Discovery of the Next-Generation Platinum-Based Anticancer Agents for Combating Oxaliplatin-Induced Drug Resistance.

Oxaliplatin-based chemotherapy has proven to be one of the most effective treatments for advanced or metastatic colorectal cancer. However, increasing clinical resistance to oxaliplatin poses unprecedented challenges for both patients and clinicians. Despite extensive efforts to combat this issue, to date, no new molecules have been discovered that can successfully replace oxaliplatin. With the aim of developing a new generation of Pt(II)-based anticancer agents in response to the challenges of oxaliplatin-induced drug resistance, we performed a systematic screening of new Pt(II)-complexes with a quantitative structure-activity relationship (QSAR) study based on their antiresistance activity against oxaliplatin-resistant colon cancer cells. The results revealed that both the structure and chirality of the chelating ligand had a significant impact on the antiresistance properties of the Pt(II)-complexes. Our study culminated in the identification of chiral R-binaphthyldiamine-ligated Pt(II)-malonatoglycoconjugates that can completely counteract oxaliplatin resistance with excellent in vitro and in vivo potency.

The mechanism and application of computer-assisted full facial skin imaging systems.

Computer-assisted full facial imaging systems are currently among the most widely used skin analysis instruments in dermatology and medical cosmetology. These systems offer objective quantitative evaluation of facial skin conditions, and as they are non-invasive, play an important role in assessing dermatological conditions such as pigmentation, inflammation, vascular diseases, skin texture, the severity of ageing, and therapeutic follow-up. Although computer-assisted full facial imaging systems enable quantitative analysis in the scope of medical treatment and cosmetic evaluation, their results may considerably vary because of the influence of environmental and postural factors for improper operation. Furthermore, manual observation is sometimes necessary for experimental work for more accuracy, and familiarity with the imaging principles and application points is necessary to best apply this technique. This report aims to discuss and interpret these systems' imaging mechanisms and explore the primary issues with their application.

Relationship Between Dermoscopic Capillary-Related Features of the Auricle and Earlobe and Rosacea Subtype and Disease Severity: A Cross-Sectional Analysis.

Background and Aim: Clinical manifestations of rosacea include transient or persistent facial erythema, telangiectasia, papules, and pustules. The existing assessment tools primarily evaluate the facial area to assess the severity of rosacea. However, in addition to the face, telangiectasia, erythema, and flushing can occur in the ear. Here, we investigated the correlation between the dermoscopic characteristics of capillaries in the earlobe and auricle and the types and severity of rosacea. Materials and Methods: Experienced dermatologists evaluated the clinical type, medical history, severity, and distribution pattern of facial erythema. The clinical severity of rosacea was assessed using the standard grading system (SGS), clinician's erythema assessment (CEA), and investigator's global assessment (IGA). Relationships of the clinical types and severity with the dermoscopic characteristics of capillaries in the earlobe and auricle were further analyzed. Results: In total, 145 patients with rosacea were enrolled in this study. We found that SGS, CEA, and IGA correlated well with the dermoscopic features of capillaries in the earlobe (R = 0.357, 0.357, and 0.314, respectively) (p < 0.001) and auricle (R = 0.423, 0.443, and 0.374, respectively) (p < 0.001). However, there was no significant correlation between the features and types of rosacea. Conclusion: The dermoscopic characteristics of capillaries in the earlobe and auricle can be used as indicators of the clinical severity of rosacea, regardless of the clinical subtype.

