Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation.

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC50) values of 2.7-63 µM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC50 of 2.0 and 0.9 µM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC50 = 1.7 µM). Notably, 6c inhibited both kinases, with IC50 values of 2.7 and 3.0 µM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

Design of Multi-Target drugs of HDACs and other Anti-Alzheimer related Targets: Current strategies and future prospects in Alzheimer's diseases therapy.

Alzheimer disease (AD) is the most prevalent form of dementia that develops spontaneously in the elderly. It's worth mentioning that as people age, the epigenetic profile of the central nervous system cells changes, which may speed up the development of various neurodegenerative disorders including AD. Histone deacetylases (HDACs) are a class of epigenetic enzymes that can control gene expression without altering the gene sequence. Moreover, a promising strategy for multi-target hybrid design was proposed to potentially improve drug efficacy and reduce side effects. These hybrids are monocular drugs that contain various pharmacophore components and have the ability to bind to different targets at the same time. The HDACs ability to synergistically boost the performance of other anti-AD drugs, as well as the ease with which HDACs inhibitor cap group, can be modified. This has prompted numerous medicinal chemists to design a novel generation of HDACs multi-target inhibitors. Different HDACs inhibitors and other ones such as acetylcholinesterase, butyryl-cholinesterase, phosphodiesterase 9, phosphodiesterase 5 or glycogen synthase kinase 3ß inhibitors were merged into hybrids for treatment of AD. This review goes over the scientific rationale for targeting HDACs along with several other crucial targets in AD therapy. This review presents the latest hybrids of HDACs and other AD target pharmacophores.

Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies.

Two new series of 1,3,4-oxadiazole and coumarin derivatives based on pyrimidine-5-carbonitrile scaffold have been synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds 10c, 10e, 10h-j, 14e-f, 14i and 16 were found to be the most potent and selective inhibitors of COX-2 (IC50 0.041-0.081 µM, SI 139.74-321.95). Eight compounds were further investigated for their in vivo anti-inflammatory activity. The most active derivatives 10c, 10j and 14e displayed superior in vivo anti-inflammatory activity (% edema inhibition 39.3-48.3, 1 h; 58.4-60.5, 2 h; 70.8-83.2, 3 h; 78.9-89.5, 4 h) to the reference drug celecoxib (% edema inhibition 38.0, 1 h; 48.8, 2 h; 58.4, 3 h; 65.4, 4 h). These derivatives were also tested for their ulcerogenic liability, compound 10j showed better safety profile with reference to celecoxib while 10c and 14e exhibited mild lesions. Molecular docking studies of 10c, 10j, and 14e in the COX-2 active site revealed similar orientation and binding interactions as selective COX-2 inhibitors with a higher liability to access the selectivity side pocket.

Microwave-Assisted Heating Reactions of N-Acetylglucosamine (GlcNAc) in Sulfolane as a Method Generating 1,6-Anhydrosugars Consisting of Amino Monosaccharide Backbones.

The microwave-assisted heating reaction of N-acetyl glucosamine (GlcNAc) in sulfolane is described. The reaction produces two major products that are assignable to 1,6-anhydro-2-acetamido-2-deoxy-ß-d-glucopyranose (AGPNAc) and 1,6-anhydro-2-acetamido-2-deoxy-ß-d-glucofuranose (AGFNAc). In order to reveal a general feature of the system, the 3, 5, and 10 min reactions were performed at 140, 160, 180, 200, and 220 °C to clarify the time course changes in the conversion of GlcNAc and the yields of the two produced 1,6-anhydrosugars. Temperature is a crucial factor that significantly affects the conversion of GlcNAc. The yields of AGPNAc and AGFNAc are also drastically changed depending on the reaction conditions. The 5-min reaction at 200 °C is shown to be the optimal condition to generate the 1,6-anhydrosugars with a high efficiency in which AGPNAc and AGFNAc are produced in the yields of 21% and 44%, respectively. Consequently, the microwave-assisted heating reaction of GlcNAc in sulfolane is shown to be a simple and promising pathway to generate 1,6-anhydrosugars consisting of amino monosaccharide backbones, which have high potentials as raw materials leading to biological oligosaccharides and biomimetic polysaccharides.

