Overcoming Radical Stability Order via DABCO-Triggered Desulfurization: Visible-Light-Promoted 1,2,4-Trifunctionalization of Butenyl Benzothiazole Sulfone with Thiosulfonate.

A radical 1,2,4-trifunctional reaction of thiosulfonate to unactivated olefin is achieved by a migration strategy under mild conditions. In this reaction, the more unstable primary free radicals are in situ generated after the migration of heteroaryl groups in the presence of DABCO. This trifunctionalization of unactivated olefins involves two C-S bond formations and one C-C bond formation.

A Superlong-Acting Growth Hormone-Polypeptide Fusion for Growth Hormone Deficiency Treatment.

Recombinant human growth hormone (rhGH) is clinically used to treat growth hormone deficiency (GHD). However, daily administration of rhGH is required due to its poor stability and short blood circulation, which causes pains and burdens as well as inconvenience to patients. In this study, a method for genetically fusing rhGH to a thermosensitive polymer of elastin-like polypeptide (ELP) is reported, using which the rhGH-ELP thermosensitive fusion protein can be purified by the thermosensitivity of ELP instead of chromatography. The ELP fusion not only drastically improves the stability of rhGH, but also enables the in situ formation of a sustained-release depot of rhGH-ELP upon subcutaneous (SC) injection, which exhibits gentle release with a platform-to-trough fluctuation in blood and a very long circulatory half-life of 594.6 h. In contrast, rhGH exhibits a peak-to-trough fluctuation in blood with a very short circulatory half-life of 0.7 h. As a result, a single subcutaneous injection of rhGH-ELP can consecutively promote the linear growth of rats and the development of major tissues and organs over 3 weeks without obvious side effects, whereas rhGH is required to be injected daily to achieve similar therapeutic results.

Reactive Molecular Dynamics Simulations of Polystyrene Pyrolysis.

Polymers' controlled pyrolysis is an economical and environmentally friendly solution to prepare activated carbon. However, due to the experimental difficulty in measuring the dependence between microstructure and pyrolysis parameters at high temperatures, the unknown pyrolysis mechanism hinders access to the target products with desirable morphologies and performances. In this study, we investigate the pyrolysis process of polystyrene (PS) under different heating rates and temperatures employing reactive molecular dynamics (ReaxFF-MD) simulations. A clear profile of the generation of pyrolysis products determined by the temperature and heating rate is constructed. It is found that the heating rate affects the type and amount of pyrolysis intermediates and their timing, and that low-rate heating helps yield more diverse pyrolysis intermediates. While the temperature affects the pyrolytic structure of the final equilibrium products, either too low or too high a target temperature is detrimental to generating large areas of the graphitized structure. The reduced time plots (RTPs) with simulation results predict a PS pyrolytic activation energy of 159.74 kJ/mol. The established theoretical evolution process matches experiments well, thus, contributing to preparing target activated carbons by referring to the regulatory mechanism of pyrolytic microstructure.

Nickel-Catalyzed Acid Chlorides with Tetrasulfides for the Synthesis of Thioesters and Acyl Disulfides.

Herein, we report a novel method for the synthesis of thioesters and acyl disulfides via nickel-catalyzed reductive cross-electrophile coupling of acid chlorides with tetrasulfides. This approach for the synthesis of thioesters and acyl disulfides is convenient and practical under mild reaction conditions, relying on easy availability. In addition, a wide range of thioesters and acyl disulfides were obtained in medium to good yields with good functional group tolerance. Moreover, thioesters and acyl disulfides can also be prepared at the gram scale, indicating that they have certain potential for industrial application.

The prognostic significance of KLRB1 and its further association with immune cells in breast cancer.

