Exploring how cation entropy influences electric double layer formation and electrochemical reactivity.

Electric double layers are crucial to energy storage and electrocatalytic device performance. While double layer formation originates in electrostatic interactions, electric double layer properties are governed by a balance of both electrostatic and entropic driving forces. Favorable ion-surface electrostatic interactions attract counterions to charged surfaces to compensate, or "screen," potentials, but the confinement of these same ions from a bulk reservoir to the interface incurs an entropic penalty. Here, we use a dicationic imidazolium ionic liquid and its monovalent analogue to explore how cation valence and entropy influence double layer formation and electrochemical reactivity using CO2 electroreduction as a model reaction. We find that divalent and monovalent cations display similar CO2 reduction kinetics but differ vastly in steady-state reactivity due to rapid electrochemically induced precipitation of insulating dicationic (bi)carbonate films. Using in situ surface-enhanced Raman scattering spectroscopy, we find that potential-dependent cation reorientation occurs at similar potentials between the two ionic liquids, but the introduction of a covalent link in the divalent cation imparts a more ordered double layer structure that favors (bi)carbonate precipitation. In mixed monovalent-divalent electrolytes, we find that the divalent cations dominate interfacial properties by preferentially accumulating at surfaces even at very low relative concentrations. Our findings confirm that ion entropy plays a key role in modulating local electrochemical environments. Furthermore, we highlight how double layer properties are sensitive to the properties of counterions that pay the lowest entropic penalty to accumulate at interfaces. Overall, we illustrate that ion entropy provides a new knob to tune reaction microenvironments and unveil how entropy plays a major role in modulating electrochemical reactivity in mixed ion electrolytes.

False negative result of polymerase chain reaction in very early stages of acute retinal necrosis.

BACKGROUND: Viral nucleic acid testing of intraocular fluid using polymerase chain reaction (PCR) is a major laboratory examination in the diagnosis of acute retinal necrosis (ARN). Importantly, false negative PCR results may occur in several special situations. We reported a case of ARN with a negative PCR result in the aqueous humour in the very early stages of disease. CASE PRESENTATION: A female patient presented to the ophthalmologist with complaints of blurred vision and redness in her left eye. Her medical history included ARN in her right eye 10 years prior. Although the result of the aqueous viral analysis by PCR in her left eye was negative the first time (one day after the appearance of ocular symptoms), ARN in her left eye was presumed based on the clinical signs. With timely antiviral and anti-inflammatory treatments, the retinal lesions diminished. The viral load of herpes simplex virus (HSV) turned positive (7.25 × 103 copies/mL) one week later, increased to 2.49 × 105 copies/mL after three weeks, and finally turned negative about five weeks after the onset of disease. The initial HSV-IgG level in the aqueous humour was 0.01 U/mL and increased to 222.64 U/mL in the final sampling. CONCLUSIONS: The results of PCR analysis can be negative in the very early stages of ARN. Diagnosis of ARN should be made based on the clinical features, and antiviral treatments should not be delayed. Repeated PCR analysis of the aqueous humour is necessary to confirm the diagnosis and monitor the disease process.

Changes in HER2 status and survival outcomes in patients with non-pathological complete response after neoadjuvant targeted treatment.

To study the changes in human epidermal growth factor receptor 2 (HER2) expression in patients with HER2-positive breast cancer before and after neoadjuvant treatment. The clinicopathologic data of 499 patients with HER2-positive breast cancer who completed neoadjuvant treatment and surgery at the Fourth Hospital of Hebei Medical University from 2018 to 2021 were retrospectively analyzed. According to the new adjuvant regimen, 298 patients were divided into the trastuzumab + pertuzumab combined chemotherapy group (dual target group), and 201 patients were divided into the trastuzumab combined chemotherapy group (single target group).The effect of different neoadjuvant regimens on HER2 status was analyzed by comparing HER2 expression before and after treatment. A total of 255 of 499 neoadjuvant patients with HER2-positive breast cancer achieved a pathological complete response (pCR). pCR was achieved in 60.07% (179/298) of the dual target group and 37.81% (76/201) of the single target group, and the difference was statistically significant (χ² = 23.795, P < .001). Among 244 cases of HER2-positive breast cancer that did not reach pCR (non-pCR), there was a certain negative conversion rate of HER2 expression after neoadjuvant treatment, and the overall negative conversion rate was 13.11% (32/244). The negative conversion rates of the dual target group was 17.65% (21/119) and single target group was 8.80% (11/125), (χ² = 4.188, P = .041). The DFS of 499 patients in the pCR group was 98.43% (251/255), which was significantly higher than that in the non-pCR group 92.21% (225/244), (χ² = 8.536, P = .003). Only 2 (0.20%) of 32 patients with negative HER2 had recurrence and metastasis. Neoadjuvant treatment had an effect on the expression status of HER2, especially in the dual target group. For patients with negative HER2, the optimal treatment strategy remains to be explored, but continued anti-HER2 treatment is still recommended.

