Fructobacillus apis sp. nov., isolated from the gut of honeybee (Apis mellifera).

A Gram-positive, facultatively anaerobic, catalase-negative, fructose-dependent strain (W13T) was isolated from the gut of honeybee (Apis mellifera). Phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain W13T represents a distinct line of descent within the genus Fructobacillus, with the closest neighbours being Fructobacillus broussonetiae BCRC 81240T (98.9 % sequence similarity) and Fructobacillus durionis DSM 19113T (96.8 % sequence similarity). Comparative sequencing of the additional phylogenetic markers rpoC and recA confirmed the 16S rRNA gene tree topology. The complete genome of strain W13T consisted of 1 292 712 bp with a G+C content of 48.3 mol%. Pairwise comparisons of the average nucleotide identity values and digital DNA-DNA hybridization values between the genomes of W13T and its close phylogenetic neighbours, F. broussonetiae BCRC 81240T and F. durionis DSM 19113T, resulted in 76.2-84.1 % and 20.2-27.6 %, respectively. The main cellular fatty acids of strain W13T were C16 : 0, C18 : 1 ω9c and C18 : 1 ω7c. Thus, we propose a novel species within the genus Fructobacillus, with the name Fructobacillus apis sp. nov. and the type strain is W13T (= NBRC 115637T=BCRC 81365T).

Differential effects of postoperative oral corticosteroid on eosinophilic vs. non-eosinophilic CRSwNP subtypes.

PURPOSE: The efficacy of postoperative oral corticosteroids on surgical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients following endoscopic sinus surgery (ESS) remains controversial. This study evaluated the potential benefits of postoperative oral corticosteroids on surgical outcomes in CRSwNP patients and investigated the differential effects on eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). MATERIALS AND METHODS: Patients with bilateral CRSwNP who underwent ESS were enrolled and randomized to receive either oral prednisolone (30 mg/day) or placebo for 2 weeks after surgery. Visual analog scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22) scores were chosen as the subjective outcomes, evaluated at preoperative baseline and 1, 3, and 6 months postoperatively. Lund-Kennedy Endoscopic Scores (LKESs) were used as the objective outcome, evaluated at preoperative baseline and at 2 weeks and 2, 3, and 6 months postoperatively. RESULTS: In total, 100 patients with bilateral CRSwNP were enrolled, of whom only 82 completed the 6-month follow-up. The subjective outcomes showed no significant difference at each follow-up points. Of the objective outcomes, the corticosteroid group reporting a trend of improvement in LKESs at 6 months postoperatively (p = 0.05). After stratification by tissue eosinophils, only patients with NECRSwNP (<10 eosinophils/HPF) demonstrated a significant improvement in LKESs at 3 months postoperatively (p = 0.03). CONCLUSIONS: Postoperative oral corticosteroids did not provide additional improvements in VAS and SNOT-22 scores; nevertheless, a trend of LKES improvement was noted at 6 months postoperatively. After stratification by tissue eosinophils, this effect was significant only among NECRSwNP patients at 3 months follow-up.

Structural basis of antizyme-mediated regulation of polyamine homeostasis.

Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az1 binding. The structural basis of the Az1-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az1 complexed with either ODC or AzIN. Structural analysis revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az1-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN may effectively compete with ODC for Az1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.

Photocyclization and Photoaddition Reactions of Arylphenols via Intermediate Quinone Methides.

