Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Exploring the relationship between pollen viability and inclusion in Paeonia lactiflora after cryopreservation.

Pollen, as the male gametophyte, carries half of plant genetic information and is an important source of germplasm. The cryopreservation of pollen can not only preserve germplasm, but also solve the problem of time and space barrier in crossbreeding. So it is of great significance to explore the mechanism of pollen viability maintenance after cryopreservation. In this paper, 10 cultivars of Paeonia lactiflora with different fresh pollen viability that did not change after cryopreservation were taken as objects and the effects of pollen inclusions such as soluble sugars, starch, soluble proteins, free amino acids, and proline were explored. The results showed that: 1) The contents of pollen inclusions in the fresh pollen of 10 cultivars were different. After cryopreservation, the contents of starch and free amino acids significantly decreased in 10 cultivars, and the soluble sugar, soluble protein, and proline varied with cultivars. 2) Correlation analysis showed that fresh pollen viability was significantly positively correlated with the soluble sugar (R-values of 0.630) and starch content (R-values of 0.694) in fresh pollen. But after cryopreservation pollen viability was only significantly positively correlated with the starch content (R-values of 0.725). These results suggest that the effects of pollen inclusions on pollen vitality are different before and after cryopreservation. The fresh pollen with higher soluble sugar and starch is more vital. But after cryopreservation, the pollen with high starch content has higher viability. The maintenance of stable pollen viability after cryopreservation appears to be related to starch content or starch metabolism, which requires further to study for a final determination.

Formation of Furan from Linoleic Acid Thermal Oxidation: (E,E)-2,4-Decadienal as a Critical Intermediate Product.

The linoleic acid reaction models were set at 150 °C for 120 min, and its oxidation process was monitored by nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS). Results showed that no furan was formed from linoleic acid without heating, while furan accumulated throughout the heating process. Linoleic acid ran out within 30 min, which indicated that furan was formed mainly from the intermediate oxidation products of linoleic acid after 30 min. It should be noticed that the content of (E,E)-2,4-decadienal reached maximum once the linoleic acid ran out and then decreased with the formation of furan. Multivariate statistical analysis suggested that (E,E)-2,4-decadienal was the most important aldehyde related to furan formation during linoleic acid oxidation. To prove this assumption, the variation of furan from (E,E)-2,4-decadienal reaction models heating at 150 °C for 60 min was also studied. Results showed that the content of furan increased with the oxidation of (E,E)-2,4-decadienal. Furthermore, NMR and GC-MS data proved that (E,E)-2,4-decadienal could be oxidized to 4,5-epoxy-(E)-2-decenal. In conclusion, our results supported (E,E)-2,4-decadienal and trans-4,5-epoxy-(E)-2-decenal as critical intermediate products of furan formation from linoleic acid oxidation.

Genomic and transcriptomic profiling of hepatocellular carcinoma reveals a rare molecular subtype.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, occurring predominantly in patients with underlying chronic liver disease and cirrhosis. Here, we describe a case of a 62-year-old man that was admitted to our hospital and diagnosed with HCC where the cancer has already metastasized to the retroperitoneum and peritoneum. In order to better characterize the HCC, both the cancerous liver tissue and the adjacent normal liver tissue of the patient were collected and subjected to a genomic, transcriptomic and proteomic analysis. Our patient carries a highly mutated HCC, which is characterized by both somatic mutation in the following genes ALK, CDK6, TP53, PGR. In addition, we observe several molecular alterations that are associated with potential therapy resistance, for example the expression of the organic-anion-transporting polypeptide (OATP) family members B1 and B3, that mediate the transport of the anticancer drugs, has been found decreased. Overall, our molecular profiling potentially classify the patient with poor prognosis and possibly displaying resistance to pharmacological therapy.

mROS­calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia.

