Study on the deformation mechanism and large deformation control method of a strongly weathered carbonaceous slate tunnel in western China

In response to the significant soft rock deformation challenges encountered during the construction of the Minxian Tunnel along the Lanzhou-Haikou Expressway (G75), this study conducted a comprehensive analysis of soft rock types and the underlying mechanical mechanisms governing the deformation of the surrounding rock. It presented tailored mechanical transformation strategies to address diverse mechanical mechanisms. Also, it introduced the application of anchor cable with high pre-tightening force, constant resistance and large deformation, a proven solution widely employed in mining and rock engineering. Furthermore, the research proposed a high-prestress and active and passive combined support technique, encompassing pre-reinforced retaining structure, optimally arranged active retaining structure with long and short NPR anchor cables, steel arches, and permanent retaining structure of shotcrete. By implementing numerical simulations and on-site monitoring, the results demonstrated a remarkable reduction in the maximum deformation of the surrounding rock in the test section to only 73 mm, and the pre-tightening forces applied to the anchor cable with constant resistance and large deformation ranged from 280 to 300 kN, underscoring the effectiveness of the optimized retaining technique in controlling surrounding rock deformation. This research highlights the pivotal role of retaining structure with constant resistance and yielding support, which significantly improves deformation control

Establishing CRISPRi for Programmable Gene Repression and Genome Evolution in Cupriavidus necator

Cupriavidus necator H16 is a “Knallgas” bacterium with the ability to utilize various carbon sources and has been employed as a versatile microbial cell factory to produce a wide range of value-added compounds. However, limited genome engineering, especially gene regulation methods, has constrained its full potential as a microbial production platform. The advent of CRISPR/Cas9 technology has shown promise in addressing this limitation. Here, we developed an optimized CRISPR interference (CRISPRi) system for gene repression in C. necator by expressing a codon-optimized deactivated Cas9 (dCas9) and appropriate single guide RNAs (sgRNAs). CRISPRi was proven to be a programmable and controllable tool and could successfully repress both exogenous and endogenous genes. As a case study, we decreased the accumulation of polyhydroxyalkanoate (PHB) via CRISPRi and rewired the carbon fluxes to the synthesis of lycopene. Additionally, by disturbing the expression of DNA mismatch repair gene mutS with CRISPRi, we established CRISPRi-Mutator for genome evolution, rapidly generating mutant strains with enhanced hydrogen peroxide tolerance and robustness in microbial electrosynthesis (MES) system. Our work provides an efficient CRISPRi toolkit for advanced genetic manipulation and optimization of C. necator cell factories for diverse biotechnology applications

Vertical Orientation of Nanocylinders in Liquid-Crystalline Block Copolymers Directed by Light

The microphase-separated nanostructures of block copolymers are ideal nanotemplates for advanced fabrication, but they are greatly limited by the rapid and precise manipulation especially at room temperature. Here we report one method of light-directed regulation of nanostructures in thin films of liquid-crystalline diblock copolymers containing azobenzene units as photoresponsive mesogens. The in-plane orientated nanocylinders in thin film can be light-directed into out-of-plane on a time scale of seconds at room temperature. This fast regulation is beneficial from the fast process of photoinduced phase transition of the mesogenic block from liquid crystal to disordered isotropic phase. Several influence factors like the molecular weight of polymer, film thickness, light intensity, and relative humidity were studied in the light-directed processes. In addition, the photoregulated nanostructures demonstrate their capability of being photopatterned and further used as nanotemplates for fabrication of nanoparticles. The light-directed method shows noncontact, precise, and reversible features, enabling it to find further applications in fast control of nanostructures for nanofabrication and nanoengineering

Synthesis of a Novel Polymeric Material Folate-Poly(2-ethyl-2-oxazoline)-Distearoyl Phosphatidyl Ethanolamine Tri-Block Polymer for Dual Receptor and pH-Sensitive Targeting Liposome

The in vivo distribution of antitumor drugs is usually lack of selectivity, and thus, leading to a low efficacy of chemotherapy on cancers and high toxicity to normal cells. Receptor-mediated targeting liposome with pH-sensitivity as a dual drug delivery system is one of the efficient approaches to overcome the disadvantages. The study was to synthesize a novel smart polymeric material (folate-poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine, F-PEOz-DSPE), which can combine with the folate-receptor (FR) over-expressed on cancer cells and respond to pH changes in endosome lysosome system in cancer cells to rapidly release drug simultaneously. The F-PEOz-DSPE was synthesized by the method of asymmetric synthesis of organic polymer and characterized by IR, H-1-NMR, electrospray ionization (ESI)-MS and gel permeation chromatography (GPC). To investigate the properties of targeting and pH-sensitivity of F-PEOz-DSPE, blank liposomes, blank fluorescently labeled liposomes and doxorubicin (DOX)-loaded liposomes containing F-PEOz-DSPE or PEOz-DSPE or DSPE were prepared. The cytotoxicity, cellular uptake and drug cumulative release in vitro were investigated. Blank liposomes modified with PEOz block had little cytotoxicity in vitro. The liposomes containing F-PEOz-DSPE showed a higher affinity to human ovarian cancer cell SKOV3, a FR+ cancer cells, than those with PEOz-DSPE. A higher drug cumulative release from DOX-loaded liposomes containing F-PEOz-DSPE or PEOz-DSPE in vitro was found in phosphate buffered saline at pH 5.0 medium than at pH 7.4. These results indicate that F-PEOz-DSPE exhibits selective targeting, pH-sensitivity and little cytotoxicity, and may be a promising polymeric material for dual receptor and pH-sensitive targeting liposome.Chemistry, MedicinalChemistry, MultidisciplinaryPharmacology & PharmacySCI(E)5ARTICLE4390-3986

