Definitive internal fracture fixation followed by staged free flap coverage ("fix followed by flap" protocol) for open Gustilo type IIIB fractures.

BACKGROUND: Although the concept of the "fix and flap" approach, in which definitive fracture fixation and flap coverage are completed in a single procedure at the earliest opportunity may seem ideal for the treatment of Gustilo type IIIB open fractures, the individual circumstances of patients, such as polytrauma or multiple fracture cases may not allow for the immediate fracture fixation and flap coverage ("fix and flap" approach). In our hospital, patients with Gustilo type IIIB open fractures are treated with definitive internal fixation of the fracture followed by staged flap coverage ("fix followed by flap" protocol) when the "fix and flap" approach was not feasible due to the patient's condition or difficulty in coordinating surgery schedules. The "fix followed by flap" protocol provides benefits in terms of flexibility in adjusting the surgical timetable, simplifying the planning of flap coverage following fracture fixation, and minimizing individual surgical invasion. METHODS: We reviewed 10 cases of severe open fractures treated with the "fix followed by flap" protocol and evaluated their outcomes. All surgical procedures, including wound debridement, fracture fixation, and flap coverage, were performed by orthoplastic surgeons specializing in both fracture surgery and microsurgery including soft tissue reconstruction. RESULTS: All free flaps survived, and no partial necrosis was observed. None of the patients developed postoperative deep infection up to the last follow-up. Fracture union was achieved in all patients with or without autologous bone grafts. The median time for union was 9.4 months (range, 4-12 months). CONCLUSIONS: This study presents favorable outcomes of treatment for Gustilo type IIIB open fractures with fracture fixation followed by staged flap coverage ("fix followed by flap" protocol). Despite a delay in flap coverage, the consistency of treatment provided by orthoplastic surgeons may have contributed to the favorable outcomes in this study.

Molecular Basis of Neuronal and Microglial States in the Aging Brain and Impact on Cerebral Blood Vessels.

Brain aging causes a wide variety of changes at the molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact on the brain microenvironment such as the blood-brain barrier (BBB).

Cyclic Azahelicene Dimers Showing Bright Circularly Polarized Luminescence and Selective Fluoride Recognition.

Although helicenes are promising molecules, the synthetic difficulty and tediousness have often been problems, and only small amounts of optically pure helicenes have been obtained by using chiral HPLC in most cases. Herein, aza[7]helicenes or closed-aza[7]helicenes with (1R)-menthyl substituents were selectively synthesized via the intramolecular Scholl reaction, and the diastereomeric pairs were separated by silica gel column chromatography. The optically pure helicenes were further transformed into the corresponding cyclic dimers, and the chiroptical properties were investigated. The rigid π-frameworks of the dimers led to the high molar extinction coefficients and fluorescence quantum yields, while the twisted helicene moieties induced clear Cotton effects and CPL in the visible region, and the high CPL brightness (BCPL) was achieved. Furthermore, the cyclic dimers were found to have the macrocyclic cavity with the two NH groups suitable for the selective binding of a fluoride anion, which induced significantly redshifted fluorescence and CPL in the red region.

Cu-catalyzed carboxylation of organoboronic acid pinacol esters with CO2.

Chemical fixation of CO2 has received much attention. In particular, catalytic C-C bond formation with CO2 giving carboxylic acids is of great significance. Among the CO2 fixation methods, multiple carboxylation is one of the challenging subjects. Here we investigated the Cu-catalyzed carboxylation of a variety of boronic acid pinacol esters (C(sp2)-, C(sp3)-, and C(sp)-B compounds) with CO2, which efficiently provided the corresponding products, including aryl, alkenyl, alkyl, and alkynyl carboxylic acids. This carboxylation was also applicable to multiple CO2 fixation giving di- and tri-carboxylic acids under robust reaction conditions (totally 29 examples).

Circularly polarized luminescence in molecular recognition systems: Recent achievements.