Background: Killer cell lectin-like receptor B1 (KLRB1) is an important member of the natural killer cell gene family. This study explored the potential value of KLRB1 as a breast cancer (BC) biomarker and its close association with the tumor immune microenvironment during the development of BC. Methods: We examined the differential expression of KLRB1 in pan-cancer. Clinical and RNA-Seq data from BC samples were evaluated in The Cancer Genome Atlas (TCGA) and validated in Gene Expression Omnibus (GEO) datasets and by immunohistochemistry (IHC) staining. The relationship between KLRB1 and clinical parameters was explored through Chi-square tests. The diagnostic value of KLRB1 was evaluated using a receiver operating characteristic (ROC) curve. Survival analysis was tested by Kaplan-Meier curves to demonstrate the relationship between KLRB1 and survival. Univariable and multivariate cox regression analyses were carried out as well. The analysis of immune infiltration level and gene set enrichment analysis (GSEA) were conducted to examine KLRB1's mechanism during the progression of BC. We used the Tumor Immune Estimation Resource (TIMER), the Cancer Single-cell Expression Map (CancerSCEM) database, the Tumor Immune Single-cell Hub (TISCH) database, and the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) method to explore KLRB1's association with immune infiltration level and different quantitative distribution of immune cells. The relevant signaling pathways in BC associated with KLRB1 were identified using GSEA. Results: The expression of KLRB1 was downregulated across the majority of cancers including BC. The lower KLRB1 expression group exhibited shorter relapse free survival (RFS) and overall survival (OS). IHC staining showed that KLRB1 staining was weaker in breast tumor tissues than in paratumors. Additionally, GSEA identified several pathway items distinctly enriched in BC. KLRB1 expression level was also positively related to the infiltrating number of immune cells in BC. Moreover, the CancerSCEM and TISCH databases as well as the CIBERSORT method demonstrated the close relationship between KLRB1 and immune cells, particularly macrophages. Conclusion: Low KLRB1 expression was considered an independent prognostic biomarker and played an important role in the tumor immune microenvironment of BC patients.

Quantitative Evaluation of the Carrier Separation Performance of Heterojunction Photocatalysts: The Case of g-C3N4/SrTiO3.

Heterojunction photocatalysts are of great interest in the energy and environmental fields, because of their potential to significantly increase the efficiency of harvesting solar energy. Advances in design have been hampered by the continued use of only qualitative analyses. Quantitative evaluation of the carrier separation performance is urgently needed for the design and application of heterojunction photocatalysts. Taking the g-C3N4/SrTiO3 heterojunction as an example, we address the conventional energy band and electronic structure issues by first-principles analysis. After interface coupling, the band edge alignment reverses from that of the respective isolated states of the heterojunction components, suggesting new ways of thinking about the catalytic mechanism of the heterojunction. More significantly, we show the carrier separation performance of heterojunction photocatalysts can be quantitatively predicted by the nonadiabatic molecular dynamics method, enabling more precisely directed research and promoting the quantified design and application of heterojunction photocatalysis, making a contribution of great scientific significance.

PCBP1-mediated regulation of WNT signaling is critical for breast tumorigenesis.

Loss of expression or protein kinase B (Akt1)-mediated post-translational modification of the RNA binding protein Poly r(C) binding protein 1 (PCBP1) is closely related to metastatic advancement of breast cancer. However, the role of PCBP1 in tumorigenesis is not completely defined. Using a xenograft orthotopic model of breast tumorigenesis (4T1-Pcbp1-/-), we show here that PCBP1 knockdown-induced tumorigenesis is inhibited by activation of the WNT signaling via treating with the glycogen synthase kinase 3 beta inhibitor TWS119, but not the Akt2/Akt3 inhibitor GSK690693. Mass cytometry-based evaluation of the tumor microenvironment (TME) revealed significantly more regulatory T cells (Tregs) and significantly less cytotoxic T cells in 4T1-Pcbp1-/-mice treated with saline control in comparison to mice treated with TWS119. Infiltrating cytotoxic T cells were phenotypically and functionally exhausted. Treatment with TWS119 resulted in rescue of cytotoxic T cell function and inhibition of suppressor activity of Tregs. Using cytotoxic T cells isolated from healthy donors, we show that TWS119-induced WNT signaling-mediated inhibition of cytotoxic T cell expansion is reliant on expression of PCBP1. In conclusion, decreased PCBP1 expression favors breast tumorigenesis by potentiating skewing of tumor infiltrating T cells towards Tregs, thereby effectively suppressing anti-tumor immunity.