A series of five benzannelated derivatives of 2-phenylphenol were prepared, and their photochemistry was investigated. Two of these (3-phenyl-2-naphthol, 10, and 1-phenyl-2-naphthol, 11) were photoinert. For 2-(1-naphthyl)phenol (12) and 1-(1-naphthyl)-2-naphthol (13), ESPT took place to either the 2'-position or the 7'-position of the naphthalene ring to give quinone methides (QMs) that underwent either reverse proton transfer (RPT) or electrocyclic ring closure to give dihydrobenzoxanthenes. The intermediate QMs for 12 and 13 were detected and characterized by laser flash photolysis. For 2-(9-phenanthryl)phenol (14), ESPT took place either to the 5'-position to give a QM that underwent quantitative electrocyclic ring closure to give the corresponding benzoxanthene or to the 10'-position to give a QM that underwent RPT. If the solution contained methanol, the QM produced on ESPT to the 10'-position in 14 could be trapped as the photoaddition product. The compounds studied in this work demonstrate three possible reactions of QMs produced following ESPT to aromatic carbon atoms: (1) reverse proton transfer (RPT) to regenerate starting material; (2) addition of hydroxylic solvents to give the photoaddition product; and (3) electrocyclic ring closure to give benzoxanthene derivatives.

Ketoprofen as a photoinitiator for anionic polymerization.

A new photoinitiating system for anionic polymerization of acrylates based on the efficient photodecarboxylation of Ketoprofen (1) and the related derivatives 3 and 4 that generate the corresponding carbanion intermediates is presented. Carbanion intermediates are confirmed by deuterium incorporation in the trapped Michael adducts and by spectroscopic detection using laser flash photolysis (LFP). This novel anionic initiating system features excitation in the near UV and visible regions, potential characteristics of photocontrolled living polymerization, and metal-free photoinitiators generated from photoexcitation, different from typical anionic polymerization where the polymerizations are initiated by heat and strong base containing alkali metals.

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols.

An antiproliferative investigation was conducted on 3 human cancer cell lines, HCT 116 (colon), MCF-7 (breast), and H 460 (lung), on a series of 4 anthrylphenols in the dark and upon exposure to light (350 nm). 9-(2-Hydroxyphenyl)anthracene (1) moderately inhibited proliferation, but irradiation considerably enhanced the effect. The other anthracenes 4­6 exhibited antiproliferative activity in the dark, which was not enhanced upon irradiation. The enhancement of the antiproliferative effect on the irradiation of 1 was rationalized as being due to the formation of quinone methide (QM 2) by excited state proton transfer. QM 2 acts as an electrophilic species capable of reacting with biological molecules. Although QM 2 reacts with nucleotides, the adducts could not be isolated. On the contrary, cysteine adduct 8 was isolated and characterized, whereas the adducts with glycine, serine and tripeptide glutathione were characterized by MS. Non-covalent binding of 1 to DNA and bovine serum albumin was demonstrated by UV-vis, fluorescence and CD spectroscopy. However, a straightforward conclusion regarding the DNA or protein alkylating (damaging) ability of 2 could not be drawn. The results obtained by the irradiation of 1 in the presence of DNA, amino acids and peptides, cell cycle perturbation analysis, and in vitro translation of GFP suggest that the effect is not only due to the damage of DNA but also due to the impact on the cellular proteins. Considering that to date all QM agents were assumed to target DNA dominantly, this is an important finding with an impact on the further development of anticancer agents based on QMs.

Synthesis of Bicyclic Isoxazoles and Isoxazolines via Intramolecular Nitrile Oxide Cycloaddition.

An efficient and straight forward procedure for the syntheses of bicyclic isoxazole/isoxazoline derivatives from the corresponding dimethyl-2-(2-nitro-1-aryl/alkyl)-2-(prop-2-yn-1yl)malonates or dimethyl 2-allyl-2-(2-nitro-1-aryl/alkyl ethyl)malonate is described. High yields and simple operations are important features of this methodology.

Excited state intramolecular proton transfer (ESIPT) from phenol to carbon in selected phenylnaphthols and naphthylphenols.