Predictive Ability of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) Score for in-Hospital and Medium-Term Mortality of Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVE: To evaluate the powers of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) score in predicting in-hospital and medium-term mortality of patients undergoing coronary artery bypass grafting (CABG). METHODS: Totally 1628 Chinese patients were included between January 2000 and January 2018. Their perioperative clinical data were collected and the patients were closely followed up. According to the length of follow-up time, the total cohort was divided into 1-year, 2-year, 3-year, 4-year and 5-year groups. The in-hospital and medium-term risk prediction of EuroSCORE II and STS score were comparatively assessed by calibration, discrimination, decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and Bland-Altman analysis. RESULTS: About 36 (2.21%) patients died during hospitalization. Both EuroSCORE II and STS score performed extremely well in predicting in-hospital mortality (area under curve = 0.900 and 0.879, respectively). However, calibration and discrimination analyses showed gradual decrease when these two risk evaluation systems were used to predict mortality during the follow-up period. At the same time, the predictive ability of EuroSCORE II was better than STS score. DCA curves showed that the performances of the two evaluation systems were roughly equal between the threshold probability of 0% to 20%. The percentage of correct reclassification of EuroSCORE II was 21.64% higher than that of STS score in predicting 2-year postoperative mortality. The IDI index showed that the predictive capabilities of these two systems were roughly equivalent. Bland-Altman analysis showed no significant difference between the values of the two systems. CONCLUSION: EuroSCORE II and STS score have excellent predictive powers in predicting in-hospital mortality of patients undergoing CABG. In particular, EuroSCORE II is superior in calibration and discrimination. The prediction efficiency of the two risk evaluation systems is still acceptable for two-year postoperative mortality, but decreases year by year.

The bioinformatics analysis of quercetin in octagonal lotus for the screening of breast cancer MYC, CXCL10, CXCL11, and E2F1.

BACKGROUND: Comprehensive bioinformatics analysis of the effective molecular screening of Podophyllum octagonal in breast cancer treatment by using network pharmacology. METHODS: We collected the active ingredients and target genes of Chinese medicine octagonal lotus through the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP); downloaded human protein annotation information on the protein database Uniport; and collected data from five databases: GeneCards, OMIM, PharmGkb, TDD, and DrugBank. Construct the practical ingredient-target gene data intersection to obtain the target gene-disease gene and draw the Venn diagram. We use Cytoscape 3.8.0 software to construct the effective component-target gene-disease gene network. The STRING database protein interaction (PPI) networks were erected, and we used Cytoscape 3.8.0 software to screen out its core sub-networks and hub gene networks. Through survival analysis, core genes and hub genes were screened to identify several key genes. We performed key target gene ontology (GO) analysis and gene interaction (KEGG) analysis, which were followed by molecular docking of the key active ingredients in the star anise corresponding to several key genes. RESULTS: 19 active ingredients, 444 drug targets, and 10,941 disease-related genes were obtained. The key active ingredient was quercetin. GO analysis revealed 2471 affected biological processes, and 167 pathways were obtained in KEGG enrichment analysis. CONCLUSION: This study initially screened the key active ingredients of star aniseed lotus and analyzed key genes and several essential pathways. Traditional Chinese medicine is expected to provide new evidence and research ideas to prevent and treat breast cancer.

Effects of peak time of myocardial injury biomarkers on mid-term outcomes of patients undergoing OPCABG.

BACKGROUND: With the development of cardiac surgery techniques, myocardial injury is gradually reduced, but cannot be completely avoided. Myocardial injury biomarkers (MIBs) can quickly and specifically reflect the degree of myocardial injury. Due to various reasons, there is no consensus on the specific values of MIBs in evaluating postoperative prognosis. This retrospective study was aimed to investigate the impact of MIBs on the mid-term prognosis of patients undergoing off-pump coronary artery bypass grafting (OPCABG). METHODS: Totally 564 patients undergoing OPCABG with normal courses were included. Cardiac troponin T (cTnT) and creatine kinase myocardial band (CK-MB) were assessed within 48 h before operation and at 6, 12, 24, 48, 72, 96 and 120 h after operation. Patients were grouped by peak values and peak time courses of MIBs. The profile of MIBs and clinical variables as well as their correlations with mid-term prognosis were analyzed by univariable and multivariable Cox regression models. RESULT: Continuous assessment showed that MIBs increased first (12 h after surgery) and then decreased. The peak cTnT and peak CK-MB occurred within 24 h after operation in 76.8% and 67.7% of the patients respectively. No significant correlation was found between CK-MB and mid-term mortality. Delayed cTnT peak (peak cTnT elevated after 24 h after operation) was correlated with lower creatinine clearance rate (69.36 ± 21.67 vs. 82.18 ± 25.17 ml/min/1.73 m2), body mass index (24.35 ± 2.58 vs. 25.27 ± 3.26 kg/m2), less arterial grafts (1.24 ± 0.77 vs. 1.45 ± 0.86), higher EuroSCORE II (2.22 ± 1.12 vs.1.72 ± 0.91) and mid-term mortality (26.5 vs.7.9%). Age (HR: 1.067, CI: 1.006-1.133), left ventricular ejection fraction (HR: 0.950, CI: 0.910-0.993), New York Heart Association score (HR: 1.839, CI: 1.159-2.917), total venous grafting (HR: 2.833, CI: 1.054-7.614) and cTnT peak occurrence within 24 h (HR: 0.362, CI: 0.196-0.668) were independent predictors of mid-term mortality. CONCLUSION: cTnT is a better indicator than CK-MB. The peak value and peak occurrence of cTnT are related to mid-term mortality in patients undergoing OPCABG, and the peak phases have stronger predictive ability. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033850. Registered 14 June 2020, http://www.chictr.org.cn/edit.aspx?pid=55162&htm=4 .