Maltotriose-conjugation to a fluorinated chlorin derivative generating a PDT photosensitizer with improved water-solubility.

Photoactive molecules with the frameworks of chlorin and/or porphyrin possessing four perfluorinated aromatic rings were conjugated with maltotriose (Mal3) via the nucleophilic aromatic substitution reaction and subsequent deprotection reaction of the oligosaccharide moieties. The resulting oligosaccharide-conjugated molecules are ultimately improved as compared to the previously reported monosaccharide-counterparts in terms of water-solubility. In particular, a water-soluble chlorin derivative surrounded by four Mal3 molecules showed an excellent biocompatibility, strong photoabsorption in the longer wavelength regions, and a very high photocytotoxicity. Thus, the present synthetic route combined with the use of an oligosaccharide was shown to be a straightforward strategy to develop a third generation photosensitizer for photodynamic therapy (PDT).

Maltopentaose-conjugated CTA for RAFT polymerization generating nanostructured bioresource-block copolymer.

We now describe the synthesis of a new family of oligosaccharide-conjugated functional molecules, which act as chain transfer agents (CTAs) for the reversible addition-fragmentation chain transfer (RAFT) polymerization. The synthesis was started from the catalyst-free direct N-glycosyl reaction of 5-azidopentylamine onto maltopentaose (Mal5) in dry methanol at room temperature and subsequent N-protected reaction with acetic anhydride, producing a stable oligosaccharide-building block, such as Mal5 with an azidopentyl group (Mal5-N3). The azido group was hydrogenated using platinum dioxide (PtO2) as a catalyst to give Mal5 with aminopentyl group (Mal5-NH2), which was then reacted with CTA molecules bearing activated ester moieties. These reactions produced Mal5-modified macro-CTAs (Mal5-CTAs, 1), which were used for the RAFT polymerizations of styrene (St) and methyl methacrylate (MMA) in DMF. The polymerizations were performed using the [M]0/[1]0 values ranging from 50 to 600, affording the Mal5-hybrid amphiphilic block copolymers (BCPs), such as Mal5-polystyrene (2) and Mal5-poly(methyl methacrylate) (3), with a quantitative end-functionality and the controlled molecular weights between 4310 and 20 300 g mol(-1). The small-angle X-ray scattering (SAXS) measurements were accomplished for 2 and 3 to ensure their abilities to form phase separated structures in their bulk states with the increasing temperatures from 30 to 190 °C. The featured results were observed for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) at temperatures above 100 °C, where ϕMal5 denotes the volume fraction of the Mal5 unit in the BCP sample. For both BCP samples, the primary scattering peaks q* were clearly observed together with the higher-ordered scattering peaks √2q* and √3q*. Thus, these Mal5-hybrid amphiphilic BCP samples have a body centered cubic (BCC) phase morphology. The domain spacing (d) values of the BCC morphology for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) were 10.4 and 9.55 nm, respectively, which were determined using Bragg's relation (d = 2π/q*). The present RAFT agents were shown to eventually provide the phase separated structural polymeric materials in which 5.4 nm bioresource-spherical domains were periodically arrayed at the interval of about 10 nm.

Metal-conjugated Maltotriose Chlorins as Novel Photosensitizers for Photodynamic Therapy.

BACKGROUND/AIM: Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. To overcome this limitation and produce ROS effectively, we focused on the better solubility of photosensitizers with heavy metals bound within the chlorin skeleton and conjugated with glucose in this study. MATERIALS AND METHODS: We established maltotriose (Mal3)-conjugation with heavy metallochlorins [M (Mal3-chlorin), M=Pt or Pd)] and evaluated its anti-tumor effect. RESULTS: M (Mal3-chlorin) showed effective ROS production and singlet oxygen induction. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro. In a xenograft tumor mouse model, PDT with M (Mal3-chlorin) showed tumor growth suppression. CONCLUSION: M (Mal3-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.

