Significant spatiotemporal pattern of nitrous oxide emission and its influencing factors from a shallow eutropic lake in Inner Mongolia, China.

Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.

Sika Deer antler protein antagonizes the inflammatory response and oxidative damage induced by jellyfish venom.

The investigation into specific treatments for jellyfish stings has consistently presented a significant medical challenge. Sika Deer antler protein (DAP), a valuable component of traditional Chinese medicine (TCM) known for its various pharmacological properties, has been widely utilized for the prevention and treatment of numerous diseases. In this study, proteome analysis and biological activity assays of DAP identified 94 distinct protein components and demonstrated its capability to scavenge free radicals. Moreover, administration of 50 mg/kg DAP notably enhanced survival rates in mice, mitigated increases in hematological indicators and inflammatory markers (IL-6, IL-1ß, and TNF-α), and alleviated pathological abnormalities induced by jellyfish venom. Additionally, DAP intervention significantly decreased the hemolysis rate and improved the viability of RAW264.7 cells, while reducing cell apoptosis and oxidative stress. Transcriptome analysis and western blotting of RAW264.7 cells further confirmed that DAP inhibited the activation of the NF-κB and MAPK signaling pathways. Overall, DAP effectively countered the toxicity of jellyfish venom by reducing oxidative damage and inflammatory response, highlighting the potential of TCM in treating jellyfish stings.

Evaluating pretreatment serum CA-125 levels as prognostic biomarkers in endometrial cancer: a comprehensive meta-analysis.

Background: In recent years, the incidence of endometrial cancer (EC) has been rising. This meta-analysis aims to clarify the prognostic significance of serum CA-125 levels in EC. Methods: Articles up to March 1, 2024, were systematically searched in EMBASE, Cochrane Library, PubMed, and Web of Science. This analysis pooled hazard ratios (HR) and 95% confidence intervals (CI) from qualifying studies to evaluate the association of CA-125 levels with overall survival (OS), progression-free survival (PFS), disease-free/relapse-free survival (DFS/RFS), and disease-specific survival (DSS). Results: 25 studies involving 7,716 patients were included. The analysis revealed that elevated CA-125 levels correlate with poorer OS (HR = 1.848, 95% CI: 1.571-2.175, p < 0.001). This association persisted across various study regions and sample sizes, and was notably strong in subgroups with a CA-125 cut-off value of less than 35 (HR = 2.07, 95% CI: 1.13-3.80, p = 0.019) and equal to 35 (HR = 2.04, 95% CI: 1.49-2.79, p < 0.001), and among type II pathology patients (HR = 1.72, 95% CI: 1.07-2.77, p = 0.025). Similarly, high CA-125 levels were linked to reduced PFS, particularly in subgroups with a CA-125 cut-off value less than 35 (HR = 1.87, 95% CI: 1.15-3.04, p = 0.012) and equal to 35 (HR = 4.94, 95% CI: 2.56-9.54, p < 0.001), and in endometrioid endometrial cancer patients (HR = 2.28, 95% CI: 1.18-4.40, p = 0.014). Elevated CA-125 levels were also indicative of worse DFS/RFS (HR = 2.17, 95% CI: 1.444-3.262, p < 0.001) and DSS (HR = 2.854; 95% CI: 1.970-4.133, p < 0.001). Conclusion: Serum CA-125 levels before treatment was highly associated with prognosis of EC patients.

Impact of Wettability on CO2 Dynamic Dissolution in Three-Dimensional Porous Media: Pore-Scale Simulation Using the Lattice Boltzmann Method.

