Evaluation of chidamide and PFI-1 as a combination therapy for triple-negative breast cancer

Purpose: To evaluate the in vitro and in vivo effects of the combination therapy of histone deacetylases (HDAsC) inhibitor, chidamide, and bromodomain-containing proteins (BETs) inhibitor, PFI-1, on triplenegative breast cancer (TNBC). Methods: Four distinct breast cancer cell lines and one TNBC mouse model were treated with vehicle, chidamide, PFI-1 alone, or chidamide and PFI-1. The inhibitory effect of chidamide or PFI-1 on HDACs and BETs was assessed by HDAC enzyme inhibition and AlphaScreen assays. Cell viability was determined by MTT assay while protein expression of p-STAT3 was evaluated by western blotting and immunohistochemistry (IHC) staining assay. Results: Chidamide exerted inhibitory effect on HDACs while PFI-1 inhibited BET proteins. The threedimensional model demonstrated the interactions between chidamide and HDAC2, and between PFI-1 and BRD4. Chidamide or PFI-1 exerted inhibitory effects on breast cancer cell proliferation in vitro. However, the combination of PFI-1 and chidamide significantly inhibit MDA-MB-231 cell viability, and decrease the expression of p-STAT3, when compared to that treated with chidamide or PFI-1 alone. Moreover, the combined inhibitory effect of PFI-1 and chidamide on tumor growth was also found in the in vivo mice experiments. Conclusion: The combination of chidamide and PFI-1 is a potential is a potential therapeutic strategy for the management of TNBC. Keywords: Triple-negative breast cancer, Histone deacetylases, Bromodomai

Long-Range Grouping Transformer for Multi-View 3D Reconstruction

Nowadays, transformer networks have demonstrated superior performance in many computer vision tasks. In a multi-view 3D reconstruction algorithm following this paradigm, self-attention processing has to deal with intricate image tokens including massive information when facing heavy amounts of view input. The curse of information content leads to the extreme difficulty of model learning. To alleviate this problem, recent methods compress the token number representing each view or discard the attention operations between the tokens from different views. Obviously, they give a negative impact on performance. Therefore, we propose long-range grouping attention (LGA) based on the divide-and-conquer principle. Tokens from all views are grouped for separate attention operations. The tokens in each group are sampled from all views and can provide macro representation for the resided view. The richness of feature learning is guaranteed by the diversity among different groups. An effective and efficient encoder can be established which connects inter-view features using LGA and extract intra-view features using the standard self-attention layer. Moreover, a novel progressive upsampling decoder is also designed for voxel generation with relatively high resolution. Hinging on the above, we construct a powerful transformer-based network, called LRGT. Experimental results on ShapeNet verify our method achieves SOTA accuracy in multi-view reconstruction. Code will be available at https://github.com/LiyingCV/Long-Range-Grouping-Transformer.Comment: Accepted to ICCV 202

IrOx core-shell nanocatalysts for cost- and energy-efficient electrochemical water splitting

A family of dealloyed metal–oxide hybrid (M1M2@M1Ox) core@shell nanoparticle catalysts is demonstrated to provide substantial advances toward more efficient and less expensive electrolytic water splitting. IrNi@IrOx nanoparticles were synthesized from IrNix precursor alloys through selective surface Ni dealloying and controlled surface oxidation of Ir. Detailed depth-resolved insight into chemical structure, composition, morphology, and oxidation state was obtained using spectroscopic, diffraction, and scanning microscopic techniques (XANES, XRD, STEM-EDX, XPS), which confirmed our structural hypotheses at the outset. A 3-fold catalytic activity enhancement for the electrochemical oxygen evolution reaction (OER) over IrO2 and RuO2 benchmark catalysts was observed for the core-shell catalysts on a noble metal mass basis. Also, the active site-based intrinsic turnover frequency (TOF) was greatly enhanced for the most active IrNi@IrOx catalyst. This study documents the successful use of synthetic dealloying for the preparation of metal-oxide hybrid core-shell catalysts. The concept is quite general, can be applied to other noble metal nanoparticles, and points out a path forward to nanostructured proton-exchange-electrolyzer electrodes with dramatically reduced noble metal content.DFG, STR 596/3-1, Nanostructured mixed metal oxides for the electrocatalytic oxidation of waterBMBF, 03SF0433A, Verbundvorhaben MEOKATS: Effiziente edelmetallfreie Katalysatorsysteme basierend auf Mangan und Eisen für flexible Meerwasserelektrolyseur