Lethal ventricular arrhythmia­sudden cardiac death (LVA­SCD) occurs frequently during the early stage of myocardial ischemia (MI). However, the mechanism underlying higher LVA­SCD incidence is still poorly understood. The present study aimed to explore the role of mitochondrial reactive oxygen species (mROS) and Ca2+ crosstalk in promoting LVA­SCD in early MI. RyR2 S2814A mice and their wild­type littermates were used. MitoTEMPO was applied to scavenge mitochondrial ROS (mROS). Mice were subjected to severe MI and the occurrence of LVA­SCD was evaluated. Levels of mitochondrial ROS and calcium (mitoCa2+), cytosolic ROS (cytoROS), and calcium (cytoCa2+), RyR2 Ser­2814 phosphorylation, CaMKII Met­282 oxidation, mitochondrial membrane potential (MMP), and glutathione/oxidized glutathione (GSH/GSSG) ratio in the myocardia were detected. Dynamic changes in mROS after hypoxia were investigated using H9c2 cells. Moreover, the myocardial phosphoproteome was analyzed to explore the related mechanisms facilitating mROS­Ca2+ crosstalk and LVA­SCD. There was a high incidence (~33.9%) of LVA­SCD in early MI. Mice who underwent SCD displayed notably elevated levels of myocardial ROS and mROS, and the latter was validated in H9c2 cells. These mice also demonstrated overloads of cytoplasmic and mitochondrial Ca2+, decreased MMP and reduced GSH/GSSG ratio, upregulated RyR2­S2814 phosphorylation and CaMKII­M282 oxidation and transient hyperphosphorylation of mitochondrial proteomes in the myocardium. mROS­specific scavenging by a mitochondria­targeted antioxidant agent (MitoTEMPO) corrected these SCD­induced alterations. S2814A mice with a genetically inactivated CaMKII phosphorylation site in RyR2 exhibited decreased overloads in cytoplasmic and mitochondrial Ca2+ and demonstrated similar effects as MitoTEMPO to correct SCD­induced changes and prevent SCD post­MI. The data confirmed crosstalk between mROS and Ca2+ in promoting LVA­SCD. Therefore, we provided evidence that there is a higher incidence of LVA­SCD in early MI, which may be attributed to a positive feedback loop between mROS and Ca2+ imbalance.

PML-mediated nuclear loosening permits immunomodulation of mesenchymal stem/stromal cells under inflammatory conditions.

Nuclear configuration plays a critical role in the compartmentalization of euchromatin and heterochromatin and the epigenetic regulation of gene expression. Under stimulation by inflammatory cytokines IFN-γ and TNF-α, human mesenchymal stromal cells (hMSCs) acquire a potent immunomodulatory function enabled by drastic induction of various effector genes, with some upregulated several magnitudes. However, whether the transcriptional upregulation of the immunomodulatory genes in hMSCs exposed to inflammatory cytokines is associated with genome-wide nuclear reconfiguration has not been explored. Here, we demonstrate that hMSCs undergo remarkable nuclear reconfiguration characterized by an enlargement of the nucleus, downregulation of LMNB1 and LMNA/C, decondensation of heterochromatin, and derepression of repetitive DNA. Interestingly, promyelocytic leukaemia-nuclear bodies (PML-NBs) were found to mediate the nuclear reconfiguration of hMSCs triggered by the inflammatory cytokines. Significantly, when PML was depleted, the immunomodulatory function of hMSCs conferred by cytokines was compromised, as reflected by the attenuated expression of effector molecules in hMSCs and their failure to block infiltration of immune cells to lipopolysaccharide (LPS)-induced acute lung injury. Our results indicate that the immunomodulatory function of hMSCs conferred by inflammatory cytokines requires PML-mediated chromatin loosening.

Comprehensive applications of metabolomics on tea science and technology: Opportunities, hurdles, and perspectives.

With the development of metabolomics analytical techniques, relevant studies have increased in recent decades. The procedures of metabolomics analysis mainly include sample preparation, data acquisition and pre-processing, multivariate statistical analysis, as well as maker compounds' identification. In the present review, we summarized the published articles of tea metabolomics regarding different analytical tools, such as mass spectrometry, nuclear magnetic resonance, ultraviolet-visible spectrometry, and Fourier transform infrared spectrometry. The metabolite variation of fresh tea leaves with different treatments, such as biotic/abiotic stress, horticultural measures, and nutritional supplies was reviewed. Furthermore, the changes of chemical composition of processed tea samples under different processing technologies were also profiled. Since the identification of critical or marker metabolites is a complicated task, we also discussed the procedure of metabolite identification to clarify the importance of omics data analysis. The present review provides a workflow diagram for tea metabolomics research and also the perspectives of related studies in the future.

Novel Oxidation Oligomer of Chlorogenic Acid and (-)-Epigallocatechin and Its Quantitative Analysis during the Processing of Keemun Black Tea.