Impact of COVID-19 pandemic on the care of severe burns in Japan: Repeated survey of specialized burn care facilities.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19), which began in 2020, has had a major impact on healthcare systems. The spread of COVID-19 has been reported to have affected the readiness to treat patients with burns worldwide. However, the existing reports have evaluated burn care status within a limited time period during the pandemic, and no report clarifies the change in the impact of infection status on burn care from the beginning of the pandemic to the present. METHODS: Japanese Society for Burn Injuries-accredited burn care facilities were surveyed using questionnaires on April 9-23, 2020; June 23-July 6, 2020; July 9-21, 2021; and January 21-31, 2022. Differences between groups were evaluated using Friedman's test or Bonferroni's multiple comparison test, as appropriate. RESULTS: From the 103 facilities included in the study, we received 85, 55, 56, and 58 responses in the first, second, third, and fourth surveys, respectively. We could continuously observe 34 facilities. The rate of acceptance of patients with severe burns improved significantly over time (P < 0.05). However, in the second and third surveys, there was an increase in the number of respondents who did not accept patients with burns irrespective of COVID-19 status. CONCLUSIONS: The number of facilities treating patients with burns who have COVID-19 is increasing; however, COVID-19 care may negatively impact routine burn care. It is necessary to continuously examine medical resource allocation through methods such as information sharing by academic societies.

Thermoresponsive Property of Poly(N,N-bis(2-methoxyethyl)acrylamide) and Its Copolymers with Water-Soluble Poly(N,N-disubstituted acrylamide) Prepared Using Hydrosilylation-Promoted Group Transfer Polymerization.

The group-transfer polymerization (GTP) of N,N-bis(2-methoxyethyl)acrylamide (MOEAm) initiated by Me2EtSiH in the hydrosilylation-promoted method and by silylketene acetal (SKA) in the conventional method proceeded in a controlled/living manner to provide poly(N,N-bis(2-methoxyethyl)acrylamide) (PMOEAm) and PMOEAm with the SKA residue at the α-chain end (MCIP-PMOEAm), respectively. PMOEAm-b-poly(N,N-dimethylacrylamide) (PDMAm) and PMOEAm-s-PDMAm and PMOEAm-b-poly(N,N-bis(2-ethoxyethyl)acrylamide) (PEOEAm) and PMOEAm-s-PEOEAm were synthesized by the block and random group-transfer copolymerization of MOEAm and N,N-dimethylacrylamide or N,N-bis(2-ethoxyethyl)acrylamide. The homo- and copolymer structures affected the thermoresponsive properties; the cloud point temperature (Tcp) increasing by decreasing the degree of polymerization (x). The chain-end group in PMOEAm affected the Tcp with PMOEAmx > MCIP-PMOEAmx. The Tcp of statistical copolymers was higher than that of block copolymers, with PMOEAmx-s-PDMAmy > PMOEAmx-b-PDMAmy and PMOEAmx-s-PEOEAmy > PMOEAmx-b-PEOEAmy.

Thermoresponsive self-assemblies of cyclic and branched oligosaccharide-block-poly(N-isopropylacrylamide) diblock copolymers into nanoparticles.

This paper discusses the thermoresponsive nanoparticles obtained by self-assemblies of nonlinear oligosaccharide-based diblock copolymer systems. These diblock copolymers were synthesized by Cu(I)-catalyzed 1,3-dipolar azide/alkyne cycloaddition ("click" reaction) of propargyl-functionalized ß-cyclodextrin (ßCyD) and xyloglucooligosaccharide (XGO) with poly(N-isopropylacrylamide) (PNIPAM) having a terminal azido group prepared by atom transfer radical polymerization (ATRP). Elastic and quasi-elastic light scattering analysis of the dibock copolymers in H(2)O indicated that thermodynamic phase transitions of the PNIPAM blocks at their cloud points (T(cp)s ≈ 34 °C), around lower critical solution temperatures (LCSTs), triggered their self-assemblies into the nanoparticles. These nanoparticles had narrow size distributions and small interphases (i.e., sharp boundaries). The mean hydrodynamic radii (R(h)s) of the ßCyD and XGO-based nanoparticles were determined to be around 150 and 250 nm upon slow heating (i.e., step-by-step heating), and 364 and 91.5 nm upon fast heating, respectively, depending on a predominance of the interchain association or the intrachain contraction. Transmission electron microscope (TEM) and field emission gun-scanning electron microscopy (FEG-SEM) images of the nanoparticles clearly showed compact spherical nanoparticles whose cores are mainly made with the PNIPAM blocks, whereas the rough shells consist in the oligosaccharidic blocks.