Understanding the dissolution behavior of supercritical CO2 (scCO2) in porous media is crucial for efficient CO2 storage. However, the precise modeling of dynamic dissolution behavior at this pore scale remains a huge challenge, and the impact of wettability on this process still needs to be clarified. In this study, the influence of rock wettability on CO2 dynamic dissolution in the three-dimensional porous media is investigated using the lattice Boltzmann method (LBM). The LBM is coupled with scCO2-water two-phase flow, solute transport, and heterogeneous and homogeneous reactions. The size, number, and dissolution pattern of scCO2 bubbles during the dissolution process are observed under strongly water-wet, weakly water-wet, intermediate-wet, and mixed-wet conditions. The CO2(aq) concentration and pH are investigated, followed by a quantitative investigation of the impact of wettability on the specific interface area and the mass transfer coefficient. An empirical relationship between the specific interface area and scCO2 saturation is established. The findings reveal that under weakly water-wet and intermediate-wet conditions, the sizes of scCO2 clusters and monomers are small and mostly distributed at the dead end of the pores. In contrast, under strongly water-wet and mixed-wet conditions, the clusters are larger and interconnected, and distributed in the center of the pore. This results in a greater scCO2-water interface area, consequently enhancing the dissolution rate. Furthermore, a strong linear correlation is observed between scCO2 saturation and specific interface area. It is noted that as the hydrophilicity of the rock increases, the mass transfer coefficient initially rises and then declines.

Hysteresis response of carbon release and nitrate reduction in polymer denitrification systems.

Polymer denitrification has received much attention in the field of advanced wastewater treatment. It can release carbon source stably during long-term operation, which can be used as electron donor for denitrification. However, the response of the polymer denitrification system to the transient changes of nitrate is not sufficiently disclosed yet. In this study, the response of a polymer denitrification system to nitrate was comprehensively investigated through a series of experiments. Therefore, real-time response and hysteresis response phenomena were identified. The time dependence of microorganisms in the system and the recovery of the hysteresis response were elucidated. The experimental results revealed distinct response patterns before and after the hysteresis tipping point. The denitrifying microorganisms, which showed a high adaptive capacity, exhibited a real-time response over a range of low nitrate concentration variations (∼20-30 mg/L). In contrast, microbial recovery is poor over a range of high nitrate concentration variation (∼35-40 mg/L), which is referred to as a hysteresis response. Finally, the hysteresis response mechanism was revealed by monitoring the recovery of denitrification enzymes, gene and microbial communities. The results showed that transient shocks of high nitrate loads affect microbial community structure stability, denitrifying enzyme activity and gene expression. Meanwhile, the abundance of Microbacterium associated with carbon release was reduced. The combination of these factors leads to a hysteresis response in denitrification and carbon release. This work contributes to a deeper understanding of the hysteresis behavior in polymer denitrification systems, offering critical insights for optimizing system performance and improving nitrogen removal efficiency.

Myeloid PGC1ß attenuates high-fat-diet induced inflammation via mitochondrial fission/mtDNA/Nlrp3 pathway.

Peroxisome proliferator-activated receptor gamma coactivators 1ß (PGC1ß) is essential in mitochondrial oxidative phosphorylation and alternative macrophages activation. To determine the contribution of PGC1ß in obesity induced inflammation, Ppargc1b (PGC1ß coding gene) myeloid conditional knockout mice (cKO) were fed with high fat diet (HFD) to examine the following effects. We found that HFD-fed cKO mice gained more fat with increased serum triglyceride (TG), low density lipoprotein (LDL), adiponectin, and leptin. Adipogenesis was stimulated while lipolysis was retarded in HFD-fed cKO mice adipose. Gluconeogenesis, lipogenesis, and fatty acid uptake were provoked while lipolysis was inhibited in HFD-fed cKO liver. Serum alanine transaminase (ALT) level, indicating fatty liver, also increased. Inflammatory cytokine including tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 was elevated in cKO mice, accompanied with glucose intolerant and insulin resistance. Energy expenditure was decreased in HFD-fed cKO mice. Further evidence showed that cKO macrophages were prone to repolarize into M1 inflammatory type in vitro. In addition to mitochondrial biogenesis and oxidative respiration, PGC1ß also modulated mitochondrial fission and cytosolic mitochondrial DNA (mtDNA) release, contributing to NLR family pyrin domain containing 3 (Nlrp3) inflammasome priming and activation. Treatment of mitochondrial fission inhibitor abolished the increased mRNA levels of Nlrp3 and IL-1ß induced by PGC1ß depletion. Nlrp3 knockdown restored the induced IL-1ß mRNA expression by PGC1ß deficiency. Myeloid PGC1ß regulated adipocyte adipogenesis and lipolysis. PGC1ß loss-of-function and mtDNA abundance correlated with obesity and diabetes. These observations uncovered the protective role of PGC1ß against obesity induced systemic inflammation. Enhancing myeloid PGC1ß function may be a potential strategy for the intervention of obesity and related diseases.