TG2 as a novel breast cancer prognostic marker promotes cell proliferation and glycolysis by activating the MEK/ERK/LDH pathway.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor among women worldwide. Tissue transglutaminase 2 (TG2) has been reported as a major player across several types of cancer. However, the effects of TG2 in breast cancer are less known. METHODS: The expression of TG2 in patients with BC was detected by immunochemistry staining and RT-qPCR. The correlation of TG2 expression and clinicopathological factors or overall survival (OS) was analyzed by Chi-square test, Kaplan-Meier, and Cox-regression analysis. The effects of TG2 on cell proliferation and glycolysis were investigated in vivo and in vitro by gain- and loss-of-function experiments. RESULT: Both mRNA and protein levels of TG2 were overexpressed in BC tissues and cultured cells. Clinical stage (p = 0.011), molecular subtype (p<0.001) and survival status (p<0.001) were significantly correlated with TG2 expression. Specifically, TG2 expression was positively associated with the clinical stage (r = 0.193, p = 0.005) and OS (r = 0.230, p = 0.001), while negatively associated with molecular subtype (r = - 0.161, p = 0.020). Overexpressed TG2 was a prognostic factor of poor OS by Cox-regression analysis. Gain- and loss-of-function experiments indicated that cell proliferation and glycolysis were regulated by TG2 via the MEK/ERK/LDH pathway. TG2-induced activation of the MEK/ERK/LDH pathway and glycolysis were attenuated by MEK inhibitor U0126. CONCLUSION: TG2 is overexpressed in BC, which can serve as an independent prognostic factor for OS. TG2 promotes tumor cell proliferation and increases glycolysis associated with the activation of the MEK/ERK/LHD pathway.

Cytokine conjugates to elastin-like polypeptides.

Cytokines are a group of pleiotropic proteins which are crucial for various biological processes and useful as therapeutics. However, they usually suffer from the poor stability, extreme short circulation half-life, difficulty in high-yield and large-scale production and side effects, which greatly restricts their applications. Over the past decades, conjugation of cytokines with elastin-like polypeptides (ELPs), a type of promising biomaterials, have showed great potential in solving these challenges due to ELP's thermal responsiveness, excellent biocompatibility and biodegradability, non-immunogenicity, and ease of design and control at the genetic level. This review presents recent progress in the design and production of a variety of ELP conjugated cytokines for extended circulation, enhanced stability, increased soluble protein expression, simplified purification, improved drug delivery, and controlled release. Notably, the unique thermoresponsive properties of cytokine-ELP conjugates make it possible to self-assemble into micelles with drastically extended circulatory half-life for targeted delivery or to in situ form drug depots for topical administration and controlled release. The challenges and issues in the emerging field are further discussed and the future directions are pointed out at the end of this review.

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients.

