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Abstract Different clay grains affect the structural strength of loess through the cementation of skeletal particles. This study investigates both clay-clay grains and quartz-clay grains. Clay-clay grains mixed loess (CM-L) and quartz-clay grains loess (Q-L) samples were prepared, and their unsaturated shear properties analyzed. X-ray diffractometry (XRD) analysis was conducted to determine the types and proportions of clay grains. Ball mill grinding and laser particle size analysis were employed to ensure comparable sizes of clay grains, while mercury intrusion porosimetry (MIP) tests confirmed similar pore characteristics. Scanning electron microscope (SEM) and unsaturated triaxial consolidation and drainage tests explored the impact of different clay grains on loess shear characteristics, assessing both microscopic and macroscopic performance. The results indicate that CM-L loess exhibits higher cohesion and a lower internal friction angle at the same matric suction level. The cohesion and internal friction angle of both CM-L and Q-L loess exhibit a linear relationship within the range of 50–200 kPa matrix suction. The cohesive force ranges for CM-L and Q-L loess are 60.31–80.07 kPa and 43.01–69.60 kPa, respectively, while the ranges for internal friction angles are 19.95°-19.59° and 25.91°-25.06°, respectively. Compared to Q-L loess, CM-L loess exhibits an average difference in cohesion of 23.18 kPa and in internal friction angle of -5.72°. The microscopic variation in shear strength can be attributed to the “fish scale-like” interlocking state between clay-clay grains and the “tower-like” scattering arrangement of quartz-clay grains. In conclusion, the effect of different clay-grain types on the shear strength of loess varies significantly. The present study elucidates the relationship between the influence of different clay grains on the mechanical properties of loess and their microscopic structural characteristics, thereby providing crucial data for investigating the microscopic effects on the structural strength of loess.

Halomonas bluephagenesis TD serves as an exceptional chassis for next generation industrial biotechnology to produce various products. However, the simultaneous editing of multiple loci in H. bluephagenesis TD remains a significant challenge. Herein, we report the development of a multiple loci genome editing system, named CRISPR-deaminase-assisted base editor (CRISPR-BE) in H. bluephagenesis TD. This system comprises two components: a cytidine (CRISPR-cBE) and an adenosine (CRISPR-aBE) deaminase-based base editor. CRISPR-cBE can introduce a cytidine to thymidine mutation with an efficiency of up to 100 % within a 7-nt editing window in H. bluephagenesis TD. Similarly, CRISPR-aBE demonstrates an efficiency of up to 100 % in converting adenosine to guanosine mutation within a 7-nt editing window. CRISPR-cBE has been further validated and successfully employed for simultaneous multiplexed editing in H. bluephagenesis TD. Our findings reveal that CRISPR-cBE efficiently inactivated all six copies of the IS1086 gene simultaneously by introducing stop codon. This system achieved an editing efficiency of 100 % and 41.67 % in inactivating two genes and three genes, respectively. By substituting the Pcas promoter with the inducible promoter PMmp1, we optimized CRISPR-cBE system and ultimately achieved 100 % editing efficiency in inactivating three genes. In conclusion, our research offers a robust and efficient method for concurrently modifying multiple loci in H. bluephagenesis TD, opening up vast possibilities for industrial applications in the future.

The rising incidence of colistin (COL) resistance poses a significant challenge, undermining the therapeutic efficacy of COL against life-threatening bacterial infections. Therefore, the urgent identification and development of new therapeutics are imperative. It has been proven that combinations of antibiotics and promising non-antibiotic agents could be a potential strategy to combat infections caused by MDR pathogens. Due to various antimicrobial properties, medicinal plants have attracted significant attention, which could be promising adjuvant. In this study, we investigated the synergistic effects of combining COL with resveratrol (RST) and baicalin (BAI) against mcr-1-positive Escherichia coli through antibiotic susceptibility testing, checkerboard method and time-killing assays. The mechanisms of combination treatment were analyzed using SEM, fluorometric assays and transcriptome analysis. The molecular docking assay was conducted to elucidate potential interactions between RST, BAI and the MCR-1 protein. Finally, we assessed the in vivo efficacy of combination against mcr-1-positive Escherichia coli. The results demonstrated that the combination of RST, BAI and COL showed significant synergistic activity both in vitro and in vivo. Further mechanistic study revealed that the combination could increase the membrane-damaging ability of COL, disrupt the homeostasis of proton motive force (PMF), inhibit the activity of efflux pumps and impair ATP supply. The molecular docking revealed that RST and BAI could bind to MCR-1 stably, indicating the combination of RST and BAI may be an effective MCR-1 inhibitor. Our findings demonstrated that the combination of RST and BAI might be potential COL adjuvant, providing an alternative approach to address mcr-1-positive Escherichia coli infections.

Colistin used to be regarded as the last-resort treatment for the infection caused by multidrug-resistant gram-negative bacteria. However, the emergence and widespread of mcr-1 seriously reduce the clinical effectiveness of colistin, constituting a serious threat to global public health. Due to the difficulties in the development of new antibiotics, restoring antibiotic susceptibility with adjuvants is undoubtedly a rational option. As naturally occurring compounds, resveratrol and capsaicin could be extracted from many natural plants, due to various antimicrobial properties, they have received significant attention. Herein, the synergistic activity of colistin combined with resveratrol and capsaicin against mcr-1-positive Escherichia coli were investigated by checkerboard method and time-killing assays. The in-depth molecular mechanisms were elucidated by scanning electron microscopy, fluorescent probe experiments, transcriptome and metabolome analysis. Molecular docking assay was taken to analyse potential interactions between resveratrol/capsaicin and MCR-1. Finally, the in vivo efficacy of combined therapy against mcr-1-positive Escherichia coli was assessed. Our results demonstrated that colistin combined with resveratrol and capsaicin acted synergistic activity against mcr-1-positive Escherichia coli both in vivo and in vitro. Further mechanistic studies showed that the combined therapy could exacerbate cell membrane damage, increase membrane permeability, disrupt the homeostasis of PMF, inhibit ATP synthesis, and efflux pump activity. In addition, the combined therapy could inhibit central carbon metabolism, and reduce tricarboxylic acid cycle and oxidative phosphorylation. Moreover, molecular docking assay revealed resveratrol/capsaicin could bind to MCR-1 stably. Our study indicated that colistin in combination with resveratrol and capsaicin as a novel therapy could provide a trustworthy foundation to establish the treatment plan for mcr-1-positive Escherichia coli.

