sj-docx-1-tam-10.1177_17588359231220501 – Supplemental material for Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients

Supplemental material, sj-docx-1-tam-10.1177_17588359231220501 for Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients by Yuehua Liang, Xiaoran Liu, Zehui Yun, Kun Li and Huiping Li in Therapeutic Advances in Medical Oncology</p

Chemical Reactions and Their Kinetics of <i>atactic</i>-Polyacrylonitrile As Revealed by Solid-State ¹³C NMR

Inter- and intramolecular chemical reactions and their kinetics for ¹³C-labeled <i>atactic</i>-polyacrylonitrile (<i>a</i>PAN) powder heat-treated at 220–290 °C under air and vacuum were investigated by various solid-state nuclear magnetic resonance (ssNMR) techniques. By applying ¹³C direct polarization magic angle spinning (DPMAS) as well as through-bond and through-space double quantum/single quantum ssNMR techniques, it was concluded that <i>a</i>PAN heat-treated under air at 290 °C for 300 min adopted the ladder formation, namely, conjugated six-membered aromatic rings with partially cross-linked and oxidized rings and polyene components. In contrast, <i>a</i>PAN heat-treated under vacuum at the same condition thermally decomposed into oligomeric chains that were mainly composed of isolated aromatic rings connected by alkyl segments. Furthermore, early stages of the chemical reactions were investigated by ¹³C cross-polarization (CP) and DPMAS spectra. The latter provided quantitative information regarding the kinetics of the chemical reactions. As a result, it was shown that chemical reactions under oxygen occurred homogeneously with a higher activation energy (<i>E</i>_a) of 122 ± 3 kJ/mol compared to that of vacuum at 47 ± 2 kJ/mol. By comparing both chemical structures and kinetics under two different conditions, the chemical reaction mechanisms of <i>a</i>PAN will be discussed in detail

Data_Sheet_1_Alcaligenes faecalis Juj3 alleviates Plasmodiophora brassicae stress to cabbage via promoting growth and inducing resistance.docx

Clubroot is a devastating disease threatening global cruciferous vegetable production caused by Plasmodiophora brassicae (Pb). We have evaluated the positive effects of the Alcaligenes faecalis Juj3 on cabbage growth promotion and Pb stress alleviation through pot and field experiments. The Juj3 strain was isolated from a healthy cabbage rhizosphere with growth-promoting characteristics and was identified as A. faecalis based on morphological traits and phylogeny. Seed germination assays revealed that Juj3 inoculation enhances cabbage bud shoot and root growth. In pot experiments, inoculation with Juj3 fermentation powder at cabbage sowing dates significantly improved the seedling biomass. Combining seed treatments with root irrigation after transplanting considerably reduced the clubroot disease index and resulted in appreciable biocontrol efficacy (83.7%). Gene expression analyses of cabbage after Juj3 inoculation showed that PR2 and EIN3 expression were significantly up-regulated. Physiologically, Juj3 inoculation enhanced cabbage chlorophyll content and root activity in a normal environment. Irrespective of whether plants were under normal environment or Pb stresses, Juj3 improved photosynthesis. Field trial analyses revealed that Juj3 exhibits satisfactory biocontrol efficacy in cabbage (51.4%) and Chinese cabbage (37.7%). Moreover, Juj3 could also enhance cabbage and Chinese cabbage biomass to improve the yield quality. These findings pave the way for future use of A. faecalis as biocontrol agents for clubroot and reveal the great potential of the rhizobacterium for plant growth-promoting applications in agriculture and horticulture.</p

Stabilization of <i>Atactic</i>-Polyacrylonitrile under Nitrogen and Air As Studied by Solid-State NMR

Solid-state (ss) NMR spectroscopy was applied to study the stabilization process of 30 wt % ¹³C-labeled <i>atactic</i>-polyacrylonitrile (<i>a</i>-PAN) heat-treated at various temperatures (<i>T</i>_s) under nitrogen and air. Direct polarization magic-angle spinning (DP/MAS) ¹³C NMR spectra provided quantitative information about the functional groups of stabilized <i>a</i>-PAN. Two dimensional (2D) refocused ¹³C–¹³C INADEQUATE and ¹H–¹³C HETCOR NMR spectra gave through-bond and through-space correlations, respectively, of the complex intermediates and final structures of <i>a</i>-PAN stabilized at different <i>T</i>_s values. By comparing 1D and 2D NMR spectra, it was revealed that the stabilization process of <i>a</i>-PAN under nitrogen is initiated via cyclization, while the stabilization under air proceeds via dehydrogenation. Different initial processes lead to the isolated aromatic ring and ladder formation of the aromatic rings under nitrogen and air, respectively. Side reactions and intermediate structures are also discussed in detail. Through this work, the stabilization index (SI) was defined on the basis of the quantified C-1 and C-3 DP/MAS spectra. The former reached 0.87 at <i>T</i>_s = 370 °C, and further higher <i>T</i>_s values did not affect SI; however, the latter continuously increased up to 0.66 at <i>T</i>_s = 450 °C. All of the experimental results indicated that oxygen plays a vital role on the whole reaction process as well as the final products of stabilized <i>a</i>-PAN