Circularly polarized luminescence (CPL) dyes are recognized to be new generation materials and have been actively developed. Molecular recognition systems provide nice approaches to novel CPL materials, such as stimuli-responsive switches and chemical sensing materials. CPL may be induced simply by mixing chiral or achiral, luminescent or nonluminescent host and guest; there are several combinations. Molecular recognition can potentially save time and effort to construct well-ordered chiral structures with noncovalent attractive interactions as compared with the multi-step synthesis of covalently bonded dyes. It is a challenging subject to engage molecular recognition events with CPL, and it is important and interesting to see how it is achieved. In fact, simple molecular recognition systems can even enable the fine adjustment of CPL performance and detailed conformational/configurational analysis of the excited state. Here we overview the recent achievements of simple host-guest complexes capable of exhibiting CPL, summarizing concisely the host/guest structures, CPL intensities, and characteristics.

Synthesis of Closed-Heterohelicenes Interconvertible between Their Monomeric and Dimeric Forms.

Oxidative fusion reaction of cyclic heteroaromatic pentads consisting of pyrrole and thiophene gave closed-heterohelicene monomers and dimers depending on the oxidation conditions. Specifically, oxidation with [bis(trifluoroacetoxy)iodo]benzene (PIFA) gave closed-[7]helicene dimers connected at the ß-position of one of the pyrrole units with remarkably elongated C-C bonds of about 1.60 Å. Although this bond was intact against thermal and physical activations, homolytic bond dissociation took place in DMSO upon irradiation with UV light to give the corresponding monomers. Thus, interconversion between the closed-helicene monomer and dimer was achieved. The optically pure dimer was photo-dissociated into the monomers associated with a turn-on of circularly polarized luminescence (CPL).

Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction.

Carbazole-based aza[7]helicenes and hetero[9]helicenes were successfully obtained via the intramolecular Scholl reaction of 3,6-bis(biphenyl-2-yl)carbazole congeners, while the reaction of 3,6-bis(naphthylphenyl)-appended carbazole gave a triple helicene via an unexpected simultaneous double aryl rearrangement. DFT calculations suggested that the rearrangement proceeded via an arenium cation intermediate. In addition, the reaction of methoxy-appended substrate gave an azahepta[8]circulene via the concurrent C-C bond formation. These helical dyes showed circularly polarized luminescence. The azahepta[8]circulene was further transformed into deeply saddle-distorted dibenzodiaza[8]circulenes as the first example of its solution-based synthesis and unambiguous structural determination.

Cystine supplementation sustains plasma mercaptalbumin levels in rats fed low-protein diets more effectively than methionine.

We recently reported that dietary cystine maintained plasma mercaptalbumin levels in rats fed low-protein diets. The present study aimed to compare the influence of low-protein diets supplemented with cystine and methionine, which is another sulfur amino acid, on plasma mercaptalbumin levels in rats. Male Sprague-Dawley rats were fed a 20% soy protein isolate diet (control group), 5% soy protein isolate diet (low-protein group) or 5% soy protein isolate diet supplemented with either methionine (low-protein + Met group) or cystine (low-protein + Cyss group) for 1 week. The percentage of mercaptalbumin within total plasma albumin of the low-protein + Met group was significantly lower than that of the control and low-protein + Cyss groups. No significant differences in the mRNA levels of tumor necrosis factor-α, interleukin-6, interleukin-1ß, and cyclooxygenase 2 in blood cells were observed between the low-protein + Met and low-protein + Cyss groups. Treatment with buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, did not influence the percentage of mercaptalbumin within total plasma albumin in rats fed the low-protein diet supplemented with cystine. These results suggest that supplementation with cystine may be more effective than that with methionine to maintain plasma mercaptalbumin levels in rats with protein malnutrition. Cystine might regulate plasma mercaptalbumin levels via the glutathione-independent pathway.

