Association of Neoadjuvant Chemotherapy With Postoperative Outcomes in Immediate Prepectoral Prosthetic Breast Reconstruction.

PURPOSE: Neoadjuvant chemotherapy (NACT) followed by total mastectomy and immediate reconstruction has become an important strategy in the treatment of breast cancer. Although the safety of subpectoral implant-based breast reconstruction with NACT has been extensively evaluated, the safety in prepectoral reconstruction has not been clearly elucidated. We aimed to evaluate the association of NACT with immediate prepectoral breast reconstruction outcomes. METHODS: A retrospective review of patients who underwent total mastectomy and immediate implant-based prepectoral breast reconstruction between May and December 2021 was conducted. Patients were categorized into 2 groups: those receiving NACT and those not receiving it. Postoperative complication rates were compared between the 2 groups. The independent association between NACT and the complication profiles was evaluated. Propensity score matching was also conducted. RESULTS: We analyzed 343 cases, including 85 who received NACT treatment and 258 who did not. Compared with the non-NACT group, the NACT group was younger, had a higher body mass index, and a higher rate of adjuvant radiotherapy. There were no differences in the rates of overall complications or type of complication between the 2 groups. In the multivariable logistic analyses, NACT did not show a significant association with the development of adverse outcomes. Similar results were observed in propensity score matching analyses. CONCLUSIONS: Our results suggest that receiving NACT may not have a significant detrimental effect on the postoperative outcomes of immediate prepectoral prosthetic reconstructions. Conducting prepectoral implant-based reconstruction in the setting of NACT might be safe and provide acceptable outcomes.

Usefulness of Free Tissue Transfer for the Reconstruction of Extensive Thigh Defects.

BACKGROUND: Despite the increasing popularity of free tissue transfer, thigh defects have been alienated from their potential indication, owing to the abundance of regional reconstruction options. However, some challenging situations where locoregional modalities may lead to suboptimal outcomes often require free flap. Due to lacking studies regarding microvascular reconstruction of thigh defects, this study aimed to investigate the versatility of free tissue transfer for reconstruction of thigh defects. METHODS: A retrospective review was performed for patients who underwent microvascular reconstruction of thigh defects between 2003 and 2021. Their demographics and operation-related data were summarized and postoperative outcomes were evaluated. RESULTS: Sixty-five patients were analyzed, with a median follow-up period of 15.5 months. Most common situations requiring free tissue transfer were extensive defects, followed by large dead space with exposure of major neurovascular bundle and chronic wounds surrounded by unhealthy regional tissue. Defects were most frequently located in the anterior compartment horizontally and in the distal thigh vertically. The median surface area of the defects was 180.0 cm2. The latissimus dorsi musculocutaneous and thoracodorsal artery perforator flaps were the two most commonly used flaps. Reliable recipient vessels could generally be easily found in the vicinity of defects. Overall complications developed in 12 cases (18.5%), including two of partial flap necrosis. No total flap loss was encountered. CONCLUSION: Free tissue transfer could provide reliable outcomes and facilitate rapid recovery, and could be actively considered for reconstruction of thigh defects in situations unfavorable to the locoregional option.

Enzymatic synthesis of avermectin B1a glycosides for the effective prevention of the pine wood nematode Bursaphelenchus xylophilus.

Avermectin produced by Streptomyces avermitilis is an anti-nematodal agent against the pine wood nematode Bursaphelenchus xylophilus. However, its potential usage is limited by its poor water solubility. For this reason, continuous efforts are underway to produce new derivatives that are more water soluble. Here, the enzymatic glycosylation of avermectin was catalyzed by uridine diphosphate (UDP)-glycosyltransferase from Bacillus licheniformis with various UDP sugars. As a result, the following four avermectin B1a glycosides were produced: avermectin B1a 4″-ß-D-glucoside, avermectin B1a 4″-ß-D-galactoside, avermectin B1a 4″-ß-L-fucoside, and avermectin B1a 4″-ß-2-deoxy-D-glucoside. The avermectin B1a glycosides were structurally analyzed based on HR-ESI MS and 1D and 2D nuclear magnetic resonance spectra, and the anti-nematodal effect of avermectin B1a 4″-ß-D-glucoside was found to exhibit the highest activity (IC50 = 0.23 µM), which was approximately 32 times greater than that of avermectin B1a (IC50 = 7.30 µM), followed by avermectin B1a 4″-ß-2-deoxy-D-glucoside (IC50 = 0.69 µM), avermectin B1a 4″-ß-L-fucoside (IC50 = 0.89 µM), and avermectin B1a 4″-ß-D-galactoside (IC50 = 1.07 µM). These results show that glycosylation of avermectin B1a effectively enhances its in vitro anti-nematodal activity and that avermectin glycosides can be further applied for treating infestations of the pine wood nematode B. xylophilus.

