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Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I–II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan–Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer.

IntroductionParticipating in multiple competing brand communities simultaneously is common for consumers, which brings challenges for companies to manage brand communities and build strong brand-consumer relationships. Although previous studies have widely examined the drivers and outcomes of consumers’ engagement in an individual community, little is known about the multi-competing brand community engagement.MethodsThis paper explores the manifestation, categories, motivational drivers, and consequences of consumers’ MBCE through two studies using two different methodologies to fill this gap.ResultsBy using netnography, study 1 shows that MBCE behaviors manifest in various ways, and can be classified into three categories: information-oriented MBCE, social-oriented MBCE, and oppositional MBCE. Study 2 indicates through a consumer survey that one reason that motivates consumers to participate in other competing brand communities is because of the attractiveness of other competing brands. Also, the results indicate that consumers’ product knowledge is positively associated with MBCE. Finally, the number of competing brand community engagements is positively related to brand switching intention.DiscussionThis article enriches the brand community literature and provides important implications on managing brand communities in a competing environment.

Abstract Background Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes. Results In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. Conclusions These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS. Graphical Abstract

Abstract Background HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear. Methods HOMER3 expression was examined by immunohistochemistry in breast cancer patient specimens, and its significance in prognosis was assessed by Kaplan–Meier survival analysis. The effects of HOMER3 in growth factor-induced β-Catenin activation were analyzed by assays such as TOP/FOP flash reporter, tyrosine phosphorylation assay and reciprocal immunoprecipitation (IP) assay. Role of HOMER3 in breast cancer metastasis was determined by cell function assays and mice tumor models. Results Herein, we find that, among the three HOMER proteins, HOMER3 is selectively overexpressed in the most aggressive triple negative breast cancer (TNBC) subtype, and significantly correlates with earlier tumor metastasis and shorter patient survival. Mechanismly, HOMER3 interacts with both c-Src and β-Catenin, thus providing a scaffolding platform to facilitate c-Src-induced β-Catenin tyrosine phosphorylation under growth factor stimulation. HOMER3 promotes β-Catenin nuclear translocation and activation, and this axis is clinically relevant. HOMER3 promotes and is essential for EGF-induced aggressiveness and metastasis of TNBC cells both in vitro and in vivo. Conclusion These findings identify a novel role of HOMER3 in the transduction of growth factor-mediated β-Catenin activation and suggest that HOMER3 might be a targetable vulnerability of TNBC.

Abstract Soil–Water characteristic Curve (SWCC) is meant to describe the mechanical behavior of unsaturated soil. The present paper focuses on the internal multi-scale microstructure of Xining untreated loess and lime-treated loess with the use of scanning electron microscopy (SEM) and image processing technique. A new SWCC model was presented based on the fractal dimension of pore size distribution. The SWCC of untreated loess was calculated from fractal dimension and fitted well with curve tested from Fredlund SWCC device. The SWCC of lime-treated loess was then calculated. Two curves of Xining untreated loess and lime-treated loess have been compared and reasons for the difference have also been discussed. The results indicate that the content of large pores in lime-treated loess decreased and the content of micro-pore increased. The bracket pores were changed into cement pores. The pore fractal dimension D of Xining untreated loess is 1.39 and the pore fractal dimension D of Xining lime-treated loess is 1.53. Air-entry value of untreated loess is 12.16 kPa, while lime-treated Loess—35.15 kPa. In transition region, matric suction of lime-treated loess was in the range of 35.15 kPa ~ 4000 kPa, while matric suction of untreated loess—12.16 kPa ~ 2600 kPa. The range of the transition region in lime-treated loess is larger than that in the loess, while in the range of saturation region, the reverse applies. Under the condition of the same matrix suction, the saturation of lime-treated loess is greater than that of untreated loess. In the residual region, the difference of SWCC of soil samples is small.

Researchers pursuing the development of third-generation solar cells, which typically include quantum dot-sensitized solar cells (QDSSCs), dye-sensitized solar cells (DSSCs), perovskite solar cells (PSCs), and organic solar cells (OSCs), continue to prioritize low cost, simple preparation, high efficiency, and stability. Polyoxometalates (POMs) are a class of inorganic anionic metallic oxygen cluster compounds with abundant charge, skeleton structure, and excellent physical and chemical properties, such as strong electron acceptability, adjustable energy band structure, and reversible multi-electron redox properties. They are also inexpensive and environmentally friendly. Owing to these exceptional characteristics, POMs are used as building blocks for synthesizing other nanomaterials. Notably, leveraging the extraordinary characteristics of POMs to reduce costs and improve the efficiency and stability of solar cells is an effective strategy for addressing the current energy crisis. In this review, we summarize the research progress of various POM molecules and their derived POM-based nanomaterials in enhancing the performance of third-generation solar cells. Promising development prospects of POMs in the field of photovoltaic devices are also highlighted.

