Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC.

BACKGROUND: Solute carrier family 7 member 2 (SLC7A2), a cationic amino acid transporter, is lowly expressed in ovarian and hepatocellular cancers, which is associated with their worse prognosis. However, its roles in the prognosis, drug resistance and immune infiltration in non-small-cell lung cancer (NSCLC) are unclear. METHODS: We chose SLC7A2 from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells, then bioinformatics, cell lines construction, RT-qPCR, and CCK8 were performed to investigate SLC7A2 role. RESULT: We analyzed the 223 differentially expressed genes (DEGs) from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells and found that SLC7A2 expression was down-regulated in NSCLC. Lower SLC7A2 expression was associated with worse recurrence-free survival (RFS) in NSCLC. SLC7A2 silencing enhanced the proliferation of NSCLC cells and their insensitivity to paclitaxel, cisplatin, and gemcitabine in vitro. Activation of AMPK has up-regulated SLC7A2 expression and enhanced the sensitivity of NSCLC cells to anti-tumor drugs, which could be attributed to E2F1's regulation. In addition, the levels of SLC7A2 expression were correlated to the numbers of infiltrated neutrophils, macrophages, dendritic cells and their marker genes, like CD86, HLA-DPA1 and ITGAM. CONCLUSIONS: SLC7A2 may act as a tumor suppressor to modulate drug sensitivity, immune infiltration and survival in NSCLC. Video abstract.

Selective Oxidative Methyl C-H Functionalization of Butylated Hydroxytoluene toward Arylimines/N-Heterocycles.

A metal-free and selective oxidative methyl C-H functionalization of BHT with aniline compounds has been developed. This innovative method enables the facile and efficient synthesis of a diverse array of BHT-functionalized N-containing skeletons, including arylamines, benzoxazoles, benzothiazoles, benzimidazoles, quinazolines, and quinazolinones, all of which are challenging to access. The control experiment involving TEMP18O suggests that the radical adduct of TEMPO with the benzyl radical of BHT may serve as an intermediate.

Ensemble habitat suitability modeling for predicting optimal sites for eelgrass (Zostera marina) in the tidal lagoon ecosystem: Implications for restoration and conservation.

Seagrass systems are in decline, mainly due to anthropogenic pressures and ongoing climate change. Implementing seagrass protection and restoration measures requires accurate assessment of suitable habitats. Commonly, such assessments have been performed using single-algorithm habitat suitability models, nearly always based on low environmental resolution information and short-term species data series. Here we address eelgrass (Zoostera marina) meadows' large-scale decline (>80%) in Shandong province (Yellow Sea, China) by developing an ensemble habitat model (EHM) to inform eelgrass conservation and restoration strategies in the Swan Lake (SL). For this, we applied a weighted EHM derived from ten single-algorithm models including profile, regression, classification, and machine learning methods to generate a high-resolution habitat suitability map. The EHM was constructed based on the predictive performances of each model, by combining a series of present-absent eelgrass datasets from recent years coupled with oceanographic and sediment data. The model was cross-validated with independent historical datasets, and a final habitat suitability map for conservation and restoration was generated. Our EHM scheme outperformed all single models in terms of habitat suitability, scoring ∼0.95 for both true statistic skill (TSS) and area under the curve (AUC) performance criteria. Machine learning methods outperformed profile, regression and classification methods. Regarding model explanatory variables, overall, topographic characteristics such as depth (DEP) and seafloor slope (SSL) are the most significant factors determining the distribution of eelgrass. The EHM predicted that the overlapping area was almost 90% of the current eelgrass habitat. Using results from our EHM, a LOESS regression model for the relationship of the habitat suitability to both the biomass and density of Z. marina outperformed better than the classic Ordinary Least Squares regression model. The EHM is a promising tool for supporting eelgrass protection and restoration areas in temperate lagoons as data availability improves.

Cardiovascular risk factors and breast cancer incidence in a large middle-aged cohort study.