Novel Chiral Self-Assembled Nano-Fluorescence Materials with AIE Characteristics for Specific Enantioselective Recognition of L-Lysine.

In this paper, two aggregation-induced emission (AIE) chiral fluorescent materials, S-1 and S-2, were synthesized. The two materials are based on BINOL and H8-BINOL backbones, respectively, and large electron-absorbing groups are attached to the chiral backbones through the Knoevenagel reaction. At the same time, the CD signals of these two chiral fluorescent materials are gradually weakened (fw gradually increases) as they continue to aggregate. However, S-2 underwent a flip-flop from a negative to positive chiral CD signal at fw ≥ 90. And both materials also showed significant enantioselective recognition of lysine, demonstrating their potential as novel chiral fluorescent probes. Among them, the enantioselective fluorescence enhancement ratios (ef) of S-1 and S-2 for lysine were 10.0 and 10.3, respectively, while different degrees of blue shifts were produced by the ICT mechanism during the recognition process. In addition, the self-assembled morphology of the two nanomaterials is different; S-1 comprises hollow-core vesicles that are more likely to aggregate to form larger self-assembled vesicles, whereas S-2 is a solid block structure. When L/D-lysine was added alone, the morphology of S-1 was more distinctly different compared to S-2. With the addition of L-lysine, S-1 was dispersed and regularly spherical, whereas with the addition of D-lysine, S-1 itself remained in the form of aggregated large vesicles. This suggests that both S-1 and S-2 are important in the fields of chiral optics, chiral recognition, and nanoscale self-assembly.

Transcriptomic and Metabolomic Analyses Reveal the Attenuating Role of Cordycepin and Cordyceps militaris Extract on Acute Liver Injury Induced by LPS in Piglets.

Cordyceps militaris extract (CME) contains many bioactive compounds, mainly cordycepin (CPN). This study aimed to investigate the possible mechanisms underlying the amelioration of LPS-induced acute liver injury in piglets by CME or CPN supplementation using multi-omics analysis. Twenty-four weaned piglets were randomly distributed into 4 groups (n = 6): the control and LPS groups were fed basal diets; the CPN + LPS (CPN-LPS) and CME + LPS (CME-LPS) groups were fed the basal diets supplemented with CME or CPN. The results showed that CPN or CME supplementation significantly decreased the C-reactive protein level (p < 0.05) and improved liver tissue pathology to prevent acute liver injury after LPS treatment. Compared with LPS, the transcriptomic analysis indicated that CPN supplementation significantly downregulated cell adhesion molecules, while CME supplementation significantly downregulated inflammatory mediator regulation of TRP channels, complement and coagulation cascades and cytokine-cytokine receptor interaction. The metabolomic results showed that CPN or CME supplementation significantly reduced disease biomarker of bicyclo-prostaglandin E2, and increased levels of deoxyinosine and 3-hydroxyanthranilic acid (p < 0.05). The combined transcriptome and metabolome helped identify two metabolites PC 34:2 and PC 36:0, which may be associated with the restoration of liver cell morphology. In conclusion, CPN and CME could attenuate LPS-induced acute liver injury by regulating immune-related genes and metabolites. This study elucidates the potential protective mechanism of CPN or CME supplementation against acute liver injury.

The relationship between the secondary structure and the emulsifying ability of protein-based particles and the Pickering emulsions stabilized by the zein-lysine complex.