ESIPT and solvent-assisted ESPT in isomeric phenyl naphthols and naphthyl phenols 5-8 were investigated by preparative photolyses in CH3CN-D2O, fluorescence spectroscopy, LFP, and ab initio calculations. ESIPT takes place only in 5 (D-exchange Φ = 0.3), whereas 6-8 undergo solvent-assisted PT with much lower efficiencies. The efficiency of the ESIPT and solvent-assisted PT is mainly determined by different populations of the reactive conformers in the ground state and the NEER principle. The D-exchange experiments and calculations using RI-CC2/cc-pVDZ show that 5 in S1 deactivates by direct ESIPT from the OH to the naphthalene position 1 through a conical intersection with S0, delivering QM 14 that was detected by LFP (τ = 26 ± 3 ns). ESIPT to position 3 in 5 is possible but it proceeds from a less-populated conformer and involves an energy barrier on S1. In solvent-assisted PT to naphthalene position 4 in 5, zwitterion 17 is formed, which cyclizes to stable naphthofuran photoproducts 9-12. The regiochemistry of the deuteration in solvent-assisted PT was correlated with the NBO charges of the corresponding phenolates/naphtholates 5(-)-8(-). Combined experimental and theoretical data indicate that solvent-assisted PT takes place via a sequential mechanism involving first deprotonation of the phenol/naphthol, followed by the protonation by H2O in the S1 state of phenolate/naphtholate. The site of protonation by H2O is mostly at the naphthalene α-position.

Solvent-dependent excited state intramolecular proton transfer (ESIPT) pathways from phenol to carbon in 2,5-dihydroxyphenyl arenes.

The ESIPT of three 2,5-dihydroxyphenyl-substituted arenes 9-11 was studied in various solvent systems, to investigate the direction of the proton transfer from the phenol to the respective carbons of naphthyl, phenanthrenyl and anthryl aromatic rings. In neat CH3CN, 9-11 undergo direct ESIPT from the phenolic OH to the ipso-position of the corresponding aromatic carbon acceptors, via an intramolecular charge transfer state (S(1,ct)), giving rise to observable zwitterions, ZIs 35, 25, 27, respectively. Surprisingly, the generated ZI in 9 proceeds via a 1,2-phenyl migration followed by re-aromatization to afford 16 (a structural isomer of 9) in quantitative yield. In 10 and 11, the corresponding ZIs proceed via electrocyclic ring closure to furnish 20 and 28, respectively. In the case of 10, another intrinsic ESIPT pathway takes place to the 10-position of a phenanthrenyl ring, giving QM 26 in high quantum efficiency (Φex = 0.72). In aqueous solution, 9 undergoes formal ESIPT to the more distal 2'- and 7'-positions of the naphthalene ring, delivering QMs 18 and 38, which either revert back to the starting material or proceed via electrocyclic ring closure, respectively. In 11 in aqueous solution, formal ESIPT to the 10-position of the anthracene ring takes place delivering QM 29, which readily aromatizes to regenerate starting material.

Epidermal structure created by canine hair follicle keratinocytes enriched with bulge cells in a three-dimensional skin equivalent model in vitro: implications for regenerative therapy of canine epidermis.

BACKGROUND: Keratinocytes in the hair follicle bulge region have a high proliferative capacity, with characteristics of epithelial stem cells. This cell population might thus be an ideal source for generating the interfollicular epidermis in a canine skin equivalent. HYPOTHESIS/OBJECTIVES: This study was designed to determine the ability of canine hair follicle bulge cell-enriched keratinocytes to construct canine living skin equivalents with interfollicular epidermis in vitro. ANIMALS: Four healthy beagle dogs from a research colony. METHODS: Bulge cell-enriched keratinocytes showing keratin 15 immunoreactivity were isolated from canine hair follicles and cultured on dermal equivalent containing canine fibroblasts. Skin equivalents were subjected to histological, immunohistochemical, western blot and RT-PCR analyses after 10-14 days of culture at the air-liquid interface. RESULTS: The keratinocyte sheets showed an interfollicular epidermal structure comprising four to five living cell layers covered with a horny layer. Immunoreactivities for keratin 14 and desmoglein 3 were detected in the basal and immediate suprabasilar layers of the epidermis, while keratin 10 and desmoglein 1 occurred in more superficial layers. Claudin 1 immunoreactivity was seen in the suprabasalar layer of the constructed epidermis, and filaggrin monomers and loricrin were detected in the uppermost layer. Basal keratinocytes in the skin equivalent demonstrated immunoreactivity to antibodies against basement membrane zone molecules. CONCLUSIONS AND CLINICAL IMPORTANCE: A bulge stem cell-enriched population from canine hair follicles formed interfollicular epidermis within 2 weeks in vitro, and thus represents a promising model for regenerative therapy of canine skin.

