Synergy of lytic phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii.

Phage-antibiotic combination treatment is a novel noteworthy drug delivery method in anti-infection. In the current study, we have isolated a new phage, pB23, against carbapenem-resistant Acinetobacter baumannii 2023. Synergistic antibacterial effect between phage pB23 and meropenem combination could be more stable, using moderate doses of phage (multiplicity of infection ranging from 0.1 to 1,000) based on results of in vitro antibacterial activity. Phage pB23 and meropenem combination could effectively clear mature biofilms and prevent biofilm formation of carbapenem-resistant Acinetobacter baumannii in vitro. Phage pB23 and meropenem combination also has good synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii in different growth phases under static culture conditions. The pig skin explant model shows that phage pB23 and meropenem combination has a synergistic effect to remove bacteria from wounds ex vivo. Phage pB23 and meropenem combination also exhibited a synergistic antibacterial effect in vivo using a zebrafish infection mode. The potential promotion of phage proliferation by meropenem and the sensitivity recovery of phage-resistant bacteria to meropenem might elucidate the mechanism of the synergistic antimicrobial activity. In summary, our study illustrates that phage pB23 and meropenem combination could produce synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii under static growth conditions. This study also demonstrates that phage-antibiotic combination will become an effective strategy to enhance antibacterial activity of individual drug and provide a new idea of the drug development for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii and other multidrug-resistant bacteria.

High-efficiency extraction of target particles in viscoelastic contraction-expansion microchannels.

The efficient and precise extraction of target particles is a crucial prerequisite for achieving accurate detection and analysis in microfluidic cell analysis. In this study, a symmetrical contraction-expansion microchannel with sheath flow was designed, aiming to extract target larger particles from particles of different sizes within the channel. This paper conducted numerical simulations to investigate the three-dimensional migration mechanisms of particles and performed experimental studies to examine the separation performance of particles with different sizes under varying flow rate ratios and different numbers of contraction-expansion structures. The experimental results indicate that at moderate sample flow rates and higher flow rate ratios, microchannels with fewer contraction-expansion structures are likely to achieve better performance in extracting target particles compared to microchannels with a greater number of these structures. Our work advances the application of viscoelastic contraction-expansion microchannels in particle separation. This device is easy to set up in parallel and significantly enhances throughput, providing an accurate and efficient solution for future particle separation applications.

Diagnostic procedure for localized constrictive pericarditis leading to bilateral pleural effusion: two case reports.

Constrictive pericarditis is a rare disease. Localized constrictive pericarditis leading to bilateral pleural effusion is more difficult to recognize, and the diagnostic procedure can be ambiguous. Here, we report two patients diagnosed with localized constrictive pericarditis who presented with bilateral pleural effusion. A thorough work-up showed that the pleural effusion was nonspecific, as was the pathology of the pleura. One patient had a history of pericardial effusion 2 years ago, and the other had undergone surgery for an anterior mediastinum teratoma. Pericardial scarring was found on their chest CT scans. The patients underwent pericardiectomy, and localized pericardial thickening was excised. The bilateral pleural effusion was effectively cured, and the patients showed satisfactory recovery on follow-up. Physicians should be aware of localized pericarditis leading to bilateral pleural effusion, and pericardiectomy is an effective diagnostic and therapeutic procedure.

Experimental investigation of the influence of mine water on mechanical properties of resin grout.

Resin grout is widely used in geotechnical and underground engineering, and is often affected by different mine water solutions. This study considered the effects of different mine water solutions and soaking times on resin grout. Soaking tests and uniaxial compression tests were conducted to investigate the changes in the solution pH, relative specimen mass, and uniaxial compressive strength (UCS), and the deterioration of the resin grout's mechanical properties caused by the mine water solution was analyzed. The corrosion mechanism of resin grout under the action of different mine water solutions was investigated through scanning electron microscopy tests. The results reveal that the pH value of the solution and the relative mass of the specimen gradually stabilized as the soaking time was extended, and the final solution was weakly alkaline. The increase in the acidity and alkalinity of the solution and the extension of the soaking time led to a gradual decrease in the UCS and elastic modulus of resin grout under the action of mine water. As the soaking was prolonged, the resin grout properties deteriorated to different degrees and Poisson's ratio increased. Moreover, owing to the different types and degrees of mine water action on resin grout in different mine water environments, the changes in the resin grout microstructure were also different. The defined damage parameters can express the damage process of the resin grout's UCS quantitatively under the action of mine water solution. Finally, beneficial engineering application countermeasures are proposed for different resin grout types used in roadway support applications in coal mines.

Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology.

This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.

Metal-Free Nitrogen-Doped Mesoporous Carbons for the Mild and Selective Synthesis of Pyrroles from Nitroarenes via Cascade Reaction.

