Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.

OBJECTIVE: Hepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified. DESIGN: A highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution. Different function units were defined by topological analysis of TME. CN relevant to the patients' prognosis was identified as specific target for HCC therapy. Transgenic mouse models were used to validate the novel immunotherapy target for HCC. RESULTS: Three major types of intratumour areas with distinct distribution patterns of tumorous, stromal and immune cells were identified. 22 cellular metaclusters and 16 CN were defined. CN composed of various types of cells formed regional function units and the regional immunity was regulated reversely by resident Kupffer cells and infiltrating macrophages with protumour and antitumour function, respectively. Depletion of Kupffer cells in mouse liver largely enhances the T cell response, reduces liver tumour growth and sensitises the tumour response to antiprogrammed cell death protein-1 treatment. CONCLUSION: Our findings reveal for the first time the various topological function units of HCC TME, which also presents the largest depository of pathological landscape for HCC. This work highlights the potential of Kupffer cell-specific targeting rather than overall myeloid cell blocking as a novel immunotherapy for HCC treatment.

Functional analysis of Dicer-2 gene in Bombyx mori resistance to BmNPV virus.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a primary pathogen in silkworm, and the molecular mechanism of B. mori defense to BmNPV infection is still unclear. RNA interference (RNAi) is well-known as an intracellular conserved mechanism that is critical in gene regulation and cell defense. The antiviral RNAi pathway processes viral double-stranded RNA (dsRNA) into viral small interfering RNAs that guide the recognition and cleavage of complementary viral target RNAs. In this study, a Dicer-2 (Dcr2) gene was identified in B. mori and its antiviral function was explored. Dcr2 messenger RNA (mRNA) expression was the highest in hemocytes and expressed in all stages of silkworm growth. After infection with BmNPV, the expression of Dcr2 mRNA was significantly increased after infection in midgut and hemocytes. The expression of Dcr2 was significantly upregulated by injecting dsRNA (dsBmSPH-1) into silkworm after 48 hr. Knocking down the expression level of Dcr2 using specific dsRNA in silkworm, which modestly enhanced the production of viral genomic DNA. Our results suggested that the Dcr2 gene in B. mori plays an important role in against BmNPV invasion.

Different mechanism of LPS-induced calcium increase in human lung epithelial cell and microvascular endothelial cell: a cell culture study in a model for ARDS.

Acute respiratory distress syndrome (ARDS) is a contemporary term incorporating the historic 'acute lung injury' and the colloquial term 'shock lung'. ARDS remains a serious and enigmatic human disease, causing significant mortality. The mechanisms involved at the alveolar cell/capillary endothelial interface have been explored but to date we lack clarity on the role of intracellular calcium ([Ca(2+)]i) fluxes across this interface. To explore the mechanisms of Ca(2+) induced inflammatory reaction in epithelial cells and pulmonary microvascular endothelial cells (HMVEC) located at the two sides of blood-air barrier, lung epithelial A549 and HMVEC cells were treated with LPS. Our results demonstrated that LPS evoked the increase of [Ca(2+)]i, TNF-α and IL-8 in both cells types. The [Ca(2+)]i increases involved intracellular but not extracellular Ca(2+) sources in A549, but both intracellular and extracellular Ca(2+) sources in HMVEC cells. The effects of LPS on both cells types were completely inhibited by the combination of LPS and CaSR-targeted siRNA. Furthermore, LPS-inhibited cell proliferations were significantly reversed by the combined treatment. Therefore, LPS induced different mechanisms of [Ca(2+)]i increase during the activation of CaSR in A549 and HMVEC cells, which translates into functional outputs related to ARDS.

Behavioral responses of cave-roosting bats to artificial light of different spectra and intensities: Implications for lighting management strategy.

