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Background: At present, basic scientific research on pancreatic trauma is rare due to the lack of ideal animal models and modeling equipment for pancreatic trauma. Therefore, we intend to develop a multifunctional impact system with simple operation, diverse impact and accurate measurement and to establish a rat pancreatic trauma model based on injury area control by using the system. Methods: The impactor was designed based on the convenience of the impact energy acquisition, the diversity of the impact operation, and the precision of the impact strength parameter measurement by the team. The efficacy and stability/repeatability of the impactor were preliminarily evaluated. An impact head with different impact areas (3 cm2 and 6 cm2) of the impactor was used to squeeze the rat pancreas in the abdomen to form different injury areas under a pressure of 400 kPa. The efficacy features of this trauma model were evaluated by detecting the outcomes of pathology and biochemistry at 24 h after injury in the two groups. Furthermore, these changes were also evaluated at 6 h, 24 h, 48 h and 72 h after injury in the 3 cm2 trauma group. Result: Multifunctional impactors were successfully explored. The impact force was continuously adjustable with a range of 0–200 kg. The compression and extrusion stress ranges were continuously adjustable from 0 to 100 kg. System adjustment verified that the impactor had fine efficacy (P 0.05). Compared with the control group, rats in the pancreatic trauma group with different injury areas exhibited obvious injuries (P

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]