Health prevention intervention for chronic tissue fibrosis: Based on the specific expression of CCL19/21 + mast cell.

Chronic tissue fibrosis is a common pathological feature of connective tissue diseases and malignant tumors, and its prevention has been a major focus of relevant research.However, the details of the mechanism of action of tissue-colonizing immune cells in fibroblast migration are unclear. In this study, connective tissue disease tissue specimens and solid tumor specimens were selected to observe the relationship between mast cells and interstitial fibrosis and the expression characteristics of mast cells. Our findings suggest that the number of mast cells in the tissue correlates with the degree of pathological fibrosis and that mast cells specifically express the chemokines CCL19 and CCL21, especially CCL19. CCR7+ fibroblasts are highly expressed in mast cell clusters. The mast cell line HMC-1 regulates CD14+ monocyte-derived fibroblasts via CCL19. In disease tissue fibrosis, mast cell activation may increase the expression of chemokines, especially CCL19, in the tissue, thereby inducing a large number of CCR7-positive fibroblasts to migrate to specific tissues. This study lays a foundation for the mechanism of tissue fibrosis and provides evidence for the mechanism by which mast cells induce fibroblast migration.Through the experimental results of this paper, we can combine the induction factors of chronic tissue fibrosis and put forward targeted health prevention strategies.

Efficacy and safety of anterior capsule polishing in cataract patients: a meta-analysis.

OBJECTIVE: This research summarizes and analyzes the effects of polishing of the anterior capsule (PAC) on visual function, maintenance of effective lens position (ELP), and postoperative complications in various studies, so as to determine whether PAC can be used to improve the surgical outcome of cataracts. METHODS: The literature related to PAC published before June 2022 was searched in PubMed, Web of Science, EMBASE, Cochrane, Google, Wanfang, Weipu and CNKI databases. Changes in visual function [uncorrected visual acuity (UCVA) and spherical equivalent refraction (SER)], effective lens position (ELP), and postoperative complications [anterior capsular opacification (ACO) and posterior capsular opacification (PCO)] in the PAC intervention group were summarized and analyzed, and the standardized mean difference (SMD) or odds ratio (OR) with 95% CI was calculated by Review Manager 5.3. RESULTS: By screening the literature, this meta-analysis finally included 10 studies with 2,639 eyes. The UCVA of patients was significantly improved in the PAC intervention group, while the root mean square of ELP (ELPRMS) level and ACO incidence decreased. In addition, PAC did not obviously reduce the incidence of PCO after cataract surgery. CONCLUSION: PAC can effectively maintain the axial stability of the implanted lens and reduce the possibility of developing ACO, thus improving patients' visual function, which can effectively improve both the efficacy and safety of cataract surgery.

Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer.