Not only do flavan-3-ols participate in the formation of chromogenic oxidation products such as theaflavins, but chlorogenic acid (3-caffeoylquinic acid, CQA) is also involved in the enzymatic oxidation during black tea processing. The critical oxidation product of CQA and (-)-epigallocatechin (EGC) were identified as an adduct containing benzobicyclo[3.2.2]nonenone structure, which was named as the dichlorogeniccatechin (DCGC) oligomer. It was composed of two molecules of CQA and one molecule of EGC. The effects of the initial reactant ratio and reaction time on the generation of DCGC were also analyzed. A high proportion of CQA promoted the production of DCGC, but a high proportion of EGC inhibited the DCGC formation. In addition, the content of DCGC in Keemun black tea during processing was determined. The content of DCGC highly increased after withering but decreased after drying. This study provides a new perspective for the investigation of other oxidation oligomers in black tea.

Whole-genome resequencing of the native sheep provides insights into the microevolution and identifies genes associated with reproduction traits.

BACKGROUND: Sheep genomes undergo numerous genes losses, gains and mutation that generates genome variability among breeds of the same species after long time natural and artificial selection. However, the microevolution of native sheep in northwest China remains elusive. Our aim was to compare the genomes and relevant reproductive traits of four sheep breeds from different climatic environments, to unveil the selection challenges that this species cope with, and the microevolutionary differences in sheep genomes. Here, we resequenced the genomes of 4 representative sheep breeds in northwest China, including Kazakh sheep and Duolang sheep of native breeds, and Hu sheep and Suffolk sheep of exotic breeds with different reproductive characteristics. RESULTS: We found that these four breeds had a similar expansion experience from ~ 10,000 to 1,000,000 years ago. In the past 10,000 years, the selection intensity of the four breeds was inconsistent, resulting in differences in reproductive traits. We explored the sheep variome and selection signatures by FST and θπ. The genomic regions containing genes associated with different reproductive traits that may be potential targets for breeding and selection were detected. Furthermore, non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds with different reproductive characteristics were found. We identified PAK1, CYP19A1 and PER1 as a likely causal gene for seasonal reproduction in native sheep through qPCR, Western blot and ELISA analyses. Also, the haplotype frequencies of 3 tested gene regions related to reproduction were significantly different among four sheep breeds. CONCLUSIONS: Our results provide insights into the microevolution of native sheep and valuable genomic information for identifying genes associated with important reproductive traits in sheep.

Orchestration of Mesenchymal Stem/Stromal Cells and Inflammation During Wound Healing.

Wound healing is a complex process and encompasses a number of overlapping phases, during which coordinated inflammatory responses following tissue injury play dominant roles in triggering evolutionarily highly conserved principals governing tissue repair and regeneration. Among all nonimmune cells involved in the process, mesenchymal stem/stromal cells (MSCs) are most intensely investigated and have been shown to play fundamental roles in orchestrating wound healing and regeneration through interaction with the ordered inflammatory processes. Despite recent progress and encouraging results, an informed view of the scope of this evolutionarily conserved biological process requires a clear understanding of the dynamic interplay between MSCs and the immune systems in the process of wound healing. In this review, we outline current insights into the ways in which MSCs sense and modulate inflammation undergoing the process of wound healing, highlighting the central role of neutrophils, macrophages, and T cells during the interaction. We also draw attention to the specific effects of MSC-based therapy on different pathological wound healing. Finally, we discuss how ongoing scientific advances in MSCs could be efficiently translated into clinical strategies, focusing on the current limitations and gaps that remain to be overcome for achieving preferred functional tissue regeneration.

Monitoring Subtle Changes of Blood-Brain Barrier Permeability via Detection of MiRNA-155 in Brain Microvasculature.

The changes of blood-brain barrier (BBB) permeability need to be sensitively reported when purposefully regulating the BBB or during some brain diseases. Currently available techniques for assessment of BBB integrity all suffer from limited sensitivity and only report serious BBB damage. Here, a targeted activatable nanoprobe is created to monitor subtle changes of BBB permeability by detecting the expression levels of BBB permeability-related miRNA (miRNA-155) in brain microvessel endothelial cells (BMECs). The probe is fabricated by coating the BMEC membrane on calcium phosphate (CaP)-mineralized metal-organic framework (MOF) nanoparticles loaded with hybridization chain reaction (HCR) probes. The coating of the BMEC membrane endows the nanoprobe with homologous targeting ability to BBB, and HCR probes released and escaped from lysosomes can be specifically lightened by miRNA-155. The activatable nanoprobe is able to monitor BBB permeability in inflammatory and AD mice. This work provides a new idea for highly sensitive evaluation of the BBB permeability, which has guiding significance in regulating BBB and formulating targeted therapeutic strategies.

