Search

Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with the tumor microenvironment (TME) playing a crucial role in its progression. Aggregated autophagy (AA) has been recognized as a factor that exacerbates CRC progression. This study aims to study the relationship between aggregated autophagy and CRC using single-cell sequencing techniques. Our goal is to explain the heterogeneity of the TME and to explore the potential for targeted personalized therapies. Objective: To study the role of AA in CRC, we employed single-cell sequencing to discern distinct subpopulations within the TME. These subpopulations were characterized by their autophagy levels and further analyzed to identify specific biological processes and marker genes. Results: Our study revealed significant correlations between immune factors and both clinical and biological characteristics of the tumor microenvironment (TME), particularly in cells expressing TUBA1B and HSP90AA1. These immune factors were associated with T cell depletion, a reduction in protective factors, diminished efficacy of immune checkpoint blockade (ICB), and enhanced migration of cancer-associated fibroblasts (CAFs), resulting in pronounced inflammation. In vitro experiments showd that silencing TUBA1B and HSP90AA1 using siRNA (Si-TUBA1B and Si-HSP90AA1) significantly reduced the expression of IL-6, IL-7, CXCL1, and CXCL2 and inhibition of tumor cell growth in Caco-2 and Colo-205 cell lines. This reduction led to a substantial alleviation of chronic inflammation and highlighted the heterogeneous nature of the TME. Conclusion: This study marks an initial foray into understanding how AA-associated processes may potentiate the TME and weaken immune function. Our findings provide insights into the complex dynamics of the TME and highlight potential targets for therapeutic intervention, suggesting a key role for AA in the advancement of colorectal cancer. [ABSTRACT FROM AUTHOR]

This study established a simple, rapid, and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of contezolid and its major metabolite M2 in human plasma and cerebrospinal fluid (CSF). We used isotope-labeled internal standards (IS) along with protein precipitation to efficiently eliminate impurities. The ion transition was m/z 409.1 → 269.1 for contezolid, m/z 414.1 → 269.0 for contezolid-d5, m/z 445.1 → 385.1 for M2, and m/z 450.2 → 390.1 for M2-d5. The flow rate was 0.4 mL/min with a run time of 2.5 min. Validation results demonstrated that the calibration range was 10–5000 ng/mL for contezolid, and 5–2500 ng/mL for M2 in plasma and CSF. Both analytes exhibit excellent linear relationships (all R2 ≥ 0.99). Intra- and inter-batch accuracy and precision for all quality control (QC) levels were within ± 15%, including the lower limit of quantification (LLOQ). The recoveries of contezolid and M2 were 92.60–100.4% and 92.26–99.61% in plasma and 93.33–99.19% and 91.31–98.21% in CSF, respectively. The matrix effects for contezolid and M2 were 97.20–110.3% and 98.27–105.47% in plasma and 105.25–112.99% and 103.35–109.84% in CSF, respectively. The coefficients of variation (CV%) were ≤ 12.58%. Conteozolid and M2 remained stable in plasma and CSF. This study has established a simple and accurate method for determining contezolid and M2 in human plasma and CSF, making it a valuable tool for monitoring the efficacy of central nervous system (CNS) drugs. [ABSTRACT FROM AUTHOR]

RNA N6-methyladenosine (m6A), as the most abundant modification of messenger RNA, can modulate insect behaviors, but its specific roles in aggregation behaviors remain unexplored. Here, we conducted a comprehensive molecular and physiological characterization of the individual components of the methyltransferase and demethylase in the migratory locust Locusta migratoria. Our results demonstrated that METTL3, METTL14 and ALKBH5 were dominantly expressed in the brain and exhibited remarkable responses to crowding or isolation. The individual knockdown of methyltransferases (i.e., METTL3 and METTL14) promoted locust movement and conspecific attraction, whereas ALKBH5 knockdown induced a behavioral shift toward the solitary phase. Furthermore, global transcriptome profiles revealed that m6A modification could regulate the orchestration of gene expression to fine tune the behavioral aggregation of locusts. In summary, our in vivo characterization of the m6A functions in migratory locusts clearly demonstrated the crucial roles of the m6A pathway in effectively modulating aggregation behaviors. [ABSTRACT FROM AUTHOR]