Toward High-Performance Map-Recovery of Air Pollution Using Machine Learning

Mobile and pervasive sampling of urban air pollution has been increasingly valued as a sustainable method, in terms of economic and operational factors, for surveying atmospheric environment with high space-time resolution. Specifically, fine-granular air quality (AQ) inference provides fundamental progress toward data-driven urban management, as it estimates grid-level pollutant concentrations constantly using pollutant measurement data collected from fixed and mobile sensors. In this paper, we propose a tree-based multicascade space-time learning model (MCST-Tree) for AQ inference to recover pollution maps by exploiting multisource AQ samples (fixed and mobile) and heterogeneous urban feature sets (land-use, meteorology, population, traffic, etc.). This is implemented and evaluated in a study case of Chengdu (4900 km2, 14 June to 14 July 2018), which achieves map-recovery of PM2.5 distribution based upon the sparse measurements (ca. 16.2% space-time coverage) with high-performance (symmetric mean average percentage error (SMAPE) (%) = 14.13%; R2 = 0.94). Detailed evaluations are presented through the analysis of model performance, space-time coverage of mobile sampling, and AQ inference. We conduct a series of sensitivity analyses of mobile sampling coverage, and the experimental results show that it is a critical issue to enhance the model trust, which contributes to improve the R-square from 0.81 (fixed data + 10% mobile data) to 0.94 (fixed data + 100% mobile data). The results show that the mobile sampling significantly improves the space-time modeling capability, and our proposed model has great potential to achieve map-recovery for air pollution at high spatial-temporal resolution with high performance

sj-tif-1-npx-10.1177_1934578X231204742 - Supplemental material for Isobavachalcone Inhibits Hyperglycemia and Hyperlipemia in Type 2 Diabetes and the Underlying Mechanisms

Supplemental material, sj-tif-1-npx-10.1177_1934578X231204742 for Isobavachalcone Inhibits Hyperglycemia and Hyperlipemia in Type 2 Diabetes and the Underlying Mechanisms by Zhenhong Xia, Xiaoran Liu, Yuqi Li, Zhiqi Li, Feixue Ni, Geng Tian and Wenguo Jiang in Natural Product Communications</p

Image6_Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.PDF

Purpose: To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients.Methods: We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings.Results: Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87–0.96], anastrozole (ANA) (0.94, 0.90–0.97), letrozole (LET) (0.93, 0.89–0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87–0.96), and TAM followed by ANA (0.92, 0.87–0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86–0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04–2.98), ANA (1.58, 1.03–2.43), and LET (1.63, 1.02–2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons.Conclusion: The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs.Systematic Review Registration: [website], identifier [registration number].</p

Image2_Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.PDF

Purpose: To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients.Methods: We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings.Results: Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87–0.96], anastrozole (ANA) (0.94, 0.90–0.97), letrozole (LET) (0.93, 0.89–0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87–0.96), and TAM followed by ANA (0.92, 0.87–0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86–0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04–2.98), ANA (1.58, 1.03–2.43), and LET (1.63, 1.02–2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons.Conclusion: The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs.Systematic Review Registration: [website], identifier [registration number].</p

Image5_Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.PDF

Purpose: To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients.Methods: We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings.Results: Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87–0.96], anastrozole (ANA) (0.94, 0.90–0.97), letrozole (LET) (0.93, 0.89–0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87–0.96), and TAM followed by ANA (0.92, 0.87–0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86–0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04–2.98), ANA (1.58, 1.03–2.43), and LET (1.63, 1.02–2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons.Conclusion: The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs.Systematic Review Registration: [website], identifier [registration number].</p

Image1_HER2 status of CTCs by peptide-functionalized nanoparticles as the diagnostic biomarker of breast cancer and predicting the efficacy of anti-HER2 treatment.TIF

Efficacy of anti-human epidermal growth factor receptor 2 (HER2) treatment is impacted by tissue-based evaluation bias due to tumor heterogeneity and dynamic changes of HER2 in breast cancer. Circulating tumor cell (CTC)-based HER2 phenotyping provides integral and real-time assessment, benefiting accurate HER2 diagnosis. This study developed a semi-quantitative fluorescent evaluation system of HER2 immunostaining on CTCs by peptide-functionalized magnetic nanoparticles (Pep@MNPs) and immunocytochemistry (ICC). 52 newly-diagnosed advanced breast cancer patients were enrolled for blood samples before and/or after first-line treatment, including 24 patients who were diagnosed with HER2+ tumors and treated with anti-HER2 drugs. We enumerated CTCs and assessed levels of HER2 expression on CTCs in 2.0 ml whole blood. Enumerating CTCs at baseline could distinguish cancer patients (sensitivity, 69.2%; specificity, 100%). 80.8% (42/52) of patients had at least one CTCs before therapy. Patients with <3 CTCs at baseline had significantly longer progression-free survival (medians, 19.4 vs. 9.2 months; log-rank p = 0.046) and overall survival (medians, not yet reached; log-rank p = 0.049) than those with ≥3 CTCs. Both HER2+ and HER2-low patients could be detected with HER2 overexpression on CTCs (CTC-HER2+) (52.6%, 44.4%, respectively), whereas all the HER2-negative patients had no CTC-HER2+ phenotype. Among HER2+ patients with ≥3 CTCs at baseline, objective response only appeared in pretherapeutic CTC-HER2+ cohort (60.0%), rather than in CTC-HER2– cohort (0.0%) (p = 0.034). In conclusion, we demonstrate the significance of CTC enumeration in diagnosis and prognosis of first-line advanced breast cancer, and highlight the value of CTC-HER2 status in predicting efficacy of anti-HER2 treatment.</p