Developing the relationship between metal ionic characters and ecological risk assessment screening values using QICAR.

Metals are widely released and distributed in soil and may have a negative impact on terrestrial organisms. Over the past years, a series of criteria or standards for assessing the ecological risks and toxicity of metals have been published in many countries; however, few studies have investigated their metal ionic properties and toxicity. In the present study, the ecological risk assessment screening values (ERASV) recommended by the Oregon Department of Environmental Quality were selected to investigate the correlation between metal toxicity and their ionic characters based on the hard and soft acids and bases (HSAB) concept. The results showed that more ionic characters were significantly correlated with ERASV using the HSAB theory, while only one metal ionic characteristic was correlated with ERASV in organisms. For borderline metal ions, maximum complex stability constants (log ßn) and the softness (δp) of borderline ions were correlated with ERASV, while log ßn and electronegativity (Xm) were significantly related to ERASV for borderline plus hard ions, and the boiling point (BP) and electron density (AR/AW) (AR indicates atomic radius and AW is atomic mass) were significantly related to ERASV for borderline plus soft ions. These results indicated that different metal ion characteristics play different roles in different types of metal toxicity in organisms and the mechanisms of toxicity are different. Based on these relationships, a set of quantitative ion characteristic parameter-activity relationship (QICAR) was developed. The QICAR predicted ERASV for metals that were reasonably consistent with those recommended by the Oregon Department of Environmental Quality, with differences between them generally < 2.0 orders of magnitude. However, there were discrepancies between the recommended and predicted values, and these discrepancies may be related to terrestrial geochemical properties. These soil properties should be further considered when developing QICAR models in future studies, such as soil type, organic matter, and pH. Overall, the QICAR models were able to determine the relationships between metal ionic properties and their toxicity and will be useful for assessing toxicity data on unknown toxic metals and will provide a basis for ecological assessment.

Dopamine-assisted one-pot synthesis of gold nanoworms and their application as photothermal agents.

Gold-based nanomaterials of various sizes and geometries have been prepared for use as photothermal agents due to their unique physical and chemical properties. Here we report a simple one-step synthesis of gold nanoworms (NWs) and characterized them with transmission electron microscopy, X-ray photoelectron spectroscopy, UV-Visible spectroscopy, and Fourier transform infrared spectroscopy. The results showed that small gold nanounits were first formed by reducing chloroaurate ions (AuCl4-) with sodium borohydride (NaBH4), and then fused together to form NWs assisted by dopamine (DA), which served a structure-director due to an oriented attachment mechanism. Then DA in the solution was further polymerized into polydopamine (PDA) to form a coating layer on the surface of gold NWs. Moreover, further experiments showed that gold NWs had low cytotoxicity and excellent performance as a photothermal bactericidal on both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. These results show that the synthesized gold NWs are a promising photothermal agent.

Quantifying correlations of metal ionic characters with ecological soil screening levels (Eco-SSLs) of metals using QICAR models.