Pemphigus vulgaris in a Welsh pony stallion: case report and demonstration of antidesmoglein autoantibodies.

HYPOTHESIS/OBJECTIVES: To describe the clinical, histological and immunological findings of an equine case of pemphigus vulgaris, including the demonstration of antidesmoglein (anti-Dsg) autoantibodies. CASE REPORT: The diagnosis of pemphigus vulgaris was confirmed in a 9-year-old Welsh pony stallion with both direct and indirect immunofluorescence and immunoprecipitation studies, the latter identifying circulating anti-Dsg3 IgG. Treatment with immunosuppressive medications was initiated. Lesions were seen in the perineal area, sheath, mane, tail, eyelids, coronary bands and mucosa of the mouth and oesophagus. Initial corticosteroid treatment improved the clinical signs, but the onset of laminitis necessitated a reduction in dosage, which was associated with a recurrence of lesions and development of oral ulcers. A corneal ulcer developed after 60 days of treatment. Despite treatment with azathioprine, gold salts and dapsone, the disease progressed and the pony was euthanized. Postmortem examination showed additional lesions of the cardia of the stomach. CONCLUSIONS AND CLINICAL IMPORTANCE: Pemphigus vulgaris is rarely diagnosed in equids. We describe a case that was substantiated by the demonstration of anti-Dsg3 IgG. Response to treatment was poor, with the best response to high doses of prednisolone. Equine pemphigus vulgaris is likely to carry a poor prognosis and if there is no response to treatment, humane euthanasia is warranted.

Survey on nitrogen removal and membrane filtration characteristics of Chlorella vulgaris Beij. on treating domestic type wastewaters.

The main objective of this study is to evaluate the nitrogen assimilation and filtration characteristics of Chlorella vulgaris Beij. when treating domestic wastewaters. Chlorella could assimilate organic nitrogen, ammonia and nitrate in wastewater, and the mean cell residence time (MCRT) to achieve the maximum biomass content in a bioreactor was different for each individual nitrogen source used. The experimental results showed that using nitrate as the only nitrogen source was the most favorable for biomass growth. With ammonia and nitrate coexisting in the aquatic phase, Chlorella possibly utilized ammonia first, and this was unfavorable to subsequent biomass growth. Nitrifying bacteria in wastewaters significantly affected Chlorella growth as they possibly competed with Chlorella in assimilating ammonia and nitrate in domestic wastewater. In a submerged ultrafiltration (UF) membrane module, with an initial concentration of 850 mg/L of Chlorella, the optimized flux was 0.02 m(3)/(m(2)·h), and the filtration cycle was 30 min. A 'dual membrane bioreactor (MBR)' configuration using UF membranes for Chlorella incubation was proposed. MBR1 provides an environment with long MCRT for efficient nitrification. The converted nitrate is assimilated by Chlorella in MBR2 to sustain its growth. UF permeate from MBR1 is bacteria-free and does not affect the growth of Chlorella in MBR2. MCRT of Chlorella growth is controlled by the UF membrane of MBR2, providing the flexibility to adjust variations of nitrogen composition in the wastewater.

Comparing Variations in Advance Directives Timing among Older Adults with End-Stage Renal Disease versus Cancer.

