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Gastric cancer (GC) is a prevalent digestive tract malignancy, and Huangqi Fuling decoction (HF) has shown potential in enhancing immune function and exhibiting anti-GC activity. However, its mechanisms remain unclear. This study utilized network pharmacology, molecular docking, and in vitro experiments to preliminarily explore the mechanisms by which HF inhibits gastric cancer invasion and metastasis while promoting apoptosis. Public databases identified differentially expressed genes (DEGs), HF targets, and GC-related genes. GO and KEGG analyses revealed signaling pathways. Clinical relevance, immune infiltration, immunotherapy, and molecular docking of hub genes were analyzed. Eight hub genes-PTGS2, MMP9, SELE, CCL2, VCAM1, ICAM1, CXCL2, and CXCL10-associated with the TNF signaling pathway were identified. HF inhibits the invasion and metastasis of GC cells by down-regulating MMP9 and PTGS2 expression, while inducing apoptosis by suppressing BCL-2 expression and promoting BAX expression. Additionally, HF can arrest the cell cycle, blocking AGS cells in the S phase and HGC-27 cells in the G0/G1 phase. This study confirms that HF promotes apoptosis and inhibits metastasis and invasion in GC cells, primarily by modulating the TNF signaling pathway. Additionally, the anti-tumor effects of HF on GC may involve immune regulatory mechanisms, but the mechanism require further experimental verification.

Background Owing to the complexity of TME components and the heterogeneity of cancer cells, the relationship between the niches of TME and prognosis in breast ductal carcinoma remains unknown. The staged characteristics of corresponding cancer cell behaviors are unclear. Our study aims to reveal spatial structures and specific cellular information of TME and cancer cells subgroups during the progression from DCIS to IDC and lymph node metastasis. Methods Single-cell sequencing, spatial transcriptomics, bulk RNA sequencing datasets were used to explore the changes in microenvironmental components and transcriptional programs of tumor cells during the progression of breast ductal carcinoma. Immunohistochemistry, multiplex immunofluorescence, flow cytometry cell cycle detection, invasion migration experiments, and WB imprinting were employed for validation. Results Analysis of TME cell type subsets revealed the accumulation of T EX , iTreg, and stress-phenotype TAM in the mammary gland in situ during the invasion process. Lymphatic metastases exhibited enrichment of nTregs and a more naïve-like CD8 T cell population. Spatial analysis and survival analysis showed that the spatial niches of CD4 T N and phagocytic-phenotype macrophages were associated with a favorable prognosis, and these niches were lost during disease progression. The proliferative subpopulation of breast ductal carcinoma was enriched in lymphatic metastatic tissues, expressing high levels of FAM111B and exhibiting intense TCA and oxidative phosphorylation metabolism. Silencing FAM111B led to cell cycle arrest, decreased invasion and migration abilities, and downregulation of core mediator genes for cuproptosis and disulfidptosis. Conclusions The stage-specific microenvironmental characteristics of breast ductal carcinoma correspond to some extent to the behavior of tumor cells. During the progression of ductal carcinoma in breast tissue, the establishment of an immunosuppressive microenvironment occurs. The microenvironmental spectrum at lymph node metastases differs somewhat, corresponding to a more enriched turnover of cancer cell proliferation and death. Inhibitors of FAM111B and inducers of cuproptosis and disulfidptosis may serve as potential therapeutic targets for proliferative subgroups.

Femtosecond-laser-assisted material restructuring employs extreme optical intensities to localize the ablation regions. To overcome the minimum feature size limit set by the wave nature of photons, there is a need for new approaches to tailored material processing at the nanoscale. Here, we report the formation of deeply-subwavelength features in silicon, enabled by localized laser-induced phase explosions in prefabricated silicon resonators. Using short trains of mid-infrared laser pulses, we demonstrate the controllable formation of high aspect ratio (>10:1) nanotrenches as narrow as ~ λ / 80 . The trench geometry is shown to be scalable with wavelength, and controlled by multiple parameters of the laser pulse train, such as the intensity and polarization of each laser pulse and their total number. Particle-in-cell simulations reveal localized heating of silicon beyond its boiling point and suggest its subsequent phase explosion on the nanoscale commensurate with the experimental data. The observed femtosecond-laser assisted nanostructuring of engineered microstructures (FLANEM) expands the nanofabrication toolbox and opens exciting opportunities for high-throughput optical methods of nanoscale structuring of solid materials. Laser machining can modify and reshape materials on the scale comparable to light’s wavelength. Here, authors use tailored microstructures to push the limit of laser machining to a scale that is almost 100 times smaller than a wavelength of light.

