Vasculogenic mimicry regulates immune infiltration and mutational status of the tumor microenvironment in breast cancer to influence tumor prognosis.

BACKGROUND: Vasculogenic mimicry (VM) refers to the direct formation of microcirculatory ducts by invasive malignant tumors via cellular phenotypic transformation. However, there is a lack of VM-based biomarkers for breast cancer. METHODS: We obtained transcriptomic expression data, single cell sequencing data, and clinical data of patients from The Cancer Genome Atlas Program (TCGA) database and GEO database, performed single cell analysis to obtain specific type annotations of breast cancer cells and analyzed their spatial expression analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses as well as Gene Set Enrichment Analysis (GSEA) analyses were performed to clarify the biological pathways and tumor functional enrichment relationships of the major expressed genes of VM in the breast cancer bulk data specimens. VM biomarkers were constructed. Meanwhile, the relationship between VM scores and tumor immune infiltration in breast cancer was analyzed using MCPcounter and ssGSEA methods. In addition, we assessed the specific relationship between NDRG1, a key VM gene in breast cancer, and tumor colonization, adhesion and invasion by biological experiments in breast cancer cell lines. RESULTS: The main cell types of breast cancer (BRCA) samples were annotated by single cell transcriptome analysis. Most of the VM-high group was present in epithelial cells, whereas the VM-low group was present in immune and stromal cells. Multiple tumor pathways such as TGFß p53 and MAPK were closely associated with VM-mediated breast cancer infiltration and invasion. A prognostic model of breast cancer based on VM key genes was constituted. Prognostic stratification of breast cancer was successfully achieved for the TCGA-BRCA and GSE58812 datasets. Through immune infiltration analysis, we found that differential expression of VM markers was associated with multiple immune cell regulation. In MDA-MB-231 and MDA-MB-453 cell lines, we found that the NDRG1 gene significantly promoted colony formation of breast cancer cells. CONCLUSION: Our constructed VM-related gene-based model of breast cancer biology holds promise for prognostic prediction and patient stratification of breast cancer. This may provide a potentially clinically valuable aid in promoting a deeper understanding of the biological regulation of VM in breast cancer and exploring the specific mechanisms of tumor angiogenesis and breast cancer development.

LncRNA PRKCQ-AS1 regulates paclitaxel resistance in triple-negative breast cancer cells through miR-361-5p/PIK3C3 mediated autophagy.

Paclitaxel (PTX) resistance is a key cause of chemotherapy failure in patients with triple negative breast cancer (TNBC). The aim of this study is to investigate the effect and mechanism of long non-coding RNA (lncRNA) on the PTX resistance of TNBC cells through autophagy. MDA-MB-231 cells are used to induce the PTX-resistant TNBC cell line MDA-MB-231.PR (MDR) by increasing dose intermittently. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA levels of phosphoinositide-3-kinase class 3 (PIK3C3), miR-361-5p and lncRNA PRKCQ-AS1 in the cells, and Western blot analysis was used to detect the protein expressions of PIK3C3, autophagy-related, drug-resistant and apoptosis-related genes. MDC staining detected the formation of autophagic vacuoles. The interactions between miR-361-5p and PIK3C3 and between lncRNA PRKCQ-AS1 and miR-361-5p were verified by dual-luciferase assay. Cell viability, apoptosis, migration and invasion were assessed by performing MTT, flow cytometry assay, and transwell assay. The mRNA level of miR-361-5p and the autophagy and drug resistance levels of TNBC PTX-resistant cells were significantly up-regulated. miR-361-5p could target autophagy-related gene PIK3C3, and overexpression of miR-361-5p could down-regulate PIK3C3 protein expression and autophagy level and PTX resistance of MDR cells. LncRNA PRKCQ-AS1 was selected through bioanalysis, and miR-361-5p could target lncRNA PRKCQ-AS1. In addition, lncRNA PRKCQ-AS1 level was up-regulated in TNBC PTX-resistant cells, and knockdown of lncRNA PRKCQ-AS1 could weaken autophagy and drug resistance level and could promote cell apoptosis. Overexpression of lncRNA PRKCQ-AS1 reversed the pro-apoptotic effect and down-regulation of autophagy and resistance levels was induced by miR-361-5p. In vivo experiments were performed to verify the role of lncRNA PRKCQ-AS1. We demonstrate that down-regulation of lncRNA PRKCQ-AS1 weakened PTX resistance and promoted cell apoptosis by miR-361-5p/PIK3C3 mediated autophagy.