Background: Having an advance directive (AD) is associated with better care at end of life and better quality of death. However, AD completion rates among End-Stage Renal Disease patients are lower than among cancer patients. ESRD patients commonly experience cognitive impairment, reducing their ability to make their own care choices as their disease progresses. Thus, having an AD earlier in the disease trajectory is important. Little is known about differences in AD completion timing among ESRD and cancer patients. Therefore, the purpose of this study was to (1) investigate difference in AD completion and timing between ESRD and cancer patients; and, (2) identify factors associated with the early and late AD completion. Setting and Participants: A retrospective cohort study was conducted. Data was drawn from the Health and Retirement Study, a United States representative longitudinal survey of older adults, using exit interviews conducted from 2006 to 2016 among 1886 proxy reporters of deceased participants with ESRD or cancer. Results: ESRD patients had lower rates of AD completion compared to those with cancer. Higher education and being older were negatively associated with late AD completion in the last 3 months of life. Additionally, decedents with a diagnosis of ESRD, older age, and with higher education had higher odds of completing ADs one year or more before death. Discussions/Conclusions: While ESRD patient were less likely to have ADs, those that had ADS were more likely than cancer patients to develop ADs earlier in the disease trajectory. Further studies are needed to determine effective strategies to increase the AD completion rate among patients with ESRD.

Identifying Paths Forward: Expanding Palliative Care to Low-Income Patients in California.

Multiple studies demonstrate most consumers do not know about palliative care. And, since January 2018, California's Medi-Cal Managed Care patients have been eligible for palliative care services under Senate Bill 1004 (SB 1004). Yet, the uptake of palliative care services was underwhelming. The purpose of this study was to explore patient-centered barriers to palliative care. We recruited 27 adult Medicaid managed care patients from community-based sites in Los Angeles and conducted semi-structured qualitative interviews. Each participant was asked questions to elicit their knowledge about, and perspectives on, palliative care as well as their preferred communication approaches for receiving a referral to palliative care. The interviews were audio-recorded and transcribed verbatim. We used a grounded theory approach to guide our analysis of primary themes. Our findings indicated that the barriers to palliative care referrals among this population included lack of knowledge about palliative care and available services; the reliance on, and trust in, primary care physicians for information; language and cultural barriers; housing instability; and patient believing they are neither old enough nor sick enough to need palliative care. These findings emphasize the critical role primary care physicians play in advocating for low-income patients and the necessity for culturally sensitive education about palliative care. Promoting knowledge and understanding of palliative care among both primary care physicians and consumers is critical to ensuring access to care.

Very efficient generation of quinone methides through excited state intramolecular proton transfer to a carbon atom.

Irradiation of 2-phenyl-1-naphthol (6) in CH(3) CN/D(2) O (3:1) leads to very efficient incorporation of deuterium at the ortho-positions of the adjacent phenyl ring (overall Φ=0.73±0.07), along with minor incorporation at the naphthalene positions 5 and 8. These finding are explained by excited state intramolecular proton transfer (ESIPT) from the phenolic OH group to the corresponding carbon atoms, the main pathway giving rise to quinone methide (QM) 7, which has been characterized by LFP (τ≈20 ns; 460 nm). The ESIPT reaction paths have been explored with the second order approximate coupled cluster (CC2) method. In nonprotic solvents the ESIPT from the naphthol O-H to the ortho-position of the phenyl ring proceeds in a barrierless manner along the (1) L(a) energy surface via a conical intersection with the S(0) state, delivering 7. In aqueous solvent, clusters with H(2) O are formed wherein proton transfer (PT) to solvent and a H(2) O-mediated relay mechanism gives rise to naphtholates and QMs. The results are compared with 2-phenylphenol (3) that also undergoes barrierless ESIPT giving a QM via a conical intersection. However, due to an unfavorable conformation in the ground state, the quantum efficiency for ESIPT of 3 is significantly lower (Φ for D-exchange=0.041). These results show that ESIPT from phenol to carbon need not be an intrinsically inefficient process.

Olfactory Outcomes After Middle Turbinate Resection in Endoscopic Transsphenoidal Surgery: A Prospective Randomized Study.