Due to the sustainability and widespread use of proteins, protein-based materials are extensively utilized in the preparation of Pickering emulsions. However, the relationship between the secondary structure of proteins and their emulsifying ability has not been further investigated. This study used the addition of three different amino acids to influence the interaction between zein chains, which may induce changes in the secondary structure of the prepared zein complex particles. This study demonstrates that the emulsifying properties of proteins, such as dispersibility, zeta potential, three-phase contact angles, interfacial affinity, adsorption rates, and the volume of the stabilized oil phase, are closely related to the ß-sheet content of the complex particles, providing a theoretical reference for protein-based stabilizers. Additionally, amino acids, as the blocks of proteins, have high compatibility with proteins, and using amino acids as modifiers aligns with the safety requirements for food processing. In this study, the prepared zein-lysine complex particles have good emulsifying ability, capable of stabilizing a 50 (v/v)% emulsion at a lower concentration (10 mg mL-1), and the prepared emulsion exhibits high-temperature stability and ionic resistance. This characteristic makes the emulsion potentially valuable for application in systems with high salt concentrations and those that may undergo heat treatment.

Aglycone Analysis and Quantitative Tracking of Correlated Terminal Glycan Pair on Spermatozoa.

Mammalian sperm glycans directly mediate several key life events. However, previous studies have not focused on two key factors that regulate these processes, the terminal glycan pattern and the anchoring sites. Herein, we group the capping monosaccharide sialic acid (Sia) and its capping substrates galactose/N-acetylgalactosamine (Gal/GalNAc) into a "correlated terminal glycan pair" (glycopair) and, for the first time, reveal the differences in the aglycone pattern of this pair on spermatozoa using glyco-selective in situ covalent labeling techniques. Sia is mainly found in glycoproteins, whereas terminal Gal/GalNAc is mainly found in glycolipids. We quantitatively track the dynamic changes of the glycopair during sperm epididymal migration and find that the Sia capping ratio decreases with the increased expression of the glycopair; caudal upswim spermatozoa also show a lower Sia capping ratio than down spermatozoa. We thus propose two new parameters reflecting the terminal glycoforms of spermatozoa, which can well distinguish the maturity of spermatozoa. By fluorescence imaging of the glycopair in different regions of the sperm, we find that different parts of the sperm contribute differently to the overall glycan changes.

Identification of unique ecosystem service bundles in farmland - A case study in the Huang-Huai-Hai Plain of China.

Ecosystem services (ESs) are essential for human well-being and are relevant to the region's sustainable development. Most studies have emphasized the importance of high ecosystem services areas for entire regions. However, some locations with particular contributions to a region's ecosystem services are still overlooked. Using the InVEST model, this study analyzed three ESs: annual water yield (WY), carbon storage (CS), and soil conservation (SC) in the farmland of the Huang-Huai-Hai Plain of China (HHHP) from 2005 to 2019. Combining climate regulation (NDVI) and food production (FP), this research calculated the city level of the diversity of ecosystem services supply (alpha-multifunctionality) and the unique contribution to the region in each city (beta-multifunctionality) from 2005 to 2019. The alpha-multifunctionality combines the number of ecosystem services and their supplies of ecosystem services. At the same time, the beta-multifunctionality assesses the average dissimilarity between the city and all other cities within that region. Furthermore, this study used Spearman correlation and self-organizing map (SOM) to analyze the relationships between these five ecosystem services and identify ecosystem service bundles. Finally, this study used random forests to analyze drivers of ecosystem service multifunctionality. Our results showed that food production in the Huang-Huai-Hai Plain increased significantly by 37.20% over time, annual water yield decreased significantly by 29.59%, and climate regulation decreased significantly by 6.09%. This may be because the Huang-Huai-Hai Plain mainly shifted from monoculture to crop rotation, and the increase in crops required more irrigation, which led to a significant decline in water yield. Furthermore, the area of grain crops in the HHHP was reduced in 2019 compared to 2005, which explains the significant decline in climate regulation. SOM found that cities with a higher beta-multifunctionality were mainly concentrated in the northern and southwest parts of HHHP. Bundles with a high alpha-multifunctionality were mainly in the southern and southeast parts of the HHHP. In addition, this research showed that farmers' per capita disposable income was the most important driver of ecosystem service multifunctionality, followed by annual average precipitation and temperature. In conclusion, this study suggests that policymakers should strengthen the protection of some high ecological value but low economic value farmlands, which are crucial for regional ecological security. Meanwhile, policymakers should introduce strict ecological protection policies for farmland to reduce the decline of ecological services caused by farmers' pursuit of economic income.