BACKGROUND: Several studies have demonstrated that cardiovascular risk factors play a role in the etiology of breast cancer. However, the combined effect of cardiovascular risk factors on the risk of breast cancer is still uncertain. METHODS: Data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged women, were used to investigate the association of individual and combined cardiovascular risk factors with breast cancer. Cox proportional hazards models were applied to calculate the hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: A total of 7501 women were included. During a mean follow-up of 19.7 years, 576 women were diagnosed with breast cancer. White women and premenopausal status were independently associated with increased risk of breast cancer. Of the individual cardiovascular risk factors, only obesity was independently associated with an increased risk of breast cancer (HR 1.29, 95% CI 1.04-1.61). Compared with women without cardiovascular risk factors, women having three or greater, but not those with fewer than three cardiovascular risk factors, had a significantly higher risk of developing breast cancer (HR 1.27, 95% CI 1.06-1.53). Subgroup analyses indicated that women with three or greater cardiovascular risk factors had higher risk of breast cancer among postmenopausal Black women, but not among premenopausal Black and White women. CONCLUSIONS: Combinations of cardiovascular risk factors are associated with increased risk of breast cancer in middle-aged women, especially in postmenopausal Black women. Joint interventions to modify cardiovascular risk factors could be used to prevent breast cancer in these higher-risk individuals.

Metal-Free Oxidative Annulation of Phenols and Amines: A General Synthesis of Benzoxazoles.

The ubiquity of benzoxazoles in natural products, drugs, and functional materials has stimulated numerous efforts toward their synthesis; however, the developed methods rely on prefunctionalized substrates and lack generality. Under metal-free conditions, a highly general synthesis of benzoxazoles direct from abundant and easily available phenols and amines is developed via a modular phenol functionalization controlled by TEMPO. In the reaction, various phenols and primary amines with a broad range of functional groups are compatible, producing structurally and functionally diverse benzoxazoles (64 examples) without or with trace observation of the byproducts of phenol transformation with amines. The practical synthesis, especially for drug tafamidis, demonstrates decisive advantages in generality, selectivity, efficiency, and atom- and step-economies over traditional methods, even in the cases of low yields. Mechanistically, the radical adducts of TEMPO with ortho-cyclohexa-2,4-dien-1-one radicals rather than the well-recognized cyclohexa-3,5-diene-1,2-diones may serve as intermediates.

TEMPO mediated oxidative annulation of aryl methyl ketones with amines/ammonium acetate for imidazole synthesis.

A facile synthesis of 1H-imidazoles by direct oxidative annulation of aryl methyl ketones and primary amines has been developed in the presence of TEMPO under weakly acidic conditions. By replacing amines with ammonium acetate, 2H-imidazole skeletons were achieved for the first time from ketones. Substrates containing various functional groups, such as alkyl, aryl, naphthyl, halogen (F, Cl, Br, I), nitro, trifluoromethyl, sulfonyl ester, furyl, thienyl, and pyridyl groups, were readily transformed into the desired products. The application potential of this method was verified by the scale-up synthesis and Sonogashira coupling functionalization of imidazoles. Mechanistically, the α-TEMPO-enamine adduct may serve as the key reaction intermediate.

Cu-Catalyzed Oxidative Thioesterification of Aroylhydrazides with Disulfides.

An alternative thioesterification reaction via copper-catalyzed oxidative coupling of readily available aroylhydrazides with disulfides is developed, in which oxidative expulsion of N2 overcomes the activation barrier between the carboxylic acid derivatives and the products. The reaction produces various thioesters in good to excellent yields with good functional group tolerance. In the reaction, stable and easily available aroylhydrazides are used as acyl sources and the relatively odorless disulfides are used as S sources. Mechanistic investigations demonstrate that the reaction of copper salt and oxidant (NH4)2S2O8 allows for achievement of tandem processes, including deprotonation, free-radical-mediated denitrogenation, and C-S bond formation.

Hope and symptom burden of women with breast cancer undergoing chemotherapy: A cross-sectional study.