Insufficient compaction of the subgrade can result in nonuniform deformation, leading to severe subgrade distress. To address this issue and find a new method for rapid detection and evaluation of subgrade compaction, we used the lightweight deflectometer (LWD) to analyze the dynamic deformation modulus (Evd) of subgrades filled with four types of soils—silt (ML), well-graded gravel (GW), lean clay (CL), and poorly graded sand (SP)—in different regions of Gansu province, China. Concurrently, we measured the degree of compaction (Doc) using the sand replacement method (SRM) to establish its correlation with dynamic deformation modulus (Evd). A strong correlation between the degree of compaction and dynamic deformation modulus was established for soils ML, GW, CL, and SP, and suitable formulas were selected based on curve variations. The developed formulas enabled back-calculation of the dynamic deformation modulus requirements corresponding to different degrees of compaction ranging from 90 to 100, facilitating direct queries and quick field checks. Results demonstrated that the LWD, as a reliable rapid detection method, effectively controlled subgrade compaction quality in field construction. Moreover, it extended the testing area and increased measurement frequency, thus providing a practical means for quickly evaluating the qualification rate and uniformity of subgrade compaction. When we build roads, most subgrade underneath the roads needs to be filled with soil. If we don't pack the soil properly in the filling process, the subgrade can crack and become uneven over time. It's hard to fix this problem once the road is open, so it's important to make sure the soil is packed tightly enough before the road is finished. There are two ways to check if the soil is packed properly: one is a traditional method called the sand replacement method, and the other is a machine called the lightweight deflectometer. These methods help identify insufficient compaction of the subgrade and prevent uneven deformation problems during the filling process. What's more, the lightweight deflectometer is a fast, convenient, and reliable tool that can assist or serve as an alternative to the traditional sand replacement method for controlling subgrade construction quality. This study is important because it helps us understand how to evaluate compaction of the filled subgrade in a different way. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming induced by Epstein‐Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV‐associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV‐associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D‐2HG, and serum D‐2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)‐driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α‐KG, which inhibits the expression of EBV lytic genes with CpG‐containing ZREs and the latent‐lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC. [ABSTRACT FROM AUTHOR]

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy. [ABSTRACT FROM AUTHOR]

In this research, long-term monitoring data from 2020 to 2023 were used to characterize O3 pollution in a typical inland city in northwest China (34°21′ N 109°30′ E), which indicated that ozone pollution yielded typical regular fluctuations and high ozone concentrations from April to September were observed. Ozone varied in the range of 16–176 μg/m3, and maximum peaks were found usually at 14:00–17:00 in June and July. Correlation analysis showed a significant positive relationship between ozone and temperature, with correlation coefficients of 0.93. The wind speed exhibits a similar variation as ozone. Meanwhile, negative correlations were not so notably observed among ozone, humidity, VOCs, and NOx. Finally, the empirical kinetic model OZIPR (Ozone Isopleth Plotting Program for Research) was employed to analyze the sensitivity relationship among ozone and precursor compounds by calculating EMKA (Empirical Kinetics Modeling Approach) curves. The EKMA analysis results showed that during the whole ozone pollution period, ozone formation is mainly dominated by VOCs due to all the ratios of VOCs/NOx which fell in the VOCs control region. Therefore, VOCs should be priority controlled and more measures should be taken for better ozone pollution control abatement. [ABSTRACT FROM AUTHOR]