OBJECTIVE: Cysteine conjugate beta-lyase 2 (CCBL2), also known as kynurenine aminotransferase 3 (KAT3) or glutamine transaminase L (GTL), plays an essential role in transamination and cytochrome P450. Its correlation with some other cancers has been explored, but breast cancer (BC) not yet. METHODS: The mRNA and protein expression of CCBL2 in BC cell lines and patient samples were detected by RT-qPCR and immunohistochemistry (IHC). BC patients' clinical information and RNA-Seq expression were acquired via The Cancer Genome Atlas (TCGA) database. Patients were categorized into high/low CCBL2 expression groups based on the optimal cutoff value (8.973) determined by receiver operating characteristic (ROC) curve. We investigated CCBL2 and clinicopathological characteristics' relationship using Chi-square tests, estimated diagnostic capacity using ROC curves and drew survival curves using Kaplan-Meier estimate. We compared survival differences using Cox regression and externally validated using Gene Expression Omnibus (GEO) database. We evaluated enriched signaling pathways using gene set enrichment analysis (GSEA), explored CCBL2 and relevant genes' relationship using tumor immunoassay resource (TIMER) databases and used the human protein atlas (HPA) for pan-cancer analysis and IHC. RESULTS: CCBL2 was overexpressed in normal human cell lines and tissues. CCBL2 expression was lower in BC tissues (n = 1104) than in normal tissues (n = 114), validated by GEO database. Several clinicopathologic features were related to CCBL2, especially estrogen receptor (ER), progesterone receptor (PR) and clinical stages. The low expression group exhibited poor survival. CCBL2's area under curve (AUC) analysis showed finite diagnostic capacity. Multivariate cox-regression analysis indicated CCBL2 independently predicted BC survival. GSEA showed enriched pathways: early estrogen response, MYC and so on. CCBL2 positively correlated with estrogen, progesterone and androgen receptors. CCBL2 was downregulated in most cancers and was associated with their survival, including renal and ovarian cancers. CONCLUSIONS: Low CCBL2 expression is a promising poor BC survival independent prognostic marker.

Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) are better responders to neoadjuvant chemotherapy; however, they are poor in the durability of response with decreased overall and progression-free survival. METHODS: Given that significant improvements have been reported with PD-L1-PD-1 blockade in different cancers, we evaluated the in vitro and in vivo effectiveness of Tomivosertib (eFT-508), an anthracycline, adriamycin, and MNK1/2 inhibitor, which has been previously shown to inhibit translation of PD-L1 in mice model of liver cancer, alone or in combination using BC cell lines and an orthotopic xenograft mice model using the TNBC cell line MDA-MB-231. RESULTS: Within the context of The Cancer Genome Atlas (TCGA) dataset, expression of CD274 mRNA, which encodes programmed death-ligand 1 (PD-L1), was found to be significantly overexpressed in TNBC patients compared to patients with HER2 + or luminal breast cancer (BC). Even within TNBC sub-types, CD274 expression was significantly higher in the immune modulatory subtype (TNBC-IM). BC cells exhibited high IC50 = 0.85 ± 0.07 nM with Adriamycin and significantly lower IC50 = 0.23 ± 0.04 nM with eFT-508 (P < 0.01). Combination treatment showed in vitro synergism on chemosensitivity. Combination therapy also exhibited a synergistic effect on inhibition of tumor growth and lung colonization in vivo. Mass cytometry-based evaluation of the tumor microenvironment revealed significant attenuation of both PD-L1 and PD-L2 following mono- or combination therapy with eFT-508. CONCLUSIONS: Treatment with eFT-508 restored effector and cytotoxic function of tumor-infiltrating CD8 + T cells in mice. The remarkable efficacy observed both in vitro and in vivo, and clinical synergism with adriamycin, highlights the potential of eFT-508 as an alternative, yet more efficacious, therapeutic option for patients with TNBC.

[Corrigendum] Rab22a is a novel prognostic marker for cell progression in breast cancer.

Following the publication of this article, the authors have realized that Table I contained an error: The number of patients who were alive in the Rab22a high expression group should have been written as 77 instead of 772.
A corrected version of the Table is shown on the next page (the corrected datum is highlighted in bold). The authors sincerely apologize for the error that was introduced during the preparation of this Table, and regret any inconvenience that this mistake has caused. [the original article was published in International Journal of Molecular Medicine 45: 1037-1046, 2020; DOI: 10.3892/ijmm.2020.4486].

Downregulated mRNA Expression of ZNF385B Is an Independent Predictor of Breast Cancer.