AIM: This research aimed to explore the level of hope and symptom burden of breast cancer women undergoing chemotherapy, and predictive factors of hope were also investigated. BACKGROUND: Chemotherapy brings physical and psychological stress to breast cancer patients. As an effective coping strategy, hope gives them the courage to overcome difficulties and improve prognosis and survival. Therefore, efforts are needed to raise hope. DESIGN/METHODS: A total of 450 women who were undergoing breast cancer chemotherapy participated in this cross-sectional study. Sociodemographic data, disease characteristics, and measures of hope and symptom burden were collected using questionnaires. Hope was assessed using the validated Herth Hope Index, and the previously validated Memorial Symptom Assessment Scale was used to assess symptom burden. This paper adhered to the STROBE guidelines. RESULTS: Chinese breast cancer chemotherapy women hope average scores of 30.15 ± 4.82 were in the medium range of the Hearth Hope Index as specified by Herth to be 24-35. Patients with age ≤45, religious beliefs and lighter symptom burden have a higher level of hope. These variables explained a total of 22.9% of the variation in hope. CONCLUSIONS: The level of hope for women undergoing breast cancer chemotherapy still needs to be further improved. Symptom burden can negatively predict hope. RELEVANCE TO CLINICAL PRACTICE: If nurses can decrease breast cancer chemotherapy women symptom burden, there is an impact on increasing levels of hope.

Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer.

BACKGROUND: Circulating tumor cells (CTCs) has been demonstrated as a promising liquid biopsy marker for breast cancer (BC). However, the intra-patient heterogeneity of CTCs remains a challenge to clinical application. We aim at profiling aggressive CTCs subpopulation in BC utilizing the distinctive metabolic reprogramming which is a hallmark of metastatic tumor cells. METHODS: Oncomine, TCGA and Kaplan-Meier plotter databases were utilized to analyze expression and survival relevance of the previously screened metastasis-promoting metabolic markers (PGK1/G6PD) in BC patients. CTCs detection and metabolic classification were performed through micro-filtration and multiple RNA in situ hybridization using CD45 and PGK1/G6PD probes. Blood samples were collected from 64 BC patients before treatment for CTCs analysis. Patient characteristics were recorded to evaluate clinical applications of CTCs metabolic subtypes, as well as morphological EMT subtypes classified by epithelial (EpCAM/CKs) and mesenchymal (Vimentin/Twist) markers. RESULTS: PGK1 and G6PD expressions were up-regulated in invasive BC tissues compared with normal mammary tissues. Increased tissue expressions of PGK1 or G6PD indicated shortened overall and relapse-free survival of BC patients (P < 0.001). Blood GM+CTCs (DAPI+CD45-PGK1/G6PD+) was detectable (range 0-54 cells/5 mL) in 61.8% of tCTCs > 0 patients. Increased GM+CTCs number and positive rate were correlated with tumor metastasis and progression (P < 0.05). The GM+CTCs ≥ 2/5 mL level presented superior AUC of ROC at 0.854 (95% CI 0.741-0.968) in the diagnosis of BC metastasis (sensitivity/specificity: 66.7%/91.3%), compared with that of tCTCs (0.779) and CTCs-EMT subtypes (E-CTCs 0.645, H-CTCs 0.727 and M-CTCs 0.697). Moreover, GM+CTCs+ group had inferior survival with decreased 2 years-PFS proportion (18.5%) than GM+CTCs- group (87.9%; P = 0.001). CONCLUSIONS: This work establishes a PGK1/G6PD-based method for CTCs metabolic classification to identify the aggressive CTCs subpopulation. Metabolically active GM+CTCs subtype is suggested a favorable biomarker of distant metastasis and prognosis in BC patients.

Phosphorous Acid-Catalyzed Alkylation of Phenols with Alkenes.

A H3PO3-catalyzed alkylation of phenols with alkenes is achieved in a facile, efficient, and selective manner. The reaction shows a unique selectivity, i.e., excellent regioselectivity, thorough suppression of overalkylation, without alkylation of a simple phenyl ring, and can selectively provide ortho-, meta-, or para-alkylated phenol derivatives in good to excellent yields. This feature along with mild reaction conditions, sensitive functional group tolerance, and scale-up synthesis and late modification of phenolic bioactive compounds make it an ideal and practical alternative for the modification of phenols.

Research trends and hotspots in caregiver studies: A bibliometric and scientometric analysis of nursing journals.