A method to detect occult pneumothorax with chest radiography.

Small pneumothoraces are often not visible on supine screening chest radiographs because they develop anteriorly to the lung. These pneumothoraces are termed occult. Occult pneumothoraces account for an astonishingly high 52% to 63% of all traumatic pneumothoraces. A 19-year-old obese woman was involved in a head-on car accident. The admission anteroposterior chest radiographs were unremarkable. Because of the presence of right chest tenderness and an abrasion, we suspected the presence of a pneumothorax. Thus, we decided to take a supine oblique chest radiograph of the right side of the thorax, which clearly revealed a visceral pleural line, consistent with a diagnosis of traumatic pneumothorax. A pneumothorax may be present when a supine chest radiograph reveals either an apparent deepening of the costophrenic angle (the "deep sulcus sign") or the presence of 2 diaphragm-lung interfaces (the "double diaphragm sign"). However, in practice, supine chest radiographs have poor sensitivity for occult pneumothoraces. Oblique chest radiograph is a useful and fast screening tool that should be considered for cases of blunt chest trauma, especially when transport of critically ill patients to the computed tomographic suite is dangerous or when imminent transfer to another hospital is being arranged and early diagnosis of an occult pneumothorax is essential.

Precise Synthesis and Thermoresponsive Property of Poly(ethyl glycidyl ether) and Its Block and Statistic Copolymers with Poly(glycidol).

In this paper, we describe a comprehensive study of the thermoresponsive properties of statistic copolymers and multiblock copolymers synthesized by poly(glycidol)s (PG) and poly(ethyl glycidyl ether) (PEGE) with different copolymerization methods. These copolymers were first synthesized by ring-opening polymerization (ROP), which was initiated by tert-butylbenzyl alcohol (tBBA) and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene) (t-Bu-P4) as the catalyst, and then the inherent protective groups were removed to obtain the copolymers without any specific chain end groups. The thermoresponsive property of the statistic copolymer PGx-stat-PEGEy was compared with the diblock copolymer PGx-b-PEGEy, and the triblock copolymers were compared with the pentablock copolymers. Among them, PG-stat-PEGE, PG-b-PEGE-b-PG-b-PEGE-b-PG, and PEGE-b-PG-b-PEGE-b-PG-b-PEGE, and even the specific ratio of PEGE-b-PG-b-PEGE, exhibited LCST-type phase transitions in water, which were characterized by cloud point (Tcp). Although the ratio of x to y affected the value of the Tcp of PGx-stat-PEGEy, we found that the disorder of the copolymer has a decisive effect on the phase-transition behavior. The phase-transition behaviors of PG-b-PEGE, part of PEGE-b-PG-b-PEGE, and PG-b-PEGE-b-PG copolymers in water present a two-stage phase transition, that is, firstly LCST-type and then the upper critical solution temperature (UCST)-like phase transition. In addition, we have extended the research on the thermoresponsive properties of EGE homopolymers without specific α-chain ends.

Molecular hybrids: A five-year survey on structures of multiple targeted hybrids of protein kinase inhibitors for cancer therapy.