Effectiveness of Hypertonic Dextrose Injection (Prolotherapy) in Plantar Fasciopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review the effectiveness of hypertonic dextrose prolotherapy (DPT) in plantar fasciopathy (PF) compared with other non-surgical treatments. DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Allied and Complementary Medicine Database, Global Health, Ovid Nursing Database, Dimensions, and WHO ICTRP were searched from inception to April 30th, 2022. STUDY SELECTION: Two independent reviewers selected randomized controlled trials (RCTs) that evaluated the effectiveness of DPT in PF compared with non-surgical treatments. Outcomes included pain intensity, foot and ankle function, and plantar fascia thickness. DATA EXTRACTION: Two independent reviewers conducted data extraction. Risk of bias (RoB) assessment was conducted using the Cochrane Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed with Grading of Recommendation Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: Eight RCTs (n=469) met the inclusion criteria. Pooled results favored the use of DPT versus normal saline (NS) injections in reducing pain (weighted mean difference [WMD] -41.72; 95% confidence interval [CI] -62.36 to -21.08; P<.01; low certainty evidence) and improving function [WMD -39.04; 95% CI -55.24 to -22.85; P<.01; low certainty evidence] in the medium term. Pooled results also showed corticosteroid (CS) injections was superior to DPT in reducing pain in the short term [standardized mean difference 0.77; 95% CI 0.40 to 1.14; P<.01; moderate certainty evidence]. Overall RoB varied from "some concerns" to "high". The overall certainty of evidence presented ranges from very low to moderate based on the assessment with the GRADE approach. CONCLUSION: Low certainty evidence demonstrated that DPT was superior to NS injections in reducing pain and improving function in the medium term, but moderate certainty evidence showed that it was inferior to CS in reducing pain in the short term. Further high-quality RCTs with standard protocol, longer-term follow-up, and adequate sample size are needed to confirm its role in clinical practice.

Exploring correlations between green coffee bean components and thermal contaminants in roasted coffee beans.

This study evaluated chemical compositions of green coffee beans from multi-production regions and correlated this information with thermal contaminants in roasted coffee. Using multivariate statistical techniques, formation of 5-hydroxymethylfurfural (5-HMF), furan, 2- and 3-methylfuran were positively correlated with lipid, sucrose, glutamic acid, phenylalanine, margaric acid, linolenic acid and trigonelline in green coffee beans. Moreover, significant positive correlations between acrylamide (AA) levels with aspartic acid, serine, alanine, histidine, asparagine, protein, and caffeine was found in green beans. Despite this, 5-HMF, furan, 2- and 3-methylfuran showed negative correlations with active constitutes (neochlorogenic acid, cryptochlorogenic acid, caffeine, total phenolics (TPC) and total flavonoids contents (TFC)), and several amino acids, and there were slight negative relationships between AA and myristic acid, palmitic acid, chlorogenic acid, sucrose, lipid, TPC and TFC. This study provides valuable enlightenment for the selection of proper coffee beans for production of coffee with high nutrition and low chemical hazardous risks.

Co-doped g-C3N4 nanotube decorated separators mediate polysulfide redox for high performance lithium sulfur batteries.

The main issue with lithium-sulfur (Li-S) batteries is the serious irreversible capacity loss caused by the polysulfide shuttle process. In this work, we propose an electro-catalytic strategy for absorbing and transferring long-chain polysulfides during the redox process, which is the key to improving the utilization of S. Reported here is a Co doped tubular g-C3N4 (CN) modified separator (Co-TCN@PP), which successfully inhibited the polysulfide shuttle by physical absorption and catalysis, thus facilitating the high utilization of S. Co-TCN with a tube-like structure ensures the uniform dispersion of Co nanoparticles, which provides abundant active sites to absorb polysulfides. Furthermore, Co-TCN exhibits fast reaction kinetics for polysulfide conversion. A Li-S battery with Co-TCN@PP achieves superior rate capacities and a long cycle life (400 times) with capacity fading as low as 0.07% per cycle at a high Li+ insertion/extraction rate of 2C. Moreover, electrodes with a high sulfur loading of 5.6 mg cm-2 can be realized by adopting the Co-TCN@PP separator.

Rehabilitation care of patients with neurogenic bladder after spinal cord injury: A literature review.

This article reviews the research progress of rehabilitation treatment and nursing care of patients with neurogenic bladder after spinal cord injury, in order to provide reference for the rehabilitation treatment and nursing care of patients. We reviewed recent medical literature on patients with neurogenic bladder, focusing on neurogenic bladder caused by spinal cord injury. We analyzed 30 recent of publications in patients with neurogenic bladder after spinal cord injury, in addition to reviewing and evaluating the commonly used rehabilitation nursing methods for neurogenic bladder. Psychological counseling is a vital aspect which cannot be neglected in the process of neurogenic bladder rehabilitation. Hitherto, the commonly used drug and surgical treatments may have negatively impacted the mental health of patients in varying degrees. However, in clinical practice, applying intermittent catheterization in patients who have neurogenic bladder with spinal cord injury may help improve patients' life quality, mitigate psychological burden, and reduce negative emotions.