This study examines biomass energy policies in the EU, US, and Japan, noting high implementation rates in Poland (86.5 %) and Finland (90.6 %). Germany's biogas utilization is particularly noteworthy, accounting for 29.6 %. The paper summarizes China's national and provincial waste biomass management and energization policies, encompassing agriculture, biomass energy, and environmental governance aspects. Analyzing China's biomass energy industry reveals challenges requiring a comprehensive development plan based on waste biomass resources and environmental zoning. Proposed solutions include establishing ecological energy agriculture demonstration zones, optimizing policies for environmental benefits, encouraging technological innovation, establishing a trade association, improving standards, setting up a waste biomass fund, introducing green certificates and quotas, and integrating waste biomass into the national carbon trading system.

Summary: Mesoscale to nanoscale three-dimensional (3D) fabrication mostly requires complicated industry processing techniques. Here, we present a protocol for 3D shaping control by solidifying a water-based TiO2 nanofluid drop on a polygonal wettability-patterned surface. We detail the steps for preparing stable TiO2 nanofluid and wettability-patterned surfaces. We then describe the experimental procedure to obtain various and precise 3D morphologies by adjusting the deposited TiO2 nanofluid drop volume. This protocol provides a promising technique for future 3D manufacturing.For complete details on the use and execution of this protocol, please refer to Jiang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundThe COVID-19 pandemic underscored the critical importance of biosafety in microbiology laboratories worldwide. In response, China has ramped up its efforts to enhance biosafety measures within its Centers for Disease Control and Prevention (CDC) laboratories. This study provides the first comprehensive assessment of biosafety practices across provincial, city, and county levels of CDC microbiology laboratories in China.MethodsWe conducted a nationwide cross-sectional survey from 2021 to 2023, targeting staff from microbiology laboratories within CDCs at all administrative levels in China. Stratified sampling was employed to select respondents, ensuring a representative mix across different CDC hierarchies, job titles, and academic qualifications. The survey encompassed questions on biosafety training, the presence of BSL-2 and BSL-3 laboratories, adherence to general biosafety guidelines, and management practices regarding specimens, reagents, and consumables. Statistical analysis was performed to identify significant differences in biosafety practices among different CDC levels.ResultsA total of 990 valid responses were received, highlighting a nearly universal presence (98.69%) of BSL-2 laboratories and a significant yet varied presence of BSL-3 laboratories across the CDC network. The survey revealed high levels of biosafety training (98.69%) and adherence to biosafety protocols. However, challenges remain in the consistent application of certain safety practices, especially at lower administrative levels. Notable differences in the management of specimens, reagents, and consumables point to areas for improvement in ensuring biosecurity.ConclusionOur findings indicate a robust foundation of biosafety practices within CDC microbiology laboratories in China, reflecting significant advancements in the wake of the Biosecurity Law's implementation. Nevertheless, the variability in adherence to specific protocols underscores the need for ongoing training, resources allocation, and policy refinement to enhance biosafety standards uniformly across all levels. This study's insights are crucial for guiding future improvements in laboratory biosafety, not just in China but potentially in other countries enhancing their public health infrastructures.

Abstract CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of CD44 gene, CD44 is divided into two isoforms, the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v). Different isoforms of CD44 participate in regulating various signaling pathways, modulating cancer proliferation, invasion, metastasis, and drug resistance, with its aberrant expression and dysregulation contributing to tumor initiation and progression. However, CD44s and CD44v play overlapping or contradictory roles in tumor initiation and progression, which is not fully understood. Herein, we discuss the present understanding of the functional and structural roles of CD44 in the pathogenic mechanism of multiple cancers. The regulation functions of CD44 in cancers‐associated signaling pathways is summarized. Moreover, we provide an overview of the anticancer therapeutic strategies that targeting CD44 and preclinical and clinical trials evaluating the pharmacokinetics, efficacy, and drug‐related toxicity about CD44‐targeted therapies. This review provides up‐to‐date information about the roles of CD44 in neoplastic diseases, which may open new perspectives in the field of cancer treatment through targeting CD44.

This study is dedicated to delving deeply into the uncertainty and interpretability of ensemble learning models in landslide susceptibility modeling. Focusing on the eastern coastal mountainous region of Zhejiang Province as the study area, this research utilizes historical Google imagery and Sentinel-2A imagery to document 552 shallow landslide events triggered by the super typhoon "Megi" in 2016. Initially, the study designs scenarios for continuous factors using non-grading, equal interval method, and natural breaks method, subsequently subdividing them into 4, 6, 8, 12, 16, 20 levels. Thereafter, the Category Boosting Model (CatBoost) is introduced to assess landslide susceptibility values under different scenarios. Coupled with the analysis of ROC (receiver operating characteristic) curves and SHAP (SHapley Additive exPlanation), in-depth investigation into uncertainty and interpretability during the modeling process is conducted, with the aim of determining the optimal modeling strategy. The results indicate that: (1) In the computations of the CatBoost model, aspect emerges as the most critical influencing factor, followed by factors related to water and geological conditions; (2) Under the non-grading scenario, the model achieves the highest AUC value, reaching 0.866; (3) Compared to the equal interval method, the natural breaks method demonstrates superior generalization capability, and the model’s predictive performance imrpoves with an increase in the number of classifications; (4) The SHAP model reveals the controlling mechanisms of the principal influencing factors (aspect, lithology, elevation, and road distance) on typhoon-induced landslides. The findings of this research can deepen our understanding of landslide susceptibility, enhance the accuracy and reliability of landslide predictions, and provide a scientific basis for disaster prevention and mitigation efforts in the related regions.

Abstract The application of continuous natural fibers as reinforcement in composite thin-walled structures offers a feasible approach to achieve light weight and high strength while remaining environmentally friendly. In addition, additive manufacturing technology provides a favorable process foundation for its realization. In this study, the printability and energy absorption properties of 3D printed continuous fiber reinforced thin-walled structures with different configurations were investigated. The results suggested that a low printing speed and a proper layer thickness would mitigate the printing defects within the structures. The printing geometry accuracy of the structures could be further improved by rounding the sharp corners with appropriate radii. This study successfully fabricated structures with various configurations characterized by high geometric accuracy through printing parameters optimization and path smoothing. Moreover, the compressive property and energy absorption characteristics of the structures under quasi-static axial compression were evaluated and compared. It was found that all studied thin-walled structures exhibited progressive folding deformation patterns during compression. In particular, energy absorption process was achieved through the combined damage modes of plastic deformation, fiber pullout and delamination. Furthermore, the comparison results showed that the hexagonal structure exhibited the best energy absorption performance. The study revealed the structure-mechanical property relationship of 3D printed continuous fiber reinforced composite thin-walled structures through the analysis of multiscale failure characteristics and load response, which is valuable for broadening their applications.