Artificial light at night has become an emerging environmental pollutant, posing a serious threat to biodiversity. Cave-roosting animals are vulnerable to light pollution due to long-term adaptation to nocturnal niches, and the problem is especially severe in the context of cave tourism and limestone mining. Mitigating the adverse impacts of artificial light on cave-dwelling animals presents a challenge. This study aimed to assess the relative contributions of spectral parameters and light intensity to the emergence behavior of nine cave-roosting bat species: Rhinolophus macrotis, Rhinolophus pearsonii, Rhinolophus rex, Rhinolophus pusillus, Rhinolophus siamensis, Rhinolophus sinicus, Hipposideros armiger, Myotis davidii, and Miniopterus fuliginosus. We manipulated light spectra and intensities through light-emitting diode (LED) lighting and gel filters at the entrance of bat roost. We monitored nightly passes per species to quantify bat emergence under the dark control and ten lighting conditions (blue, green, yellow, red, and white light at high and low intensities) using ultrasonic recording. Our analyses showed that the number of bat passes tended to be reduced in the presence of white, green, and yellow light, independent of light intensity. In contrast, the number of bat passes showed no pronounced differences under the dark control, blue light, and red light. The number of bat passes was primarily affected by LED light's blue component, red component, peak wavelength, and half-width instead of light intensity. These results demonstrate that spectral parameters of LED light can significantly affect emergence behavior of cave-dwelling bats. Our findings highlight the importance of manipulating light colors to reduce the negative impacts of light pollution on cave-roosting bats as a function of their spectral sensitivity. We recommend the use of gel filters to manage existing artificial lighting systems at the entrance of bat-inhabited caves.

Tough Structural Adhesives with Ultra-Resistance to Both High and Cryogenic Temperature.

Structural adhesion at high temperature has been a challenge for organic adhesives, and the commercially available adhesives that can work at a temperature above 150 °C is rather limited. Herein, two novel polymers were designed and synthesized via facile strategy, which involves polymerization between melamine (M) and M-Xylylenediamine (X), as well as copolymerization of MX and urea (U). With well-balanced rigid-flexible structures, the obtained MX and MXU resins were proved to be outstanding structural adhesives at a wide range temperature of -196~200 °C. They provided room-temperature bonding strength of 13~27 MPa for various substrates, steel bonding strength of 17~18 MPa at cryogenic temperature (-196 °C), and 15~17 MPa at 150 °C. Remarkably, high bonding strength of 10~11 MPa was retained even at 200 °C. Such superior performances were attributed to a high content of aromatic units, which leads to high glass transition temperature (Tg) up to ~179 °C, as well as the structural flexibility endowed by the dispersed rotatable methylene linkages.

Chitosan-tannin adhesive: Fully biomass, synthesis-free and high performance for bamboo-based composite bonding.

Inspired by phenol-amine chemistry of mussels, a synthesis-free and fully biomass adhesive composed of chitosan and tannin (CST) was successfully developed by a facile method. The performance of CST adhesive for bonding bamboo, wood and bamboo-wood substrates were tested. When 160 °C hot-press temperature was used, dry lap shear strength above 5.00 MPa was obtained. The CST adhesive has remarkable water resistance and low cure temperature as high wet shear strength of 2.37 MPa for plybamboo specimens was achieved after 3 h boiling in water even though low hot-press temperature of 100 °C was applied. Further, high strength of 1.78 MPa remained after 72 h boiling. With higher hot-press temperatures used, wet shear strength above 3.60 MPa was achieved. The adhesion performance for wood substrate was also superior to other phenol-amine adhesives reported in literatures. The bamboo-wood composites assembled with CST adhesive show excellent mechanical performance, specifically modulus of rupture (MOR) of 100-133 MPa and modulus of elasticity (MOE) of 10-13 GPa were achieved with different hot-press temperatures used. Given the advantages including outstanding water resistance, facile preparation, fully biomass, and low cure temperature, CST adhesive exhibited great potential to be an ideal alternative to formaldehyde-based resin for wood and bamboo bonding.

Effects of the Addition of Amino-Terminated Highly Branched Polyurea on Curing Properties of Phenol-Formaldehyde Resin.

In this work, a highly branched polyurea (HBP-NH2) similar to urea structure was introduced to phenol-formaldehyde (PF) resin to accelerate itscuring speed The results of gel time and bonding strength were combined to obtain a good modified additional stage and amount of HBP-NH2. The relative molar mass changes of HBP-NH2-modified PF resin were investigated by gel permeation chromatography (GPC). The effects of HBP-NH2 on the curing of PF resin were investigated by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The effect of HBP-NH2 on the structure of PF resin was also investigated by nuclear magnetic resonance carbon spectroscopy (13C-NMR). The test results show that the gel time of the modified PF resin was reduced by 32% and 51% at 110 °C and 130 °C, respectively. Meanwhile, the addition of HBP-NH2 increased the relative molar mass of PF resin. The bonding strength test showed that the bonding strength of modified PF resin increased by 22% after soaking in boiling water (93 °C ± 2) for 3 h. The DSC and DMA analysis indicated that the curing peak temperature decreased from 137 °C to 102 °C, and the curing rate of the modified PF resin was also faster than that of the pure PF resin. The 13C-NMR results showed that HBP-NH2 in the PF resin reacted to produce a co-condensation structure. Finally, the possible reaction mechanism of HBP-NH2 for the modification of PF resin was given.

Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma.

Rationale: Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade (ICB). Methods: Here, we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization, bioavailability, and biocompatibility for direct oxygen delivery into tumor sites by interfacial polymerization. Results: We observed oxygen microcapsules enhanced the oxygen concentration in the hypoxia environment and maintained the oxygen concentration for a long period both in vitro and in vivo. We found that oxygen microcapsules could significantly improve the efficiency of ICB against PDAC in vivo. Mechanismly, combined treatments using oxygen microcapsules and ICB could reduce the infiltration of tumor-associated macrophages (TAMs) and polarized pro-tumor M2 macrophages into anti-tumor M1 macrophages. In addition, combined treatments could elevate the proportion of T helper subtype 1 cells (Th1 cells) and cytotoxic T lymphocytes cells (CTLs) to mediate anti-tumor immune response in TME. Conclusion: In summary, this pre-clinical study indicated that reversing hypoxia in TME by using oxygen microcapsules was an effective strategy to improve the performances of ICB on PDAC, which holds great potential for treating PDAC in the future.

Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer that typically demonstrates resistance to chemotherapy. Tumor-associated macrophages (TAMs) are essential in tumor microenvironment (TME) regulation, including promoting chemoresistance. However, the specific TAM subset and mechanisms behind this promotion remain unclear. We employ multi-omics strategies, including single-cell RNA sequencing (scRNA-seq), transcriptomics, multicolor immunohistochemistry (mIHC), flow cytometry, and metabolomics, to analyze chemotherapy-treated samples from both humans and mice. We identify four major TAM subsets within PDAC, among which proliferating resident macrophages (proliferating rMφs) are strongly associated with poor clinical outcomes. These macrophages are able to survive chemotherapy by producing more deoxycytidine (dC) and fewer dC kinases (dCKs) to decrease the absorption of gemcitabine. Moreover, proliferating rMφs promote fibrosis and immunosuppression in PDAC. Eliminating them in the transgenic mouse model alleviates fibrosis and immunosuppression, thereby re-sensitizing PDAC to chemotherapy. Consequently, targeting proliferating rMφs may become a potential treatment strategy for PDAC to enhance chemotherapy.

Application of Nano-SiO2 Reinforced Urea-Formaldehyde Resin and Molecular Dynamics Simulation Study.

Nano-SiO2 is a typical modifier used for urea-formaldehyde (UF) resins to balance the reduced formaldehyde content and maintain bond strength. However, the microstructure of UF resin and the interaction between UF resin and nano-SiO2 are microscopic phenomena; it is difficult to observe and study its intrinsic mechanism in traditional experimental tests. In this work, the enhancement mechanism was explored by molecular dynamics simulations combined with an experiment of the effect of nano-SiO2 additions on UF resin. The results showed that the best performance enhancement of UF resin was achieved when the addition of nano-SiO2 was 3 wt%. The effects caused by different additions of nano-SiO2 were compared and analyzed by molecular dynamics simulations in terms of free volume fraction, the radius of gyration, and mechanical properties, and the results were in agreement with the experimental values. Meanwhile, the changes in hydrogen bonding and radial distribution functions in these systems were counted to explore the interaction between nano-SiO2 and UF resin. The properties of the UF resin were enhanced mainly through the large number of different forms of hydrogen bonds with nano-SiO2, with the strongest hydrogen bond occurring between H(SiO2)… O = (PHMU).

Global protected areas boost the carbon sequestration capacity: Evidences from econometric causal analysis.

