Evaluation of the Mammalian Aquaporin Inhibitors Auphen and Z433927330 in Treating Breast Cancer.

AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment.

Evolutionary game study of crowdsourcing open innovation synergy mechanism.

Open innovation crowdsourcing can help enterprises meet the challenges of a rapidly changing environment and improve their innovation performance. This study introduces network externalities as influencing factors of the crowdsourcing open innovation synergy mechanism. This study constructed the game payment matrix of the crowdsourcing open innovation synergy mechanism, and the evolutionary game method obtained the equilibrium solution of the crowdsourcing open innovation synergy mechanism.

The Effect of Defect Charge and Parasitic Surface Conductance on Aluminum Nitride RF Filter Circuit Loss.

When AlN thin films are deposited directly on the high-resistance silicon (HR-Si) substrate, a conductive layer will be formed on the HR-Si surface. This phenomenon is called the parasitic surface conduction (PSC) effect. The presence of the PSC effect will increase the power consumption of electronic components.

Study on the Evolution of the Game of Willingness to Cooperate between Residents and Separation Enterprises in Waste Separation Considering the Convenience of Separation Facilities.

The distributivity and complexity of separation facilities in waste separation cooperation are incorporated into the factors influencing the payoff of waste separation cooperation. The game payment matrix of waste separation cooperation is constructed based on the distributivity and complexity of separation facilities. The equilibrium solution of waste separation cooperation is obtained through the evolutionary game.

Evolutionary Game Analysis of Government and Residents' Participation in Waste Separation Based on Cumulative Prospect Theory.

Government and residents' participation in waste separation is a complex non-cooperative game process, and the evolutionary game can explain the behavior of participating subjects well. Considering that the traditional evolutionary game cannot satisfactorily explain the irrational psychology and risk preference factors of the participating issues, this study combines the prospect theory and evolutionary game, uses the prospect value function to supplement and improve the parameters of the evolutionary game payment matrix, and analyzes the evolutionary stabilization strategy. To verify the theoretical results, simulation experiments and impact analysis were conducted, and meaningful results were obtained: There are two stable evolutionary strategies in the system, namely higher participation benefits for residents and lower participation costs and opportunity costs, and reasonable direct benefit distribution coefficients all help to increase the participation rate of waste separation.

Low Temperature Hydrophilic SiC Wafer Level Direct Bonding for Ultrahigh-Voltage Device Applications.

SiC direct bonding using O plasma activation is investigated in this work. SiC substrate and n SiC epitaxy growth layer are activated with an optimized duration of 60s and power of the oxygen ion beam source at 20 W. After O plasma activation, both the SiC substrate and SiC epitaxy growth layer present a sufficient hydrophilic surface for bonding.

Metagenomics combined with comprehensive validation as a public health risk assessment tool for urban and agricultural run-off.

Early detection of emerging and life-threatening pathogens circulating in complex environments is urgently required to combat infectious diseases. This study proposed a public health risk assessment workflow with three stages, pathogen screening, pathogen genotyping, and risk assessment. In stage one, pathogens were screened with metagenomic sequencing, microfluidic chip, and qPCR.

Distinct dynamics of Vibrio parahaemolyticus populations in two farming models.

Aims: Despite the recent prosperity of shrimp cultivation in China, very little is known about how different shrimp farming models influence the dynamics of Vibrio parahaemolyticus populations and the antibiotic resistance of this bacterium.

Methods And Results: To this end, we conducted continuous surveillance of V. parahaemolyticus on four farms over 3 years: two traditional shrimp farms with daily water exchange and two farms operated in the recirculating aquaculture systems (RAS).

In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma.

Background: Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies.

Methods: In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells.

Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217.

Women with dense breasts have an increased lifetime risk of malignancy that has been attributed to a higher epithelial density. Quantitative proteomics, collagen analysis, and mechanical measurements in normal tissue revealed that stroma in the high-density breast contains more oriented, fibrillar collagen that is stiffer and correlates with higher epithelial cell density. microRNA (miR) profiling of breast tissue identified miR-203 as a matrix stiffness-repressed transcript that is downregulated by collagen density and reduced in the breast epithelium of women with high mammographic density.

Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer.

The complex yet interrelated connections between cancer metabolism, gene expression, and oncogenic driver genes have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. Here we effectively integrated metabolomics and gene expression data from breast cancer mouse models through a novel unbiased correlation-based network analysis. This approach identified 35 metabolite and 34 gene hubs with the most network correlations.

Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy.

Here, we report rationally engineered peptide-targeted liposomal doxorubicin nanoparticles that have an enhanced selectivity for HER2-positive breast tumor cells with high purity, reproducibility, and precision in controlling stoichiometry of targeting peptides. To increase HER2-positive tumor cell selective drug delivery, we optimized the two most important design parameters, peptide density and linker length, via systematic evaluations of their effects on both in vitro cellular uptake and in vivo tumor accumulation and cellular uptake. The optimally designed nanoparticles were finally evaluated for their tumor inhibition efficacy using in vivo MMTV-neu transplantation mouse model.

Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer.

Lacking targetable molecular drivers, triple-negative breast cancer (TNBC) is the most clinically challenging subtype of breast cancer. In this study, we reveal that Death Effector Domain-containing DNA-binding protein (DEDD), which is overexpressed in > 60% of TNBCs, drives a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain of cytosolic DEDD enhances cyclin D1 expression by interacting with heat shock 71 kDa protein 8 (HSC70).

Versatility of CoPcS in CoPcS/TiO for MB degradation: photosensitization, charge separation and oxygen activation.

In this report, a composite photocatalyst consisting of cobalt phthalocyanine sulfate (CoPcS) and TiO was prepared by a facile synthesis. Careful characterizations and measurements indicate a covalent grafting of CoPcS onto TiO through Ti-O-S linkages, acquiring an intimate heterojunction between TiO and CoPcS. The obtained composite was evaluated for its photocatalytic activity toward the degradation of methyl blue (MB) under visible light irradiation.

Phosphorylation of TIP60 Suppresses 53BP1 Localization at DNA Damage Sites.

A proper balance between the repair of DNA double-strand breaks (DSBs) by homologous recombination and nonhomologous end joining is critical for maintaining genome integrity and preventing tumorigenesis. This balance is regulated and fine-tuned by a variety of factors, including cell cycle and the chromatin environment. The histone acetyltransferase TIP60 was previously shown to suppress pathological end joining and promote homologous recombination.

The AKT inhibitor triciribine in combination with paclitaxel has order-specific efficacy against Zfp217-induced breast cancer chemoresistance.

We previously identified the transcription factor ZNF217 (human) / Zfp217 (mouse) as an oncogene and prognostic indicator of reduced survival, increased metastasis, and reduced response to therapy in breast cancer patients. Here we investigated the role of Zfp217 in chemotherapy resistance. Preclinical animal models of Zfp217 overexpression were treated with a combination therapy of the microtubule inhibitor epothilone B, doxorubicin (Adriamycin), and cyclophosphamide (EAC).

MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links.

MERIT40 is an essential component of the RAP80 ubiquitin recognition complex that targets BRCA1 to DNA damage sites. Although this complex is required for BRCA1 foci formation, its physiologic role in DNA repair has remained enigmatic, as has its relationship to canonical DNA repair mechanisms. Surprisingly, we found that Merit40(-/-) mice displayed marked hypersensitivity to DNA interstrand cross-links (ICLs) but not whole-body irradiation.

Analysis of a lung defect in autophagy-deficient mouse strains.

Yeast Atg1 initiates autophagy in response to nutrient limitation. The Ulk gene family encompasses the mammalian orthologs of yeast ATG1. We created mice deficient for both Ulk1 and Ulk2 and found that the mice die within 24 h of birth.

A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses.

Lysine63-linked ubiquitin (K63-Ub) chains represent a particular ubiquitin topology that mediates proteasome-independent signaling events. The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis. RAP80 targets the five-member nuclear BRCC36 complex to K63-Ub chains at DNA double-strand breaks.

The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.

Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet.

Asymmetric B cell division in the germinal center reaction.

Lifelong antibody responses to vaccination require reorganization of lymphoid tissue and dynamic intercellular communication called the germinal center reaction. B lymphocytes undergo cellular polarization during antigen stimulation, acquisition, and presentation, which are critical steps for initiating humoral immunity. Here, we show that germinal center B lymphocytes asymmetrically segregate the transcriptional regulator Bcl6, the receptor for interleukin-21, and the ancestral polarity protein atypical protein kinase C to one side of the plane of division, generating unequal inheritance of fate-altering molecules by daughter cells.

Ammonia-induced autophagy is independent of ULK1/ULK2 kinases.

Autophagy, a lysosome-mediated catabolic process, contributes to maintenance of intracellular homeostasis and cellular response to metabolic stress. In yeast, genes essential to the execution of autophagy have been defined, including autophagy-related gene 1 (ATG1), a kinase responsible for initiation of autophagy downstream of target of rapamycin. Here we investigate the role of the mammalian Atg1 homologs, uncoordinated family member (unc)-51-like kinase 1 and 2 (ULK1 and ULK2), in autophagy by generating mouse embryo fibroblasts (MEFs) doubly deficient for ULK1 and ULK2.

The role of cell death in sexually dimorphic muscle development: male-specific muscles are retained in female bax/bak knockout mice.

The bulbocavernosus (BC) and levator ani (LA) muscles are present in males but absent or severely reduced in females, and the fate of these muscles controls the survival of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus. However, the mechanism underlying the sex difference in BC and LA development has been controversial. We examined the role of cell death in sexual differentiation of the bulbocavernosus BC/LA muscles in mice.