Patient preferences in the treatment of chronic musculoskeletal pain: a systematic review of discrete choice experiments.

ABSTRACT: Chronic musculoskeletal pain (CMP) is a preference-sensitive condition for which numerous treatment options are available, each with benefits and risks. Thus, patient preferences play a critical role in decision making. This study summarized evidence from discrete choice experiments (DCEs) to quantify patient preferences for CMP treatment and identified important treatment attributes. A systematic review of DCEs on patient preferences for CMP treatment was conducted. Studies were included if they used DCE to determine patient preferences for CMP. A previously described methodological assessment tool was used to assess the risk of bias. The treatment attributes were summarized and sorted according to the frequency of citation and relative weight. Subgroup analyses were conducted to explore the intervention-specific attributes. A total of 15 eligible studies with 4065 participants were included. We identified "capacity to realize daily life activities," "risk of adverse events," "effectiveness in pain reduction," and "out-of-pocket cost" as important attributes. Although "treatment frequency" and "onset of treatment efficacy" were less frequently mentioned, they were also important attributes. The attribute of "risk of adverse events" was especially important for drug treatment. The "out-of-pocket cost" and "treatment location and mode" were important attributes of exercise therapy. The attributes identified in this review will inform the design of future DCE studies, facilitate the translation of measurement-based care to value-based care, and provide the rationale to promote shared decision making and patient-centered care.

Development of QuEChERS clean-up based on EMR-lipid for simultaneous analysis of 9 mycotoxins, acaylamide and 5-Hydroxymethylfurfural in biscuit by UHPLC-MS/MS.

A robust and sensitive analytical method for the simultaneous determination of 9 mycotoxins, AA, and 5-HMF by UHPLC-MS/MS was developed. Clean-up of the extracts was achieved by d-SPE with EMR-lipid. A new column phase (C18-PFP) was selected for HPLC separation after comparison with the C18 column. Finally, the method gave good linear relations with regression coefficients R2 > 0.99. The recovery of all the tested compounds was within the range of 70.67 to 104.88%, and the intraday and interday relative standard deviations (RSD) were lower than 12.49. The proposed method was then applied to investigate the mycotoxins, AA and 5-HMF in 20 food samples sold in the retail market. AA and 5-HMF were widely detected, and half of the samples were found to contain at least one mycotoxin contamination. Therefore, this method is potential to be used as a convenient and effective method for the cookies product quality control in the future.

The pathogenesis and regulatory role of HIF-1 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1 α/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-κB pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

Food polyphenols and Maillard reaction: regulation effect and chemical mechanism.

Maillard reaction is a non-enzymatic thermal reaction during food processing and storage. It massively contributes to the flavor, color, health benefits and safety of foods and could be briefly segmented into initial, intermediate and final stages with the development of a cascade of chemical reactions. During thermal reaction of food ingredients, sugar, protein and amino acids are usually the main substrates, and polyphenols co-existed in food could also participate in the Maillard reaction as a modulator. Polyphenols including flavan-3-ols, hydroxycinnamic acids, flavonoids, and tannins have shown various effects throughout the process of Maillard reaction, including conjugating amino acids/sugars, trapping α-dicarbonyls, capturing Amadori rearrangement products (ARPs), as well as decreasing acrylamide and 5-hydroxymethylfurfural (5-HMF) levels. These effects significantly influenced the flavor, taste and color of processed foods, and also decreased the hazard products' level. The chemical mechanism of polyphenols-Maillard products involved the scavenging of radicals, as well as nucleophilic addition and substitution reactions. In the present review, we concluded and discussed the interaction of polyphenols and Maillard reaction, and proposed some perspectives for future studies.

HighlightsFood polyphenols regulate Maillard reaction through substrates, initial, intermediate and final stages/products of Maillard reaction.The trapping ability of food polyphenols on α-dicarbonyls relied on the structural properties, and was also affected by reaction conditions such as pH value.Food polyphenols could act as potential inhibitors toward the formation of harmful compounds during advanced and final stages of Maillard reaction.The chemical mechanism of polyphenols-Maillard reaction products involved the scavenging of radicals, as well as nucleophilic addition and substitution.