Progress in the Total Synthesis of Antitumor Tetrahydroisoquinoline Alkaloids.

Among the tetrahydroisoquinoline(THIQ) of natural products, a family of THIQ alkaloids has the characteristics of similar biosynthetic pathway. Such THIQ alkaloids family mainly include Renieramycins, Ecteinasicdins, Tetrazaomine, Lemonomycin, etc. Most of these natural compounds have strong antitumor activities, and its family member Ecteinasicdins743 (ET-743, Trabectedin) has been marketed in the European Union and the United States for the treatment of advanced soft tissue tumors and ovarian cancer. Because of the excellent biological activity and complex chemical structure of this kind of THIQ products, it has aroused great interest of biologists and chemists, and many synthetic chemists have paid considerable efforts to their total synthesis over the past decade. Based on this, the recent advances in the total synthesis of such THIQ alkaloids are reviewed.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

3-Methyl-2-(4-methyl-phen-oxy)benzoic acid.

In the title compound, C15H14O3, the dihedral angle between the aromatic rings is 86.7 (9)°. In the crystal, carb-oxy-lic acid inversion dimers linked by pairwise O-H⋯O hydrogen bonds are formed.

Highly selective CO2 electroreduction to CO by the synergy between Ni-N-C and encapsulated Ni nanoparticles.

Efficient catalysts are highly desirable for the selective electrochemical CO2 reduction reaction (CO2RR). Ni single-atom catalysts are known as promising CO2RR catalysts, while Ni NPs are expected to catalyze the competing HER. In this work, we have modified the Ni NPs by encapsulating them into porous Ni-N-C nanosheets (Ni@Ni-N-C), to boost the synergy between Ni NPs and dispersed Ni-N species towards CO2RR. The CO faradaic efficiency (FECO) reached 96.4% at -0.9 V and retained over 90% in a wide potential window. More importantly, FECO values of over 94% have been obtained from -50 to -170 mA cm-2 with a peak FECO of 99% in a flow cell. Our work demonstrates that the surface modification of Ni NPs can inhibit the unexpected HER and activate the surface sites, offering a practical design strategy for CO2RR catalysts.

SemiCurv: Semi-Supervised Curvilinear Structure Segmentation.

Recent work on curvilinear structure segmentation has mostly focused on backbone network design and loss engineering. The challenge of collecting labelled data, an expensive and labor intensive process, has been overlooked. While labelled data is expensive to obtain, unlabelled data is often readily available. In this work, we propose SemiCurv, a semi-supervised learning (SSL) framework for curvilinear structure segmentation that is able to utilize such unlabelled data to reduce the labelling burden. Our framework addresses two key challenges in formulating curvilinear segmentation in a semi-supervised manner. First, to fully exploit the power of consistency based SSL, we introduce a geometric transformation as strong data augmentation and then align segmentation predictions via a differentiable inverse transformation to enable the computation of pixel-wise consistency. Second, the traditional mean square error (MSE) on unlabelled data is prone to collapsed predictions and this issue exacerbates with severe class imbalance (significantly more background pixels). We propose a N-pair consistency loss to avoid trivial predictions on unlabelled data. We evaluate SemiCurv on six curvilinear segmentation datasets, and find that with no more than 5% of the labelled data, it achieves close to 95% of the performance relative to its fully supervised counterpart.

Male Breast Carcinoma Metastatic to the Choroid: A Case Report and Opinions of Management.