In this study, a three-dimensional microchannel model of a single hollow-core glass fiber was constructed and the Finite Integral Technique and Monte Carlo method were combined to comprehensively simulate the electron multiplication process in a single channel under DC mode. The electron dynamic trajectory in DC electron emission mode was achieved. The effects of different structural parameters and applied bias voltage on the electron gain and the most probable exit energy at the output end of MCP were investigated. The results show that the electrons with a certain initial current can be continuously and stably multiplied in the channel under DC mode and eventually reach a stable value because of the space charge effect; additionally, the electron gain increases with the increase in the bias angle and DC bias voltage and decreases with the increase in the penetration depth of the MCP output electrode. The electron gain at the output end of the MCP increases with the length-to-diameter ratio under the normalized voltage but shows a maximum value under the constant voltage. The simulation results are consistent with the reported experimental trend and theoretical analyses. The method provides data support for the optimal structural design of the microchannel plate.

Both polyoxometalates (POMs) and metalloporphyrins exhibit high Arial. 9 efficiency. In this work, we designed two new composite catalysts with [5,10,15,20-tetra-(4-carboxylphenyl)-porphyrinato]-ferric chloride (FeTCPP) and H3PW12O40 (PW12)/H3PMo12O40 (PMo12), forming FeTCPP-PW12 and FeTCPP-PMo12 composite catalysts. The diameter of the catalyst particles was controlled by varying the dosage of the two reactants. The synthesis method of the catalysts is simple to operate and it can be obtained by ordinary precipitation after dissolution. Furthermore, the catalysts exhibited satisfactory activity and stability under the condition of repetitive tests. Our findings showed that phenol was almost completely degraded in 10 min under photocatalytic conditions catalyzed by the FeTCPP-PMo12 photocatalyst. This work provides new concepts for developing new types of materials for environmental applications.

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.

Under the technological innovation network, loosely coupled organizations featured by weak connections and relative independence have formed through the dynamic division of labor and knowledge sharing of enterprises. The loosely coupled organizations greatly enhance cooperation performance, but face problems such as poor flexible matching between partners and low innovation efficiency. Meanwhile, modular organizations can connect with other organizations to realize a specific operational goal via contracts and carry prominent features such as collaborative innovation, adaptive division of labor, and dynamic capabilities, offering an effective network governance model for collaboration between enterprises. Based on the two dimensions (looseness and coupling) between organizations, this paper uses the design dependency matrix (DDM) to map demands for functional/design modules, under the division of labor within products and the decisions on product modules, and preliminarily decouple the functional/design modules. Based on clustering DDM, a decision structure matrix (DSM) was constructed, and the clustering decoupling algorithm was adopted to create clustering design structure modules. Referring to these clustering modules, intraproduct division of labor was performed to realize the modular cooperation between organizations.

Despite advances in the treatment of cervical cancer (CC), the prognosis of patients with CC remains to be improved. This study aimed to explore candidate gene targets for CC. CC datasets were downloaded from the Gene Expression Omnibus database. Genes with similar expression trends in varying steps of CC development were clustered using Short Time-series Expression Miner (STEM) software. Gene functions were then analyzed using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein interactions among genes of interest were predicted, followed by drug-target genes and prognosis-associated genes. The expressions of the predicted genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Red and green profiles with upward and downward gene expressions, respectively, were screened using STEM software. Genes with increased expression were significantly enriched in DNA replication, cell-cycle-related biological processes, and the p53 signaling pathway. Based on the predicted results of the Drug-Gene Interaction database, 17 drug-gene interaction pairs, including 3 red profile genes (TOP2A, RRM2, and POLA1) and 16 drugs, were obtained. The Cancer Genome Atlas data analysis showed that high POLA1 expression was significantly correlated with prolonged survival, indicating that POLA1 is protective against CC. RT-qPCR and Western blotting showed that the expressions of TOP2A, RRM2, and POLA1 gradually increased in the multistep process of CC. TOP2A, RRM2, and POLA1 may be targets for the treatment of CC. However, many studies are needed to validate our findings.

Triple‐negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor, and the HER2 receptor; it is highly proliferative and becomes the deadliest forms of breast cancer. Effective prognostic methods and therapeutic targets for TNBC are required to improve patient outcomes. Here, we report that acidic nuclear phosphoprotein 32 family member E (ANP32E), which promotes cell proliferation in mammalian development, is highly expressed in TNBC cells compared to other types of breast cancer. High expression of ANP32E correlates significantly with worse overall survival (OS; P

Abstract We present an investigation on carbon quantum dots (CQDs) synthesized from wastewater induced during the production of tofu. We find that tofu wastewater is a good source of raw material in making fluorescent CQDs. The corresponding CQDs can be fabricated simply via hydrothermal reaction to carbonize the organic matter in the yellow serofluid of tofu wastewater. Two sorts of CQDs can be obtained within the deionized water and NaOH solution, respectively, where the CQDs in water (NaOH solution) can emit blue (green) light under the UV irradiation. It is found from X-ray photoelectron spectroscopy (XPS) that the basic difference between these two sorts of CQDs is the contents of C–O and C=O bonds on the surface of the CQDs. This difference can cause different features of the photoluminescence (PL) spectra of the CQDs. On the basis of the obtained results from the XPS and PL measurements, we propose a mechanism in understanding and explaining the photon-induced light emission from CQDs. This study is relevant to the fabrication and application of fluorescent CQDs as, e.g., light display materials.