Protein tyrosine phosphatases non-receptor 13 (PTPN13) could be a potential biomarker in breast cancer (BRCA), but its genetic variation and biological significance in BRCA remain undefined. Hereon, we comprehensively investigated the clinical implication of PTPN13 expression/gene mutation in BRCA. In our study, a total of 14 cases of triple-negative breast cancers (TNBC) treated with neoadjuvant therapy were enrolled, and post-operation TNBC tissues were collected for next-generation sequencing (NGS) analysis (422 genes including PTPN13). According to the disease-free survival (DFS) time, 14 TNBC patients were divided into Group A (long-DFS) and Group B (short-DFS). The NGS data displayed that the overall mutation rate of PTPN13 was 28.57% as the third highest mutated gene, and PTPN13 mutations appeared only in Group B with short-DFS. In addition, The Cancer Genome Atlas (TCGA) database demonstrated that PTPN13 was lower expressed in BRCA than in normal breast tissues. However, PTPN13 high expression was identified to be related to a favorable prognosis in BRCA using data from the Kaplan-Meier plotter. Moreover, Gene Set Enrichment Analysis (GSEA) revealed that PTPN13 is potentially involved in interferon signaling, JAK/STAT signaling, Wnt/ß-catenin signaling, PTEN pathway, and MAPK6/MAPK4 signaling in BRCA. This study provided evidence that PTPN13 might be a tumor suppressor gene and a potential molecular target for BRCA, and genetic mutation and/or low expression of PTPN13 predicted an unfavorable prognosis in BRCA. The anticancer effect and molecular mechanism of PTPN13 in BRCA may be associated with some tumor-related signaling pathways.

Lymph Node Fibroblastic Reticular Cells Attenuate Immune Responses Through Induction of Tolerogenic Macrophages at Early Stage of Transplantation.

BACKGROUND: Fibroblastic reticular cells (FRCs) are a type of stromal cells located in the T zone in secondary lymphoid organs. Previous studies showed that FRCs possess the potential to promote myeloid differentiation. We aim to investigate whether FRCs in lymph nodes (LNs) could induce tolerogenic macrophage generation and further influence T-cell immunity at an early stage of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: LNs were assayed to confirm the existence of proliferating macrophages after allo-HSCT. Ex vivo-expanded FRCs and bone marrow cells were cocultured to verify the generation of macrophages. Real-time quantitative PCR and ELISA assays were performed to observe the cytokines expressed by FRC. Transcriptome sequencing was performed to compare the difference between FRC-induced macrophages (FMs) and conventional macrophages. Mixed lymphocyte reaction and the utilization of FMs in acute graft-versus-host disease (aGVHD) mice were used to test the inhibitory function of FMs in T-cell immunity in vitro and in vivo. RESULTS: We found a large number of proliferating macrophages near FRCs in LNs with tolerogenic phenotype under allo-HSCT conditions. Neutralizing anti-macrophage colony-stimulating factor receptor antibody abolished FMs generation in vitro. Phenotypic analysis and transcriptome sequencing suggested FMs possessed immunoinhibitory function. Mixed lymphocyte reaction proved that FMs could inhibit T-cell activation and differentiation toward Th1/Tc1 cells. Injection of FMs in aGVHD mice effectively attenuated aGVHD severity and mortality. CONCLUSIONS: This study has revealed a novel mechanism of immune regulation through the generation of FRC-induced tolerogenic macrophages in LNs at an early stage of allo-HSCT.

The Rashba effect in two-dimensional hybrid perovskites: the impacts of halogens and surface ligands.

Two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs) have gained much research interest nowadays due to their outstanding optoelectronic properties; however, the properties of the Rashba effect in 2D HOIPs have not been fully interpreted. In this work, a detailed thickness dependent structural distortion along with the Rashba splitting energy were investigated. Three types of HOIPs, 2D MAPbCl3, 2D MAPbBr3 and 2D MAPbI3, were adopted to compare the effect of halogens; and three surface ligands, BA, tert-BA and PEA, were adopted to explore the effect of ligands. It turns out that the structural distortion degree decreases with oscillations as the thickness increases, the Rashba splitting magnitude follows the same tendency, and 2D MAPbI3 is less sensitive to the thickness change compared to 2D MAPbBr3 or 2D MAPbCl3. Furthermore, different ligands and their orientations could have dramatically different impacts on the Rashba splitting. The PEA ligands enhance the Rashba splitting magnitude while the BA ligands have the reverse effect, and the impact of tert-BA ligands is insensitive to the increasing thickness. The partial charge density analysis shows that the band edges could be contributed by a charge density at a specific layer in the structure; thus, the Rashba effect is layer dependent in 2D HOIPs. These results provide some new perspectives on the Rashba effect in 2D HOIPs.

Immature olfactory sensory neurons provide behaviourally relevant sensory input to the olfactory bulb.