Surgical treatment of multivalvular endocarditis: Twenty-one–year single center experience

ObjectiveLittle information is available about surgical outcomes in patients with multivalvular endocarditis. The aim of this article is to review the 21-year experience with surgical treatment of patients with multivalvular endocarditis at our institution and, in particular, to determine the incidence, pathologic status, diagnosis, surgical strategies, and outcomes of patients with this disease.MethodsFrom January 1986 to December 2006, a total of 48 patients (40 men, 8 women), with a mean age of 42 ± 12 years, underwent surgery for multivalvular endocarditis. Endocarditis was active in 32 patients and healed in 16. Preoperative transthoracic echocardiographic evaluation was performed in all 48 patients with addition of transesophageal echocardiography in 22 (45.8%). Intraoperative findings showed that the endocarditis involved mostly the mitral and aortic valves (40/48 patients). Triple or quadruple valve involvement was found in 1 and 2 patients, respectively. Preoperative, perioperative, and postoperative data were retrospectively analyzed and risk factors for early and late survival were determined.ResultsIn only 24 (50.0%) patients was multivalvular endocarditis diagnosed by preoperative transthoracic echocardiography; 17 (77.3%) patients had multivalvular endocarditis confirmed by preoperative transesophageal echocardiography. The 30-day hospital mortality was 12.5% (n = 6). Preoperative renal failure, New York Heart Association class IV, and emergency surgery were identified as independent risk factors for hospital mortality. Overall long-term survival was 74% ± 6% at 5 years and 62% ± 3% at 10 years. Multivariate analysis revealed that renal failure and recurrent endocarditis were associated with increased late mortality. Ten-year freedom from recurrent endocarditis was 74% ± 5% and 10-year freedom from reoperation was 73% ± 6%.ConclusionsIn our institution, multivalvular endocarditis was diagnosed by transthoracic echocardiography in only half of the patients. Intraoperative transesophageal echocardiography provided a more effective means to identify this disease. Radical resection of all infected tissues for patients with multivalvular endocarditis and additional intraoperative interventions, depending on the intraoperative pathologic condition, produced satisfactory in-hospital and long-term results, similar to those in patients with a single infected heart valve

A new method of load identification in time domain

Abstract. The main idea of the paper is to identify the load in time domain through inversely analyzing the Duhamel integral process, a time domain algorithm is developed without tedious theoretical derivation, the simulated results show that the proposed method is effective and of high accuracy

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers

In this paper, novel liver-targeting nanoparticles (NPs), lactosyl-norcantharidin (Lac-NCTD)-associated N-trimethyl chitosan (TMC) NPs (Lac-NCTD-TMC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, and encapsulation efficiency of the nanoparticles were then investigated. The continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell monolayer model was used to study the transport mechanism of Lac-NCTD, and the effects of factors such as time, temperature, pH level, drug concentration, enhancers, and inhibitors. This model was also used to indicate the differences among Lac-NCTD, Lac-NCTD-associated chitosan NPs (Lac-NCTD-CS-NPs), and Lac-NCTD-TMC- NPs in the absorption and transportation of membranes. Drug concentration levels were measured using high-performance liquid chromatography. Active transport and paracellular transport were suggested to be both the primary and secondary mechanisms for Lac-NCTD absorption, respectively. Lac-NCTD uptake and absorption were not controlled by pH levels, but were positively correlated to uptake time, and negatively correlated to temperature. The basolateral to apical apparent permeability coefficients (Papps) were higher than those of the apical to basolateral values. The inhibitor of P-glycoprotein and the multidrug resistance-associated protein 2 significantly enhanced the uptake amount of Lac-NCTD. Compared with Lac-NCTD, Lac-NCTD-CS-NPs and Lac-NCTD-TMC-NPs significantly enhanced drug absorption. Additionally, the latter exhibited stronger action. Lac-NCTD-NPs could penetrate the plasma membrane of Caco-2 cells and translocate into the cytoplasm and even into the nucleus. Nanoparticles were uptaken into Caco-2 cells through the endocytosis pathway