synchrotron infrared microspectroscopy and multivariate calculation, for quantitatively evaluating the cellular responses to drug perturbation with single cell resolution. In a human hepatocellular carcinoma HepG2 cell model, the phenotypic changes induced by two types of drugs, taxol (TAX) and protopanaxadiol (PPD), were analyzed and revealed the response heterogeneity in drug concentration and chemical components. These findings not only provide a label-free strategy for determining the drug response at the single cell level, but also demonstrate the great potential of vibrational phenomics as a drug discovery platform.

Human mesenchymal stromal cells ameliorate cisplatin induced acute and chronic kidney injury via TSG-6.

Cisplatin is widely employed in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rhTSG-6), or PBS through tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. hBM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen (BUN), tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, knockdown of TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviate cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.

Terahertz Spectroscopic Insight into the Hydrogelation of Copper Ion-Coordinated Poly(vinyl alcohol).

Metal-coordinated hydrogels are becoming increasingly popular in the biomedical field due to their unique properties. However, the mechanism behind gel forming involving metal ions is not yet fully understood. In this work, terahertz spectroscopy was used to investigate the role of interfacial water in the gelation process of copper ion-coordinated poly(vinyl alcohol) hydrogels. The results showed that the binding of copper ions could alter the interfacial hydration dynamics of the poly(vinyl alcohol) polymers. Combined with the results of differential scanning calorimetry (DSC), we propose a possible hydration layer-mediated mechanism for the formation of cooper ion-coordinated hydrogel during the freeze-thaw cycle. These results highlight the value of terahertz spectroscopy as a sensor for studying the hydration process in hydrogels and provide an important clue for understanding the mechanism of hydrogelation in ion-coordinated hydrogels.

Nanomechanical collective vibration of SARS-CoV-2 spike proteins.

The development of effective therapeutics against COVID-19 requires a thorough understanding of the receptor recognition mechanism of the SARS-CoV-2 spike (S) protein. Here the multidomain collective dynamics on the trimer of the spike protein has been analyzed using normal mode analysis (NMA). A common nanomechanical profile was identified in the spike proteins of SARS-CoV-2 and its variants. The profile involves collective vibrations of the receptor-binding domain (RBD) and the N-terminal domain (NTD), which may mediate the physical interaction process. Quantitative analysis of the collective modes suggests a nanomechanical property involving large-scale conformational changes, which explains the difference in receptor binding affinity among different variants. These results support the use of intrinsic global dynamics as a valuable perspective for studying the allosteric and functional mechanisms of the S protein. This approach also provides a low-cost theoretical toolkit for screening potential pathogenic mutations and drug targets.

Comparative analysis of biofilm characterization of probiotic Escherichia coli.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Protopanaxadiol Targeting Membrane Induces HepG2 Cell Apoptosis Via Raft-like Formation and Tubulation Disruption.

Protopanaxadiol (PPD), which has a molecular structure similar to cholesterol, is a potent anticancer agent that has been proposed to target the lipid membrane for the pharmacological effects. However, the underlying mechanism by which PPD modulates the cell membrane leading to cancer cell death is not be fully understood. In this work, we used single cell infrared spectroscopy, scanning electron microscopy and confocal microscopy to investigate the effects of PPD on human hepatocellular carcinoma (HepG2) cells, focusing on the change in membrane structure. We found that PPD significantly reduced the number of membrane tubules over the course of treatment. Interestingly, the addition of PPD could promote the formation of lipid raft-like domains (PPD rafts) and even restore the domain disruption caused by methyl-beta-cyclodextrin depletion of membrane cholesterol. In addition, PPD pre-treatment may increase the induction effect of FasL, which impairs cell viability, although it does not appear to be beneficial for Fas clustering in the PPD rafts. Collectively, these results highlight a non-classical mechanism by which PPD induces HepG2 apoptosis by directly affecting the physical properties of the cell membrane, providing a novel insight into understanding membrane-targeted therapy.

Numerical simulation of rock blasting under different in-situ stresses and joint conditions.

