Fibroblast growth factor 3 promotes spontaneous mammary tumorigenesis in Tientsin albino 2 mice via the FGF3/FGFR1/STAT3 pathway

IntroductionTientsin albino 2 (TA2) mice can develop spontaneous breast cancer (SBC), which is associated with multiple pregnancies and infection with the mouse mammary tumor virus (MMTV). In this study, we sought to elucidate the molecular mechanisms underlying the development of SBC in TA2 mice induced by MMTV.MethodsThe integration site of MMTV in TA2 SBC was identified using whole-genome sequencing. The expression of fibroblast growth factor 3 (FGF3) in SBCs and normal breast tissues was compared. The primary cell line, TA-1106, derived from SBC, was cultured. The proliferation, cell cycle, migration, invasion, and tumorigenicity abilities, as well as the expression of epithelial-mesenchymal transition-related proteins, phosphorylated STAT3, and phosphorylated Akt, were assessed in MA-891cell line from TA2 and TA-1106 cells after FGF3 knockdown. The binding of FGF3 to FGF receptor 1 (FGFR1) was determined by co-immunoprecipitation. Additionally, the relationship between STAT3 and Akt phosphorylation was investigated using a small molecule inhibitor and STAT3 knockdown.ResultsMMTV integrated upstream of the FGF3 gene, and the FGF3 protein was highly expressed in TA2 SBCs. FGF3 knockdown in MA-891 and TA-1106 decreased their proliferation, migration, and invasion abilities, affected the cell cycle and expression of epithelial-mesenchymal transition-related proteins, and inhibited the growth of animal xenografts. FGF3 binds to FGFR1, and either FGF3 or FGFR1 knockdown decreases STAT3 and Akt phosphorylation levels. Inhibition of phosphorylation or expression of STAT3 resulted in decreased Akt phosphorylation levels. Inhibition of Akt phosphorylation also resulted in decreased STAT3 phosphorylation levels. Furthermore, treatment of MA-891 and TA-1106 cells with Wortmannin or Stattic caused FGFR1 upregulation in addition to inhibiting Akt or STAT3 phosphorylation.ConclusionThe results of this study demonstrate that FGF3 plays a significant role in the development of SBC through the FGF3/FGFR1/STAT3 signaling pathway. There is a reciprocal activation between STAT3 and Akt. Inhibition of STAT3 or Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions obtained in this study in human breast cancer (HBC) may contribute to targeted therapy and it is worth exploring whether the homologous sequences of MMTV in HBC have a similar oncogenic effect

An improved YOLO v4 used for grape detection in unstructured environment

Visual recognition is the most critical function of a harvesting robot, and the accuracy of the harvesting action is based on the performance of visual recognition. However, unstructured environment, such as severe occlusion, fruits overlap, illumination changes, complex backgrounds, and even heavy fog weather, pose series of serious challenges to the detection accuracy of the recognition algorithm. Hence, this paper proposes an improved YOLO v4 model, called YOLO v4+, to cope with the challenges brought by unstructured environment. The output of each Resblock_body in the backbone is processed using a simple, parameterless attention mechanism for full dimensional refinement of extracted features. Further, in order to alleviate the problem of feature information loss, a multi scale feature fusion module with fusion weight and jump connection structure was pro-posed. In addition, the focal loss function is adopted and the hyperparameters α, γ are adjusted to 0.75 and 2. The experimental results show that the average precision of the YOLO v4+ model is 94.25% and the F1 score is 93%, which is 3.35% and 3% higher than the original YOLO v4 respectively. Compared with several state-of-the-art detection models, YOLO v4+ not only has the highest comprehensive ability, but also has better generalization ability. Selecting the corresponding augmentation method for specific working condition can greatly improve the model detection accuracy. Applying the proposed method to harvesting robots may enhance the applicability and robustness of the robotic system

Bubble in the Whale: Identifying the Optical Counterparts and Extended Nebula for the Ultraluminous X-ray Sources in NGC 4631