Tetrameric and Hexameric Porphyrin Nanorings: Template Synthesis and Photophysical Properties.

Hexameric and tetrameric porphyrin nanorings, Z6·T6 and Z4·T4, were synthesized in 53% and 14% yields, respectively, by the Sonogashira-type self-oligomerization of porphyrin monomer 1 using hexadentate template T6 and tetrapyridylporphyrin template T4. Template-free nanorings Z6 and Z4 were also prepared. The femtosecond transient absorption measurements revealed fast excitation energy hopping (EEH) along these nanorings with hopping rates of 2-5 ps. Treatment of Z6 with chiral template CT6 gave Z6·CT6 showing circular dichroism (CD) and circularly polarized luminescence (CPL) in the absorption and fluorescence regions of Z6, respectively, which indicates chirality transfer from CT6 to Z6.

Aggregation-Induced Circularly Polarized Luminescence from Boron Complexes with a Carbazolyl Schiff Base.

A variety of carbazolyl-appended Schiff bases were readily synthesized from 1-formylcarbazoles and aniline derivatives. Boron complexation of the resulting ligands allowed for facile preparation of new carbazole-based BODIPY analogues showing solid-state fluorescence. Furthermore, some dyes were converted into chiral compounds through the Et2 AlCl-mediated incorporation of a binaphthyl unit. The chiral dyes showed aggregation-induced fluorescence and circularly polarized luminescence (CPL) with the ΦF and glum of up to 0.22 and -3.5×10-3 , respectively, in the solid state. The solid-state fluorescence and CPL were well characterized by the crystal packing analyses and DFT calculations.

Synthesis and Chiroptical Properties of Chiral Carbazole-Based BODIPYs.

A series of carbazole-based boron dipyrromethenes (BODIPYs) 2 a-g bearing binaphthyl units have been synthesized by the Et2 AlCl-mediated reaction of the corresponding BODIPY difluorides 1 a-g with 1,1'-binaphthalene-2,2'-diol. Substituents such as halogen, nitrile, and amino groups were tolerated under the reaction conditions, and the reaction of the phenylethynyl-substituted 1 h gave (R,R)-3 h bearing two binaphthyl units. The chiroptical properties of these dyes with different substituents were investigated by UV/Vis, CD, fluorescence, and circularly polarized luminescence (CPL) spectroscopy. The CD spectra showed Cotton effects in the absorption region of the BODIPY moieties. In addition, they showed CPL both in solution and in the solid state. Interestingly, several dyes recorded higher glum values in the solid state, probably due to intermolecular interactions. Because (R,R)-3 h recorded relatively low glum values, the diastereomer (R,S)-3 h was prepared. The (R,S) diastereomer showed intense CPL, which suggests a synergetic effect of the two binaphthyl groups. Finally, chiral carbazole-based BODIPY dimers have been synthesized for the first time and their chiroptical properties were investigated. They showed redshifted fluorescence and CPL, which reached the near-IR (NIR) region in the solid state.

Azahelicene-Fused BODIPY Analogues Showing Circularly Polarized Luminescence.

Helical carbazole-based BODIPY analogues were readily synthesized via aza[7]helicenes. The structures of azahelicene-incorporated BF2 dyes were elucidated by x-ray diffraction analysis. DFT calculations revealed that the π-conjugated system expanded from the helicene moiety to the BODIPY framework. The azahelicene-fused boron complexes showed the Cotton effects and the circularly polarized luminescence (CPL) in the visible region. Furthermore, an axially chiral binaphthyl group was attached to the helically chiral dyes, which enhanced the chiroptical properties.

Carbazole-based BODIPYs with ethynyl substituents at the boron center: solid-state excimer fluorescence in the VIS/NIR region.