Postnatal neurogenesis provides an opportunity to understand how newborn neurons integrate into circuits to restore function. Newborn olfactory sensory neurons (OSNs) wire into highly organized olfactory bulb (OB) circuits throughout life, enabling lifelong plasticity and regeneration. Immature OSNs form functional synapses capable of evoking firing in OB projection neurons but what contribution, if any, they make to odor processing is unknown. Here, we show that immature OSNs provide odor input to the mouse OB, where they form monosynaptic connections with excitatory neurons. Importantly, immature OSNs respond as selectively to odorants as mature OSNs and exhibit graded responses across a wider range of odorant concentrations than mature OSNs, suggesting that immature and mature OSNs provide distinct odor input streams. Furthermore, mice can successfully perform odor detection and discrimination tasks using sensory input from immature OSNs alone. Together, our findings suggest that immature OSNs play a previously unappreciated role in olfactory-guided behavior.

Inhibition of SRPK1, a key splicing regulator, exhibits antitumor and chemotherapeutic-sensitizing effects on extranodal NK/T-cell lymphoma cells.

BACKGROUND: Increasing evidence has convincingly shown that abnormal pre-mRNA splicing is implicated in the development of most human malignancies. Serine/arginine-rich protein kinase 1 (SRPK1), a key splicing regulator, is reported to be overexpressed in leukemia and other cancer types, which suggests the therapeutic potential of targeting SRPK1. METHODS: SRPK1 expression was measured in 41 ENKTL patients by immunohistochemistry and mRNA expression was analyzed by qRT‒PCR. We knocked down SRPK1 expression in the ENKTL cell line YT by siRNA transfection and inhibited SRPK1 using inhibitors (SPHINX31 and SRPIN340) in YT cells and peripheral blood lymphocytes (PBLs) isolated from ENKTL patients to investigate its role in cell proliferation and apoptosis. Then, RNA-seq analysis was performed to predict the potential signaling pathway by which SRPK1 inhibition induces cell death and further verified this prediction by Western blotting. RESULTS: In the present study, we initially evaluated the clinical significance of SRPK1 in extranodal natural killer/T-cell lymphoma (ENKTL), a very aggressive subtype of non-Hodgkin lymphoma. The expression of SRPK1 in ENKLT patients was examined by immunohistochemistry and qRT‒PCR, which revealed SRPK1 overexpression in more than 60% of ENKTL specimens and its association with worse survival. Cellular experiments using the human ENKTL cell line YT and PBLs from ENKTL patients, demonstrated that inhibition of SRPK1 suppressed cell proliferation and induced apoptosis. Subsequently, we investigated the downstream targets of SRPK1 by RNA-seq analysis and found that SRPK1 inhibition induced ATF4/CHOP pathway activation and AKT1 inhibition. Furthermore, ENKTL patients presenting high SRPK1 expression showed resistance to cisplatin-based chemotherapy. The association of SRPK1 expression with cisplatin resistance was also confirmed in YT cells. SRPK1 overexpression via pLVX-SRPK1 plasmid transfection dramatically decreased the sensitivity of YT cells to cisplatin, while siRNA-mediated SRPK1 knockdown or SRPK1 inhibitor treatment significantly increased cisplatin cytotoxicity. CONCLUSION: In summary, these results support that SRPK1 might be a useful clinical prognostic indicator and therapeutic target for ENKTL, especially for patients who relapse after cisplatin-based chemotherapies.

The expression landscape of FOXP3 and its prognostic value in breast cancer.