The long-term use of air filters causes dust to accumulate on their surfaces or fill in the fibers of their internal filtering materials over time, thereby greatly reducing their effectiveness; therefore, the cleaning and replacement of air filter materials in public buildings are of great concern. The most commonly used non-woven fabric materials currently on the market are taken as the research object for this work, in which experiments are conducted on ultrasonic cleaning parameters, cleaning performance, regeneration effects, etc. The results showed that the best cleaning performance was achieved when the ultrasonic cleaning parameter was set to 120 W, and the cleaning time to 11.2 s, with a significant effect on particulate matter with a particle size of less than 2.5 μm. Under the premise of repeated dust containment, when PM10, PM2.5, and PM1.0 are cleaned nine, six, and seven times, respectively, the filtration performance for these particles can also recover to over 85% of the performance of the fresh filter material before cleaning; however, after ten ultrasonic cleanings, the filtration resistance decreased within the range of 4.6~20.7 Pa. In this study, we aim to effectively reduce the replacement of old filters and the generation of incineration pollution, thereby reducing carbon-dioxide-equivalent emissions and providing a reference value for achieving the efficient utilization of filter materials in public buildings under the dual carbon target.

Abstract Urgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This vaccine was created by incorporating the receptor‐binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5‐Beta/Deta vaccine induced robust broad‐spectrum neutralization against Omicron BA.5‐included variants. IN immunization with Ad5‐Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue‐resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5‐Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5‐Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5‐Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants of concern and BA.5‐included Omicron subvariants.

Cadmium (Cd) is a toxic heavy metal found in natural and industrial environments. Exposure to Cd can lead to various metabolic disturbances, notably disrupting glucose and lipid homeostasis. Despite this recognition, the direct impact of Cd exposure on lipid metabolism within adipose tissue, and the mechanisms underlying these effects, have not been fully elucidated. In this study, we found that Cd accumulates in adipose tissues of mice subjected to Cd exposure. Intriguingly, Cd exposure in itself did not induce significant alterations in the adipose tissue under normal conditions. However, when subjected to cold stimulation, several notable changes were observed in the mice exposed to Cd, including a reduction in the drop of body temperature, a decrease in the size of inguinal white adipose tissue (WAT), and an increase in the expression of thermogenic genes UCP1 and PRDM16. These results indicate that Cd exposure might enhance the responsiveness of adipose tissue to external stimuli and increase the energy expenditure of the tissue. RNA-seq analysis further revealed that Cd exposure altered gene expression profiles, particularly affecting peroxisome proliferator-activated receptor (PPAR)-mediated metabolic pathways, promoting metabolic remodeling in adipose tissue and resulting in the depletion of lipids stored in adipose tissue for energy. Non-targeted metabolomic analysis of mouse serum showed that Cd exposure significantly disrupted metabolites and significantly increased serum fatty acid and triglyceride levels. Correspondingly, population-level data confirmed an association between Cd exposure and elevated levels of serum total cholesterol, total triglycerides, and low-density lipoprotein cholesterol. In summary, we provide substantial evidence of the molecular events induced by Cd that are relevant to the regulation of lipid metabolism in adipose tissue. Our findings suggest that the toxic effects of Cd can impact adipocyte functionality, positioning adipose tissue as a critical target for metabolic diseases resulting from Cd exposure.

Abstract Postnatal leukocytosis reflects the general condition of inflammatory. Infection and inflammatory reaction have been proven to affect the occurrence of ROP and other visual dysfunction. Infants with a gestational age of

In recent years, cerium dioxide (CeO2) has attracted considerable attention owing to its remarkable performance in various applications, including photocatalysis, fuel cells, and catalysis. This study explores the effect of nickel (Ni) doping on the structural, thermal, and chemical properties of CeO2 nanorods, particularly focusing on oxygen vacancy-related phenomena. Utilizing X-ray powder diffraction (XRD), alterations in crystal structure and peak shifts were observed, indicating successful Ni doping and the formation of Ni2O3 at higher doping levels, likely due to non-equilibrium reactions. Thermal gravimetric analysis (TGA) revealed changes in oxygen release mechanisms, with increasing Ni doping resulting in the release of lattice oxygen at lower temperatures. Raman spectroscopy corroborated these findings by identifying characteristic peaks associated with oxygen vacancies, facilitating the assessment of Ni doping levels. Ni-doped CeO2 can catalyze the ultrasonic degradation of methylene blue, which has good application prospects for catalytic ultrasonic degradation of organic pollutants. Overall, this study underscores the substantial impact of Ni doping on CeO2 nanorods, shedding light on tailored catalytic applications through the modulation of oxygen vacancies while preserving the nanorod morphology.

The complex air environment makes it urgent to build good and safe indoor environments, and the study and application of new materials have become the focus of current research. In this study, we tested and analyzed the structural parameters and filtration performances of the four most commonly used new filter materials in the current market. The results showed that all four new filter materials showed a trend of first increasing and then decreasing their filtration efficiency with an increase in filtration velocity. The filtration efficiency of the materials was as follows: PTFE > glass fiber > nanomaterial > electret. The filtration efficiency of all materials reached its maximum when the filtration velocity was 0.2 m/s. The filtration efficiency of the PTFE for PM10, PM2.5, and PM1.0 was higher than that of the other three materials, with values of 0.87% to 24.93%, 1.21% to 18.69%, and 0.56% to 16.03%, respectively. PTFE was more effective in capturing particles smaller than 1.0 μm. Within the testing velocity range, the resistance of the filter materials was as follows: glass fiber > PTFE > electret > nanomaterial, and the resistance of the four materials showed a good fitting effect. It is also necessary to match the resistance with the filtration efficiency during use, as well as to study the effectiveness of filter materials in blocking microorganisms and absorbing toxic gases. Overall, PTFE showed the best comprehensive performance, as well as providing data support for the selection of related materials or the synthesis and research of filter materials in the future.