High primary rock stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different rock breaking states under different primary rock stress conditions. There are a large number of naturally formed joints in rock mass, due to the limitations of laboratory tests, a numerical model of jointed rock mass was established using LS-DYNA software to investigate the evolution of blasting damage under various in-situ stresses and open joints. In this simulation, using the Lagrange-Euler (ALE) procedure and the equation of state (JWL) that defines explosive materials, the study considered different joint thicknesses (2cm, 4cm, and 6cm), joint angles (0°, 30°, 60°, and 90°), and in-situ stress conditions (lateral stress coefficients of 0.5, 1, and 2, with vertical in-situ stresses of 10MPa and 20MPa), through stress analysis and damage area comparison, the relationship between damage crack propagation and horizontal and vertical stress difference is explored. The research aimed to understand the mechanisms underlying crack initiation and propagation. The results show that: (1) The presence of joints exerts a barrier effect on the expansion and penetration of cracks. When explosion stress waves reach the joint surface, their propagation is impeded, leading to the diffusion of wing cracks at the joint ends. When the lateral stress coefficient and joint angle are the same, an increase in initial in-situ stress results in a reduction in the area of the blasting damage zone. (2) Under the same initial in-situ stress conditions, the area of the blasting damage zone initially increases and then decreases with an increasing joint angle. However, it remains larger than that without a joint, and there exists an optimal angle that maximizes the damage area. In the simulated conditions, the area of damage cracks is greatest when the joint angle is 60° dip angle. (3) The presence of initial in-situ stress has a certain impact on the initiation and expansion of blasting cracks. The degree and nature of this influence are not solely related to the lateral stress coefficient but also depend on the joint's angle and thickness. When in-situ stress is present, the initial in-situ stress field's pressure is not conducive to the initiation and propagation of blasting cracks. However, the existence of a joint has a noticeable guiding and promoting effect on crack propagation, and the pattern of crack propagation is influenced by both joint and in-situ stress conditions.

Research on rockburst prevention systems based on the attenuation law of coal and rock vibration wave energy.

During the coal and rock mass fracture process, elastic properties are released and vibration waves are radiated outward. The energy attenuation characteristics of these waves can describe the cumulative damage and elastic energy accumulation of the mass. To investigate coal and rock mass failure characteristics and energy attenuation rules during rockburst, numerical simulation and laboratory testing were utilized to study the energy transfer laws under various parameters. Six variables, including elastic modulus, Poisson's ratio, bulk density, cohesion, internal friction angle, and void ratio, were selected to simulate the rockburst energy release process under different parameter combinations by adding surface pressure to the model. The coal and rock mass energy attenuation coefficient was obtained by fitting the node energy straight line using the least squares method. The six variables' influence on vibration wave energy transfer was obtained using analytic hierarchy process program written in MATLAB, and a comprehensive calculation formula was proposed. Using the energy attenuation coefficient, the rock layer energy diffusion distance was calculated and compared with the roof collapse rock layer step distance, resulting in the roof rock layer cutting distance determination. By roof rock strata precutting, rockburst occurrence can be prevented, ensuring safe and efficient coal mine production.

Three-dimensional simulation of the influence of different flotation media in the dissolved air flotation tank through the population balance model.

Gas-liquid flow in the dissolved air flotation (DAF) tank was studied through computational fluid dynamics through the realizable k-ε model and the population balance model (PBM) to predict the gas content of different flotation mediums (air, carbon dioxide, and chlorine) at different heights of the separation zone in the DAF tank. Simultaneously, a particular focus was placed on studying the effects of bubble aggregation and breakage on gas content. The results indicated that there were virtually no bubbles present in the region below 0.1 m of the separation zone. The gas content in the separation zone could meet the needs for gas content in the DAF tank when all these three gases were adopted as flotation medium. The introduction of models for bubble aggregation and breakage resulted in lower gas content at the bottom of the separation zone and higher gas content at the top, aligning more closely with experimental data. Due to the structural similarity and similar physicochemical characteristics of carbon dioxide and water molecules, the impact of bubble aggregation and breakage on the gas content is minimal.

Vibrational phenomics decoding of the stem cell stepwise aging process at single-cell resolution.

We introduce vibrational spectroscopy to quantitatively measure the phenotypic heterogeneity of senescent stem cells in the aging process at the single cell level. Using an aging model of serially passaged human mesenchymal stem cells (MSCs), we characterized the phenotypic changes of MSCs during different aged stages and discovered a stepwise aging process with several distinct subtypes.

Formaldehyde Ambient-Temperature Decomposition over Pd/Mn3O4-MnO Driven by Active Sites' Self-Tandem Catalysis.