Protein kinases have grown over the past few years as a crucial target for different cancer types. With the multifactorial nature of cancer, and the fast development of drug resistance for conventional chemotherapeutics, a strategy for designing multi-target agents was suggested to potentially increase drug efficacy, minimize side effects and retain the proper pharmacokinetic properties. Kinase inhibitors were used extensively in such strategy. Different kinase inhibitor agents which target EGFR, VEGFR, c-Met, CDK, PDK and other targets were merged into hybrids with conventional chemotherapeutics such as tubulin polymerization and topoisomerase inhibitors. Other hybrids were designed gathering kinase inhibitors with targeted cancer therapy such as HDAC, PARP, HSP 90 inhibitors. Nitric oxide donor molecules were also merged with kinase inhibitors for cancer therapy. The current review presents the hybrids designed in the past five years discussing their design principles, results and highlights their future perspectives.

JNK signaling as a target for anticancer therapy.

The JNKs are members of mitogen-activated protein kinases (MAPK) which regulate many physiological processes including inflammatory responses, macrophages, cell proliferation, differentiation, survival, and death. It is increasingly clear that the continuous activation of JNKs has a role in cancer development and progression. Therefore, JNKs represent attractive oncogenic targets for cancer therapy using small molecule kinase inhibitors. Studies showed that the two major JNK proteins JNK1 and JNK2 have opposite functions in different types of cancers, which need more specification in the design of JNK inhibitors. Some of ATP- competitive and ATP non-competitive inhibitors have been developed and widely used in vitro, but this type of inhibitors lack selectivity and inhibits phosphorylation of all JNK substrates and may lead to cellular toxicity. In this review, we summarized and discussed the strategies of JNK binding inhibitors and the role of JNK signaling in the pathogenesis of different solid and hematological malignancies.

Maltotriose-Chlorin e6 Conjugate Linked via Tetraethyleneglycol as an Advanced Photosensitizer for Photodynamic Therapy. Synthesis and Antitumor Activities against Canine and Mouse Mammary Carcinoma Cells.

Glycoconjugated chlorins represent a promising class of compounds that meet the requirements for the third-generation photosensitizer (PS) for photodynamic therapy (PDT). We have focused on the use of glucose (Glc) to improve the performance of the PS based on the Warburg effect-a phenomenon where tumors consume higher Glc levels than normal cells. However, as a matter of fact, Glc-conjugation has a poor efficacy in hydrophilic modification; thus, the resultant PS is not suitable for intravenous injection. In this study, a Glc-based oligosaccharide, such as maltotriose (Mal3), is conjugated to chlorin e6 (Ce6). The conjugation is assisted by two additional molecular tools, such as propargyl amine and a tetraethylene glycol (TEG) derivative. This route produced the target Mal3-Ce6 conjugate linked via the TEG spacer (Mal3-TEG-Ce6), which shows the required photoabsorption properties in the physiological media. The PDT test using canine mammary carcinoma (SNP) cells suggested that the antitumor activity of Mal3-TEG-Ce6 is extremely high. Furthermore, in vitro tests against mouse mammary carcinoma (EMT6) cells have been demonstrated, providing insights into the photocytotoxicity, subcellular localization, and analysis of cell death and reactive oxygen species (ROS) generation for the PDT system with Mal3-TEG-Ce6. Both apoptosis and necrosis of the EMT6 cells occur by ROS that is generated via the photochemical reaction between Mal3-TEG-Ce6 and molecular oxygen. Consequently, Mal3-TEG-Ce6 is shown to be a PS showing the currently desired properties.

Thermoresponsive vesicular morphologies obtained by self-assemblies of hybrid oligosaccharide-block-poly(N-isopropylacrylamide) copolymer systems.