Carbazole-based BODIPYs 1-6 with several different substituents at the boron atom site were synthesized. These dyes fluoresced in the solid state, and 3a with phenylethynyl groups exhibited a red-shifted and broad fluorescence spectrum, which suggested an excimer emission. Its derivatives 3b-n were synthesized, and the relationship between the solid-state emission and crystal packing was investigated. The X-ray crystal structures revealed cofacial dimers that might form excimers. From the structural optimization results, we found that the introduction of mesityl groups hindered intermolecular access and led to reduced interactions between the dimers. In addition, the red-shifted excimer fluorescence suppressed self-absorption, and dyes with ethynyl groups showed solid-state fluorescence in the vis/NIR region.

Synthesis of carbazole-based BODIPY dimers showing red fluorescence in the solid state.

Carbazole-based BODIPY dimers 2a-g were synthesized via direct arylation. They showed red-shifted solid-state fluorescence spectra as compared with the corresponding monomer. In addition, unsymmetrical dimers 2d, 2f, and 2g with two different substituents showed red fluorescence with improved quantum yields in the solid state.

Color-Tunable Solid-State Fluorescence Emission from Carbazole-Based BODIPYs.

Several carbazole-based boron dipyrromethene (BODIPY) dyes were synthesized by organometallic approaches. Thiazole, benzothiazole, imidazole, benzimidazole, triazole, and indolone substituents were introduced at the 1-position of the carbazole moiety, and boron complexation of each dipyrrin generated the corresponding compounds 1, 2 a, and 3-6. The properties of these products were investigated by UV/Vis and fluorescence spectroscopy, cyclic voltammetry, X-ray crystallography, and DFT calculations. These compounds exhibited large Stokes shifts, and compounds 1, 2 a, and 3-5 fluoresced both in solution and in the solid state. Complex 2 a showed the highest fluorescence quantum yield (ΦF ) in the solid state, therefore boron complexes of the carbazole-benzothiazole hybrids 2 b-f, which had several different substituents, were prepared and the effects of the substituents on the photophysical properties of the compounds were examined. The fluorescence properties showed good correlation with the results of crystal-packing analyses, and the dyes exhibited color-tunable solid-state fluorescence.

Highly Active and Robust Metalloporphyrin Catalysts for the Synthesis of Cyclic Carbonates from a Broad Range of Epoxides and Carbon Dioxide.

Bifunctional metalloporphyrins with quaternary ammonium bromides (nucleophiles) at the meta, para, or ortho positions of meso-phenyl groups were synthesized as catalysts for the formation of cyclic carbonates from epoxides and carbon dioxide under solvent-free conditions. The meta-substituted catalysts exhibited high catalytic performance, whereas the para- and ortho-substituted catalysts showed moderate and low activity, respectively. DFT calculations revealed the origin of the advantage of the meta-substituted catalyst, which could use the flexible quaternary ammonium cation at the meta position to stabilize various anionic species generated during catalysis. A zinc(II) porphyrin with eight nucleophiles at the meta positions showed very high catalytic activity (turnover number (TON)=240 000 at 120 °C, turnover frequency (TOF)=31 500 h(-1) at 170 °C) at an initial CO2 pressure of 1.7 MPa; catalyzed the reaction even at atmospheric CO2 pressure (balloon) at ambient temperature (20 °C); and was applicable to a broad range of substrates, including terminal and internal epoxides.

Theoretical Study on Highly Active Bifunctional Metalloporphyrin Catalysts for the Coupling Reaction of Epoxides with Carbon Dioxide.

Highly active bifunctional metalloporphyrin catalysts were developed for the coupling reaction of epoxides with CO2 to produce cyclic carbonates. The bifunctional catalysts have both quaternary ammonium halide groups and a metal center. To elucidate the roles of these catalytic groups, DFT calculations were performed. Control reactions using tetrabutylammonium halide as a catalyst were also investigated for comparison. In the present article, the results of our computational studies are overviewed. The computational results are consistent with the experimental data and are useful for elucidating the structure-activity relationship. The key features responsible for the high catalytic activity of the bifunctional catalysts are as follows: 1) the cooperative action of the halide anion (nucleophile) and the metal center (Lewis acid); 2) the near-attack conformation, leading to the efficient opening of the epoxide ring in the rate-determining step; and 3) the conformational change of the quaternary ammonium cation to stabilize various anionic species generated during catalysis, in addition to the robustness (thermostability) of the catalysts.