AIMS: To explore the intellectual landscape of care-giving studies and identify research trends and hotspots in this field. DESIGN: A bibliometric and scientometric analysis of care-giving literature was undertaken from January - February 2020. METHODS: CiteSpace was used to analyse research published between 1900 - 2019. A references-based co-citation analysis was used to identify the intellectual landscape of care-giving research. A keywords-based co-occurrence analysis with citation bursts was used to explore research hotspots and frontiers. Lastly, a co-authorship network analysis was used to identify co-operation among authors, countries, and institutions. RESULTS: There has been an increasing trend in the number of publications on care-giving research with light fluctuations. Relevant literature mainly focused on the fields of oncology and psychiatry. The keywords-based analysis indicated that the main research targets had previously been informal caregivers of patients with stroke, Alzheimer's disease, and schizophrenia. In recent years, focus has shifted onto informal caregivers of patients with cancer, heart failure, and those at end-of-life. CONCLUSION: This bibliometric and scientometric analysis helps us understand the current state of caregiver research and its recent developments. IMPACT: Caregivers' mental health and care experience have become research hotspots. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: This research allows the development of future research on care-giving. Future researchers should explore effective interventions for the health of patient-caregiver dyads.

Cu(I)-Catalyzed 6- endo-dig Cyclization of Terminal Alkynes, 2-Bromoaryl Ketones, and Amides toward 1-Naphthylamines: Applications and Photophysical Properties.

Functional group substituted 1-naphthylamines, especially N-methylated ones, play important roles in numerous chemical and biological processes. However, these compounds' general and step-economic syntheses are highly limited, which seriously restricts efforts to improve the properties and develop new functions for this kind of compound. In this report, we describe the development of an efficient, convenient, and general method for the synthesis of valuable functionalized 1-naphthylamines directly from readily available terminal alkynes, 2-bromoaryl ketones, and amides via Cu(I)-catalyzed benzannulation in a green solvent (i.e., water) under Pd- and ligand-free conditions. A total of 82 functionalized 1-naphthylamines, especially synthetically and biologically useful N-methylated compounds, are synthesized in isolated yields up to 95%. Some unique features of the reaction are as follows: (1) exclusive 6 -endo-dig selectivity, (2) ready incorporation of a broad range of functional groups directly from easily available substrates, and (3) amides that can be used as aminating agents and that are excellent alternatives to toxic and/or odorous amines. Due to facile tuning of functional groups for the reaction, the products possess good electronic donor-acceptor structures and exhibit intriguing photophysical properties, such as tunable and polarity-sensitive fluorescence emission and large Stokes shifts (up to 258 nm). Utilizing the products' unique polarity-sensitive fluorescence response, we successfully applied the 1-naphthylamine derivatives, such as compound 91, to image lipid droplets (LDs) and monitor cellular LDs growth. The previously mentioned advantages of this methodology, along with the mild conditions, simple operation, and scalable synthesis, may allow this novel reaction to be extended to varied applications in chemistry, biology, and materials science.

Transition-Metal-Free C-P Bond Formation via Decarboxylative Phosphorylation of Cinnamic Acids with P(O)H Compounds.

A novel, transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds has been developed via radical-promoted decarboxylation under mild conditions. This method provides simple, efficient, and versatile access to valuable ( E)-alkenylphosphine oxides in satisfactory yields with a wide variety of substrates.

Palladium-Catalyzed Desulfitative Cross-Coupling of Arylsulfonyl Hydrazides with Terminal Alkynes: A General Approach toward Functionalized Internal Alkynes.

A palladium-catalyzed Sonogashira-type coupling between arylsulfonyl hydrazides and terminal alkynes via Ar(C)-S bond cleavage is disclosed, which enables the general synthesis of functionalized internal alkynes, especially the Br-substituted ones, in good to excellent yields under acid- and base-free conditions.

Manganese(iii) acetate catalyzed oxidative amination of benzylic C(sp3)-H bonds with nitriles.

Mn-Catalyzed oxidative amination of benzylic C(sp3)-H bonds with nitriles is disclosed, which enables the synthesis of a broad range of secondary amides in moderate to excellent yields under mild conditions. The interaction between Mn(iii) and DDQ facilitates the oxidation and makes it highly efficient and selective.

Copper Catalysis for Selective Heterocoupling of Terminal Alkynes.

A Cu-catalyzed selective aerobic heterocoupling of terminal alkynes is disclosed, which enables the synthesis of a broad range of unsymmetrical 1,3-diynes in good to excellent yields. The results disprove the long-held belief that homocouplings are exclusively favored in the Glaser-Hay reaction.

Breast fine needle aspiration continues to be relevant in a large academic medical center: experience from Massachusetts General Hospital.