Dielectric capacitors are desired for electronics and electrical power systems because of their fast charge–discharge speed and high‐power density. Nevertheless, dielectric capacitors typically exhibit lower energy densities in comparison to other energy storage systems like batteries or fuel cells. Among dielectrics, antiferroelectrics have shown great promise for high energy density because of their characteristic double hysteresis loops. However, current antiferroelectric capacitors still face challenges of low efficiency and low breakdown strength due to their large hysteresis, which is harmful to energy efficiency and reliability of the system. Herein, by engineering the nanoscale heterogeneity to mitigate hysteresis and controlling orientation to enhance the polarization, the exceptional energy storage performance of antiferroelectric (Pb0.97La0.02)(Zr0.55Sn0.45)O3 epitaxial thin films is demonstrated. Atomic‐resolution transmission electron microscopy and X‐ray reciprocal space mapping confirm the presence of nanoscale structural heterogeneity, characterized by fragmented antipolar nanodomains. These films exhibit remarkable energy densities, reaching up to ≈84.5 J cm−3, coupled with ultrahigh efficiencies of up to ≈98.5% and superior stability, maintaining efficiencies above 92% across a wide field range of ≈5 MV cm−1. Notably, these findings surpass the capabilities of previously reported dielectric materials, opening new avenues for advanced energy storage applications. [ABSTRACT FROM AUTHOR]

Background: As a vital type of noncoding RNAs, circular RNAs (circRNAs) play important roles in plant growth and development and stress response. However, little is known about the biological roles of circRNAs in regulating the stability of male fertility restoration for cytoplasmic male sterility (CMS) conditioned by Gossypium harknessii cytoplasm (CMS-D2) cotton under high-temperature (HT) stress. Results: In this study, RNA-sequencing and bioinformatics analysis were performed on pollen grains of isonuclear alloplasmic near-isogenic restorer lines NH [N(Rf1rf1)] and SH [S(Rf1rf1)] with obvious differences in fertility stability under HT stress at two environments. A total of 967 circRNAs were identified, with 250 differentially expressed under HT stress. We confirmed the back-splicing sites of eight selected circRNAs using divergent primers and Sanger sequencing. Tissue-specific expression patterns of five differentially expressed circRNAs (DECs) were also verified by RT-PCR and qRT-PCR. Functional enrichment and metabolic pathway analysis revealed that the parental genes of DECs were significantly enriched in fertility-related biological processes such as pollen tube guidance and cell wall organization, as well as the Pentose and glucuronate interconversions, Steroid biosynthesis, and N-Glycan biosynthesis pathways. Moreover, we also constructed a putative circRNA-mediated competing endogenous RNA (ceRNA) network consisting of 21 DECs, eight predicted circRNA-binding miRNAs, and their corresponding 22 mRNA targets, especially the two ceRNA modules circRNA346-miR159a-MYB33 and circRNA484-miR319e-MYB33, which might play important biological roles in regulating pollen fertility stability of cotton CMS-D2 restorer line under HT stress. Conclusions: Through systematic analysis of the abundance, characteristics and expression patterns of circRNAs, as well as the potential functions of their parent genes, our findings suggested that circRNAs and their mediated ceRNA networks acted vital biological roles in cotton pollen development, and might be also essential regulators for fertility stability of CMS-D2 restorer line under heat stress. This study will open a new door for further unlocking complex regulatory mechanisms underpinning the fertility restoration stability for CMS-D2 in cotton. [ABSTRACT FROM AUTHOR]