The widespread presence of formaldehyde (HCHO) pollutant has aroused significant environmental and health concerns. The catalytic oxidation of HCHO into CO2 and H2O at ambient temperature is regarded as one of the most efficacious and environmentally friendly approaches; to achieve this, however, accelerating the intermediate formate species formation and decomposition remains an ongoing obstacle. Herein, a unique tandem catalytic system with outstanding performance in low-temperature HCHO oxidation is proposed on well-structured Pd/Mn3O4-MnO catalysts possessing bifunctional catalytic centers. Notably, the optimized tandem catalyst achieves complete oxidation of 100 ppm of HCHO at just 18 °C, much better than the Pd/Mn3O4 (30%) and Pd/MnO (27%) counterparts as well as other physical tandem catalysts. The operando analyses and physical tandem investigations reveal that HCHO is primarily activated to gaseous HCOOH on the surface of Pd/Mn3O4 and subsequently converted to H2CO3 on the Pd/MnO component for deep decomposition. Theoretical studies disclose that Pd/Mn3O4 exhibits a favorable reaction energy barrier for the HCHO → HCOOH step compared to Pd/MnO; while conversely, the HCOOH → H2CO3 step is more facilely accomplished over Pd/MnO. Furthermore, the nanoscale intimacy between two components enhances the mobility of lattice oxygen, thereby facilitating interfacial reconstruction and promoting interaction between active sites of Pd/Mn3O4 and Pd/MnO in local vicinity, which further benefits sustained HCHO tandem catalytic oxidation. The tandem catalysis demonstrated in this work provides a generalizable platform for the future design of well-defined functional catalysts for oxidation reactions.

A New Strategy for Obesity Treatment: Revealing the Frontiers of Anti-obesity Medications.

Obesity dramatically increases the risk of type 2 diabetes, fatty liver, hypertension, cardiovascular disease, and cancer, causing both declines in quality of life and life expectancy, which is a serious worldwide epidemic. At present, more and more patients with obesity are choosing drug therapy. However, given the high failure rate, high cost, and long design and testing process for discovering and developing new anti-obesity drugs, drug repurposing could be an innovative method and opportunity to broaden and improve pharmacological tools in this context. Because different diseases share molecular pathways and targets in the cells, anti-obesity drugs discovered in other fields are a viable option for treating obesity. Recently, some drugs initially developed for other diseases, such as treating diabetes, tumors, depression, alcoholism, erectile dysfunction, and Parkinson's disease, have been found to exert potential anti-obesity effects, which provides another treatment prospect. In this review, we will discuss the potential benefits and barriers associated with these drugs being used as obesity medications by focusing on their mechanisms of action when treating obesity. This could be a viable strategy for treating obesity as a significant advance in human health.

The association between the number of pregnancies and depressive symptoms: A population-based study.

BACKGROUND: Depression is a psychosomatic disorder that affects reproductive health. The number of pregnancies is an important indicator of reproductive health. Multiple pregnancies and births may aggravate the risk of depression in females. However, the evidence of the connection between the number of pregnancies and depression is unclear. We aimed to investigate the relationship between the number of pregnancies and depressive symptoms. METHODS: We used the National Health and Nutrition Examination Survey (NHANES) data with a total of 17,216 women from 2005 to 2020. The number of pregnancies obtained from the self-report questionnaire. Depressive symptoms were measured by the nine-item patient health questionnaire (PHQ-9). Multivariate logistic regression models were used to examine the risk factors of depression. The restricted cubic spline (RCS) was applied to explore the nonlinear relationship. In addition, subgroup analysis was used to support the accuracy of our findings. RESULTS: We found that the number of pregnancies is positively associated with the prevalence of depression. According to the multivariable logistic regression analysis, pregnant women was 1.52-fold higher than the normal group to experience depression in the fully-adjusted model. No interaction between number of pregnancies and covariates in subgroups. LIMITATIONS: This study was cross-sectional, which limits its ability to draw conclusions about the causal relationship between the number of pregnancies and depression. CONCLUSION: In the United States, the number of pregnancies was positively associated with the prevalence of depression. It is critical to register the number of pregnancies for monitoring depressive symptoms.

Polarization-dependent photoinduced metal-insulator transitions in manganites.

In correlated oxides, collaborative manipulation on light intensity, wavelength, pulse duration and polarization has yielded many exotic discoveries, such as phase transitions and novel quantum states. In view of potential optoelectronic applications, tailoring long-lived static properties by light-induced effects is highly desirable. So far, the polarization state of light has rarely been reported as a control parameter for this purpose. Here, we report polarization-dependent metal-to-insulator transition (MIT) in phase-separated manganite thin films, introducing a new degree of freedom to control static MIT. Specifically, we observed giant photoinduced resistance jumps with striking features: (1) a single resistance jump occurs upon a linearly polarized light incident with a chosen polarization angle, and a second resistance jump occurs when the polarization angle changes; (2) the amplitude of the second resistance jump depends sensitively on the actual change of the polarization angles. Linear transmittance measurements reveal that the origin of the above phenomena is closely related to the coexistence of anisotropic micro-domains. Our results represent a first step to utilize light polarization as an active knob to manipulate static phase transitions, pointing towards new pathways for nonvolatile optoelectronic devices and sensors.