The cascade synthesis of pyrroles from nitroarenes is an attractive alternative strategy. However, metal catalysts and relatively high temperatures cover the existing reported catalytic systems for this strategy. The development of nonmetallic heterogeneous catalytic systems for the one-pot synthesis of pyrrole from nitroarenes under mild conditions is both worthwhile and challenging. Herein, we describe an exceptionally efficient method for the synthesis of N-substituted pyrroles by the reductive coupling of nitroarenes and diketones over heterogeneous metal-free catalysts under mild conditions. Nonmetallic NC-X catalysts with high activity were prepared from the pyrolysis of well-defined ligands via simple sacrificing hard template methods. Hydrazine hydrate, formic acid, and molecular hydrogen can all be used as reducing agents in the hydrogenation/Paal-Knorr reaction sequence to efficiently synthesize various N-substituted pyrroles, including drugs and bioactive molecules. The catalytic system was featured with good tolerance to sensitive functional groups and no side reactions such as dehalogenation and aromatics hydrogenation. Hammett correlation studies have shown that the electron-donating substituents are beneficial for the one-pot synthesis of N-substituted pyrroles. The results established that the outstanding performance of the catalyst is mainly attributed to the contribution of graphitic N in the catalyst as well as the promotion effect of the mesoporous structure on the reaction.

Topological differences of striato-thalamo-cortical circuit in functional brain network between premature ejaculation patients with and without depression.

INTRODUCTION: Premature ejaculation (PE), a common male sexual dysfunction, often accompanies by abnormal psychological factors, such as depression. Recent neuroimaging studies have revealed structural and functional brain abnormalities in PE patients. However, there is limited neurological evidence supporting the comorbidity of PE and depression. This study aimed to explore the topological changes of the functional brain networks of PE patients with depression. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 60 PE patients (30 with depression and 30 without depression) and 29 healthy controls (HCs). Functional brain networks were constructed for all participants based on rs-fMRI data. The nodal parameters including nodal centrality and efficiency were calculated by the method of graph theory analysis and then compared between groups. In addition, the results were corrected for multiple comparisons by family-wise error (FWE) (p < .05). RESULTS: PE patients with depression had increased degree centrality and global efficiency in the right pallidum, as well as increased degree centrality in the right thalamus when compared with HCs. PE patients without depression showed increased degree centrality in the right pallidum and thalamus, as well as increased global efficiency in the right precuneus, pallidum, and thalamus when compared with HCs. PE patients with depression demonstrated decreased degree centrality in the right pallidum and thalamus, as well as decreased global efficiency in the right precuneus, pallidum, and thalamus when compared to those without depression. All the brain regions above survived the FWE correction. CONCLUSION: The results suggested that increased and decreased functional connectivity, as well as the capability of global integration of information in the brain, might be related to the occurrence of PE and the comorbidity depression in PE patients, respectively. These findings provided new insights into the understanding of the pathological mechanisms underlying PE and those with depression.

Causal role of immune cells in inflammatory bowel disease: A Mendelian randomization study.

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.

Metal-organic framework integrated hydrogel bioreactor for smart detection of metal ions.

Bioreactors with environment responsiveness for smart detection has attracted widespread interest. Bioreactors that operate in liquid have excellent reaction speed and sensitivity, and those that operate at a solid interface have unique portability and stability. However, bioreactors that can simultaneously take advantage of both properties are still limited. Here, we developed a metal-organic framework (MOF) integrated hydrogel bioreactor that can accommodate both solid and liquid properties by using a hydrogel as a quasi-liquid medium. To enhance the stability and intelligence of the hydrogel bioreactor, we have opted for the utilization of europium metal-organic framework (Eu-MOF) as the optical output to withstand long-term storage challenges, and DNA as the highly programmable substance for intelligent target response. On this basis, smart detection of metal ions and biological micro-molecules have been achieved. Notably, this quasi-liquid hydrogel bioreactor has effectively tackled the intrinsic issues of inadequate dispersion stability of Eu-MOF in liquid systems and poor stability of DNA against environmental interference. Moreover, this MOF integrated hydrogel bioreactor has been applied to the construction of a portable hydrogel bioreactor, which enables platform-free and arrayed target detection via a smartphone, providing a new perspective for further promoting the application of quasi-liquid hydrogel bioreactors and intelligent nanobiological sensors.

Strengthening Device for Improving Shear Performance of Anchor Cable in Rock Support.

Many designs of anchor cables are currently in use for rock support in civil and mining operations. Because of the exposed surface and weak shear performance of the cable bolt's free section (CBFS) in end-anchored structures, breaking failure frequently occurs. Numerical simulations and laboratory experiments were performed in this study to develop measures to improve CBFS resistance to shear failure. Analysis of shear characteristics of the CBFS showed that higher axial tension weakens the cable bolt's shear resistance, and that shear damage on the cable surface and uneven distribution of shear stress aggravate CBFS tensile-shear failure. A high-strength steel pipe is proposed to protect the shear cable bolt, and the preliminary design of a CBFS-strengthening device (CFSD) is presented. Numerical simulation revealed that the CFSD effectively improved CBFS shear resistance and provided protection from harmful shear damage. The optimal performance of a Q-type (slotted steel pipe) CFSD was confirmed. The mechanism of improvement of the cable's shear resistance to surrounding rock by employing the CFSD was analyzed. Double-shear tests were carried out on a bare cable bolt and a cable bolt with a Q-CFSD. The results revealed that the CFSD increased the peak shear force on the joint plane, cable peak axial force, and ultimate shear displacement by 31%, 18%, and 11%, respectively. The proposed device is effective in improving the shear performance of end-anchored cable bolts and enhancing surrounding rock stability.