Background: Hair follicle stem cells (HFSCs) typically remain quiescent and are activated only during the transition from telogen to anagen to ensure that the hair follicle enters a new cycle. The metabolic behavior of stem cells in tissues is regulated by macroautophagy/autophagy, and changes in HFSC metabolism directly affect their activation and maintenance. However, the role of autophagy in the regulation of HFSC metabolism and function remains unclear. Methods: Back skin samples were obtained from mice at different hair follicle cycle stages, and immunofluorescence staining was used to monitor autophagy in HFSCs. Mouse and human hair follicles were treated with rapamycin (Rapa, an autophagy activator) or 3-methyladenine (3-MA, an autophagy inhibitor). The effects of autophagy on the hair follicle cycle and HFSC were investigated by imaging, cell proliferation staining, and HFSC-specific marker staining. The influence and mechanism of autophagy on HFSC metabolism were explored using RNA sequencing, real-time polymerase chain reaction, immunohistochemical staining, and detection of lactate and glucose concentrations. Finally, the influence of autophagy-induced glycolysis on HFSC and the hair follicle cycle was verified by stem cell characteristics and in vivo functional experiments. Results: Autophagy in HFSC was highest during the transition from telogen to anagen. Inhibiting autophagy with 3-MA led to early entry into catagen and prolonged telogen, whereas Rapa promoted autophagy and hair growth. Autophagy activated HFSC by increasing the expression and activity of HFSC lactate dehydrogenase (Ldha), thereby transforming HFSC metabolism into glycolysis. Inhibition of Ldha expression counteracted the effects of autophagy. Conclusions: Autophagy activated HFSC by promoting the transition from HFSC metabolism to glycolysis, ultimately initiating the hair follicle cycle and promoting hair growth. [ABSTRACT FROM AUTHOR]

Summary: Rice false smut caused by Ustilaginoidea virens is a devastating rice (Oryza sativa) disease worldwide. However, the molecular mechanisms underlying U. virens–rice interactions are largely unknown. In this study, we identified a secreted protein, Uv1809, as a key virulence factor. Heterologous expression of Uv1809 in rice enhanced susceptibility to rice false smut and bacterial blight. Host‐induced gene silencing of Uv1809 in rice enhanced resistance to U. virens, suggesting that Uv1809 inhibits rice immunity and promotes infection by U. virens. Uv1809 suppresses rice immunity by targeting and enhancing rice histone deacetylase OsSRT2‐mediated histone deacetylation, thereby reducing H4K5ac and H4K8ac levels and interfering with the transcriptional activation of defence genes. CRISPR‐Cas9 edited ossrt2 mutants showed no adverse effects in terms of growth and yield but displayed broad‐spectrum resistance to rice pathogens, revealing a potentially valuable genetic resource for breeding disease resistance. Our study provides insight into defence mechanisms against plant pathogens that inactivate plant immunity at the epigenetic level. [ABSTRACT FROM AUTHOR]

Laser‐induced periodic surface structure (LIPSS) can form structural color on the metal surfaces with high production efficiency and thermal stability, and has been used in various industrial applications such as unfaded color marking and anti‐counterfeiting. Herein, a novel fabrication scheme of multilayer LIPSS is proposed by multiple writing in situ with changing the laser polarization direction, to exhibit an effect of color superposition. To verify this approach, the color formation mechanism of LIPSS on the stainless‐steel surface is analyzed by finite‐element numerical calculation and reveals that the high‐angular dispersion of LIPSS is mainly the result of optical diffraction occurring on the surface of periodic structures. The relationship between the angular dispersion of multilayer LIPSS and laser‐processing parameters is established. Through the proposed multilayer LIPSS coloring technology, vivid full‐color patterns on the steel surface are demonstrated, and the in situ superposition of three‐layer graphs is realized, which can greatly enrich the color levels and be competitive in industrial applications. [ABSTRACT FROM AUTHOR]

This article explores the relationship between the fungus Ustilaginoidea virens and the WRKY transcription factor OsWRKY31 in rice plants. The researchers discovered that a specific protein, UvSec117, is a key factor in the virulence of U. virens and interacts with OsWRKY31. They also found that OsWRKY31 positively regulates rice's resistance to various diseases. Through further experiments, they identified the target genes of OsWRKY31, which are involved in induced systemic resistance and the salicylic acid/jasmonic acid signaling pathways. This research provides valuable insights into the molecular mechanisms of rice's resistance to grain-infecting pathogens and has implications for breeding disease-resistant rice varieties. [Extracted from the article]