Abstract Background Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term outcomes are lacking. The aim of this study was to analyze the clinical manifestations, imaging features, and long-term neurodevelopmental outcomes in preterm infants and term infants with leukomalacia. Methods Newborns diagnosed with leukomalacia by head magnetic resonance imaging (MRI) and who were admitted to intensive care units from January 2015 to June 2020 were enrolled. All infants were followed up to June 2022 (2–7 years old), and their neurodevelopmental outcomes were evaluated. The clinical data and long- term outcomes of preterm infants and term infants was analyzed by Chi-square tests. Results A total of 218 surviving infants with leukomalacia including 114 preterm infants and 104 term infants completed the follow-up. The major typesof leukomalacia on MRI were periventricular leukomalacia in the preterm group and subcortical cystic leukomalacia in the term group, respectively (χ2 = 55.166; p

Abstract Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young’s moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa—over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices.

Commented Article: CHEN, Meixu. Marxist Foundation and Historical Development: Interpretation and Practice in China’s New Era. Trans/Form/Ação: Unesp Journal of Philosophy, v. 47, n. 4, e0240048, 2024. Available at: https://revistas.marilia.unesp.br/index.php/transformacao/article/view/14619.

Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3–5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a−/−, Angptl4−/−, and Il17a−/−Angptl4−/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Abstract Objectives CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Because of the uncertainty of the structure and environment of the electric driving system (EDS), the fault signature of the rotating mechanism is complicated. A novel method based on Hilbert transform with modified fast kurtogram (HTMFK), which is used for identifying the bearing faults in the EDS, is proposed. The modified principle and algorithm flow of the proposed method are derived. A high pass filter based on the frequency band identified by HTMFK is constructed and applied to fault diagnosis. Simulation signals demonstrate the ability of demodulating signals and identifying the fault resonance band. The bearing fault bench experiment of EDS is carried out in a semianechoic chamber. The corresponding fault tests are conducted according to different operating conditions. The applicability of HTMFK is verified by comparing the square envelope spectrums. Compared with other methods, the proposed method identifies the fault resonance frequency band more effectively and expands the application range of bearing fault diagnosis in EDS.

Carbapenem-resistant Escherichia coli (E. coli) strains are widely distributed and spreading rapidly, creating significant challenges for clinical therapeutics. NDM-5, a novel mutant of New Delhi Metallo-β-Lactamase-1 (NDM-1), exhibits high hydrolase activity toward carbapenems. Since the genetic backgrounds of clinically isolated carbapenem-resistant E. coli are heterogeneous, it is difficult to accurately evaluate the impact of blaNDM–5 on antibiotic resistance. Herein, E. coli BL21 was transformed with a plasmid harboring blaNDM–5, and the resultant strain was named BL21 (pET-28a-blaNDM–5). Consistent with the findings of previous studies, the introduction of exogenous blaNDM–5 resulted in markedly greater resistance of E. coli to multiple β-lactam antibiotics. Compared with BL21 (pET-28a), BL21 (pET-28a-blaNDM–5) exhibited reduced motility but a significant increase in biofilm formation capacity. Furthermore, transcriptome sequencing was conducted to compare the transcriptional differences between BL21 (pET-28a) and BL21 (pET-28a-blaNDM–5). A total of 461 differentially expressed genes were identified, including those related to antibiotic resistance, such as genes associated with the active efflux system (yddA, mcbR and emrY), pili (csgC, csgF and fimD), biofilm formation (csgD, csgB and ecpR) and antioxidant processes (nuoG). Finally, the pGS21a plasmid harboring blaNDM–5 was transformed into E. coli Rosetta2, after which the expression of the NDM-5 protein was induced using isopropyl-β-D-thiogalactoside (IPTG). Using glutathione-S-transferase (GST) pull-down assays, total proteins from E. coli were scanned to screen out 82 proteins that potentially interacted with NDM-5. Our findings provide new insight into the identified proteins to identify potential antibiotic targets and design novel inhibitors of carbapenem-resistant bacteria.

Objective Granular cells (GCs) are involved in polycystic ovarian syndrome (PCOS) progression. MicroRNA (miR)-23a downregulation is linked to PCOS development. Therefore, this research explored the influences of miR-23a-3p on GC proliferation and apoptosis in PCOS.Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to examine miR-23a-3p and HMGA2 expression in GCs of patients with PCOS. Then, miR-23a-3p and/or HMGA2 expression was altered in GCs (KGN and SVOG), after which miR-23a-3p, HMGA2, Wnt2, and β-catenin expression, GC viability, and GC apoptosis were measured by RT-qPCR and western blotting, MTT assay, and flow cytometry, respectively. A dual-luciferase reporter gene assay was utilized to assess the targeting relationship between miR-23a-3p and HMGA2. Finally, GC viability and apoptosis were tested after the combined treatment of miR-23a-3p mimic and pcDNA3.1-HMGA2.Results miR-23a-3p was poorly expressed but HMGA2 was overexpressed in GCs of patients with PCOS. Mechanistically, HMGA2 was negatively targeted by miR-23a-3p in GCs. Furthermore, miR-23a-3p inhibition or HMGA2 upregulation elevated viability and reduced apoptosis of KGN and SVOG cells, along with increased Wnt2 and β-catenin expression. In KNG cells, HMGA2 overexpression abrogated the impacts of miR-23a-3p overexpression on GC viability and apoptosis.Conclusions Collectively, miR-23a-3p decreased HMGA2 expression to block the Wnt/β-catenin pathway, thereby depressing viability and facilitating apoptosis of GCs.

One of the primary obstacles in current cancer treatments lies in the extensive heterogeneity of genetic and epigenetic changes that occur in each arising tumour. However, an additional challenge persists, as certain types of cancer display shared immune deficiencies in the antigen processing machinery (APM). This includes the downregulation of human leukocyte antigen (HLA) class I molecules, which serve as peptide antigen receptors for T lymphocyte recognition that plays a crucial role in killing emerging tumours. Consequently, this contributes to immune escape in metastatic disease. Notably, current cell-based immunotherapies primarily focusing on T lymphocytes and the implementation of immune checkpoint inhibitor modalities have largely ignored the crucial task of reversing immune escape. This oversight may explain the limited success of these approaches becoming more effective cancer immunotherapies. Hence, there is a critical need to prioritize the discovery of new therapeutic candidates that can effectively address immune escape and synergize with evolving immunotherapy strategies. In this context, we identified curcuphenol in a cell-based screen from a library of marine extracts as a chemical entity that reverses the immune-escape phenotype of metastatic cancers. To advance these findings toward clinical efficacy, the present study describes the synthesis of analogues of naturally occurring curcuphenol with enhanced chemical properties and biological efficacy. Here we test the hypothesis that these curcuphenol analogues can evoke the power of the immune system to reduce the growth of metastatic disease in tumour bearing animals. Our findings indicate that these compounds effectively restore the expression of APM genes in metastatic tumours and inhibit the growth of highly invasive tumours in preclinical models, thereby counteracting the common immune evasion phenomenon observed in metastatic cancers. We conclude that cancer immunotherapies capable of boosting APM expression, hold great potential in maximizing the effectiveness of immune blockade inhibitors and eradicating invasive tumours.

