This study investigates the transport of particles in turbulent channel flow with friction Reynolds number $Re_\tau = 1000$ by direct numerical simulation. We focus on how large-scale flow structures, namely the $Qs$ structures (Lozano-Durán et al. 2012, J. Fluid Mech., vol. 694, pp. 100–130), affect the wall-normal transport of particles. Despite occupying less than $10\,\%$ of the physical domain, our results highlight the critical role played by $Qs$ structures in the particle transport, namely that the particle number and momentum flux inside the $Qs$ structures are substantially higher than outside. The fraction of particle wall-normal momentum flux inside $Qs$ structures is considerably larger than their volume fraction, suggesting highly efficient transport inside the $Qs$ structures. This prominent role played by $Qs$ structures in the transport of inertial particles is more effective by diminishing the inertia of particles. Notably, the long-distance transport of particles in the wall-normal direction is driven primarily by the continuous effect of $Qs$ structures. In summary, our findings advance the understanding of the effects of $Qs$ structures on particle transport, and demonstrate their significant role in the process.

Overnutrition during before and pregnancy can cause maternal obesity and raise the risk of maternal metabolic diseases during pregnancy, and in offspring. Lentinus edodes may prevent or reduce obesity. This study aimed to to assess Lentinus edodes fermented products effects on insulin sensitivity, glucose and lipid metabolism in maternal and offspring, and explore its action mechanism. A model of overnutrition during pregnancy and lactation was developed using a 60 % kcal high-fat diet in C57BL6/J female mice. Fermented Lentinus edodes (FLE) was added to the diet at concentrations of 1 %, 3 %, and 5 %. The results demonstrated that FLE to the gestation diet significantly reduced serum insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant mice. FLE can regulate maternal lipid metabolism and reduce fat deposition. Meanwhile, the hepatic phosphoinositide-3-kinase-protein kinase (PI3K/AKT) signaling pathway was significantly activated in the maternal mice. There is a significant negative correlation between maternal FLE supplementation doses and offspring body fat percentage and visceral fat content. Furthermore, FLE supplementation significantly increased offspring weaning litter weight, significantly reduced fasting glucose level, serum insulin level, HOMA-IR and serum glucose level, significantly activated liver PI3K/AKT signaling pathway in offspring, and upregulated the expression of liver lipolytic genes adipose triglyceride lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1 mRNA. Overall, FLE supplementation can regulate maternal lipid metabolism and reduce fat deposition during pregnancy and lactation, and it may improve insulin sensitivity in pregnant mothers and offspring at weaning through activation of the PI3K/AKT signaling pathway.

The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane, leading to cartilage destruction and bone erosion. Due to the complex pathogenesis of RA and the limitations of current therapies, increasing research attention has been directed towards novel strategies targeting fibroblast-like synoviocytes (FLS), which are key cellular components of the hyperplastic pannus. Recent studies have highlighted the pivotal role of FLS in the initiation and progression of RA, driven by their tumour-like transformation and the secretion of pro-inflammatory mediators, including cytokines, chemokines and matrix metalloproteinases. The aggressive phenotype of RA-FLS is marked by excessive proliferation, resistance to apoptosis, and enhanced migratory and invasive capacities. Consequently, FLS-targeted therapies represent a promising avenue for the development of next-generation RA treatments. The efficacy of such strategies – particularly those aimed at modulating FLS signalling pathways – has been demonstrated in both preclinical and clinical settings, underscoring their therapeutic potential. This review provides an updated overview of the pathogenic mechanisms and functional roles of FLS in RA, with a focus on critical signalling pathways under investigation, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), Notch and interleukin-1 receptor-associated kinase 4 (IRAK4). In addition, we discuss the emerging understanding of FLS-subset-specific contributions to immunometabolism and explore how computational biology is shaping novel targeted therapeutic strategies. A deeper understanding of the molecular and functional heterogeneity of FLS may pave the way for more effective and precise therapeutic interventions in RA.