Background: Forkhead Box Protein 3 (FOXP3), as an essential marker of regulatory T cell (Treg) development, is reportedly overexpressed in invasive breast carcinoma (BRCA) and could be a potential prognostic factor for BRCA. However, the biological function of FOXP3 in BRCA is still unclear. In this study, we comprehensively explored the expression landscape of FOXP3 and its prognostic value in BRCA. Methods: FOXP3 transcriptomic expression data were mainly obtained from The Cancer Genome Atlas (TCGA). The Kaplan-Meier plotter and receiver operating characteristic (ROC) curve were used to assess the prognostic and diagnostic value of FOXP3 in BRCA. UALCAN, cBio-Portal, and MethSurv were used to evaluate the genomic variation of FOXP3. Gene set enrichment analysis (GSEA) was performed to explore the FOXP3 pathways involved in BRCA. Morover, we detected the expression of FOXP3 in 123 BRCA specimens and 5 BRCA cell lines to verify the biological value of FOXP3 in BRCA. The Kaplan-Meier method was adopted for the overall survival (OS) analysis, and a Cox proportional hazards model was used to estimate the hazard ratio (HR) for OS. Results: FOXP3 was more highly expressed in BRCA than in normal tissues (2.808±1.020 vs. 1.409±0.656, P<0.001), and overexpressed FOXP3 was associated with a better prognosis. The ROC curve demonstrated a significant diagnostic value of FOXP3 in BRCA (area under the ROC curve, AUC: 0.877). Genomic analysis revealed that promoter hypomethylation of FOXP3 may be the underlying mechanism of FOXP3's upregulation in BRCA. GSEA found that FOXP3 coexpressed genes were mainly involved in the Toll-like receptor pathway, JAK/STAT pathway, cell cycle, and apoptosis. Moreover, high FOXP3 expression was an independent protective factor for OS in our 123 BRCA tissues (HR: 0.367; P=0.036). In vitro, we found that FOXP3 knockdown with siRNA promoted migration and invasion in MCF-7 cells. Conclusions: This study demonstrated that FOXP3 shows prognostic and diagnostic value for BRCA. We provided evidence that promoter hypomethylation and a high expression of FOXP3 were both related to a favorable prognosis in BRCA, which maybe associated with the Toll-like receptor pathway, JAK/STAT pathway, cell cycle, and apoptosis.

Blocking the Notch signal transduction pathway promotes tumor growth in breast cancer by promoting the expression of suppressible inflammatory factors.

Background: Breast cancer is the most common malignant tumor among all female tumors. It seriously affects the health and lives of patients, and poses a significant economic burden. The study of the molecular mechanisms of breast cancer occurrence, proliferation and growth and development is of great clinical significance. Methods: Notch1 knockout mice were obtained by gene targeting. The expression of inflammatory factor arginase-1 in each group of tumors was observed by immunofluorescence staining. Semi-quantitative detection of Notch1, Arginase-1, and proteins belonging to the PI3K-AKT pathway by western blot. The expression level of interleukin-3 (IL-3), and IL-4 in serum was quantified by enzyme linked immunosorbent assay (ELISA). Results: In this study, Notch1 knockout in mice promoted the cell proliferation of breast cancer. Further study on molecular mechanisms demonstrated that the increased cell proliferation resulted from the activation of the PI3K-AKT signal transduction pathway. In addition, the expression of the M2-type inflammatory factor arginase-1 significantly increased, which was dependent on the activation of the PI3K-AKT pathway, indicating that Notch1 knockout in mice promoted the polarization of tumor-associated macrophages (TAMs). Consistent with this, IL-3 and IL-4 expression also significantly increased in the serum of Notch1 knockout mice. Conclusions: According to our results, Notch1 knockout in mice significantly promoted the cell proliferation of breast cancer, not only by activating the PI3K-AKT pathway, but also by promoting the polarization of TAMs towards the M2-type phenotype.

The beneficial role of Asian-based RecurIndex test in the prognostic prediction in Chinese male breast cancer patients.

RecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.

Free and self-trapped exciton emission in perovskite CsPbBr3 microcrystals.

The all-inorganic perovskite CsPbBr3 has been capturing extensive attention due to its high quantum yield in luminescence devices and relatively high stability. Its luminescence is dominated by free exciton (FE) recombination but additional emission peaks were also commonly observed. In this work, a CsPbBr3 microcrystal sample in the orthorhombic phase was prepared by the chemical vapor deposition method. In addition to the FE peak, a broad emission peak was found in this sample and it was attributed to self-trapped excitons (STEs) based on its photophysical properties. The STE emission can only be observed below 70 K. The derived Huang-Rhys factor is ∼12 and the corresponding phonon energy is 15.3 meV. Its lifetime is 123 ns at 10 K, much longer than that of FE emission. The STE emission is thought to be an intrinsic property of CsPbBr3.