Ferrous iron chelating property of low-molecular weight succinoglycans isolated from Sinorhizobium meliloti.

Iron is an essential nutrient for nitrogen-fixing legume root nodules, and the chelation of ferrous iron plays an important role in the mobility and availability of iron to the legume. In the present study, we investigated the iron-binding properties of low-molecular weight succinoglycans isolated from the nitrogen-fixing bacterium, Sinorhizobium meliloti. The low-molecular weight succinoglycans comprising three monomers (M1-M3), four dimers (D1-D4), and six trimers (T1-T6) of the succinoglycan repeating unit were purified by various chromatographic techniques. Interestingly, the colorimetric ferrozine method showed that the succinoglycans T6, M3, and D3 demonstrated a ferrous iron chelating ability of 83, 63, and 38 % per mg, respectively. The individual binding constants were determined as 43703, 2313, and 760 M(-1) for succinoglycans T6, M3, and D3 using ultraviolet-visible spectroscopy. The complexation of succinoglycan and ferrous iron can cause structural changes, which were analyzed by circular dichroism spectroscopy. Furthermore, the complex could provide antioxidant activity through an anti-Fenton reaction. These results demonstrate that the low-molecular weight succinoglycans can effectively modulate iron biochemistry as a novel ferrous iron-acquisition system of S. meliloti.

Enhancement of methane production in anaerobic digestion of sewage sludge by thermal hydrolysis pretreatment.

This study was performed to optimize thermal hydrolysis pretreatment (THP) of sewage sludge for enhanced anaerobic digestion (AD). Using the response surface methodology (RSM), the optimal conditions were found 180 °C of reaction temperature and 76 min of reaction time. Through THP under optimal conditions, high molecular substances in sewage sludge such as soluble microbial by-products (SMPs) and extracellular polymeric substances (EPSs) were hydrolyzed into low molecular ones without the generation of refractory compounds. The microbial community analysis revealed that relative abundances of Methanomicrobia such as Methanosarcina, Methanosaeta (acetoclastic methanogens), and Methanoculleus (hydrogenotrophic methanogens) in AD with THP were higher than those in conventional AD.

Enhanced Solubilization of Fluoranthene by Hydroxypropyl ß-Cyclodextrin Oligomer for Bioremediation.

Fluoranthene (FT) is a polycyclic aromatic hydrocarbon (PAH), consisting of naphthalene and benzene rings connected by a five-member ring. It is widespread in the environment. The hydrophobicity of FT limits its availability for biological uptake and degradation. In this study, hydroxypropyl ß-cyclodextrin oligomers (HP-ß-CD-ol) were synthesized with epichlorohydrin (EP), while the solubility enhancement of FT by HP-ß-CD-ol was investigated in water. The synthesized HP-ß-CD-ol was characterized by MALDI-TOF mass spectrometry (MS), ¹H NMR, and 13C NMR spectroscopy. The solubility of FT increased 178-fold due to the complex formation with HP-ß-CD oligomers. The inclusion complexes of FT/HP-ß-CD-ol were analyzed using Fourier-Transform Infrared (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM), and Nuclear Overhauser Effect Spectroscopy Nuclear magnetic resonance (NOESY NMR) spectroscopy. On the basis of these results, HP-ß-CD-ol is recommended as a potential solubilizer for the development of PAH removal systems.

Pentynyl Ether of ß-Cyclodextrin Polymer and Silica Micro-Particles: A New Hybrid Material for Adsorption of Phenanthrene from Water.

A new hybrid material for the removal of polycyclic aromatic hydrocarbons (PAH) from water was prepared by the polymerization of pentynyl beta-cyclodextrin (PyßCD) and silica micro-particles (SMP). Phenanthrene, being one of the important members of the PAH family and a potential risk for environmental pollution, was selected for this study. Results show that phenanthrene removal efficiency of the SMP was improved significantly after hybridization with PyßCD-polymer. Approximately 50% of the phenanthrene was removed in the first 60 min and more than 95% was removed in less than 7 h when 25 mL of the 2 ppm aqueous phenanthrene solution was incubated with the 100 mg of SMP-PyßCD-polymer material. Infrared spectroscopy and thermal gravimetric analysis show that the enhanced efficiency of the SMP-PyßCD-polymer compared to the unmodified SMP was due to the formation of the inclusion complexation of phenanthrene with the PyßCD. These results indicate that SMP-PyßCD polymers have a potential to be applied as molecular filters in water purification systems and also for waste water treatment.