Understanding the vertical coherence of the pressure structure and its interaction with velocity fields is critical for elucidating the mechanisms of acoustic generation and radiation in hypersonic turbulent boundary layers. This study employs linear coherence analysis to examine the self-similar coherent structures in the velocity and pressure fields within a Mach 6 hypersonic boundary layer, considering a range of wall-to-recovery temperature ratios. The influence of wall cooling on the geometric characteristics of these structures, such as inclination angles and three-dimensional aspect ratios, is evaluated. Specifically, the streamwise velocity exhibits self-similar coherent structures with the streamwise/wall-normal aspect ratio ranging from 16.5 to 38.7, showing a linear increases with decreasing wall temperatures. Similar linear dependence between the streamwise/wall-normal aspect ratio and the wall temperatures are observed for the Helmholtz-decomposed streamwise velocity and the pressure field. In terms of velocity–pressure coupling, the solenoidal component exhibits stronger interactions with the pressure fields in the near-wall region, while the dilatational component has stronger interactions with the pressure field at large scales with the increase of height. Such coupling generally follows the distance-from-the-wall scaling of the pressure field, except in cooled wall cases. Using the linear stochastic estimation, the pressure field across the boundary layer is predicted by inputting the near-wall pressure/velocity signal along with the transfer kernel. The result demonstrates that near-wall pressure signals provide the most accurate description of the pressure field in higher regions of the boundary layer. As wall-mounted sensors can measure near-wall pressure fluctuations, this study presents a potential approach to predict the off-wall pressure field correlated with the near-wall structures based on wall-pressure measurements.

This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.

MicroRNAs (miRNAs) play important roles in regulating salt tolerance in Dongxiang wild rice (DXWR, Oryza rufipogon Griff.). The development of salt-responsive miRNA-simple sequence repeat (SSR) markers will significantly bolster research on DXWR, providing novel tools for exploring salt-tolerant genetic resources and advancing the development of salt-tolerant rice varieties. In the present study, a total of 137 miRNA-SSR markers were successfully developed, specifically derived from miRNAs responsive to salt stress in DXWR. Subsequently, a subset of 20 markers was randomly selected for validation across three distinct DXWR populations, along with 35 modern rice varieties. Notably, 13 of these markers exhibited remarkable polymorphism. The polymorphic markers collectively amplified 52 SSR loci, averaging four alleles per locus. The polymorphism information content values associated with these loci spanned from 0.23 to 0.70, with a mean value of 0.49. Particularly noteworthy is the miR162a-SSR marker, which demonstrated distinct allelic patterns and holds potential as a diagnostic marker for discriminating the salt-tolerant rice varieties from the non-tolerant varieties. This study provides a valuable tool for genetic analysis and precision breeding, facilitating the identification and utilization of valuable salt-tolerant genetic resources.

We demonstrate efficient and economical all-solid-state post-compression based on dual-stage periodically placed thin fused silica plates driven by a more than 100 W ytterbium-doped yttrium aluminum garnet Innoslab amplifier seeded by a fiber frontend. Not only is a more than eight-fold pulse compression with 94% transmission achieved, but also the pulse quality and spatial mode are improved, which can be attributed to the compensation for the residual high-order dispersion and the spatial mode self-cleaning effect during the nonlinear process. It enables a high-power ultrafast laser source with 64 fs pulse duration, 96 W average power at 175 kHz repetition rates and good spatiotemporal quality. These results highlight that this all-solid-state post-compression can overcome the bandwidth limitation of Yb-based lasers with exceptional efficiency and mitigate the spatiotemporal degradation originating from the Innoslab amplifier and fiber frontend, which provides an efficient and economical complement for the Innoslab laser system and facilitates this robust and compact combination as a promising scheme for high-quality higher-power few-cycle laser generation.

Based on a contingent valuation method survey on air quality improvement in northern China, we construct several subjective perception determinants of respondents' valuation uncertainty from both the demand and perceived supply sides. Using the individual-level uncertainty measurements initially proposed by Wang and He (2011) and their alternative transformations, we analyze how these factors of demand and perceived supply sides affect people's valuation uncertainty. Our results demonstrate the significant contribution of these determinants in explaining respondents' uncertainty. On the demand side, people who ‘don't know much’ about benefits-related factors have the highest level of uncertainty, and those claiming to ‘know nothing’ most often report the lowest level of uncertainty. On the supply side, people who either do not trust or are not satisfied with the control policies tend to be more certain of their valuation. The subsequent analyses also suggest that these results be interpreted as negative certainty, which is attributed to a lack of interest.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