Tumor Cells Interleukin-22 Expression Associates with Elevated Tumor-Associated Macrophages Infiltrating and Poor Prognosis in Patients with Breast Cancer.

Interleukin-22 (IL-22), secreted by tumor infiltrated lymphocytes, is identified as a tumor-promoting factor in certain cancers, which was secreted by tumor infiltrated lymphocytes. However, the role of IL-22 in breast cancer remains conflicting. In this study, we assessed the expression of IL-22, IL-22 receptor 1 (IL-22R1), CD4, CD8, FOXP3, and CD68 in breast cancer by immunohistochemistry. IL-22 expression was exhibited in 105 (69.1%) cases in tumor cells (tIL-22), whereas only 24 (15.8%) samples displayed IL-22 expression in stromal cells. Multivariate analysis showed that tIL-22 expression was a poor prognostic factor for overall survival (OS) (p = 0.04). Meanwhile, IL-22R1 was predominantly presented in tumor cells (84.9%), which was associated with tIL-22 expression. The CD68-positive tumor-associated macrophages (TAMs) displayed the highest infiltration rate (50.7%) compared with CD4-, CD8-, and FOXP3-positive cells. Kaplan-Meier analysis confirmed patients with high TAM infiltration displayed significantly worse relapse-free survival (RFS) compared with low TAMs group (p = 0.017). TAM infiltration was also positively associated with tIL-22 and IL-22R1 expression. Furthermore, tIL-22 expression together with high TAM infiltration displayed the worst prognosis outcomes both in OS (p = 0.039) and RFS (p = 0.008). Instead of lymphocytes, our data indicated that tumor cells express IL-22 in breast cancer that is associated with IL-22R1, high TAM infiltrating, and poor prognosis.

A Randomized Parallel Controlled Phase II Trial of Recombinant Human Endostatin Added to Neoadjuvant Chemotherapy for Stage III Breast Cancer.

BACKGROUND: To explore the potential advantage of preoperative anti-angiogenosis therapy, we implemented a study to evaluate the efficacy of recombinant human endostatin (EN) in combination with neoadjuvant chemotherapy in the treatment of stage III breast cancer. PATIENTS AND METHODS: Eighty-seven patients were randomized to neoadjuvant TEC (docetaxel, epirubicin, and cyclophosphamide) or to EN+TEC, followed by surgery. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), relapse-free survival (RFS), overall survival (OS), and safety. RESULTS: Patients receiving EN+TEC achieved significantly higher ORR (81.82%; 36/44) compared with those receiving TEC (58.14%; 25/43; P=0.016). There was a non-significant trend of increased pCR with EN treatment (15.91% vs. 6.98%). The median follow-up was 54 months and revealed a significantly higher RFS with EN+TEC (median, 67.3 months; 95% confidence interval [CI], 61.0-73.7 months), compared with TEC (median, 55.0 months; 95% CI, 48.3-61.7 months; P =0.014). EN+TEC also significantly improved OS (74.2 months; 95% CI, 68.9-79.6 months), compared with TEC (59.1 months; 95% CI, 52.0-66.1 months; P =0 .006). The 3- and 5-year OS rates are estimated to be 88.5% and 82.8% with EN+TEC and 76.7% and 54.4% with TEC, respectively. Cox proportional regression analyses showed that EN+TEC was associated with improved OS (hazard ratio, 0.377; 95% CI, 0.418-0.959; P =0 .041). There was no significant difference in adverse events between EN+TEC and TEC. CONCLUSION: The combination of EN+TEC neoadjuvant chemotherapy significantly improved the ORR and OS, suggesting a benefit of adding anti-angiogenesis to standard chemotherapy in the treatment of locally advanced breast cancer.

In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells.

AMG 487 is the targeted blocker of chemokine receptor CXCR3 and improves inflammatory symptoms by blocking the inflammatory cycle. Here we investigated whether AMG 487 affects dendritic cell (DC) biology and function. The expression of co-stimulatory markers on DCs was reduced, indicating the semi-mature state of DC when AMG 487 was added throughout the in vitro differentiation period. Additionally, when added solely during the final lipopolysaccharide-induced activation step, AMG 487 inhibited DC activation, as demonstrated by a decreased expression of activation markers. AMG487 also promoted the expression of PD-L2 and impaired the ability to induce antigen-specific T cell responses. Our results demonstrated that AMG 487 significantly affects DC maturity in vitro and function leading to impaired T cell activation, inducing DCs to have characteristics similar to tolerogenic DCs. AMG 487 may directly play an immunomodulatory role during DC development and functional shaping.