Carbon sequestration capacity is the key factor in maintaining biodiversity and ecosystem services. However, further research is required on how to evaluate the impact of protected areas on carbon sequestration capacity from a global scale. To date, we propose a carbon density index of global protected areas (>10 km2, 32,756 samples) by the Integrated Valuation of Ecosystem Services and Trad'eoffs carbon model over the period 1994-2015. Then, we use the propensity score matching and difference-in-difference methods to separate the time effect and policy effect of the construction of protected areas on carbon sequestration capacity. Our analysis reveals that the carbon sequestration capacity can be improved by 0.39% by constructing global protected areas. There are regional differences with carbon sequestration capacity improvement globally. Africa has the largest value of increased carbon sequestration capacity, followed by Asia, Oceania and Europe. Upgrading protected areas (0.05%), strictly implementing planning (0.18%) and enhancing the power of local governments (0.08%) are conducive to improving carbon sequestration capacity. The assessment of the carbon sequestration capacity dynamic with protected areas is of great significance to meet the Convention on Biological Diversity.

Effects of Molar Ratio and pH on the Condensed Structures of Melamine-Formaldehyde Polymers.

The base-catalyzed melamine-formaldehyde (MF) reactions were studied in both diluted and concentrated solutions. The influences of F/M molar ratio and pH on the polymer structures were investigated based on the quantitative 13C-NMR analysis. The results show that both F/M molar ratio and pH influence the competitive formation of ether and methylene bridges. For the cases of F/M = 2.0, and 3.0, methylene bridge formation is minor in contrast to ether bridges either at pH = 9.3⁻9.8 or at 7.3⁻7.8. When the molar ratio was lowered to 1.0, methylene bridges became competitive with ether bridges at pH = 9.3⁻9.8, but the latter is still more favorable. When the lower molar ratio overlaps with the lower pH, significant changes were found. The content of methlylene bridges was over three times that of ether bridges with M/F = 1.0 and at pH = 7.3⁻7.8. The results in this study were compared with those previously obtained for base-catalyzed urea-formaldehyde reactions. It was found that molar ratio and pH influence the structures of the MF and UF polymers in similar ways. The different synthesis conditions of UF and MF resin were also addressed by comparing the structures of UF polymers with MF polymers.

Characterization of the Low Molar Ratio Urea⁻Formaldehyde Resin with 13C NMR and ESI⁻MS: Negative Effects of the Post-Added Urea on the Urea⁻Formaldehyde Polymers.

The structural changes during three-step synthesis of low-molar ratio urea⁻formaldehyde (UF) resin were tracked by quantitative 13C nuclear magnetic resonance (13C NMR) analysis and electrospray ionization-mass spectrometry (ESI⁻MS). Condensations that produced polymers were found to be linked by ether bonds in addition to hydroxymethylation reactions at the first alkaline stage with a formaldehyde to urea ratio of 2:1. Considerable formation of branched methylene linkages, with the highest content among all the condensed structures, was the key feature of the acidic stage. Notable changes were observed for the chemical structures and molecular masses of the resin components after the formaldehyde to urea molar ratio was lowered to 1.2 by adding post-urea at the final alkaline stage. Specifically, most of the branched hydroxymethyl groups on the polymers were cleaved, resulting in a significant decrease in the branching degree of the polymers. The performance degradation of the UF resin was attributed to this debranching effect and the production of components with low molecular masses. Based on the observations, the curing pattern of low molar ratio UF resin was postulated and branched polymeric formaldehyde catcher bearing urea-reactivity was proposed.

Electrochemical recognition of nitrophenol isomers by assembly of pillar[5]arenes mutifilms.

The rational design of electrochemical methods for isomer recognition is a focus of research in the molecular recognition and separation fields. In this work, a novel, rapid, and convenient electrochemical approach for recognition of nitrophenol isomers was constructed based on the alternating layer-by-layer (LbL) assembly of water-soluble cationic and anionic pillar [5]arene on a carboxylic graphene (C-Gra) modified glass carbon electrode. The electrochemical recognition of nitrophenol isomers was investigated by differential pulse voltammetry (DPV). The electrochemical results reveal that both the peak currents of m-nitrophenol (m-NP) and p-nitrophenol (p-NP) increased with the increasing of the layer number of the assembled pillar [5]arene, whereas the peak current of o-nitrophenol (o-NP) decreased with the increased layers, which demonstrated an efficient route for discriminating the nitrophenol isomers. The molecular recognition mechanism was studied by 1H NMR spectra, which indicated that the m-NP and p-NP can be included in the cavity of the pillar [5]arene host. However, the o-NP could not enter into the host of pillar [5]arene, which was ascribed to the formation of intramolecular hydrogen bond of o-NP. The LbL assembly modified GCE was used for detecting p-NP and m-NP. A low detection limit of 0.33 µM (S/N = 3) and a linear response range of 1-90 µM for p-NP were obtained by using this method. And the detection limit of 0.16 µM (S/N = 3) and a linear response range of 0.5-70 µM for m-NP were obtained. This method of LbL assembly modified GCE has potential application in molecular recognition and separation.