BACKGROUND: ZNF385B, a zinc finger protein, has been known as a potential biomarker in some neurological and hematological studies recently. Although numerous studies have demonstrated the potential function of zinc finger proteins in tumor progression, the effects of ZNF385B in breast cancer (BC) are less studied. METHODS: The Oncomine database and "ESurv" tool were used to explore the differential expression of ZNF385B in pan-cancer. Furthermore, data of patients with BC were downloaded from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve of ZNF385B expression was established to explore the diagnostic value of ZNF385B and to obtain the cut-off value of high or low ZNF385B expression in BC. The chi-square test as well as Fisher exact test was used for identification of the relationships between clinical features and ZNF385B expression. Furthermore, the effects of ZNF385B on BC patients' survival were evaluated by the Kaplan-Meier and Cox regression. Data from the Gene Expression Omnibus (GEO) database were employed to validate the results of TCGA. Protein expression of ZNF385B in BC patient specimens was detected by immunohistochemistry (IHC) staining. RESULTS: ZNF385B expression was downregulated in most types of cancer including BC. Low ZNF385B expression was related with survival status, overall survival (OS), and recurrence of BC. ZNF385B had modest diagnostic value, which is indicated by the area under the ROC curve (AUC = 0.671). Patients with lower ZNF385B expression had shorter OS and RFS (relapse-free survival). It had been demonstrated that low ZNF385B expression represented independent prognostic value for OS and RFS by multivariate survival analysis. The similar results were verified by datasets from the GEO database as well. The protein expression of ZNF385B was decreased in patients' samples compared with adjacent tissues by IHC. CONCLUSIONS: Low ZNF385B expression was an independent predictor for worse prognosis of BC patients.

Pyrroline-5-carboxylate synthase senses cellular stress and modulates metabolism by regulating mitochondrial respiration.

Pyrroline-5-carboxylate synthase (P5CS) catalyzes the synthesis of pyrroline-5-carboxylate (P5C), a key precursor for the synthesis of proline and ornithine. P5CS malfunction leads to multiple human diseases; however, the molecular mechanism underlying these diseases is unknown. We found that P5CS localizes in mitochondria in rod- and ring-like patterns but diffuses inside the mitochondria upon cellular starvation or exposure to oxidizing agents. Some of the human disease-related mutant forms of P5CS also exhibit diffused distribution. Multimerization (but not the catalytic activity) of P5CS regulates its localization. P5CS mutant cells have a reduced proliferation rate and are sensitive to cellular stresses. Flies lacking P5CS have reduced eclosion rates. Lipid droplets accumulate in the eyes of the newly eclosed P5CS mutant flies, which degenerate with aging. The loss of P5CS in cells leads to abnormal purine metabolism and lipid-droplet accumulation. The reduced lipid-droplet consumption is likely due to decreased expression of the fatty acid transporter, CPT1, and few ß-oxidation-related genes following P5CS knockdown. Surprisingly, we found that P5CS is required for mitochondrial respiratory complex organization and that the respiration defects in P5CS knockout cells likely contribute to the metabolic defects in purine synthesis and lipid consumption. This study links amino acid synthesis with mitochondrial respiration and other key metabolic processes, whose imbalance might contribute to P5CS-related disease conditions.

Wntless (Wls): A Prognostic Index for Progression and Patient Survival of Breast Cancer.

BACKGROUND: Wntless (Wls) is an essential protein that is necessary for the secretion of Wnt proteins. While numerous researches have demonstrated that aberrations in Wnt/ß-catenin expression lead to tumorigenesis and progression in many cancer types, the effects of Wls in breast cancer (BC) are less studied. METHODS: The mRNA and protein expression of Wls in BC cell lines were detected by RT-qPCR and Western blot; the protein expression of patient samples was detected by immunohistochemistry (IHC). The associations between Wls expression and clinicopathological factors as well as survival time, including overall survival (OS) and disease-free survival (DFS) were analyzed. Bioinformatics analysis was used to reveal the correlation between Wls genes and associated genes or pathways. RESULTS: Wls was overexpressed in BC cell lines and tissues. The expression level of Wls was significantly correlated with tumor size, estrogen receptor (ER), progesterone receptor (PR), Ki-67, molecular classification, and follow-up status. Spearman correlation analysis showed that Wls protein expression was negatively correlated with ER and PR, which was confirmed by bioinformatics analysis in mRNA level. However, there were positive relationships with MBNG (modified Black's nuclear grade), tumor size, Ki-67, molecular classification, follow-up, and vital status. Univariate and multivariate analysis showed that Wls was an independent prognostic factor for OS and DFS in BC patients. Moreover, Wls was a significant prognostic indicator of OS and DFS in a hormone receptor-positive (HR+) subgroup. GSEA showed that estrogen and androgen response, as well as epithelial-mesenchymal transition pathways, were up-regulated in the Wls high-expression group. CONCLUSION: Overexpression of Wls is a significant marker of worse prognosis in BC and might play a crucial role in the HR+ subgroup.