Effect of topography and protecting barriers on revegetation of sandy land, Southern Tibetan Plateau.

Revegetation on sandy land has attracted worldwide attention, especially on the extremely fragile alpine eco-region of the Tibetan Plateau. However, the effectiveness of revegetation and its controlling factors have rarely been reported. We collected plant growths and species composition from seven field sites in 2011 and conducted a follow-up random investigation in 2016. The indicators, including richness and diversity, were used to compare the differences among these sites based on redundancy and cluster analyses. The results indicated that plant growth has different characteristics in different land types. The distribution and growth of Artemisia sphaerocephala, Artemisia younghusbandii and Heteropappus gouldii varied with topography, and the crown widths of A. sphaerocephala were 100.6 cm × 87.2 cm on barchan dune and 26.0 cm × 25.4 cm on moving sandy land at valley slopes. These species are likely the pioneer plants for revegetation on sandy land. It seems that sand-protecting barriers play an important role in revegetation. The stone and plastic checkerboard barriers increase plant diversity, while straw barrier promotes the plant growth. These findings provide useful guidance to the ongoing vegetation recovery on sandy land, an important component of the Project on Construction and Protection of Ecological Security Barriers on the Tibetan Plateau.

Identification and editing of stem-like cells in methylcholanthrene-induced sarcomas.

The cancer stem cell (CSC) paradigm posits that specific cells within a tumor, so-called CSC-like cells, have differing levels of tumorigenicity and chemoresistance. Original studies of CSCs identified them in human cancers and utilized mouse xenograft models to define the cancer initiating properties of these cells, thereby hampering the understanding of how immunity could affect CSCs. Indeed, few studies have characterized CSCs in the context of cancer immunoediting, and it is currently not clear how immunity could impact on the levels or stem-like behavior of CSCs. Using the well-studied 3'methylcholanthrene (MCA) model of primary sarcoma formation, we have defined a CSC-like population within MCA-induced sarcomas as expressing high levels of stem cell antigen-1 (Sca-1) and low levels of CD90. These Sca-1+CD90- CSC-like cells had higher tumor initiating ability, could spontaneously give rise to Sca-1-negative cells, and formed more sarcospheres than corresponding non-CSC-like cells. Moreover, when examining MCA-induced sarcomas that were in the equilibrium phase of cancer growth, higher levels of CSC-like cells were found compared to MCA-induced sarcomas in the escape phase of cancer progression. Notably, CSC-like cells also emerged during escape from anti-PD-1 or anti-CTLA4 therapy, thus suggesting that CSC-like cells could evade immune therapy. Finally, we demonstrate that paradoxically, interferon (IFN)-γ produced in vivo by immune cells could promote the emergence of CSC-like cells. Our findings define the existence of a Sca1+CD90- CSC-like population in the MCA-sarcoma model capable of differentiation, tumorsphere formation, and increased tumor initiation in vivo. These cells may also act as mediators of immune resistance during cancer immunoediting and immune therapy.

Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance.

Cells undergoing xenobiotic or oxidative stress activate the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), which initiates an intrinsic "stress surveillance" pathway. We recently found that the cytokine IL-17D effects a form of extrinsic stress surveillance by inducing antitumor immunity, but how IL-17D is regulated remains unknown. Here, we show that Nrf2 induced IL-17D in cancer cell lines. Moreover, both Nrf2 and IL-17D were induced in primary tumors as well as during viral infection in vivo. Expression of IL-17D in tumors and virally infected cells is essential for optimal protection of the host as il17d(-/-) mice experienced a higher incidence of tumors and exacerbated viral infections compared to wild-type (WT) animals. Moreover, activating Nrf2 to induce IL-17D in established tumors led to natural killer cell-dependent tumor regression. These data demonstrate that Nrf2 can initiate both intrinsic and extrinsic stress surveillance pathways and highlight the use of Nrf2 agonists as immune therapies for cancer and infection.