The Influence of pH on the Melamine-Dimethylurea-Formaldehyde Co-Condensations: A Quantitative 13C-NMR Study.

1,3-dimethylurea (DMU) was used to mimic urea and to model melamine-urea-formaldehyde (MUF) co-condensation reactions. The products of 1,3-dimethylurea-formaldehyde (DMUF), melamine-formaldehyde (MF), and melamine-1,3-dimethylurea-formaldehyde (MDMUF) reactions under alkaline and weak acidic conditions were compared by performing quantitative carbon-13 nuclear magnetic resonance (13C-NMR) analysis. The effect of pH on the co-condensation reactions was clarified. With the presence of the methyl groups in DMU, the appearance or absence of the featured signal at 54⁻55 ppm can be used to identify the co-condensed methylene linkage ⁻N(⁻CH3) ⁻CH2⁻NH⁻. Under alkaline condition, MDMUF reactions produced primarily MF polymers and the featured signal at 54⁻55 ppm was absent. Even though the co-condensations concurrently occurred, undistinguishable and very minor condensed structures with ether linkage were formed. Differently, under weak acidic condition, the relative content of co-condensed methylene carbons accounts for over 40%, indicating the MDMUF co-condensation reactions were much more competitive than the self-condensations. The formation of reactive carbocation intermediate was proposed to rationalize the results.

Mechanism of Base-Catalyzed Resorcinol-Formaldehyde and Phenol-Resorcinol-Formaldehyde Condensation Reactions: A Theoretical Study.

The base-catalyzed resorcinol-formaldehyde condensation reactions were theoretically investigated in this study by employing a quantum chemistry method. The condensation reaction includes two steps: (1) formation of the quinonemethide (QM) intermediate from hydroxymethylresorcinol; (2) Michael addition between the quinonemethide and resorcinol anion. The first step is the rate-determining step. Two mechanisms, unimolecular elimination of the conjugate base (E1cb) and water-aided elimination (WAE), were identified for the formation of QM. The hydroxymethylresorcinol anion produces neutral QM while the dianion produces a quinonemethide anion (QMA). The calculated potential energy barriers suggested that the QMA formation is much more favorable. Although resorcinol-formaldehyde and phenol-formaldehyde condensations share a common mechanism, the former would be faster if the QMA participates in condensations. The potential energy barriers for formation of 2-QM, 4-QM, 6-QM, 2-QMA, and 4-QMA were calculated. The results show that the formations of 6-QM and 4-QMA have relatively lower energy barriers. This rationalized previous experimental observations that the 2,4-(2,6-) and 6,6'-(4,4'-) methylene linkages were dominant, whereas the 2,2'-linkage was almost absent. The resorcinol-phenol-formaldehyde co-condensations were also calculated. The cold-setting characteristic of phenol-resorcinol-formaldehyde co-condensed resin can be attributed to participation of resorcinol quinonemethides in condensations.

The Reaction between Furfuryl Alcohol and Model Compound of Protein.

To guide the preparation of protein-based adhesive, especially the soy-based adhesive, the reaction between a simple dipeptide N-(2)-l-alanyl-l-glutamine (AG), being used as a model compound of protein, and its cross-linker furfuryl alcohol were studied in this paper. The products that were prepared with furfuryl alcohol and AG under different pHs were analyzed by ESI-MS, 13C NMR, and FT-IR. It was found that the medium environment had great effects on the competition of the co-condensation reaction between furfuryl alcohol and AG and self-condensation reaction of furfuryl alcohol molecules in the mixing system with furfuryl alcohol and AG. Under alkaline conditions, both co- and self-condensation were not obviously detected. Only when the value of pH was higher than 11, were a few co-condensation reaction products gotten. The reaction occurred mainly between furfuryl alcohol and the primary amido groups of AG. Under acid conditions, both co- and self-condensation were observed. The more acid the preparation conditions were, the easier to be observed the self-condensation of furfuryl alcohol molecules would be than the co-condensation between furfuryl alcohol and AG. When the value of pH was higher than 5, both co- and self-condensation were not outstanding. In this study, under pH 3, the co- and self-condensation found equilibrium. There was a great possibility for the primary amido and aliphatic amino groups of AG molecules to react with furfuryl alcohol molecules. No reaction was detected between the secondary amido groups of AG and furfuryl alcohol.