Soil pollution by heavy metals is a major challenge for soil ecosystems; therefore, many countries have published thresholds or standards for protecting soil organisms based on toxicity testing. However, there have been few studies on the mechanism of metal toxicity on organisms in soils, especially relationships between metal's ionic properties and its toxicity. Herein, we selected environmental soil screening levels (Eco-SSLs), which are internationally recognized ecotoxicity values recommended by the United States Environmental Protection Agency (USEPA), and investigated relationships between Eco-SSLs and metal ionic characteristics. The results showed that several ionic characteristics were significantly correlated with Eco-SSL using a classification of metal ions according to hard and soft acids and bases. Electrochemical potential, atomic ionization potential, the first hydrolysis constant, the maximum complex stability constant, a polarization force parameter and covalent radius showed significant correlations with Eco-SSLs for borderline plus hard ions, while the soft index exhibited significant fitting for borderline plus soft ions, suggesting that ionic bonding and covalent bonding played important roles in metal toxicity on borderline plus hard ions and soft ions, respectively. Then, we chose characteristics that had the strongest correlations with Eco-SSLs, and developed quantitative ion character-activity relationship (QICAR) for soil organisms. The QICARs predicted Eco-SSLs for metals that were reasonably consistent with those recommended by USEPA, with differences between them generally <0.5 orders of magnitude. Overall, QICAR provide a basis for ecological risk assessment and could be useful to interpret relationships between metal's ionic properties and its toxicity.

Development of a coupled model of quantitative ion character-activity relationships-biotic ligand model (QICARs-BLM) for predicting toxicity for data poor metals.

The biotic ligand model (BLM) is proposed as a tool to quantitatively evaluate biological toxicity of metals considering both metal speciation and the influence of environmental conditions. The model assumes that biological sites bind to metals as biotic ligands (BLs) and obtains a series of BLM parameters including conditional binding constants (K). However, developing a BLM for each metal and biology takes a lot of experimentation. In the present study, relationships between metal ionic characters and BLM parameter K were respectively investigated for three terrestrial organisms. The results showed that ionization potential was the most strongly related to log K for barley (R2 = 0.845, p < 0.01) and earthworm (R2 = 0.881, p < 0.01), and electronegativity index most significantly related to log K for lettuce (R2 = 0.835, p < 0.01). Based on these relationships, a set of quantitative ion character-activity relationships (QICARs) were developed for predicting log K of metals. Then the QICAR were coupled with BLM and a novel QICAR-BLM was constructed. Finally, the QICAR-BLM was applied to predict EC50 of other unknown-toxicity metals for selected species, and compensate for the lack of toxicity data for a large number of metals in soil.

The prediction of combined toxicity of Cu-Ni for barley using an extended concentration addition model.

Environment pollution often occurs as an obvious combined effect involving two (or more) elements, and this effect changes with the concentrations of the different elements. The effects on barley root elongation were studied in hydroponic systems to investigate the toxicity of Cu-Ni combined at low doses and at a fixed concentration ratio. For low doses of Cu-Ni, the addition of Ni (<0.5 µM) to Cu significantly decreased Cu toxicity for barley, but the addition of Cu (<0.25 µM) had no significant effect on Ni toxicity. At a fixed concentration ratio, according to the single effective concentration (EC) (barley root elongation inhibitory concentration) values of Cu and Ni, five sets of Cu-Ni fixed ratios were used: ECn(Cu)+ECm(Ni) (n + m = 100) (ECn and ECm indicate toxicity unit value for n% and m% inhibition of barley root length, respectively). The calculated toxicity unit value for 50% inhibition of root length ranged from 0.44 to 0.98 (i.e., <1), indicating a synergistic effect. To consider the interactions between the metal ions, the extended concentration addition model (e-CA) was established by integrating the Cu-Ni interaction into the concentration addition model (CA), and the data of two groups (the low doses of Cu-Ni and at a fixed concentration ratio) were respectively fitted. The e-CA accurately predicted the root length of barley under the Cu-Ni combined action. The correlation coefficient (r) and the root-mean-square error (RMSE) between predicted and observed values were 0.97 and 6.6 (low-dose group) and 0.96 and 8.12 (fixed-ratio group), respectively, and e-CA significantly improved the prediction accuracy compared to the traditional CA model without consideration of the Cu-Ni competition (r = 0.89, RMSE = 14.16). The results provided a theoretical basis for evaluation and remediation of soil contaminated with heavy metal composites.