Uniform In Situ Grown ZIF-L Layer for Suppressing Hydrogen Evolution and Homogenizing Zn Deposition in Aqueous Zn-Ion Batteries.

The hydrogen evolution and dendrite of Zn anode are the major troubles hindering the commercialization of aqueous Zn-ion batteries (AZIBs). ZIF-Ls, a typical metal-organic framework (MOF) with a highly ordered structure and abundant functional groups, seem to be the answer for the above bottlenecks. In this paper, a uniform ZIF-L layer was obtained on the Zn surface (Zn@ZIF-L) via an in situ synthesis method to moderate the solvation structure of solid-liquid interface electrolyte reducing the contact between water and Zn, thereby relieving the hydrogen evolution and corrosion. Furthermore, density functional theory (DFT) analysis reveals the binding energy of H (-4.01 eV) and Zn (-0.82 eV) for ZIF-L is superior to that of pure Zn (H (-1.49 eV) and Zn (-0.68 eV)). Due to the multifunctional ZIF-L layer, the Zn@ZIF-L can regulate Zn deposition to overcome the dendrite for obtaining a long-life Zn anode. Consequently, the modified Zn@ZIF-L anode can cycle for 800 h at 0.25 mA cm-2 for 0.25 mAh cm-2, while the bare Zn anode is only maintained for 422 h. Finally, a designed V2O5 grown on carbon cloth (V2O5@CC) was used as the cathode and coupled with the Zn@ZIF-L anode to assemble the full-cell. The Zn@ZIF-L//V2O5@CC full-cell possesses a capacity retention rate of 84.9% after 250 cycles at 0.5 C, prominently higher than Zn//V2O5@CC (40.7%).

TMB and TCR Are Correlated Indicators Predictive of the Efficacy of Neoadjuvant Chemotherapy in Breast Cancer.

Immune characteristics were reported correlated to benefit neoadjuvant chemotherapy (NAC) in breast cancer, yet integration of comprehensive genomic alterations and T-cell receptors (TCR) to predict efficacy of NAC needs further investigation. This study simultaneously analyzed TMB (Tumor Mutation Burden), TCRs, and TILs (tumor infiltrating lymphocyte) in breast cancers receiving NAC was conducted in a prospective cohort (n = 22). The next-generation sequencing technology-based analysis of genomic alterations and TCR repertoire in paired breast cancer samples before and after NAC was conducted in a prospective cohort (n = 22). Fluorescent multiplex immunohistochemistry was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in those paired samples. TMB in pretreatment tumor tissues and TCR diversity index are higher in non-pCR patients than in pCR patients (10.6 vs. 2.3; p = 0.043) (2.066 vs. 0.467; p = 0.010). TMB and TCR diversity index had linear correlation (y = 5.587x - 0.881; r = 0.522, p = 0.012). Moreover, infiltrating T cells are significantly at higher presence in pCR versus non-pCR patients. Dynamically, the TMB reduced significantly after therapy in non-pCR patients (p = 0.010) but without TCR index change. The CDR3 peptide AWRSAGNYNEQF is the most highly expressed in pre-NAC samples of pCR patients and in post-NAC samples of non-pCR patients. In addition to pCR, high clonality of TCR and high level of CD8+ expression are associated with disease-free survival (DFS). TCR index and TMB have significant interaction and may guide neo-adjuvant treatment in operable breast cancers. Response to NAC in tumors with high TCR clonality may be attributable to high infiltration and expansion of tumor-specific CD8 positive effector cells.

Quantitative multiplex immunofluorescence analysis identifies infiltrating PD1+ CD8+ and CD8+ T cells as predictive of response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. METHODS: Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). RESULTS: In pretreatment tumors, the percentages of infiltrating CD8+ , PD1+ , PD1+ CD8+ , and the ratio of PD1+ CD8+ /CD8+ cells, were higher in pCR than non-pCR patients in either the stromal or intratumoral area, but PD1+ CD4+ , TIM3+ CD4+ , TIM3+ CD8+ cells and CD4+ /CD8+ ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8+ cells (OR, 1.712; 95% CI: 1.052-2.786; P = 0.030) and stromal PD1+ CD8+ /CD8+ ratio (OR, 1.109; 95% CI: 1.009-1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1+ , CD8+ and PD1+ CD8+ cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1+ CD8+ cells, rather than TIM3+ CD8+ , were shown in tumors from non-pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. CONCLUSIONS: PD1+ CD8+ rather than TIM3+ CD8+ cells are main predictive components within tumor-infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1+ CD8+ cells occurred in non-pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: PD1+ CD8+ , rather than TIM3+ CD8+ , T cells are the main component to predict the response of neoadjuvant therapies in breast cancer. WHAT THIS STUDY ADDS: Incremental levels of PD1+ CD8+ T cells in non-pCR post-NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting.

Cullin7 enhances resistance to trastuzumab therapy in Her2 positive breast cancer via degrading IRS-1 and downregulating IGFBP-3 to activate the PI3K/AKT pathway.

Patients with Her2-positive breast cancer exhibit de novo resistance or develop acquired resistance in less than one year after Her2 targeting treatment, but the mechanism is not fully elucidated. Compensatory pathways such as the IGF-1R/IRS-1 pathway, are activated, leading to aberrant enhanced PI3K/Akt/mTOR pathway activity to attenuate the efficacy of trastuzumab. Cullin7 could participate in the degradation of IRS-1 in a mTOR/S6K dependent manner. Whether Cullin7 participates in trastuzumab resistance needs to be further investigated. Here, we reveals that Cullin7 is overexpressed in trastuzumab-resistant Her2 positive breast cancer cells. Knockdown of Cullin7 reduces degradation of Ser phosphorylation of IRS-1, attenuates activation of the PI3K/AKT pathway, and partly restores trastuzumab sensitivity in trastuzumab-resistant Her2 positive breast cancer cells. IGFBP-3 expression is decreased in trastuzumab-resistant Her2 positive breast cancer cells, which leads to release of the Wnt signaling pathway inhibition and an increase in Cullin7 expression, as mediated by TCF7L2. Overexpression of Cullin7 in Her2-amplified breast cancer tissues has clinical implications because it positively correlates with shorter disease-free survival (DFS) and inadequate response to trastuzumab. Thus, our results suggest a critical role for Cullin7 in response to trastuzumab, which has significant implications for selection of the optimal therapeutic strategy for Her2 positive breast cancers.