Abstract Brain white matter (WM) networks have been widely studied in neuropsychiatric disorders. However, few studies have evaluated alterations in WM network topological organization in patients with methamphetamine (MA) dependence. Therefore, using machine learning classification methods to analyze WM network topological attributes may give new insights into patients with MA dependence. In the study, diffusion tensor imaging-based probabilistic tractography was used to map the weighted WM networks in 46 MA-dependent patients and 46 control subjects. Using graph-theoretical analyses, the global and regional topological attributes of WM networks for both groups were calculated and compared to determine inter-group differences using a permutation-based general linear model. In addition, the study used a support vector machine (SVM) learning approach to construct a classifier for discriminating subjects with MA dependence from control subjects. Relative to the control group, the MA-dependent group exhibited abnormal topological organization, as evidenced by decreased small-worldness and modularity, and increased nodal efficiency in the right medial superior temporal gyrus, right pallidum, and right ventromedial putamen; the MA-dependent group had the higher hubness scores in 25 regions, which were mainly located in the default mode network. An SVM trained with topological attributes achieved classification accuracy, sensitivity, specificity, and kappa values of 98.09% ± 2.59%, 98.24% ± 4.00%, 97.94% ± 4.26%, and 96.18% ± 5.19% for patients with MA dependence. Our results may suggest altered global WM structural networks in MA-dependent patients. Furthermore, the abnormal WM network topological attributes may provide promising features for the construction of high-efficacy classification models.

This study focuses on the Liangshuijing landslide in the Three Gorges Reservoir area, using theoretical analysis and numerical simulations methods to construct a strength weakening model for the sliding zone and proposes a criterion for seepage-driven landslide initiation. The influence of different water level rise and fall rates on landslide stability is analyzed using the finite element program Geo-Studio, and the evolution laws of bank slope seepage field under the rise and fall of reservoir water and the starting and sliding mechanism caused by seepage are revealed. The research finds that changes in seepage pressure and time are crucial in weakening the strength of sliding zone soil. Once it reaches the critical strength, seepage causes pressure shear failure, leading to the initiation of the landslide, which progresses from local to overall failure. During the reservoir water level rise and fall process, the hysteresis of pore water pressure in the slope body is evident, and the rate of water level change affects the response time of groundwater in the slope. A faster rate of water level change leads to a greater change in pore water pressure, more driving force from seepage, and a faster change in landslide stability and a closer approach to progressive failure. When the reservoir water level drops from 175 m to 145 m, the normal stress on the sliding surface of the Liangshuijing landslide decreases by 38.19%, and the shear stress decreases by 22.20%. The maximum decrease in the effective normal stress is 168.64 kPa and the maximum decrease in shear strength is 63.45 kPa. The above findings provide a scientific basis and theoretical methods for the analysis of landslide initiation and sliding mechanisms, instability research of reservoir bank landslides, and emergency prevention and control engineering.

Linolenic acid (LA) has poor oxidative stability since it is a polyunsaturated fatty acid. Soybean oil has a high LA content and thus has poor oxidative stability. To identify candidate genes that affect the linolenic acid (LA) content in soybean seeds, a genome-wide association study (GWAS) was performed with 1,060 soybean cultivars collected in China between 2019–2021 and which LA content was measured using matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF IMS). A candidate gene, GmWRI14, encoding an APETALA2 (AP2)-type transcription factor, was detected by GWAS in cultivars from all three study years. Multiple sequence alignments showed that GmWRI14 belongs to the plant WRI1 family. The fatty acid contents of different soybean lines were evaluated in transgenic lines with a copy of GmWRI14, control lines without GmWRI14, and the gmwri14 mutant. MALDI-TOF IMS revealed that GmWRI14 transgenic soybeans had a lower LA content with a significant effect on seed size and shape, whereas gmwri14 mutants had a higher LA content. compared to control. The RNA-seq results showed that GmWRI14 suppresses GmFAD3s (GmFAD3B and GmFAD3C) and GmbZIP54 expression in soybean seeds, leading to decreased LA content. Based on the RNA-seq data, yeast one-hybrid (Y1H) and qRT-PCR were performed to confirm the transcriptional regulation of FAD3s by GmWRI14. Our results suggest that FAD3 is indirectly regulated by GmWRI14, representing a new molecular mechanism of fatty acid biosynthesis, in which GmWRI14 regulates LA content in soybean seeds.

The cultivated soybean (Glycine max (L.) Merrill) is domesticated from wild soybean (Glycine soja) and has heavier seeds with a higher oil content than the wild soybean. In this study, we identified a novel candidate gene associated with SW using a genome-wide association study (GWAS). The candidate gene GmWRI14-like was detected by GWAS analysis in three consecutive years. By constructing transgenic soybeans overexpressing the GmWRI14-like gene and gmwri14-like soybean mutants, we found that overexpression of GmWRI14-like increased the SW and increased total fatty acid content. We then used RNA-seq and qRT-PCR to identify the target genes directly or indirectly regulated by GmWRI14-like. Transgenic soyabeans overexpressing GmWRI14-like showed increased accumulation of GmCYP78A50 and GmCYP78A69 than non-transgenic soybean lines. Interestingly, we also found that GmWRI14-like proteins could interact with GmCYP78A69/GmCYP78A50 using yeast two-hybrid and bimolecular fluorescence complementation. Our results not only shed light on the genetic architecture of cultivated soybean SW, but also lays a theoretical foundation for improving the SW and oil content of soybeans.