Male breast carcinoma metastatic to the choroid is very rare and often related to poor prognosis. Herein, we report the findings in a Chinese male breast cancer patient who developed choroidal metastasis, and give opinions on systemic treatments. A 45-year-old Chinese male represented with difficulty breathing and visual impairment in the left eye 6 years after his breast cancer surgery and postoperative adjuvant treatment. PET/CT revealed multi-organs metastasis of the patient. The IHC indicated the lung lesion to be originated from the breast (ER+/PR+/HER2-). Eye examination provided evidence for breast cancer choroidal metastasis. Two cycles of TX (docetaxel + capecitabine) followed by two courses of GP (gemcitabine + cis-platinum) were applied as salvage chemotherapy. Metastases in his lung and bone remained stable. As for choroidal metastasis, a regimen of CDK4/6 inhibitor (Palbociclib) plus fulvestrant was recommended to the patient, which led to a good response. Notably, CDK4/6 inhibitor combined with endocrine therapy may be considered as an effective treatment for hormonal receptor-positive breast cancer patients with choroidal metastasis. We recommend that eye examination should not be neglected in breast cancer patients.

Real-world outcomes for Chinese breast cancer patients with tumor location of central and nipple portion.

Background: The association between tumor location and breast cancer prognosis has been controversial. We sought to explore the relationship between tumors located in central and nipple portion (TCNP) and Chinese breast cancer. Patients and methods: A total of 1,427 breast cancer patients were recruited. There were 328 cases of TCNP and 1,099 cases of tumors in the breast peripheral quadrant (TBPQ). The chi-square test was used to compare different variables between TCNP and TBPQ groups. A one-to-one propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of TCNP and TBPQ groups. Kaplan-Meier curves were used for survival analysis of disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS). The Cox proportional hazards regression model was applied to identify prognostic risk factors. Results: The median follow-up time was 58 months. Compared to TBPQ, TCNP patients had significantly larger tumor size, more frequent metastasis to lymph nodes (LN) and more proportions of TNM stage II-III. DFS, OS and BCSS rates were markedly lower in the TCNP group as compared to the TBPQ group before and after PSM (all p < 0.05). Multivariate Cox analysis showed that TCNP was an independent prognostic factor for breast cancer. Subgroup analysis indicated that for breast molecular subtypes and TNM stage II-III breast cancer, TCNP were related to worse prognosis. Multivariate logistic regression revealed that TCNP was an independent contributing factor for LN metastasis. Conclusion: In Chinese breast cancer, compared to TBPQ, TCNP is associated with more LN metastasis and poorer prognosis.

Coronavirus disease 2019 epidemic prediction in Shanghai under the "dynamic zero-COVID policy" using time-dependent SEAIQR model.

It's urgently needed to assess the COVID-19 epidemic under the "dynamic zero-COVID policy" in China, which provides a scientific basis for evaluating the effectiveness of this strategy in COVID-19 control. Here, we developed a time-dependent susceptible-exposed-asymptomatic-infected-quarantined-removed (SEAIQR) model with stage-specific interventions based on recent Shanghai epidemic data, considering a large number of asymptomatic infectious, the changing parameters, and control procedures. The data collected from March 1st, 2022 to April 15th, 2022 were used to fit the model, and the data of subsequent 7 days and 14 days were used to evaluate the model performance of forecasting. We then calculated the effective regeneration number (R t) and analyzed the sensitivity of different measures scenarios. Asymptomatic infectious accounts for the vast majority of the outbreaks in Shanghai, and Pudong is the district with the most positive cases. The peak of newly confirmed cases and newly asymptomatic infectious predicted by the SEAIQR model would appear on April 13th, 2022, with 1963 and 28,502 cases, respectively, and zero community transmission may be achieved in early to mid-May. The prediction errors for newly confirmed cases were considered to be reasonable, and newly asymptomatic infectious were considered to be good between April 16th to 22nd and reasonable between April 16th to 29th. The final ranges of cumulative confirmed cases and cumulative asymptomatic infectious predicted in this round of the epidemic were 26,477 âˆ¼ 47,749 and 402,254 âˆ¼ 730,176, respectively. At the beginning of the outbreak, R t was 6.69. Since the implementation of comprehensive control, R t showed a gradual downward trend, dropping to below 1.0 on April 15th, 2022. With the early implementation of control measures and the improvement of quarantine rate, recovery rate, and immunity threshold, the peak number of infections will continue to decrease, whereas the earlier the control is implemented, the earlier the turning point of the epidemic will arrive. The proposed time-dependent SEAIQR dynamic model fits and forecasts the epidemic well, which can provide a reference for decision making of the "dynamic zero-COVID policy".