Follicular dendritic cell sarcoma in the right chest wall: A case report.

RATIONALE: Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor that originates from germinal center follicular dendritic cells, and can occur at both nodal and extranodal sites. There are very few described cases of FDCS arising in the chest wall. PATIENT CONCERNS: A 44-year-old male patient presented with a history of right chest wall pain for 5 months. DIAGNOSES: Positron emission tomography/computed tomography showed a significant increase in F-fluorodeoxyglucose uptake and multiple small axillary lymph nodes without hypermetabolic lesions. Immunohistochemistry results of a core-needle biopsy indicated FDCS, which was consistent with the postoperative pathological examination. INTERVENTIONS: The patient underwent tumor resection with lymphadenectomy of level I axillary nodes. No metastasis in the lymph nodes was observed in the postoperative pathological examination. The patient did not accept chemotherapy or radiotherapy. OUTCOMES: After 18 months, the patient remains in good condition with no evidence of disease recurrence. LESSONS: This report highlights a rare case of a FDCS arising in the chest wall. Accurate clinical diagnosis and staging of this rare malignant sarcoma is essential for the developmnt of effective treatment strategies. Preoperative F-fluorodeoxyglucose positron emission tomography/computed tomography scanning combined with core-needle biopsy could provide differentiation between benign and malignant tumors, as well as lymph node involvement and metastatic status.

Lipocalin-1 Expression as a Prognosticator Marker of Survival in Breast Cancer Patients.

PURPOSE: LCN1 (lipocalin-1), a gene that encodes tear lipocalin (or von Ebner's gland protein), is mainly expressed in secretory glands and tissues, such as the lachrymal and lingual gland, and nasal, mammary, and tracheobronchial mucosae. Analysis of the Cancer Genome Atlas (TCGA) Breast Carcinoma (BRCA) level 3 data revealed a relationship between LCN1 expression and survival in breast cancer patients. METHODS: The χ2 test and Fisher exact test were applied to analyze the clinical data and RNA sequencing expression data, and the association between LCN1 expression and clinicopathologic features was determined. The receiver-operating characteristic (ROC) curve of LCN1 was drawn to assess its ability as a diagnostic marker, and the optimal cutoff value was obtained from the ROC curve to distinguish groups with high and low LCN1 expression. Cox regression was used to compare both groups, and a log-rank test was applied to calculate p values and compare the -Kaplan-Meier curves. Furthermore, GEO datasets were employed for external data validation. RESULTS: Analysis of 1,104 breast cancer patients with a primary tumor revealed that LCN1 was overexpressed in breast cancer. High LCN1 expression was associated with clinicopathologic features and poor survival. Analyzing the area under the ROC curve (AUC) of LCN1, it was found that its diagnostic ability was limited. Multivariate analysis indicated that LCN1 expression is an independent predictor of survival in breast cancer patients. Through validation in GEO datasets, LCN1 expression was higher in tumor than normal tissue of the breast. High LCN1 expression was associated with poor survival in breast cancer patients. CONCLUSIONS: High LCN1 expression is an independent prognosticator of a poor prognosis in breast cancer.

Risk factors of breast intraductal lesions in patients without pathological nipple discharge.