OBJECTIVES/GOALS: The 'field effect' is a concept in pathology that pre-malignant tissue changes forecast health. Spatial transcriptomics could detect these changes earlier than histopathology, suggesting new early cancer screening methods. Knowing how normal tissue damage relates to cancer’s origin and progression may improve long-term outcomes. METHODS/STUDY POPULATION: We trained DEGAS, our machine learning framework, with prostate cancer data, combining both general cancer patterns and in-depth genetic information from individual tumors. The Tumor Cancer Genome Atlas (TCGA) shows how gene patterns in tumors relate to patient outcomes, emphasizing the differences between tumors from different patients (intertumor). On the other hand, spatial transcriptomics (ST) shows the genetic variety within a single tumor (intratumor) but has limited samples, making it hard to know which genetic differences are important for treatment. DEGAS bridges these areas by finding tissue sections that resemble those in TCGA profiles and are key indicators of patient survival. DEGAS serves as a valuable tool for generating clinically-important hypotheses. RESULTS/ANTICIPATED RESULTS: DEGAS identified benign-appearing glands in a normal prostate as being highly associated with poor progression-free survival. These glands have transcriptional signatures similar to high-grade prostate cancer. We confirmed this finding in a separate prostate cancer ST dataset. By integrating single cell (SC) data we demonstrated that cells annotated as cancerous in the SC data map to regions of benign glands in the ST dataset. We pinpoint several genes, chiefly Microseminoprotein-β (MSMB, PSP94), where reduced expression is highly correlated with poor progression-free survival. Cell type specific differential expression analysis further revealed that loss of MSMB expression associated with poor outcomes occurs specifically in luminal epithelia, the putative progenitor of prostate cancer. DISCUSSION/SIGNIFICANCE: DEGAS reveals that normal-appearing tissue can be highly-associated with tumor progression and underscores the importance of the 'field effect' in cancer research. Traditional analysis may miss such nuance, hiding key transitional cell states. Validating gene markers could boost early cancer detection and understanding of metastasis.

During the early stages of human pregnancy, successful implantation of embryonic trophoblast cells into the endometrium depends on good communication between trophoblast cells and the endometrium. Abnormal trophoblast cell function can cause embryo implantation failure. In this study, we added cyclosporine A (CsA) to the culture medium to observe the effect of CsA on embryonic trophoblast cells and the related mechanism. We observed that CsA promoted the migration and invasion of embryonic trophoblast cells. CsA promoted the expression of leukaemic inhibitory factor (LIF) and fibroblast growth factor (FGF). In addition, CsA promoted the secretion and volume increase in vesicles in the CsA-treated group compared with the control group. Therefore, CsA may promote the adhesion and invasion of trophoblast cells through LIF and FGF and promote the vesicle dynamic process, which is conducive to embryo implantation.

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

OBJECTIVES/GOALS: Single-cell and spatial transcriptomics have revealed high heterogeneity in the tumor and microenvironment. Identifying populations of cells that impact a patient’s prognosis is an important research goal, so researchers can generate hypotheses and clinicians can provide targeted treatment. METHODS/STUDY POPULATION: DEGAS uses deep-transfer-learning to identify patterns between patient tumor RNA-seq and clinical outcomes and map these associations on to higher-resolution data like spatial and single-cell transcriptomics. We apply DEGAS to prostate and pancreatic cancer spatial transcriptomics samples, as well as one normal sample of prostate tissue. We used the TCGA prostate cancer cohort to with the accompanying survival information and publicly accessible prostate cancer ST data from 10X Genomics to predict survival associations in the ST slides derived from the TCGA patients. Based on these survival associations, we identify higher risk subsections of ST slides which can be further studied. RESULTS/ANTICIPATED RESULTS: We were able to validate our method by comparing it to Scissor and were able to show that the number of high-risk regions in prostate cancer slides increased with the stage of disease. Furthermore, we identify transcriptomic signatures enriched for ontology terms associated with growth regulation and apoptosis, inflammation, immune signaling, and autophagy in histologically normal prostate tissues and adjacent normal pancreatic cancer tissues that were identified as high-risk by DEGAS. The regions highlighted by DEGAS could reflect transcriptional precursors to intraepithelial neoplasia–a well-recognized premalignant morphological change in glandular epithelium. DISCUSSION/SIGNIFICANCE: Identifying biomarkers of tissue stress that precede morphologic diagnosis of high-grade pre-malignant lesions by a pathologist may help triage patients at high risk for future development of cancer, or aid in better understanding whether histologically normal pre-malignant tissues at tumor margins contribute to recurrence.