Direct One-Pot Synthesis of Chemically Anisotropic Particles with Tunable Morphology, Dimensions, and Surface Roughness

Previously, synthesis of anisotropic particles by seeded polymerizations has involved multiple process steps. In conventional one-pot dispersion polymerization (Dis.P) with a cross-linker added, only spherical particles are produced due to rapid and high cross-linking. In this Article, a straightforward one-pot preparation of monodisperse anisotropic particles with tunable morphology, dimensions, surface roughness, and asymmetrically distributed functional groups is described. With a cross-linker of divinylbenzene (DVB, 8%), ethylene glycol dimethacrylate (EGDMA, 6%), or dimethacryloyloxybenzophenone (DMABP, 5%) added at 40 min, shortly after the end of nucleation stage in Dis.P of styrene (St) in methanol and water (6/4, vol), the swollen growing particles are inhomogeneously cross-linked at first. Then, at low gel contents of 59%, 49%, and 69%, corresponding to the cases using DVB, EGDMA, and DMABP, respectively, the growing particle phase separates and snowman- or dumbbell-like particles are generated. Thermodynamic and kinetic analyses reveal that moderate cross-linking and sufficient swelling of growing particles determine the formation and growth of anisotropic particles during polymerization. Morphology, surface roughness, sizes, and cross-linking degrees of each domain of final particles are tuned continuously by varying start addition time and contents of cross-linkers. The snowman-like particles fabricated with DVB have a gradient cross-linking and asymmetrical distribution of pendant vinyl groups from their body to head. The dumbbell-like particles prepared using DMABP have only one domain cross-linked; i.e., only one domain contains photosensitive benzophenone (BP) groups. With addition of glycidyl methacrylate (GMA) or propargyl methacrylate (PMA) together with DVB or EGDMA, epoxy or alkynyl groups are asymmetrically incorporated. With the aid of these functional groups, carboxyl, amino, or thiol groups and PEG (200) are attached by thiol–ene (yne) click and photocoupling reactions

Asymmetric Hydrovinylation of Vinylindoles. A Facile Route to Cyclopenta[<i>g</i>]indole Natural Products (+)-<i>cis</i>-Trikentrin A and (+)-<i>cis</i>-Trikentrin B

Vinylindoles undergo Ni­(II)-catalyzed asymmetric hydrovinylation under very mild conditions (−78 °C, 1 atm ethylene, 4 mol % catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantioselectivities. Hydroboration of the alkene and oxidation to an acid, followed by Friedel–Crafts annulation, gives an indole-annulated cyclopentanone that is a suitable precursor for the syntheses of <i>cis</i>-trikentrins and all known herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is converted into (+)-<i>cis</i>-trikentin A in four steps (Wittig reaction, alkene isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The previous synthesis of this molecule from (<i>S</i>)-(−)-malic acid involved more than 20 steps and a preparative HPLC separation of diastereomeric intermediates

Diagnosis for Chinese patients with light chain amyloidosis: a scoping review

Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China. The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized. Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis. This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. REGISTRATION: INPLASY2022100096KEY MESSAGESThis scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China.Biopsy is the most important method for AL Amyloidosis diagnosis in China.Combined tests and some adjuvant methods played essential roles in the diagnosis. This scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. Combined tests and some adjuvant methods played essential roles in the diagnosis.</p

Image_2_Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines.PDF

<p>Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.</p><p>Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.</p><p>Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values.</p><p>Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet.</p

Table_1_Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines.DOCX

<p>Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.</p><p>Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.</p><p>Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values.</p><p>Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet.</p

Image_1_Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines.PDF

<p>Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.</p><p>Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.</p><p>Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values.</p><p>Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet.</p

Additional file 1: Table S1. of Antitumor activity of TY-011 against gastric cancer by inhibiting Aurora A, Aurora B and VEGFR2 kinases

The inhibitory activities of novel TY derivatives against Aurora A and B kinases and proliferation of MGC-803 cells. Figure S1. Time evolution of root-mean-square deviations (RMSD) of backbone atoms during MD simulations. (PDF 224 kb

Image4_The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma.TIF

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive.Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software.Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes.Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients.</p

Table3_The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma.xlsx

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive.Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software.Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes.Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients.</p

Image3_The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma.TIF

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive.Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software.Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes.Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients.</p