Effect of preoperative oral carbohydrate on the postoperative recovery quality of patients undergoing daytime oral surgery: a randomized controlled trial.

BACKGROUND: Preoperative oral carbohydrate intake can improve the postoperative recovery of fasting patients in many kinds of surgeries; however, the effect of carbohydrates on patients undergoing daytime oral surgery is still unclear. This study was designed to evaluate the effect of preoperative oral carbohydrate intake on the quality of recovery of patients undergoing daytime oral surgery using the quality of recovery-15 (QoR-15) questionnaire. METHODS: Ninety-two patients scheduled for daytime oral surgery were randomly allocated to the midnight fasting group (F group, n = 45) or the carbohydrate-Outfast loading group (O group, n = 47). Participants in the F group fasted from midnight the day before surgery. Patients in the O group also fasted but received the Outfast drink (4 ml/kg) 2-3 h before the induction of anesthesia. QoR-15 questionnaire, patient well-being, and satisfaction were assessed before anesthesia induction and 24 h after surgery. Perioperative blood glucose, postoperative exhaust time, and adverse events were also recorded. RESULTS: The QoR-15 scores were significantly higher in the O group than in the F group preoperatively and postoperatively. Seven parameters representing patient well-being evaluated on a numeric rating scale (NRS, 0-10) were lower in the O group than in the F group postoperatively, except for the hunger and sleep quality scores. Patient satisfaction scores on a 5-point scale were higher in the O group than in the F group preoperatively and postoperatively. Meanwhile, the postoperative exhaust time was significantly shorter in the O group compared to the F group, while there were no significant differences in blood glucose concentrations between two groups. CONCLUSIONS: Preoperative oral carbohydrate intake could improve postoperative recovery quality, well-being, and satisfaction of patients undergoing daytime oral surgery 24 h after surgery, and may serve as a treatment option for patients undergoing daytime oral surgery. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100053753) on 28/11/2021.

ADAM8 promotes alcoholic liver fibrosis through the MAPK signaling pathway.

The effect and molecular regulatory mechanism of A Disintegrin and Metalloproteinase 8 (ADAM8) were explored in alcoholic liver fibrosis (ALF). C57BL/6N male mice were randomly divided into control, alcohol, and ADAM8-sgRNA3 plasmid groups. The control group received control liquid diet, while the alcohol and ADAM8-sgRNA3 plasmid groups were given alcohol liquid feed diet combined with ethanol gavage treatment for 8 weeks to induce ALF modeling. In addition, the ADAM8-sgRNA3 plasmid group was injected with the effective ADAM8-sgRNA3 plasmid, while the alcohol and control group mice were injected with an equivalent amount of physiological saline. LX-2 human hepatic stellate cells were divided into control, alcohol, si-ADAM8-2, and si-ADAM8-NC groups and induced for 48 h for model establishment in vitro. Serological detection, pathological staining, Western blotting, qRT-PCR and CCK8 assay were performed for experiments. Compared with the alcohol group, ADAM8 mRNA, protein and, positive area rate, serological indicators, pathological changes, and the expression of liver fibrosis marker and MAPK signaling pathway-related factors in the ADAM8-sgRNA3 plasmid group significantly decreased in vivo. Compared with the alcohol group, ADAM8 mRNA and protein expression, cell viability, and the expression of liver fibrosis markers and MAPK signaling pathway-related factors (p-ERK1/2, PCNA, Bcl-2, p-c-Jun, TGFß1, p-p38 MAPK and HSP27) reduced significantly in the si-ADAM8-2 group. Therefore, ADAM8 promotes ALF through the MAPK signaling pathway, a promising target for treating ALF.

Nanoswimmers statistical mechanics: Unlocking whole-blood viscosity sensing for tumor microenvironment.