Solubility and bioavailability enhancement of ciprofloxacin by induced oval-shaped mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin.

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used to treat bacterial infections; however, its limited aqueous solubility inhibits its broader clinical uses. This study investigated the complexation effect of mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin on the aqueous solubility and bioavailability of ciprofloxacin. During complexation, the oval-shaped cavity induced by mono-aminoethylamine substitution on the primary rim of ß-cyclodextrin, was considered to be a key factor according to NMR spectroscopy and molecular modeling studies. The ciprofloxacin with mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin complex was characterized using FE-SEM, DSC, FT-IR, T1 relaxation, 2D NOESY, and DOSY NMR spectroscopy and molecular modeling studies. The solubility property of ciprofloxacin complexed with mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin was enhanced by seven-fold compared to that of pure ciprofloxacin. Furthermore antibacterial activity of that complex against methicillin-resistant Staphylococcus aureus was enhanced and it clearly showed the growth inhibition. The mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin has the potential to be utilized for other oblong guest molecules besides ciprofloxacin based on the novel induced elliptical cavity.

SERS-Based Flavonoid Detection Using Ethylenediamine-ß-Cyclodextrin as a Capturing Ligand.

Ethylenediamine-modified ß-cyclodextrin (Et-ß-CD) was immobilized on aggregated silver nanoparticle (NP)-embedded silica NPs (SiO2@Ag@Et-ß-CD NPs) for the effective detection of flavonoids. Silica NPs were used as the template for embedding silver NPs to create hot spots and enhance surface-enhanced Raman scattering (SERS) signals. Et-ß-CD was immobilized on Ag NPs to capture flavonoids via host-guest inclusion complex formation, as indicated by enhanced ultraviolet absorption spectra. The resulting SiO2@Ag@Et-ß-CD NPs were used as the SERS substrate for detecting flavonoids, such as hesperetin, naringenin, quercetin, and luteolin. In particular, luteolin was detected more strongly in the linear range 10-7 to 10-3 M than various organic molecules, namely ethylene glycol, ß-estradiol, isopropyl alcohol, naphthalene, and toluene. In addition, the SERS signal for luteolin captured by the SiO2@Ag@Et-ß-CD NPs remained even after repeated washing. These results indicated that the SiO2@Ag@Et-ß-CD NPs can be used as a rapid, sensitive, and selective sensor for flavonoids.

Enhancing bio-availability of ß-naphthoflavone by supramolecular complexation with 6,6'-thiobis(methylene)-ß-cyclodextrin dimer.

The aryl hydrocarbon receptor (AhR) is a ligand activated transcriptional regulator, which governs key biological processes including detoxification of carcinogens. ß-Naphthoflavone (ß-NF) is a non-toxic flavonoid, and a potent AhR agonist. Thus, ß-NF can induce the representative detoxifying enzyme cytochrome P4501A1, thereby enhancing the detoxification potential. However, its low water solubility hampers the use. We found that supramolecular complexation of ß-NF with the synthetic 6,6'-thiobis(methylene)-ß-cyclodextrin (ß-CD-S) dimer significantly enhanced ß-NF's role as an AhR agonist. The water solubility of ß-NF was increased to 469 fold by effective supramolecular complexation with the ß-CD-S dimer, and caused significant induction of cytochrome P4501A1. Stable formation of the supramolecular complex of ß-NF with ß-CD-S-dimer was verified by various analyses. In summary, supramolecular complexation of ß-NF with ß-CD-S dimer greatly enhanced bio-availability of ß-NF as an AhR agonist. Our findings provide an easy, non-destructive, and alternative approach to enhance the bio-availability of therapeutics.

ß-CD Dimer-immobilized Ag Assembly Embedded Silica Nanoparticles for Sensitive Detection of Polycyclic Aromatic Hydrocarbons.