This work discusses the self-assembly properties of thermoresponsive hybrid oligosaccharide-block-poly(N-isopropylacrylamide) copolymer systems: maltoheptaose-block-poly(N-isopropylacrylamide) (Mal(7)-b-PNIPAM(n)) copolymers. Those systems at different molar masses and volume fractions were synthesized using Cu(I)-catalyzed 1,3-dipolar azide/alkyne cycloaddition, so-called "click" chemistry, between an alkynyl-functionalized maltoheptaose (1) and poly(N-isopropylacrylamide) having a terminal azido group (N(3)-PNIPAM(n)) prepared by atom transfer radical polymerization (ATRP). While the cloud point (T(cp)) of the N(3)-PNIPAM(n) ranged from 36.4 to 51.5 degrees C depending on the degree of polymerization, those obtained of the diblock copolymers ranged from 39.4 to 73.9 degrees C. The self-assembly of such systems is favored due to the hydrophobicity of the PNIPAM in water above the T(cp). While the N(3)-PNIPAM(n) present polydisperse globular shape with a mean diameter of 500 nm, well-defined vesicular morphologies with an approximate diameter of 300 nm are obtained in diblock copolymer systems. These results were obtained and confirmed using static and dynamic light scattering as well as imaging techniques such as transmission electron microscope experiments.

[Delayed massive hemothorax due to diaphragmatic injury by lower rib fracture].

We report a case of delayed massive hemothorax, a 72-year-old women, due to diaphragmatic injury by multiple lower rib fracture on 4th day aftrer traffic injury. We tried to stop bleeding by transcatheter arterial embolization, but the control of bleeding was difficult, necessitating the emergency surgery. The diaphragmatic injury about 3 cm diameter was found, and was sutured with absorption thread. The post operative course was uncomplicated. Patient was discharged on 51th day after injury. Careful observation is important for delayed hemothorax after lower rib fracture.

Novel Photosensitizer ß-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells.

A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer ß-mannose-conjugated chlorin e6 (ß-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells. U251 cells were incubated with ß-M-Ce6, followed by laser irradiation. Cell viability was determined using the Cell Counting Kit-8 assay. The PDT effects of ß-M-Ce6 were compared with those of talaporfin sodium (TS) and our previously reported photosensitizer ß-glucose-conjugated chlorin e6 (ß-G-Ce6). Cellular uptake of each photosensitizer and subcellular distribution were analyzed by fluorescence microscopy. ß-M-Ce6 showed 1000× more potent PDT effects than those of TS, and these were similar to those of ß-G-Ce6. ß-M-Ce6 accumulation in U251 cells was much faster than TS accumulation and distributed to several organelles such as the Golgi apparatus, mitochondria, and lysosomes. This rapid cellular uptake was inhibited by low temperature, which suggested that ß-M-Ce6 uptake uses biological machinery. ß-M-Ce6 showed potent PDT anti-cancer effects compared with clinically approved TS, which is a possible candidate as a next generation photosensitizer in cancer therapy.

Evaluation of Ring Expansion-Controlled Radical Polymerization System by AFM Observation.

We here present a direct link between the reaction mechanisms for the ring-expansion "vinyl" polymerization system and atomic force microscopy (AFM) observations. The brush-modification clearly discriminates the desired cyclic species with the contour lengths (Lc) of 28-132 nm and molar masses (MAFM) of 60.2-283 kg mol-1 from the other linear ones. The 293 polymer blushes observed in a 1.0 µm × 1.0 µm AFM image are individually characterized, eventually providing clear answers about the mechanisms of this rare polymerization system, which include ring-expansion vinyl polymerizations to generate cyclic polymers, fusions of the generated cycles to form multimers, and their scission to form linear or ring-opened species. The relationship between the molecular chain lengths and the cyclic versus linear morphologies is highlighted.

Thermochemical transformation of glucose to 1,6-anhydroglucose in high-temperature steam.

An aqueous solution of glucose was reacted at temperatures from 200 to 400 degrees C under atmospheric pressure using a continuous flow reactor. For reaction temperatures above 300 degrees C, the liquid product yield was not sensitive to the temperature change; on the other hand, below 300 degrees C, it decreased rapidly with decreasing temperature. 1,6-Anhydro-beta-D-glucopyranose (AGP) and 1,6-anhydro-beta-D-glucofuranose (AGF) were the major components in the liquid product. The yields of AGP and AGF were 40% and 19%, respectively, at 360 degrees C and a feed rate of 0.5 mL/min. The optimum space time to produce AGP and AGF was about 0.2-0.4s under the present temperature conditions.