Bacterial wilt disease caused by Ralstonia solanacearum is a widespread, severe plant disease. Tomato (Solanum lycopersicum), one of the most important vegetable crops worldwide, is particularly susceptible to this disease. Biological control offers numerous advantages, making it a highly favorable approach for managing bacterial wilt. In this study, the results demonstrate that treatment with the biological control strain Bacillus subtilis R31 significantly reduced the incidence of tomato bacterial wilt. In addition, R31 directly inhibits the growth of R. solanacearum, and lipopeptides play an important role in this effect. The results also show that R31 can stably colonize the rhizosphere soil and root tissues of tomato plants for a long time, reduce the R. solanacearum population in the rhizosphere soil, and alter the microbial community that interacts with R. solanacearum. This study provides an important theoretical basis for elucidating the mechanism of B. subtilis as a biological control agent against bacterial wilt and lays the foundation for the optimization and promotion of other agents such as R31.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a treatable autoimmune disorder affecting the central nervous system. Despite extensive research, the exact etiology and pathogenesis of this condition remain unclear. In recent years, autoimmune encephalitis (AE) after viral encephalitis (VE) has gathered significant attention. Here, we present a case report of autoimmune GFAP astrocytopathy after VE in a 43-year-old Asian male with a history of oral and labial herpes. The patient presented with high-grade fever, headache, urinary retention, unresponsiveness, and apathy. Elevated levels of protein and GFAP-IgG were observed in the cerebrospinal fluid (CSF), and enhanced brain magnetic resonance imaging (MRI) revealed linear enhancement oriented radially to the ventricles. Treatment with intravenous immunoglobulin (IVIG) resulted in symptom relief, reduced lesion enhancement, and decreased protein levels. This case report highlights bimodal encephalitis with no discernible interval between VE and autoimmune GFAP astrocytopathy, which poses diagnostic challenges. Notably, autoimmune GFAP astrocytopathy is a novel form of autoimmune encephalitis, and its treatment lacks sufficient clinical experience. Intriguingly, our patient demonstrated sensitivity to IVIG, a treatment that differed from past reports. Therefore, further exploration of treatment strategies for this condition is warranted.

In this study, a numerical investigation of the uncooled polycrystalline concentrated photovoltaic (CPV) module was established using ANSYS software. The main objective is to estimate the maximum allowable solar concentration ratio (CR) at which the CPV module can safely operate without overheating. The numerical model was validated using data from the literature, resulting in a very good agreement. The thermal and electrical performance of the CPV module was studied at different ambient temperatures (0, 10, 20, 30, and 40 °C), wind speeds (1, 2, 3, 4, and 5 m/s), and CR number of (1.0,1.5, and 2.0 suns). This smaller CR can be achieved using a compound parabolic concentrator (CPC). The CPV system can safely operate when CR ranges from 1.0 to 1.5 suns, (1 Sun = 1000 W/m2), at all studied values of ambient temperatures and wind speeds. However, increasing the CR up to 2.0 makes results in a safe operation at wind speed values from 3 to 5 m/s. Further, the electrical efficiency increases rapidly by increasing the wind speed from 1 to 2 m/s and this increase gradually drops by growing the wind speed from 3 to 5 m/s. Furthermore, the minimum solar cell efficiency reached 12.56% at CR of 2.0 and 1 m/s. The highest heat dissipation from the CPV module is occurred at the lower ambient temperature and gradually decreases as wind speed rises.

Abstract Financial fraud arises from the exaggeration of business interests, and an accurate detection or prediction is a useful tool for both corporate management and capital market systems. A collection of computer technologies has been made on this problem so far, and one of the most important solutions is unsupervised learning algorithms. Among them, most approaches work by analysing the internal relations in financial data and finding a new description of non‐fraud firms. However, current studies focus a lot on the geometry attribute of financial data, while overlooking the obvious behaviour patterns and peer effects among firms. This has limited the accuracy of representation and furthermore the detection performance. In this work, a very general class of functions is allowed to represent firms, constraining them by peer effects between firms and presenting an error‐distribution‐based financial fraud firm detection approach. Experimental results have shown great performance of the proposed approach.

Staphylococcus aureus secrete numerous effectors to evade or inhibit the host immune response, yet the mechanism underlying the effectors ability to manipulate the signalling pathways of macrophages remain unclear. Authors utilise in vitro and in vivo models to explore the role of extracellular fibrinogen-binding protein (Efb) in immune response modulation and pathogenicity.

Abstract Background Mycoplasma pneumoniae can be divided into different subtypes on the basis of the sequence differences of adhesive protein P1, but the relationship between different subtypes, macrolide resistance and clinical manifestations are still unclear. In the present study, we established a molecular beacon based real-time polymerase chain reaction (real-time PCR) p1 gene genotyping method, analyzed the macrolide resistance gene mutations and the relationship of clinical characteristics with the genotypes. Methods A molecular beacon based real-time PCR p1 gene genotyping method was established, the mutation sites of macrolide resistance genes were analyzed by PCR and sequenced, and the relationship of clinical characteristics with the genotypes was analyzed. Results The detection limit was 1–100 copies/reaction. No cross-reactivity was observed in the two subtypes. In total, samples from 100 patients with positive M. pneumoniae detection results in 2019 and 2021 were genotyped using the beacon based real-time PCR method and P1-1 M. pneumoniae accounted for 69.0%. All the patients had the A2063G mutation in the macrolide resistance related 23S rRNA gene. Novel mutations were also found, which were C2622T, C2150A, C2202G and C2443A mutations. The relationship between p1 gene genotyping and the clinical characteristics were not statistically related. Conclusion A rapid and easy clinical application molecular beacon based real-time PCR genotyping method targeting the p1 gene was established. A shift from type 1 to type 2 was found and 100.0% macrolide resistance was detected. Our study provided an efficient method for genotyping M. pneumoniae, valuable epidemiological monitoring information and clinical treatment guidance to control high macrolide resistance.

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.

Summary: Lauryl alcohol, a natural compound found in plants and other organisms, is widely used to make surfactants, food, and pharmaceuticals. GZM, a plant protection preparation with lauryl alcohol as its major component is thought to establish a physical barrier on the plant surface, but its physiological functions are unknown. Here, we show that GZM improves the performance of peanut (Arachis hypogaea) plants in both the laboratory and the field. We demonstrate that the treatment with GZM or lauryl alcohol raises the contents of several specific lysophospholipids and induces the biosynthesis of phenylpropanoids, flavonoids, and wax in various plant species. In the field, GZM improves crop immunity, yield, and quality. In addition, GZM and lauryl alcohol can inhibit the growth of some pathogenic fungi. Our findings provide insights into the physiological and biological effects of GZM treatment on plants and show that GZM and lauryl alcohol are promising preparations in agricultural production.