We designed a ß-CD dimer on silver nanoparticles embedded with silica nanoparticles (Ag@SiO2 NPs) structure to detect polycyclic aromatic hydrocarbons (PAHs). Silica NPs were utilized as a template for embedding silver NPs to create hot spot structures and enhance the surface-enhanced Raman scattering (SERS) signal, and a thioether-bridged dimeric ß-CD was immobilized on Ag NPs to capture PAHs. The assembled Ag NPs on silica NPs were confirmed by TEM and the presence of ß-CD dimer on Ag@SiO2 was confirmed by UV-vis and attenuated total reflection-Fourier transform infrared spectroscopy. The ß-CD dimer@Ag@SiO2 NPs were used as SERS substrate for detecting perylene, a PAH, directly and in a wide linearity range of 10(-7) M to 10(-2) M with a low detection limit of 10(-8) M. Also, the ß-CD dimer@Ag@SiO2 NPs exhibited 1000-fold greater sensitivity than Ag@SiO2 NPs in terms of their perylene detection limit. Furthermore, we demonstrated the possibility of detecting various PAH compounds using the ß-CD dimer@Ag@SiO2 NPs as a multiplex detection tool. Various PAH compounds with the NPs exhibited their distinct SERS bands by the ratio of each PAHs. This approach of utilizing the assembled structure and the ligands to recognize target has potential for use in sensitive analytical sensors.

Novel magnetic nanoparticles coated by benzene- and ß-cyclodextrin-bearing dextran, and the sorption of polycyclic aromatic hydrocarbon.

We present the synthesis of novel magnetic nanoparticles functionalized by benzene- and ß-cyclodextrin-derivatized dextran. The grafting strategy was based on the [alkynyl-iron] cluster in the modified dextrans, which were prepared by click reaction from alkyne-modified dextran and benzyl azide or mono-6-O-deoxy-monoazido ß-cyclodextrin. Characterization was then carried out by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. Using the developed magnetic nanoparticles, the potential for removing polycyclic aromatic hydrocarbons such as phenanthrene and pyrene by sorption onto the nanomaterials was assessed. In the sorption, pi-stacking interactions of the benzene-derivatized dextran and host-guest chemistry of the ß-cyclodextrin-derivatized dextran were considered to be significant. Furthermore, the polysaccharide derivative-coated magnetic adsorbents could be recovered by an external magnet for reuse.

Hydroxypropyl cyclic ß-(1 → 2)-D-glucans and epichlorohydrin ß-cyclodextrin dimers as effective carbohydrate-solubilizers for polycyclic aromatic hydrocarbons.

The removal of polycyclic aromatic hydrocarbons by soil washing using water is extremely difficult due to their intrinsic hydrophobic nature. In this study, the effective aqueous solubility enhancements of seven polycyclic aromatic hydrocarbons by chemically modified hydroxypropyl rhizobial cyclic ß-(1 → 2)-D-glucans and epichlorohydrin ß-cyclodextrin dimer have been investigated for the first time. In the presence of hydroxypropyl cyclic ß-(1 → 2)-D-glucans, the solubility of benzo[a]pyrene is increased up to 38 fold of its native solubility. The solubility of pyrene and phenanthrene dramatically increased up to 160 and 359. Coronene, chrysene, perylene, and fluoranthene also show an increase of 11, 23, 23, and 97 fold, respectively, of enhanced solubility by complexation with synthetic epichlorohydrin ß-cyclodextrin dimer. The physicochemical properties of the complex are characterized by Fourier-transform infrared spectra and differential scanning calorimetry. Utilizing a scanning electron microscopy, the morphological structures of native benzo[a]pyrene, pyrene, phenanthrene, coronene, chrysene, perylene, fluoranthene and their complex with novel carbohydrate-solubilizers are studied. These results elucidate that polycyclic aromatic hydrocarbons are able to form an efficient complex with hydroxypropyl cyclic ß-(1 → 2)-D-glucans and ß-cyclodextrin dimer, suggesting the potential usage of chemically modified novel carbohydrate-solubilizers.

NsdD is a key repressor of asexual development in Aspergillus nidulans.

Asexual development (conidiation) of the filamentous fungus Aspergillus nidulans occurs via balanced activities of multiple positive and negative regulators. For instance, FluG (+) and SfgA (-) govern upstream regulation of the developmental switch, and BrlA (+) and VosA (-) control the progression and completion of conidiation. To identify negative regulators of conidiation downstream of FluG-SfgA, we carried out multicopy genetic screens using sfgA deletion strains. After visually screening >100,000 colonies, we isolated 61 transformants exhibiting reduced conidiation. Responsible genes were identified as AN3152 (nsdD), AN7507, AN2009, AN1652, AN5833, and AN9141. Importantly, nsdD, a key activator of sexual reproduction, was present in 10 independent transformants. Furthermore, deletion, overexpression, and double-mutant analyses of individual genes have led to the conclusion that, of the six genes, only nsdD functions in the FluG-activated conidiation pathway. The deletion of nsdD bypassed the need for fluG and flbA∼flbE, but not brlA or abaA, in conidiation, and partially restored production of the mycotoxin sterigmatocystin (ST) in the ΔfluG, ΔflbA, and ΔflbB mutants, suggesting that NsdD is positioned between FLBs and BrlA in A. nidulans. Nullifying nsdD caused formation of conidiophores in liquid submerged cultures, where wild-type strains do not develop. Moreover, the removal of both nsdD and vosA resulted in even more abundant development of conidiophores in liquid submerged cultures and high-level accumulation of brlA messenger (m)RNA even at 16 hr of vegetative growth. Collectively, NsdD is a key negative regulator of conidiation and likely exerts its repressive role via downregulating brlA.