Fine needle aspiration (FNA) is increasingly being supplanted by core needle biopsy. However, breast surgeons continue to rely on FNA at our institution. This retrospective study evaluated breast FNA for its diagnostic accuracy and breast cancer biomarker testing utility. All breast FNAs performed at Massachusetts General Hospital 2009-2015 were reviewed. Cytology diagnoses were compared with subsequent tissue or clinical diagnoses. Immunohistochemistry and fluorescence in situ hybridization (FISH) results using formalin-fixed paraffin-embedded (FFPE) cell blocks and histologic tissue blocks were compared. 1654 consecutive breast FNAs were included. Breast FNA demonstrated the following diagnostic performance: positive predictive value of malignant cytology diagnosis 100 %, negative predictive value of benign cytology diagnosis 97.5 %, complete sensitivity 91.6 %, and specificity 95.5 %. Concordance rates for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) immunohistochemistry, and HER2 FISH were 98.2 % (κ = 0.95, p < 0.001), 100.0 % (κ = 1.000, p < 0.001), 83.1 % (κ = 0.69, p < 0.001), and 93.5 % (κ = 0.785, p < 0.001), respectively. Review of consecutive breast FNAs in a large cohort confirmed the excellent accuracy of this biopsy technique for breast lesion diagnosis. FNA FFPE cell blocks collected in the course of routine clinical care are adequate, practical, and reliable for breast cancer biomarker testing.

Experimental Study of Magnetic Multi-Walled Carbon Nanotube-Doxorubicin Conjugate in a Lymph Node Metastatic Model of Breast Cancer.

BACKGROUND The lymphatic system plays a significant role in the defense of a subject against breast cancer and is one of the major pathways for the metastasis of breast cancer. To improve the prognosis, many means, including surgery, radiotherapy, and chemotherapy, have been used. However, the combination of all these modalities has limited efficacy. Lymph nodes, therefore, have become an exceptionally potential target organ in cancer chemotherapy. MATERIAL AND METHODS A lymph node metastatic model of breast cancer was established in BALB/c mice. Magnetic multi-walled carbon nanotube carrier with good adsorption and lymph node-targeting capacity was prepared and conjugated with doxorubicin to make the magnetic multi-walled carbon nanotube-doxorubicin suspension. Dispersions of doxorubicin, magnetic multi-walled carbon nanotube-doxorubicin, and magnetic multi-walled carbon nanotube were injected into lymph node metastatic mice to compare their inhibitory effects on tumor cells in vivo. Inhibition of these dispersions on EMT-6 breast cancer cells was detected via MTT assay in vitro. RESULTS Although no significant difference was found between the effects of doxorubicin and magnetic multi-walled carbon nanotube-doxorubicin with the same concentration of doxorubicin on EMT-6 breast cancer cells in vitro, in terms of sizes of metastatic lymph nodes and xenograft tumors, apoptosis in metastatic lymph nodes, and adverse reactions, the magnetic multi-walled carbon nanotube-doxorubicin group differed significantly from the other groups. CONCLUSIONS The magnetic multi-walled carbon nanotube-doxorubicin clearly played an inhibitory role in lymph node metastases to EMT-6 breast cancer cells.

Use of Acellular Dermal Matrices in One-stage Implant-based Breast Reconstruction.

Implant-based breast reconstruction is the most common choice in breast cancer patients. Recently,the acellular dermal matrix (ADM) technique has been widely used in implant-based breast reconstruction in the western countries. This article briefly reviews the biological characteristics,history,types,surgical techniques,and postoperative complications of ADM.

Metal- and Oxidant-Free Synthesis of Quinazolinones from ß-Ketoesters with o-Aminobenzamides via Phosphorous Acid-Catalyzed Cyclocondensation and Selective C-C Bond Cleavage.

A general and efficient phosphorous acid-catalyzed cyclocondensation of ß-ketoesters with o-aminobenzamides via selective C-C bond cleavage leading to quinazolinones is developed. This reaction proceeds smoothly under metal- and oxidant-free conditions, giving both 2-alkyl- and 2-aryl-substituted quinazolinones in excellent yields. This strategy can also be applied to the synthesis of other N-heterocycles, such as benzimidazoles and benzothiazoles.