BACKGROUND AND OBJECTIVE: The ability to sense the biological microenvironment surrounding early-stage tumor tissues is critical for tumorigenesis tracing and tumor detection and treatment. An efficient tumor microenvironment (TME) sensing strategy remains a significant challenge. We propose a novel "seeing is sensing" approach that has the potential to discern the whole-blood viscosity (WBV) information of the TME by using a swarm of nanoswimmers (NS). METHODS: In this study, we employ statistical mechanics methods to derive the relationship between the aggregation of NS in the microscale and their macroscopic concentration distribution. We utilize the finite difference method to develop a discrete numerical model of the NS diffusion in the blood. We further develop a novel model for TME sensing that can dynamically detect the WBV by analyzing the kinematic motion of the NS swarm, which enables real-time detection of WBV by observing the Full Width at Half Maximum (FWHM) of the NS swarm motion. RESULTS: The viscosity value obtained with our sensing method is benchmarked against the gold standard results obtained from the Brookfield viscometer. The measurements obtained from both methods exhibit an excellent correlation, with a coefficient of determination (R2) of 0.9617. Furthermore, the constructed Bland-Altman plot reveals that the majority of observed data points lie within the limits of agreement of the 95% clinical confidence interval (lower limit of agreement = -0.0660, upper limit of agreement = 0.1130), thus validating the feasibility of our sensing strategy. CONCLUSIONS: We present a new sensing strategy that utilizes the diffusion dynamics of the NS swarm within the vascular network to infer variations in WBV. Comparative analysis with gold standard data substantiates the accuracy and applicability of this method in assessing WBV parameters in the vicinity of tumor tissues. Our work demonstrates relevant prospects for visualizing, comprehending, and evaluating the pathological progression of blood-related disorders in real-time.

Developmentally controlled subcellular remodeling and VND-initiated vacuole-executed PCD module shape xylem-like cells in peat moss.

Peat moss (Sphagnum) is a non-vascular higher plant with unique xylem-like hyaline (H) cells that are accompanied by photosynthetic chlorophyllous cells. These cellular structures play crucial roles in water storage and carbon sequestration. However, it is largely unknown how peat moss develops the H cells. This study systematically explored the Sphagnum Developmental Cell Atlas and Lineage and classified leaf cell development into two lineages with six stages (S0-S5) based on changes in key cellular traits, including the formation of spiral secondary cell walls (S4) and the presence of water pores (S5). Cell lineage-specific subcellular remodeling was transcriptionally regulated during leaf development, and vacuole-mediated clearance of organelles and cell death led to mature dead H cells. Interestingly, expression of land plant conserved Vascular-related NAC Domain (VND) genes correlated with H cell formation. Overall, these results suggest that the origination of xylem-like H cells is related to VND, likely through the neofunctionalization of vacuole-mediated cell death to attempt xylem formation in peat moss, suggesting potential uncoupling of xylem and phloem cell origins. This study positions peat moss as a potential model organism for studying integrative evolutionary cell biology.

Barrel rifling node offset detection and subsequent optimization based on thin film in-mold decoration characteristics of the Johnson-Cook model.

In this paper, a nodal detection method for the detection and optimization of barrel helix offsets is proposed. The barrel used in this experiment is a 6-helix barrel. Moreover, the special properties of the film of Polyetheretherketone (PEEK) material are used to cover the surface of the barrel helix with a virtual in-mold decoration (IMD) film, and the unique nature of the film die offset in the IMD is utilized to detect the position of the barrel helix. The area with a large die index is the area with a large helix offset in the barrel, and the IMD die index is introduced to quantify the data. The IMD die index is used to determine the helix offset of the damaged barrel. The novelty of this work is that each node can use the die index to efficiently detect the position of the barrel helix deviation, carry out subsequent optimization and repair work through the optimization of the injection molding parameters and the design optimization of the barrel and verify the experiment by comparing the results. Through the steady-state simulation research mode, different permutations and combinations of the two process parameters are simulated to study their effects. Quantitative reference indicators include but are not limited to dependent variables such as the fluid flow velocity, shear rate, temperature distribution and phase transition, and the shear heating process of the injection screw is taken into account in the mold flow analysis to ensure that the die index value is more accurate. It can be seen from the analysis results that the temperature of the barrel changes after the groove depth and groove width are changed, and the effect ratio of the groove depth is lower than that of the groove width in the same degree of size change.