The majority of breast cancer arises from the ductal epithelium. It is crucial in the diagnosis and treatment of breast cancer by detecting intraductal lesions at an early stage. The typical clinical characteristic of intraductal lesions is pathological nipple discharge (PND), although many patients with intraductal lesions do not exhibit PND. It is a serious challenge for clinicians to detect patients with intraductal lesions without PND at an early stage. The aim of the present study was to investigate the risk factors associated with intraductal lesions in patients without PND. This retrospective database review, conducted between April 2016 and April 2017, included 370 lesions from 255 patients with intraductal lesions (intraductal papilloma, atypical intraductal hyperplasia, intraductal carcinoma in situ) and non-intraductal lesions (fibroadenoma, adenosis, cysts, lobular carcinoma in situ), diagnosed through surgical pathology. The patients were divided into two groups based on pathological diagnosis and clinical parameters were evaluated using univariate and multivariate analyses. Univariate analysis revealed that 9 of 14 factors were statistically significant. Five factors were identified to be associated risk factors in patients without PND through the multivariate logistic regression analysis: Age between 35 and 49 years and age ≥50 years [odds ratio (OR)=4.749, 95% confidence interval (CI)=2.371-9.513, P<0.001; OR=2.587, 95% CI=2.587-14.891, P<0.001; respectively], non-menstrual breast pain (OR=1.922, 95% CI=1.037-3.564, P=0.038), breast duct dilatation as seen using ultrasonography (OR=9.455, 95% CI=3.194-27.987, P<0.001), lesion distance from nipple ≤2 cm (OR=2.747, 95% CI=1.668-4.526, P<0.001) and lesion size ≤1 cm (OR=1.903, 95% CI=1.155-3.136, P=0.012). In conclusion, for patients without PND but with risk factors, such as the patient being >35 years, with non-menstrual breast pain, breast duct ectasia, lesion distance from nipple ≤2 cm and lesion size ≤1 cm as seen using ultrasonography, clinicians should be highly concerned about the possibility of intraductal lesions, in order to prevent misdiagnosis and reduce the misdiagnosis rate.

Borane-Catalyzed Chemoselective and Enantioselective Reduction of 2-Vinyl-Substituted Pyridines.

Herein, we report that highly chemoselective and enantioselective reduction of 2-vinyl-substituted pyridines has been achieved for the first time. The reaction, which uses chiral spiro-bicyclic bisboranes as catalysts and HBpin and an acidic amide as reducing reagents, proceeds through a cascade process involving 1,4-hydroboration followed by transfer hydrogenation of a dihydropyridine intermediate. The retained double bond in the reduction products permits their conversion to natural products and other useful heterocyclic compounds by simple transformations.

Rab22a is a novel prognostic marker for cell progression in breast cancer.

Breast cancer (BC) is the most common female malignant tumor worldwide. The mechanism of tumorigenesis is still unclear. Ras­related proteins in brain (Rab)22a belongs to the Ras superfamily, which may act as an oncogene and participate in carcinogenesis. The present study aims to identify whether Rab22a could be a novel biomarker of prognosis and determine the effects of Rab22a on BC cell progression. A total 258 BC and 56 para­tumor or non­tumor formalin fixed paraffin embedded tissues were stained through immunohistochemistry. The association between Rab22a expression and clinicopathological features, as well as overall survival status were analyzed. The expression level of Rab22a in breast cell lines were detected using reverse transcription­quantitative PCR and western blotting. SK­BR­3 cells were infected with Rab22a short hairpin RNA lenti­virus and the ability of cell proliferation, migration and invasion were measured. Gene Set Enrichment Analysis (GSEA) was employed to analyze the pathways involved in the Rab22a mRNA high level group. Rab22a was found to be overexpressed in BC tissues and upregulated in BC cells. High expression of Rab22a was related to a poor prognosis of patients with BC. Knockdown of Rab22a decreased the proliferation, migration and invasion ability of BC cells. GSEA indicated that certain pathways, including mammalian target of rapamycin complex 1 and protein secretion were upregulated, while pathways, such as hypoxia and KRas were downregulated in the Rab22a high level group. Rab22a is of prognostic value for BC and necessary for BC cell proliferation.