Theoretical Confirmation of the Quinone Methide Hypothesis for the Condensation Reactions in Phenol-Formaldehyde Resin Synthesis.

The mechanisms for the base-catalyzed condensation reactions in phenol-formaldehyde resin synthesis were investigated by using the density functional theory method. The structures of the intermediates and transition states, as well as the potential energy barriers of the involved reactions, were obtained. The hypothesis of quinine methide (QM) formation was theoretically confirmed. Two mechanisms were identified for QM formation, namely E1cb (elimination unimolecular conjugate base) and water-aided intra-molecular water elimination. The latter is energetically more favorable and is proposed for the first time in this work. Based on the QM mechanism, the condensation should be a unimolecular reaction because the following condensation between an ionized species (dissociated phenol or hydroxymethylphenol) with QM is much faster. The previously proposed SN2 condensation mechanism was found to be not competitive over the QM mechanism due to a much higher energy barrier. The condensation reaction between neutral phenol or hydroxymethylphenol and QM was also found to be possible. The energy barrier of this reaction is close to or higher than that of QM formation. Therefore, the overall condensation reaction may appear to be bimolecular if such a reaction is incorporated. The theoretical calculations in this work rationalized the discrepant results reported in previous kinetics studies well.

New Mechanism Proposed for the Base-Catalyzed Urea⁻Formaldehyde Condensation Reactions: A Theoretical Study.

Base-catalyzed urea⁻formaldehyde condensation reactions were investigated by using a quantum chemistry method. It was found that monomethylolurea or N,N'-dimethylolurea can produce the methyleneurea intermediate (⁻HN⁻CO⁻N=CH2) with the catalysis of base. The E1cb (unimolecular elimination of conjugate base) mechanism was identified for the formation of such an intermediate. The potential energy barrier was theoretically predicted to be 59.6 kJ/mol for the E1cb step, which is about half of that of previously proposed SN2 (bimolecular nucleophilic substitution) mechanism. In the subsequentcondensation reactions, Michael addition reactions that lead to different condensed structures can occur between the methyleneurea intermediate and the anions produced from methylolureas under alkaline conditions. Based on the theoretical calculations on the kinetics and thermodynamics of the selected reactions, the competitive formations of methylene linkages, ether linkages and uron were discussed in combination with our previous experimental observations.

A 13C-NMR Study on the 1,3-Dimethylolurea-Phenol Co-Condensation Reaction: A Model for Amino-Phenolic Co-Condensed Resin Synthesis.

The reactions of di-hydroxymethylurea with phenol under alkaline (pH = 10), weak (pH = 6) and strong acidic (pH = 2) conditions were investigated via the 13C-NMR method. Based on the proposed reaction mechanisms, the variations of the structures of different condensed products were analyzed and the competitive relationship between self- and co-condensation reactions was elucidated. The required experimental conditions for co-condensations were clearly pointed out. The main conclusions include: (1) the self-condensation between urea formaldehyde (UF) or phenol formaldehyde (PF) monomers were dominant while the co-condensations were very limited under alkaline conditions. This is because the intermediates produced from urea, methylolurea and phenol are less reactive in co-condensations with respect to self-condensations; (2) under weak acidic conditions, the self-condensations occurred exclusively among the UF monomers. The co-condensation structures were not observed; and (3) the co-condensations became much more competitive under strong acidic conditions as the relative content of the co-condensed methylenic carbon accounts for 53.3%. This result can be rationalized by the high reactivity of the methylolphenol carbocation intermediate toward urea and methylolurea. The revealed reaction selectivity and mechanisms may also be applied to the synthesis of those more complex co-condensed adhesives based on natural phenolic and amino compounds.