New Hypothesis on Enhancing ß-Sheet Formation during the Tau Fragment Dimer Transition from a Flexible Monomer: Insights into Primary Nucleation Processes by Histidine Behaviors.

Slight perturbations in pH can have significant effects on the primary nucleation processes of the tau protein. The behaviors of histidine due to its pivotal role in modulating H-bonding network interactions and electrostatic interactions have garnered considerable attention, as it can influence the structural characteristics and aggregation properties. However, the nucleation mechanisms and related intermediates are still unclear. In the current study, we performed nine independent replica exchange molecular dynamics simulations to investigate dimer formation involving R3(εδ) in conjunction with the R1, R2, and R4 monomers. Our findings substantiate that, in comparison to R1-R3(εδ) and R4-R3(εδ) systems, the R2-R3(εδ) systems consistently manifest the highest averaged ß-sheet content, with the fundamental feature of R3(εδ) promoting R2 rearrangement. Our comprehensive analysis reveals that high-ß-sheet-rich systems exhibit a conserved three/five ß-strand structure. In these ß-strand-rich systems, one chain [R1/R2/R4 or R3(εδ)] with robust intrachain H-bonding interactions coordinates with another chain through interchain H-bonding interactions, contributing to the overall stability. Furthermore, we discuss distinct histidine behaviors, including backbone/side chain interactions and donor/acceptor roles. This study provides a comprehensive understanding of the aggregation propensities of soluble tau oligomers and sheds light on the primary nucleation mechanism. It contributes to a new perspective for understanding protein folding and misfolding.

Virus-like Particles vaccine based on co-expression of G5 Porcine rotavirus VP2-VP6-VP7 induces a powerful immune protective response in mice.

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65 nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40 µg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

Lapatinib: A Potential Therapeutic Agent for Colon Cancer Targeting Ferroptosis.

BACKGROUND: Colon cancer poses a significant threat to the lives of several patients, impacting their quality of life, thus necessitating its urgent treatment. Lapatinib, a new generation of targeted anti-tumor drugs for clinical application, has yet to be studied for its molecular mechanisms in treating colon cancer. OBJECTIVES: This study aimed to uncover the underlying molecular mechanisms through which lapatinib exerts its therapeutic effects in colon cancer treatment. METHODS: We accessed pertinent data on patients with colon cancer from the Cancer Genome Atlas (TCGA) database and performed bioinformatics analysis to derive valuable insights. The cell counting kit-8 (CCK8) assay was employed to assess whether lapatinib has a potential inhibitory effect on the growth and proliferation of HT- 29 cells. Additionally, we employed western blot and real-time quantitative polymerase chain reaction methods to investigate whether lapatinib regulates the expression of the ferroptosis-associated protein GPX4 in HT-29 cells. Furthermore, we utilized specific assay kits to measure the levels of reactive oxygen species (ROS) and malondialdehyde in HT-29 cells treated with lapatinib, aiming to elucidate the precise pattern of cell damage induced by this compound. RESULTS: GPX4 exhibited high expression levels in tissues from patients with colon cancer and was significantly associated with patient prognosis and diagnosis. Lapatinib inhibited the growth and proliferation of the colon cancer cell line HT-29. Additionally, lapatinib suppressed the expression of GPX4 in HT-29 cells, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially restored its expression. Lapatinib induced an increase in intracellular ROS levels and malondialdehyde content in HT-29 cells, with Fer-1 partially restoring these levels. CONCLUSION: Our findings demonstrated that lapatinib could effectively suppress the mRNA and protein expression of GPX4 in colon cancer cells, which elevates intracellular levels of ROS and malondialdehyde, ultimately inducing ferroptosis in these cells. This mechanism underscores the potential of lapatinib as a therapeutic strategy for targeting tumors.