Strategies toward anode stabilization in nonaqueous alkali metal-oxygen batteries.

Alkali metal-O2 batteries exhibit ultra-high theoretical energy density which is even on par with fossil energy and are expected to become the next generation energy storage devices. However, to maintain the advantages of high energy density of alkali metal-O2 batteries, the reversibility of alkali metal anodes with high capacity is of vital importance. But the alkali metal anode with high chemical activity often faces a variety of challenges, including various side reactions, dendrite formation and volume expansion. In this highlight, we focus on the challenges faced by alkali metal anodes in alkali metal-O2 batteries and introduce the latest strategies to effectively stabilize the metal anode. Future perspectives are pointed out, which are valuable for the further development of nonaqueous alkaline metal-O2 batteries.

Timing of Endovascular Interventions for Iliac Vein Compression Syndrome With Thrombus.

The aim of this study is to explore the timing and method of endovascular intervention for iliac vein compression syndrome (IVCS) with thrombus. Data from 111 patients with IVCS, complicated acute deep vein thrombosis (DVT), or post-thrombotic syndrome (PTS) who underwent endovascular interventions were analyzed retrospectively. Patients were divided into Group A (DVT group), including 56 patients with IVCS and iliofemoral DVT, with or without femoropopliteal DVT, with sudden lower limb swelling, and Group B (PTS group) included 55 patients with IVCS and PTS, including 18 with lower extremity wet ulcers and 32 with lower limb infections. Interventional therapies were used to treat the thrombus and eliminate stenosis and occlusion of the iliac vein. In both groups, clinical symptoms in the lower limbs after surgery were reduced significantly, and PTS incidence was low during long-term follow-up. The cumulative patency rate was 75.2% in the DVT group and 88.6% in the PTS group. Comprehensive interventional therapies are safe and effective in patients with IVCS and thrombi. Long-term efficacy in the PTS group tended to be better than that in the DVT group.

Influence of the Chemical Compositions of Bismuth Oxyiodides on the Electroreduction of Carbon Dioxide to Formate.

Bismuth oxyiodides with varying chemical compositions were fabricated to effectively electrochemical reduce CO2 to formate. Bi5 O7 I and Bi7 O9 I3 nanosheets assemble irregularly, and BiOI nanosheets form a sphere-like structure. Compared with BiOI and Bi7 O9 I3 , Bi5 O7 I exhibits an excellent Faradaic efficiency of 89 % for formate production with the partial current density of 13.2 mA/cm2 at -0.89 V vs. RHE owing to the elevated amounts of Bi metal sites reduced from Bi3+ during electrolysis. The partial current densities of formate on BiOI were higher than those on Bi7 O9 I3 which is attributed to the higher iodine content. The synergistic effect of bismuth and iodine of bismuth oxyiodides is responsible for their electrocatalytic properties during CO2 reduction in aqueous solutions.

Monolithically integrated two-axis microgripper for polarization maintaining in optical fiber assembly.

Polarization maintaining optical fiber (PMOF) is a kind of special optical fiber that is designed to transmit the linearly polarized light. Unlike the general optical fiber, it is critical to conduct the rotational alignment between two PMOFs to guarantee the efficiency of light transmission. Until now, this alignment task still cannot be addressed with an efficient and economical way. Hence, we propose a monolithically integrated two-axis flexure-based microgripper that has the grasping and rubbing functions. To achieve a compact structure, the microgripper is designed with an asymmetric architecture. In this paper, the pseudo-rigid body model approach and finite element analysis are conducted to provide the essential guideline to accomplish the theoretical design. The prototype is fabricated by wire electrical discharge machining, with which two experiments are conducted to validate the performance of the microgripper. The experimental results demonstrate that the proposed microgripper can firmly grasp the optical fiber with the diameter of 250 µm and meanwhile can rub it more than 90° accurately and effectively, which indicate that it can satisfy the operating requirements well in the PMOF assembly.