Residential land is the basic unit of urban-scale carbon emissions (CEs). Quantifying and predicting CEs from residential land are conducive to achieving urban carbon neutrality. This study took 84 residential communities in Susong County, Anhui Province as its research object, exploring the nonlinear relationship between the urban built environment and CEs from residential land. By identifying CEs from residential land through building electricity consumption, 14 built environment indicators, including land area (LA), floor area ratio (FAR), greening ratio (GA), building density (BD), gross floor area (GFA), land use mix rate (Phh), and permanent population density (PPD), were selected to establish an interpretable machine learning (ML) model based on the XGBoost-SHAP attribution analysis framework. The research results show that, first, the goodness of fit of the XGBoost model reached 91.9%, and its prediction accuracy was better than that of gradient boosting decision tree (GBDT), random forest (RF), the Adaboost model, and the traditional logistic model. Second, compared with other ML models, the XGBoost-SHAP model explained the influencing factors of CEs from residential land more clearly. The SHAP attribution analysis results indicate that BD, FAR, and Phh were the most important factors affecting CEs. Third, there was a significant nonlinear relationship and threshold effect between built environment characteristic variables and CEs from residential land. Fourth, there was an interaction between different dimensions of environmental factors, and BD, FAR, and Phh played a dominant role in the interaction. Reducing FAR is considered to be an effective CE reduction strategy. This research provides practical suggestions for urban planners on reducing CEs from residential land, which has important policy implications and practical significance.

The chirped pulse amplification technique has enabled the generation of pulses of a few femtosecond duration with peak powers multi-Tera and Peta–Watt in the near infrared. Its implementation to realize even shorter pulse duration, higher energy, and higher repetition rate laser systems relies on overcoming the limitations imposed by laser damage of critical components. In particular, the laser damage of coatings in the amplifiers and in post-compression optics have become a bottleneck. The robustness of optical coatings is typically evaluated numerically through steady-state simulations of electric field enhancement in multilayer stacks. However, this approach cannot capture crucial characteristics of femtosecond laser induced damage (LID), as it only considers the geometry of the multilayer stack and the optical properties of the materials composing the stack. This approach neglects that in the interaction of an ultrashort pulse and the materials there is plasma generation and associated material modifications. Here, we present a numerical approach to estimate the LID threshold of dielectric multilayer coatings based on strong field electronic dynamics. In this dynamic scheme, the electric field propagation, photoionization, impact ionization, and electron heating are incorporated through a finite-difference time-domain algorithm. We applied our method to simulate the LID threshold of bulk fused silica, and of multilayer dielectric mirrors and gratings. The results are then compared with experimental measurements. The salient aspects of our model, such as the implementation of the Keldysh photoionization model, the impact ionization model, the electron collision model for ‘low’-temperature, dense plasma, and the LID threshold criterion for few-cycle pulses are discussed.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics. Here the authors report that the yeast ubiquitin E3 ligase Bre1 and its human homolog RNF20 function as recombination mediator proteins by promoting Rad51-ssDNA assembly, Rad51 replacement of ssDNA-bound RPA while antagonizing the activities of Srs2 or FBH1 anti-recombinase.

Background Mild fetal ventriculomegaly (VM) is a nonspecific finding common to several pathologies with varying prognosis and is, therefore, a challenge in fetal consultation. We aimed to perform a constant, detailed analysis of prenatal findings and postnatal outcomes in fetuses with early-onset and late-onset mild ventriculomegaly, and provide a new evidence basis and new perspective for prenatal counseling. Methods This is a retrospective cohort study of women with a diagnosis of mild fetal VM between January 2018 and October 2020. The population was divided into two groups according to the gestational ages (GAs) at initial diagnosis: the early-onset group (diagnosed at/before 24 +6  weeks) and the late-onset group (diagnosed after 24 +6  weeks). Clinical data and pregnancy outcomes were obtained from hospital records. The children’s neurodevelopment status was assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and telephone interviews. Results Our study cohort comprised 324 fetuses, out of which 94 (29%) were classified as early-onset group and 230 (71%) late-onset group. Early-onset group was more likely to have concurrent additional abnormalities, whereas in the late-onset group, isolated enlargement was more common ( P  = 0.01). Unilateral enlargement was more common in the late-onset group ( P  = 0.05), and symmetrical enlargement in the early-onset group ( P  < 0.01). In addition, early-onset mild VM cases were more likely to have intrauterine progression ( P  = 0.03), and many had a higher proportion of complex multisystem abnormalities. Compared with the late-onset group, the early-onset group was more often associated with congenital brain structure malformations. Approximately 11% of fetuses with mild VM had postnatal neurodevelopmental delay/disorders, and the risk was higher in the early-onset group (19.4% vs. 7.4%). Regression analysis showed that the GA at first diagnosis, non-isolated, and intrauterine progression significantly correlated with neurodevelopmental abnormalities. Conclusions Early-onset and late-onset mild VM had significantly different ultrasound features and outcomes. Early-onset mild VM may have more complex potential abnormalities and are more likely to predict poor prognosis than the late-onset.