The fiber-filled polymer composite is one of the best materials which provides a symmetrical superior strength and stiffness to structures. With the strengthening of people’s environmental protection and resource reuse consciousness, the development of renewable materials, especially natural fiber-filled polymer composites, is receiving great attention. This study investigated the mechanical properties of polymer composites incorporating waste materials from the food processing industry and agricultural sources. Waste vegetal fiber-filled polymer biocomposites (WVFFPBs) with varying fiber types and 3D printing orientations were systematically fabricated. Subsequently, the tensile tests were executed to comprehensively assess the anisotropic mechanical behaviors of the WVFFPBs. The results demonstrated that WVFFPBs performed excellent anisotropic mechanical properties compared to pristine matrix samples as print orientation changed. As the printing angle increased from 0° to 90°, the tensile mechanical properties of the WVFFPBs displayed a decreasing trend. Moreover, the print orientation–anisotropic mechanical behavior relationship of 3D-printed WVFFPBs was revealed through the analysis of the material manufacturing characteristics and damage features.

Abstract Multiple myeloma (MM) is a hematological malignancy with a high prevalence and is characterized by the clonal expansion of malignant plasma cells. As a new tumor suppressor, defective in sister chromatid joining (DIS3) was reported to be a gene closely related to MM. This study elucidated the biological functions and underlying mechanisms of DIS3 in MM. DIS3 mRNA and protein levels were detected using RT–qPCR and western blotting, respectively. Methyl thiazolyl tetrazolium assays, flow cytometry analyses, Transwell assays, and wound healing assays were performed to detect the proliferation, apoptosis, invasion, and migration of MM cells. The binding relationship between miR‐125a/b‐5p and DIS3 was verified using luciferase reporter assays and RNA pulldown assays. Xenograft tumor models were established in nude mice to investigate the effects of miR‐125a/b‐5p and DIS3 on tumor growth in vivo. DIS3 levels were downregulated in MM cells, and DIS3 upregulation inhibited the malignant behaviors of MM cells. Mechanistically, miR‐125a/b‐5p directly targeted the 3′ untranslated region of DIS3. The expression of miR‐125a/b‐5p was upregulated in MM cells, miR‐125a/b‐5p knockdown inhibited the malignant behaviors of MM cells, and the inhibitory effect was reversed by DIS3 downregulation. The results of in vivo experiments indicated that miR‐125a/b‐5p promoted tumor growth by downregulating DIS3. Overall, miR‐125a/b‐5p promotes MM cellular processes and xenograft tumor growth by targeting DIS3.

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

Aflatoxin B1 (AFB1) is an extremely hazardous and unavoidable pollutant for cereals and feedstuff. AFB1 can cause testicular lesion, and how to alleviate its testicular toxicity has received much attention in recent years. Lycopene (LYC), a foodborne nutrient derived from red fruits and vegetables, has protective effects against sperm abnormality and testicular lesions. To confirm the beneficial effects and mechanisms of LYC on AFB1-induced testicular lesion, 48 male mice were exposed to 0.75 mg/kg AFB1 or/and 5 mg/kg LYC for consecutive 30 days. Results demonstrated the LYC significantly restored the lesions of testicular microstructure and ultrastructure, and sperm abnormalities in AFB1-exposed mice. Furthermore, LYC effectively attenuated AFB1-induced oxidative stress and mitochondrial damage, including ameliorative mitochondrial structural, and elevated mitochondrial biogenesis for maintaining mitochondrial function. Meanwhile, LYC resisted AFB1-induced mitochondrial-dependent apoptosis. In addition, LYC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and upregulated the Nrf2 signaling pathway. Collectively, our findings demonstrate LYC ameliorates AFB1-induced testicular lesion by attenuating oxidative stress and mitochondrial damage, which is related to the activation of Nrf2.

Glioblastomas (GBMs) are highly aggressive brain tumors that have developed resistance to currently available conventional therapies, including surgery, radiation, and systemic chemotherapy. In this study, we investigated the safety of a live attenuated Japanese encephalitis vaccine strain (JEV-LAV) virus as an oncolytic virus for intracerebral injection in mice. We infected different GBM cell lines with JEV-LAV to investigate whether it had growth inhibitory effects on GBM cell lines in vitro. We used two models for evaluating the effect of JEV-LAV on GBM growth in mice. We investigated the antitumor immune mechanism of JEV-LAV through flow cytometry and immunohistochemistry. We explored the possibility of combining JEV-LAV with PD-L1 blocking therapy. This work suggested that JEV-LAV had oncolytic activity against GBM tumor cells in vitro and inhibited their growth in vivo. Mechanistically, JEV-LAV increased CD8+ T cell infiltration into tumor tissues and remodeled the immunosuppressive GBM microenvironment that is non-conducive to immunotherapy. Consequently, the results of combining JEV-LAV with immune checkpoint inhibitors indicated that JEV-LAV therapy improved the response of aPD-L1 blockade therapy against GBM. The safety of intracerebrally injected JEV-LAV in animals further supported the clinical use of JEV-LAV for GBM treatment.

During colonization of soil and plants, biocontrol bacteria can effectively regulate the physiological metabolism of plants and induce disease resistance. To illustrate the influence of Bacillus subtilis R31 on the quality, transcriptome and metabolome of sweet corn, field studies were conducted at a corn experimental base in Zhuhai City. The results show that, after application of B. subtilis R31, sweet corn was more fruitful, with a 18.3 cm ear length, 5.0 cm ear diameter, 0.4 bald head, 403.9 g fresh weight of single bud, 272.0 g net weight of single ear, and 16.5 kernels sweetness. Combined transcriptomic and metabolomic analyses indicate that differentially expressed genes related to plant-pathogen interactions, MAPK signaling pathway-plant, phenylpropanoid biosynthesis, and flavonoid biosynthesis were significantly enriched. Moreover, the 110 upregulated DAMs were mainly involved in the flavonoid biosynthesis and flavone and flavonol biosynthesis pathways. Our study provides a foundation for investigating the molecular mechanisms by which biocontrol bacteria enhance crop nutrition and taste through biological means or genetic engineering at the molecular level.

Abstract Myxobacteria, as predatory bacteria, have good application potential in the biocontrol of pathogenic microorganisms. Extracellular enzymes are thought to play an important role in their predation and also provide resources for discovering new antibacterial molecules. We previously isolated a myxobacterium, Corallococcus silvisoli c25j21 GDMCC 1.1387, which is predatory to plant pathogenic bacteria. In this study, we identified an endolysin-like GH19 glycoside hydrolase, C25GH19B, from the genome of c25j21. After its heterologous expression and purification from E. coli, the enzymatic properties of C25GH19B were characterized. C25GH19B showed lysozyme activity with the optimal reaction conditions at 40 °C and pH 4.5–5.0. Moreover, C25GH19B showed bacteriolytic activity against both Gram-positive and Gram-negative plant pathogenic bacteria. Our research provides not only a candidate enzyme for the development of novel biocontrol agents but also an experimental basis for further study on the function and mechanisms of extracellular enzymes in myxobacterial predation.