Oxidative stress is an important cause of dopaminergic (DA) neuron apoptosis in Parkinson’s disease (PD). Mesenchymal stromal cells (MSCs) possess antioxidative features. In this study, we investigated whether MSCs could reduce oxidative stress and protect DA neurons from apoptosis by intravenous (I.V.) injection in the early stage of a 6-hydroxydopamine (6-OHDA)-induced PD model. MSCs were injected into the tail vein of mice, and behavioral tests, immunofluorescence staining, western blot, and oxidative stress levels were assessed at different time points. After 6-OHDA exposure, DA neuron apoptosis was detected, together with severe oxidative stress in brain and periphery. Compared with the non-transplanted sham controls, motor function in the 6-OHDA-lesioned group after I.V. injection of MSCs was significantly improved, and the levels of DA neuron apoptosis and oxidative stress decreased. The results demonstrate that MSCs can rescue DA neurons from ongoing apoptosis by reducing oxidative stress, and provide insights on developing new therapeutic strategies to offset the degenerative process of PD.

Kinetic transport equations are notoriously difficult to simulate because of their complex multiscale behaviors and the need to numerically resolve a high-dimensional probability density function. Past literature has focused on building reduced order models (ROM) by analytical methods. In recent years, there has been a surge of interest in developing ROM using data-driven or computational tools that offer more applicability and flexibility. This paper is a work toward that direction. Motivated by our previous work of designing ROM for the stationary radiative transfer equation in [Z. Peng, Y. Chen, Y. Cheng, and F. Li, J. Sci. Comput., 91 (2022), pp. 1--27] by leveraging the low-rank structure of the solution manifold induced by the angular variable, we here further advance the methodology to the time-dependent model. Particularly, we take the celebrated reduced basis method (RBM) approach and propose a novel micro-macro decomposed RBM (MMD-RBM). The MMD-RBM is constructed by exploiting, in a greedy fashion, the low-rank structures of both the micro- and macro-solution manifolds with respect to the angular and temporal variables. Our reduced order surrogate consists of reduced bases for reduced order subspaces and a reduced quadrature rule in the angular space. The proposed MMD-RBM features several structure-preserving components: (1) an equilibrium-respecting strategy to construct reduced order subspaces which better utilize the structure of the decomposed system, and (2) a recipe for preserving positivity of the quadrature weights thus to maintain the stability of the underlying reduced solver. The resulting ROM can be used to achieve a fast online solve for the angular flux in angular directions outside the training set and for arbitrary order moment of the angular flux. We perform benchmark test problems in 2D2V, and the numerical tests show that the MMD-RBM can capture the low-rank structure effectively when it exists. A careful study in the computational cost shows that the offline stage of the MMD-RBM is more efficient than the proper orthogonal decomposition method, and in the low-rank case, it even outperforms a standard full-order solve. Therefore, the proposed MMD-RBM can be seen both as a surrogate builder and a low-rank solver at the same time. Furthermore, it can be readily incorporated into multiquery scenarios to accelerate problems arising from uncertainty quantification, control, inverse problems, and optimization. [ABSTRACT FROM AUTHOR]

Abstract Fruit color is a crucial trait for bell pepper. To investigate the mechanism of color formation, three bell pepper lines with different color (yellow, orange and red) were used as materials to conduct comprehensive targeted metabolomic and transcriptomic analyses. During the process of fruit development, 54 carotenoids metabolites were discovered, exhibiting unique accumulation patterns and notable variety specificity. The types and content of carotenoids in orange fruit (OM) were notably greater compared to the other two varieties. Red pigment (capsanthin and capsorubin) was specifically enriched in red fruit (RM), and yellow pigment (lutein and zeaxanthin) is the highest in yellow fruit (YM) and OM. Five modules positively correlated with carotenoid accumulation and one negative module was determined by weighted gene co-expression network analysis (WGCNA). Additionally, transcription factors (TFs) and hub genes related to carotenoid synthesis were predicted. By elucidating the regulation of 7 key carotenoid metabolites by 14 critical genes and 5 key TFs, we constructed a comprehensive carotenoid biosynthesis metabolic network that comprehensively explains the pigment changes observed in green and mature pepper fruit. Overall, the results not only provide important insights into carotenoid synthesis pathway, but also lay a solid base for revealing the mechanism of bell pepper color transformation.