We present a deep optical imaging campaign on the starburst galaxy NGC 4631 with CFHT/MegaCam. By supplementing the HST/ACS and Chandra/ACIS archival data, we search for the optical counterpart candidates of the five brightest X-ray sources in this galaxy, four of which are identified as ultraluminous X-ray sources (ULXs). The stellar environments of the X-ray sources are analyzed using the extinction-corrected color-magnitude diagrams and the isochrone models. We discover a highly asymmetric bubble nebula around X4 which exhibits different morphology in the H$\alpha$ and [O III] images. The [O III]/H$\alpha$ ratio map shows that the H$\alpha$-bright bubble may be formed mainly via the shock ionization by the one-sided jet/outflow, while the more compact [O III] structure is photoionized by the ULX. We constrain the bubble expansion velocity and interstellar medium density with the MAPPINGS V code, and hence estimate the mechanical power injected to the bubble as $P_w \sim 5\times10^{40}$ erg s$^{-1}$ and the corresponding bubble age of $\sim7\times 10^{5}$ yr. Relativistic jets are needed to provide such level of mechanical power with a mass-loss rate of $\sim10^{-7}\ M_{\odot}\ \rm yr^{-1}$. Besides the accretion, the black hole spin is likely an additional energy source for the super-Eddington jet power.Comment: 17 pages, 10 figures, accepted by Ap

The Mass-Metallicity Relation of Dwarf Galaxies at the Cosmic Noon in the JWST Era

We present the mass-metallicity relation (MZR) at $z=2-3$ in the stellar mass range of $M_\star\approx 10^{6.5}-10^{9.5}M_\odot$ using 55 dwarf galaxies in the Abell 2744 and SMACS J0723-3732 galaxy cluster fields. These dwarf galaxies are identified and confirmed by deep JWST/NIRISS imaging and slitless grism spectroscopic observations. Taking advantage of the gravitational lensing effect, we extend the previous MZR relation at $z=2-3$ to a much lower mass regime by more than 2.5 orders of magnitude compared with previous studies. We find that the MZR has a shallower slope at the low-mass end ($M_\star<10^{9}M_\odot$) compared to that at the high-mass end ($M_\star>10^{9}M_\odot$), with a slope turnover point at around the stellar mass of $10^9 M_\odot$. This implies that dominating feedback processes in dwarf galaxies may be different from that in galaxies with higher mass. From $z=3$ to $z=2$, the metallicity of the dwarf galaxies is enhanced by $\approx0.1$ dex for a given stellar mass, consistent with the mild evolution found in galaxies with higher mass. Further, we confirm the existence of a 3D relation between the gas-phase metallicity, stellar mass, and star formation rate, i.e., fundamental metallicity relation (FMR), in dwarf galaxies at $z=2-3$. Our derived FMR, which has no significant redshift evolution, can be used as a benchmark to understand the origin of the anti-correlation between SFR and metallicity of dwarf galaxies in the high-redshift Universe.Comment: 16 pages, 4 figures, 1 table, submitted to AAS Journal; welcome comment

Searching for C ii Emission from the First Sample of z ∼ 6 O i Absorption-associated Galaxies with the Atacama Large Millimeter/submillimeter Array

We report the first statistical analyses of [C ii ] and dust continuum observations in six strong O i absorber fields at the end of the reionization epoch obtained by the Atacama Large Millimeter/submillimeter Array (ALMA). Combined with one [C ii ] emitter reported in Wu et al., we detect one O i -associated [C ii ] emitter in six fields. At redshifts of O i absorbers in nondetection fields, no emitters are brighter than our detection limit within impact parameters of 50 kpc and velocity offsets between ±200 km s ^−1 . The averaged [C ii ]-detection upper limit is 50 kpc) and having larger outflow velocities within ±600 km s ^−1 . If these detections are confirmed in the future, then the mechanism of pushing metals at larger distances with higher velocities needs to be further explored from the theoretical side

Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer

BACKGROUND: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. METHODS: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. RESULTS: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. CONCLUSIONS: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC

Acetylated-PPARγ expression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells

Objective: Polyploid giant cancer cells (PGCCs) with daughter cells express epithelial–mesenchymal transition (EMT)-associated proteins. Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells. In this study, we elucidated the potential for, and underlying mechanism of, adipogenic differentiation of PGCCs with daughter cells (PDCs). Methods: Cobalt chloride was used to induce PGCC formation in HEY (wild-type P53) and MDA-MB-231 (mutant P53) cells; these cells were then cultured in adipogenic differentiation medium. Oil red O staining was used to confirm adipogenic differentiation, and the cell cycle was detected with flow cytometry. The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation. Animal xenograft models were used to confirm the adipogenic differentiation of PDCs. Results: PDCs transdifferentiated into functional adipocytes. Two different cell cycle distributions were observed in PDCs after adipogenic differentiation. The expression levels of PPARγ, Ace-PPARγ, and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation. Ace-PPARγ and FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown. A485 treatment increased Ace-P53, Ace-PPARγ, and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53. In MDA-MB-231 PDCs, A485 treatment decreased Ace-P53, Ace-PPARγ, and FABP4 expression. Animal experiments also confirmed the adipogenic differentiation of PDCs. Conclusions: Acetylation of P53 and PPARγ plays an important role in the adipogenic differentiation of PDCs