Abstract Accumulating evidence indicates that hepatitis B virus X protein (HBx) plays a key role in HBV-related hepatocellular carcinoma (HCC) aggressiveness; however, the underlying mechanisms are not entirely clear. Long non-coding RNAs (lncRNAs), which participate in the regulation of diverse biological processes, may be critical for the function of HBx. Our research indicated that HBx induced changes in the expression of numerous lncRNAs and implicated the novel lncRNA RP11-241J12.3 in HBx-mediated HCC aggressiveness. Although RP11-241J12.3 expression was downregulated in transient HBx-expressing HCC cells (similar to the early stage of HBV infection), its oncogenic properties remained. The results showed that RP11-241J12.3 not only accelerated DNA synthesis and upregulated the expression of pyruvate carboxylase (PC) and MSH3, which is a key protein in pyruvate metabolism and DNA mismatch repair (MMR), but also promoted tumor growth in vitro and in vivo, thus promoting HCC aggressiveness. More importantly, we revealed that RP11-241J12.3 may interact with PC and identified its location in the cytoplasm close to the nucleus using fluorescence in situ hybridization (FISH). We also observed RP11-241J12.3 expression was upregulated in HCC tissues compared with the paracarcinomatous tissues. Furthermore, RP11-241J12.3 expression levels showed a close relationship with clinical stage and tumor size and that low RP11-241J12.3 expression was significantly correlated with longer HCC patient survival. These results further our understanding of the lncRNAs regulated by HBx in HCC, and provide evidence that dysregulation of RP11-241J12.3 contributes to HCC aggressiveness.

To measure and evaluate the impact of vibration on the surrounding buildings and structures during highway rock burst removal and to formulate scientific and reasonable protective technical measures, the authors used the blasting perilous rock removal project of the K2227+920–K2228+000 section of the Shaanxi G316 road as a case study. The application of frequency modulation blasting vibration damping technology adopting digital electronic detonators was investigated. The difference in vibration peak and frequency between the perforation-by-hole initiation of the detonator and the frequency modulation initiation of the digital electronic detonator is compared. The results showed that by adopting an accurate delay of digital electronic detonators and the damping scheme of adjusting the blasting vibration frequency using the electronic detonators a reduction in blasting vibration velocity can be achieved. For an unchanged blasting scale, hole mesh parameters, and explosive unit consumption, the total blasting time was adjusted in the test. Compared to the hole-by-hole initiation, the blasting vibration velocity at a pier of the G85 Baohan highway bridge located 52 m away was reduced from 0.367 cm/s to 0.229 cm/s, a decrease of 36.7%. The field test demonstrated that frequency modulation and vibration attenuation using digital detonators can reduce blasting vibrations and effectively reduce the influence of blasting construction on surrounding buildings and structures.

IntroductionRed-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns due to residual chemical reagents. Halomonas bluephagenesis is a versatile chassis for the production of fine chemicals because of its open growth property without sterilization.MethodsA heterologous mevalonate (MVA) pathway was introduced into H. bluephagenesis strain TD1.0 to engineer a bacterial host for lycopene production. A pTer7 plasmid mediating the expression of six MVA pathway genes under the control of a phage PMmp1 and an Escherichia coli Ptrc promoters and a pTer3 plasmid providing lycopene biosynthesis downstream genes derived from Streptomyces avermitilis were constructed and transformed into TD1.0. The production of lycopene in the engineered H. bluephagenesis was evaluated. Optimization of engineered bacteria was performed to increase lycopene yield.ResultsThe engineered TD1.0/pTer7-pTer3 produced lycopene at a maximum yield of 0.20 mg/g dried cell weight (DCW). Replacing downstream genes with those from S. lividans elevated the lycopene production to 0.70 mg/g DCW in the TD1.0/pTer7-pTer5 strain. Optimizing the PMmp1 promoter in plasmid pTer7 with a relatively weak Ptrc even increased the lycopene production to 1.22 mg/g DCW. However, the change in the Ptrc promoter in pTer7 with PMmp1 did not improve the yield of lycopene.ConclusionWe first engineered an H. bluephagenesis for the lycopene production. The co-optimization of downstream genes and promoters governing MVA pathway gene expressions can synergistically enhance the microbial overproduction of lycopene.

Chronic liver diseases (CLDs) are characterized by progressive necrosis of hepatocytes, which leads to liver fibrosis and cirrhosis, and ultimately liver dysfunction. The statistics of 2020 shows that the number of patients with CLDs, including chronic hepatitis, fatty liver, and cirrhosis, may exceed 447 million in China. The liver is a crucial organ for the metabolism of various substances, including sex hormones and lipids. CLDs frequently result in abnormalities in the metabolism of sex hormones, glucose, and lipids, as well as mental and psychological illnesses, all of which are significant risk factors for erectile dysfunction (ED). It has been reported that the prevalence of ED in male patients with CLDs ranges from 24.6 to 85.0%. According to a survey of Caucasians, liver transplantation may improve the erectile function of CLDs patients with ED. This finding supports the link between CLDs and ED. In addition, ED is often a precursor to a variety of chronic diseases. Given this correlation and the significant prevalence of CLDs, it is important to evaluate the epidemiology, risk factors, etiology, and treatment outcomes of ED in male patients with CLDs, expecting to attract widespread attention.

Malignant ascites frequently occur in patients with advanced ovarian cancer at initial diagnosis, and in almost all cases of relapse, they are closely related to poor prognosis, chemoresistance, and metastasis. To date, effective management strategies have been limited. In this study, we aimed to investigate the effects of oncolytic adenovirus (OV) on malignant ascites in a mouse model of advanced ovarian cancer. The results suggested that OV conferred an effective ability to reduce ascites development and prolong overall survival. Further analysis of the ascitic immune microenvironment revealed that OV treatment promoted T cell infiltration, activation, and differentiation into the effector phenotype; reprogrammed macrophages toward the M1-like phenotype; and increased the ratios of both CD8+ T cells to CD4+ T cells and M1 to M2 macrophages. However, immunosuppressive factors such as PD-1, LAG-3, and Tregs emerged after treatment. Combination therapy including OV, CSF-1R inhibitor PLX3397, and anti-PD-1 remarkably delayed the progression of ascites, and combination therapy induced a greater extent of T cell infiltration, proliferation, and activation. This study provides experimental and theoretical evidence for oncolytic virus-based treatment of malignant ascites, which may further contribute to advanced ovarian cancer therapy.