Association between tumor necrosis factor alpha-238G/a polymorphism and tuberculosis susceptibility: a meta-analysis study

Abstract Background Tumor necrosis factor alpha (TNF-α) plays a key role in the containment of tuberculosis. The relationship between the TNF -238G/A polymorphism and tuberculosis susceptibility remains inconclusive. A comprehensive meta-analysis was made to provide a more precise estimate of the relationship between them. Methods Multiple search strategies were used. A fixed effect model was takentook to estimate pooled OR with 95% confidence interval (CI) for the association between the TNF -238G/A polymorphism and tuberculosis susceptibility. The Chi-squared-based Q-test and I-squaredI2 statistic were calculated to examine heterogeneity. Begg’s funnel plot and Egger’s test were used to assess publication bias. Results 9 case-control studies were included in this meta-analysis. No significant heterogeneity was demonstrated, and no obvious publication bias was detected among the included studies. The meta-analysis indicated that there was no significant association between the TNF -238G/A polymorphism and tuberculosis susceptibility (GA+AA versus GG model: OR=1.005, 95% CI: 0.765-1.319; A versus G model: OR=1.000, 95% CI: 0.769-1.300). In the subgroup analyses by ethnicity, types of TB and human immunodeficiency virus (HIV) status, no significant association were identified. Conclusions The meta-analysis involving 2723 subjects did not detect any association between the TNF -238G/A polymorphism and tuberculosis susceptibility.</p

Vertical Orientation of Nanocylinders in Liquid-Crystalline Block Copolymers Directed by Light

The microphase-separated nanostructures of block copolymers are ideal nanotemplates for advanced fabrication, but they are greatly limited by the rapid and precise manipulation especially at room temperature. Here we report one method of light-directed regulation of nanostructures in thin films of liquid-crystalline diblock copolymers containing azobenzene units as photoresponsive mesogens. The in-plane orientated nanocylinders in thin film can be light-directed into out-of-plane on a time scale of seconds at room temperature. This fast regulation is beneficial from the fast process of photoinduced phase transition of the mesogenic block from liquid crystal to disordered isotropic phase. Several influence factors like the molecular weight of polymer, film thickness, light intensity, and relative humidity were studied in the light-directed processes. In addition, the photoregulated nanostructures demonstrate their capability of being photopatterned and further used as nanotemplates for fabrication of nanoparticles. The light-directed method shows noncontact, precise, and reversible features, enabling it to find further applications in fast control of nanostructures for nanofabrication and nanoengineering

Characterization of a Carbapenem-Resistant Kluyvera Cryocrescens Isolate Carrying Blandm-1 from Hospital Sewage

Carbapenem-resistant Enterobacteriaceae have been a global public health issue in recent years. Here, a carbapenem-resistant Kluyvera cryocrescens strain SCW13 was isolated from hospital sewage, and was then subjected to whole-genome sequencing (WGS). Based on WGS data, antimicrobial resistance genes were identified. Resistance plasmids were completely circularized and further bioinformatics analyses of plasmids were performed. A conjugation assay was performed to identify a self-transmissible plasmid mediating carbapenem resistance. A phylogenetic tree was constructed based on the core genome of publicly available Kluyvera strains. The isolate SCW13 exhibited resistance to cephalosporin and carbapenem. blaNDM-1 was found to be located on a ~53-kb self-transmissible IncX3 plasmid, which exhibited high similarity to the previously reported pNDM-HN380, which is an epidemic blaNDM-1-carrying IncX3 plasmid. Further, we found that SCW13 contained a chromosomal blaKLUC-2 gene, which was the probable origin of the plasmid-born blaKLUC-2 found in Enterobacter cloacae. Phylogenetic analysis showed that K. cryocrescens SCW13 exhibited a close relationship with K. cryocrescens NCTC10483. These findings highlight the further dissemination of blaNDM through clonal IncX3 plasmids related to pNDM-HN380 among uncommon Enterobacteriaceae strains, including Kluyvera in this case