Intermolecular complexation of low-molecular-weight succinoglycans directs solubility enhancement of pindolol.

The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are repeating octasaccharide units consisting of monomers, dimers, and trimers. Pindolol is a beta-blocker used to treat cardiovascular disorders. We investigated the formation of complexes between pindolol and low-molecular-weight succinoglycan monomers (SGs). Even though SGs have a linear structure, the solubility of pindolol in the presence of SGs was increased up to 7-fold compared with methyl-ß-cyclodextrin reported as the best solubilizer of pindolol. Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Formation constants of complexes were determined from phase solubility diagrams. Conformation of complex was suggested based on a molecular docking study. The present study indicated that formation of pindolol/SGs complexes not only resulted in increased pindolol solubility but also could be useful for improving its clinical application as it did not affect cell viability.

Complexation of fisetin with novel cyclosophoroase dimer to improve solubility and bioavailability.

Rhizobium species produce cyclosophoraose (Cys), which is an unbranched cyclic ß-(1,2)-glucan. We synthesized novel cationic cyclosophoraose dimer (Cys dimer) and its structure was confirmed via NMR spectroscopy and MALDI-TOF mass spectrometry analysis. In this study, we investigated the complexation of hardly soluble drug fisetin (3,3',4',7-tetrahydroxyflavone) with Cys dimer to improve the solubility of fisetin, and its solubility was increased up to 6.5-fold. The solubility of fisetin with Cys dimer showed 2.4-fold better than with ß-cyclodextrin. The fisetin-Cys dimer complex was characterized by using, phase solubility diagram, 2D NMR, FT-IR spectroscopy, SEM, DSC analysis and molecular modeling. Through the molecular docking simulations, complexation ability of fisetin with host molecules were in the following order: Cys dimer>Cys monomer>ß-CD. The fisetin-Cys dimer complex showed also higher cytotoxicity to HeLa cells than free fisetin, indicating that the Cys dimer to improve bioavailability of fisetin.

Functional interplay between the cell cycle and cell phenotypes.

Cell cycle distribution of adherent cells is typically assessed using flow cytometry, which precludes the measurements of many cell properties and their cycle phase in the same environment. Here we develop and validate a microscopy system to quantitatively analyze the cell-cycle phase of thousands of adherent cells and their associated cell properties simultaneously. This assay demonstrates that population-averaged cell phenotypes can be written as a linear combination of cell-cycle fractions and phase-dependent phenotypes. By perturbing the cell cycle through inhibition of cell-cycle regulators or changing nuclear morphology by depletion of structural proteins, our results reveal that cell cycle regulators and structural proteins can significantly interfere with each other's prima facie functions. This study introduces a high-throughput method to simultaneously measure the cell cycle and phenotypes at single-cell resolution, which reveals a complex functional interplay between the cell cycle and cell phenotypes.

Solubilization of haloperidol by acyclic succinoglycan oligosaccharides.

The isolated succinoglycan octasaccharide dimers isolated from Sinorhizobium meliloti 1021 have unique acyclic structures, displaying amphipathic properties against water. Thus, their potential usage as solubilizers of various water-insoluble drugs through non-covalent complexation are possible. In this study, we examined the solubility of a poorly water-soluble drug, haloperidol, in the presence of the acyclic form of succinoglycan dimers, and demonstrated that its solubility was increased up to 87 fold, Interestingly, the level of its solubility was even 7-10 fold higher than that achieved with ß cyclodextrin or its derivatives that are cyclic forms, which is possibly due to the molecular flexibility of the acyclic structure of the dimers as well as the hydrophobic nature. Analyses of the stoichiometry and the stability constants for each complex were performed using phase solubility method, respectively. Additional analyses were also performed to confirm the formation of succinoglycan-drug complexes. Furthermore hypothetical 3-dimesional conformation of the complex was estimated through molecular docking simulations. Upon cytotoxicity test with a human cell line, the succinoglycan dimers displayed little effect up to 1000 µM, suggesting their potential usage to improve solubility and bioavailability of poorly soluble therapeutic agents.