Effects of cyano, ethynyl and ethylenedioxy groups on the photophysical properties of carbazole-based porphyrins.

The synthesis and photophysical properties of cyano and ethynyl substituted carbazole-based porphyrins were investigated. The introduction of ethynyl groups induced red shifts, while that of cyano groups induced blue shifts of their absorption bands, which was supported by MO calculations. Ethylenedioxy-appended porphyrins were also prepared via a coupling reaction. The conjugated and electronic substituent effects on the photophysical properties of the carbazole-based porphyrins have been elucidated by using both experimental results and calculations. Among these porphyrins, the ethylenedioxy-appended selenaporphyrin displayed intensified and red-shifted absorption in the NIR region up to 1178 nm.

Bifunctional catalysts based on m-phenylene-bridged porphyrin dimer and trimer platforms: synthesis of cyclic carbonates from carbon dioxide and epoxides.

Highly active bifunctional diporphyrin and triporphyrin catalysts were synthesized through Stille coupling reactions. As compared with a porphyrin monomer, both exhibited improved catalytic activities for the reaction of CO2 with epoxides to form cyclic carbonates, because of the multiple catalytic sites which cooperatively activate the epoxide. Catalytic activities were carefully investigated by controlling temperature, reaction time, and catalyst loading, and very high turnover number and turnover frequency were obtained: 220 000 and 46 000 h(-1) , respectively, for the magnesium catalyst, and 310 000 and 40 000 h(-1) , respectively, for the zinc catalyst. Results obtained with a zinc/free-base hybrid diporphyrin catalyst demonstrated that the Br(-) ions on the adjacent porphyrin moiety also function as nucleophiles.

Bifunctional porphyrin catalysts for the synthesis of cyclic carbonates from epoxides and CO2: structural optimization and mechanistic study.

We prepared bifunctional Mg(II) porphyrin catalysts 1 for the solvent-free synthesis of cyclic carbonates from epoxides and CO2. The activities of 1d, 1h, and 1i, which have Br(-), Cl(-), and I(-) counteranions, respectively, increased in the order 1i < 1h < 1d. Catalysts 1d and 1j-m, which bear four tetraalkylammonium bromide groups with different alkyl chain lengths, showed comparable but slightly different activities. Based on the excellent catalyst 1d, we synthesized Mg(II) porphyrin 1o with eight tetraalkylammonium bromide groups, which showed even higher catalytic activity (turnover number, 138,000; turnover frequency, 19,000 h(-1)). The catalytic mechanism was studied by using 1d. The yields were nearly constant at initial CO2 pressures in the 1-6 MPa range, suggesting that CO2 was not involved in the rate-determining step in this pressure range. No reaction proceeded in supercritical CO2, probably because the epoxide (into which the catalyst dissolved) dissolved in and was diluted by the supercritical CO2. Experiments with (18)O-labeled CO2 and D-labeled epoxide suggested that the catalytic cycle involved initial nucleophilic attack of Br(-) on the less hindered side of the epoxide to generate an oxyanion, which underwent CO2 insertion to afford a CO2 adduct; subsequent intramolecular ring closure formed the cyclic carbonate and regenerated the catalyst. Density functional theory calculations gave results consistent with the experimental results, revealing that the quaternary ammonium cation underwent conformational changes that stabilized various anionic species generated during the catalytic cycle. The high activity of 1d and 1o was due to the cooperative action of the Mg(II) and Br(-) and a conformational change (induced-fit) of the quaternary ammonium cation.