Design and modeling analysis of a changeable stiffness robotic leg working with magnetorheological technology

Since animals can adjust the stiffness of their bodies and/or appendages to adapt to changing environments and internal states and tasks, a robotic leg with changeable stiffness would be of assistance in developing mobile terrestrial robots. In this article, we present an improved model of a robotic leg that can alter its stiffness in real time by changing the characteristics of magnetorheological fluid. This particular robotic leg has a changeable stiffness module, which consists of a rotating magnetorheological fluid damper, a torsional spring, and a linear spring. The rotary magnetorheological fluid damper is used to control the deformation of a torsional spring, which alters the stiffness of the leg. To describe the mechanical features of the leg, a simplified mechanical model was built and then various experiments were carried out to verify the changeable stiffness characteristics. The simulation experiments of dual-leg locomotion were carried out to investigate the locomotive performance, including walking speed, maximum torque of motor, height variants, and mechanical cost of transport. These results demonstrate the adaptability and advantages of this changeable stiffness robotic leg and also indicated that developing a terrestrial robot which can adapt to various complex environments and tasks would be a worthwhile exercise

The Applicability of the Drought Index and Analysis of Spatiotemporal Evolution Mechanisms of Drought in the Poyang Lake Basin

Poyang Lake, the largest freshwater lake in China, is an important regional water resource and a landmark ecosystem. In recent years, it has experienced a period of prolonged drought. Using appropriate drought indices to describe the drought characteristics of the Poyang Lake Basin (PLB) is of great practical significance in the face of severe drought situations. This article explores the applicability of four drought indices (including the precipitation anomaly index (PJP), standardized precipitation index (SPI), China Z-index (CPZI), and standardized precipitation evapotranspiration index (SPEI)) based on historical facts. A systematic study was conducted on the spatiotemporal evolution patterns of meteorological drought in the PLB based on the optimal drought index. The results show that SPI is more suitable for the description of drought characteristics in the PLB. Meteorological droughts occur frequently in the summer and autumn in the PLB, with the frequency of mild drought being 17.29% and 16.88%, respectively. The impact range of severe drought or worse reached 22.19% and 28.33% of the entire basin, respectively. The probability of drought occurrence in the PLB shows an increasing trend in spring, while in most areas, it shows a decreasing trend in other seasons, with only a slight increase in the upper reaches of the Ganjiang River (UGR). One of the important factors influencing drought in the PLB is atmospheric circulation. The abnormal variation of the Western Pacific Subtropical High was one of the key factors contributing to the severe drought in the PLB in 2022. This study is based on a long-term series of meteorological data and selects the drought index for the PLB. It describes the spatiotemporal distribution characteristics and evolution patterns of drought and investigates the developmental path and influencing factors of drought in typical years. This study provides a reliable scientific basis for similar watershed water resource management

The Function of SUMOylation and Its Role in the Development of Cancer Cells under Stress Conditions: A Systematic Review

Malignant tumors still pose serious threats to human health due to their high morbidity and mortality. Recurrence and metastasis are the most important factors affecting patient prognosis. Chemotherapeutic drugs and radiation used to treat these tumors mainly interfere with tumor metabolism, destroy DNA integrity, and inhibit protein synthesis. The upregulation of small ubiquitin-like modifier (SUMO) is a prevalent posttranslational modification (PTM) in various cancers and plays a critical role in tumor development. The dysregulation of SUMOylation can protect cancer cells from stresses exerted by external or internal stimuli. SUMOylation is a dynamic process finely regulated by SUMOylation enzymes and proteases to maintain a balance between SUMOylation and deSUMOylation. An increasing number of studies have reported that SUMOylation imbalance may contribute to cancer development, including metastasis, angiogenesis, invasion, and proliferation. High level of SUMOylation is required for cancer cells to survive internal or external stresses. Downregulation of SUMOylation may inhibit the development of cancer, making it an important potential clinical therapeutic target. Some studies have already begun to treat tumors by inhibiting the expression of SUMOylation family members, including SUMO E1 or E2. The tumor cells become more aggressive under internal and external stresses. The prevention of tumor development, metastasis, recurrence, and radiochemotherapy resistance by attenuating SUMOylation requires further exploration. This review focused on SUMOylation in tumor cells to discuss its effects on tumor suppressor proteins and oncoproteins as well as classical tumor pathways to identify new insights for cancer clinical therapy