Predictive value of microtubule-associated protein Tau in patients with recurrent and metastatic breast cancer treated with taxane-containing palliative chemotherapy.

Tau is a member of microtubule-associated proteins (MAPs) and expressed in normal breast epithelium and breast cancer cells. Tau expression levels in early breast cancer were correlated with the responsiveness of taxane-containing chemotherapy. However, it is unknown whether Tau contributes to breast cancer progression. Herein, Tau expression in recurrent and metastatic breast cancer (RMBC) and its predictive significance in taxane-containing palliative chemotherapy were investigated. Immunohistochemical (IHC) staining was conducted to detect Tau protein expression levels in biopsies from 285 patients with RMBC, and the correlation between Tau expression and sensitivity to taxane was evaluated. One hundred twenty-one (42.46 %, 121/285) patients were Tau positive in their tumor. One hundred ninety-four (68.07 %, 194/285) patients were effective clinical remission, which evaluated with response evaluation criteria in solid tumors (RECIST) criteria. In this group, 141 (85.98 %, 141/194) patients were Tau negative. We further analyzed the correlation between Tau expression and clinicopathological characteristics. Tau expression was positively correlated to estrogen receptor (ER) status. Multivariate logistic regression analysis showed that Tau expression significantly differentiated patients with effective response to treatment (95 % confidence interval (CI): 4.230-13.88, P < 0.01). Tau expression was identified as an independent factor to predict the sensitivity of tumors to taxane-containing palliative chemotherapy in RMBC, suggesting that Tau expression in RMBC may serve as a clinical predictor for taxane-containing palliative chemotherapy.

Implanting totally implantable venous access port via the internal jugular vein guided by ultrasonography is feasible and safe in patients with breast cancer.

BACKGROUND: Because of long-term use for chemotherapy and fluid administration in cancer patients, a totally implantable venous access port (TIVAP) has been advised as a feasible catheter. The purpose of this study was to evaluate the effectiveness and safety of ultrasound (US)-guided internal jugular vein (IJV) puncture for TIVAP implantation in patients with breast cancer. METHODS: We reviewed the medical records of 492 patients who underwent US-guided IJV puncture for TIVAP implantation at our oncology department between 2010 and 2013. Indications, surgical complications, and early and long-term complications were analyzed. RESULTS: All TIVAPs were implanted successfully. Indications for TIVAP were chemotherapy alone (88 patients), chemoradiotherapy (387 patients), surgery (12 patients), and parenteral nutrition (5 patients). Complications were observed in 65 (13.21%) patients. The median duration of the TIVAP was 359 days (range, 28 to 712 days) without damage to the port or catheter, or leakage of drugs outside of the port system. CONCLUSIONS: A TIVAP can be employed for chemotherapy and parenteral nutrition on the implantation day. Using a US-guided IJV puncture to completely implant a TIVAP is feasible and safe in patients with breast cancer.

A preliminary study of the relationship between breast cancer metastasis and loss of heterozygosity by using exome sequencing.

We explored the feasibility of studying loss of heterozygosity (LOH) by using exome sequencing and compared the differences in genetic LOH between primary breast tumors and metastatic lesions. Exome sequencing was conducted to investigate the genetic LOH in the peripheral blood, a primary tumor, and a metastatic lesion from the same patient. LOH was observed in 30 and 48 chromosomal loci of the primary tumor and metastatic lesion, respectively. The incidence of LOH was the highest on chromosome 19, followed by chromosomes 14, 3, and 11 in the metastatic lesion. Among these 'hot' regions, LOH was observed for multiple genes of the CECAM, MMP and ZNF families. Therefore, the use of exome sequencing for studying LOH is feasible. More members of gene families appeared with LOH in 'hot' regions, suggesting that these gene families had synergistic effects in tumorigenesis.

Nonlinear feature extraction of sleeping EEG signals.

This study calculated the spectrum entropy (SE), approximate entropy (ApEn), and Lem-Ziv complexity (LZC) of sleeping EEG signals of eight healthy adults. The statistical results show that all the three nonlinear features can clearly reflect sleeping stage. Among them, the SE is easy to calculate and traces varying sleeping periods fairly and consistently, while the ApEn performs even better but is relatively complicated. The LZC is also simple but loses information details in its preprocessing of original measurement data, which consequently down grades its consistency. Based on a tradeoff of efficiency and efficacy, we consider the SE would be a good feature for real-time tracing sleep stages. Some conclusions are reported based on this study.

[Feature extraction and classification of EEG for mental tasks based on wavelet packet analysis].

This paper explores the use of wavelet packet analysis to extract features from spontaneous electroencephalogram (EEG) during three different mental tasks. Artifact-free EEG segments are transformed to multi-scale representations by dyadic wavelet packet decomposition channel by channel. Their feature vectors formed by energy values of different sub-spaces EEG components are used as inputs of a radial basis function network to test the classification accuracies of three task pairs. The results indicate that the classification accuracies of the wavelet packet analysis method are significantly better than those of autoregressive model method. Wavelet packet analysis would be a promising method to extract features from EEG signals.