OBJECTIVE: Endoscopic endonasal transsphenoidal surgery is safe and effective for sellar and parasellar tumor removal. Partial middle turbinate (MT) resection is sometimes performed to optimize the surgical field and facilitate postoperative care. Disturbances in olfaction are concerning because of the lack of randomized studies in this field. STUDY DESIGN: Prospective randomized trial. SETTING: Single academic medical center. METHODS: We resected the lower halves of bilateral MTs in the resected group and laterally fractured bilateral MTs in the preserved group. Olfactory outcomes and sinonasal conditions were assessed by using the validated Taiwan Smell Identification Test and Lund-Kennedy Endoscopy Score, respectively. Forty-nine patients were enrolled in the final analysis, of whom 23 underwent partial MT resection. RESULTS: The average Taiwan Smell Identification Test result was 36.9 one month after surgery, with a significant change of -4.4 ± 3.1 (mean ± SD; P < .01) from baseline. The impact was not significant at 3 months (-2.1 ± 2.6, P = .13) or 6 months (0.3 ± 2.0, P = .79). Between the MT resection and preservation groups, there were no significant differences at postoperative 1 month (P = .60), 3 months (P = .86), and 6 months (P > .99). Lund-Kennedy Endoscopy Score was still higher at 3 months (P = .006) after surgery but returned to the preoperative level at 6 months (P = .63). CONCLUSIONS: Endoscopic endonasal transsphenoidal surgery may affect olfaction at 1 month after surgery, and olfactory function is expected to return after 3 months. Partial MT resection did not result in additional olfactory loss. It is safe to perform partial MT resection during surgery without compromising the olfactory outcomes.

Excited state intramolecular proton transfer (ESIPT) in dihydroxyphenyl anthracenes.

The photochemistry of three 9-(dihydroxyphenyl)anthracenes 6-8 was studied in neat CH(3)CN and selected organic solvents, to investigate excited state intramolecular proton transfer (ESIPT) from the phenol to the anthracene moiety. In D(2)O-CH(3)CN mixtures, the observed deuterium exchange of 6-8 is consistent with water-mediated (formal) ESIPT process from the ortho phenolic OH to the 10'-position of the anthracene ring, giving rise to quinone methide (QM) intermediates 12-14. There is no ESIPT for the corresponding methoxy-substituted compounds. Introduction of an extra hydroxyl group onto the phenol ring at different positions led to a range of deuterium exchange quantum yields (Φ = 0.03 to 0.15). In addition to the anticipated ESIPT process to the 10'-position, in neat CH(3)CN and other organic solvents, 6 (but not 7 or 8) undergoes a clean photocyclization to give bridged product 19 in quantitative yield. The mechanism of this unique photocyclization may involve a direct ESIPT or a 1,4-hydrogen transfer from the ortho phenolic OH to the 9'-position of the anthracene ring, generating a zwitterion (20) or diradical (21) intermediate, respectively, followed by ring closure. Fluorescence studies of 6 in various solvents show the existence of both local excited and intramolecular charge transfer states whereas only the former was present for 7 and 8, offering a possible rationalization for the photocyclization pathway.

Measurement equivalence/invariance of the abusive supervision measure across workers from Taiwan and the United States.

Growing international research interest in negative-leadership behaviors prompts the need to examine whether measures of ineffective leadership developed in the United States are equivalent across countries outside the United States. B. J. Tepper's (2000) abusive supervision measure has been used widely inside and outside the United States and merits research attention on its construct equivalence across different cultural settings. The authors conducted a series of multigroup confirmatory factor analyses to investigate the measurement equivalence of this measure across Taiwan (N = 256) and the United States (N = 389). Configural invariance was established, suggesting that both U.S. and Taiwanese samples perceive abusive supervision as a single-factor concept. Furthermore, the establishment of partial metric invariance and partial scalar invariance suggests that the abusive supervision measure is applicable to crosscultural comparisons in latent means, construct variance, construct covariances, and unstandardized path coefficients with the caution that workers from different cultures calibrate their responses differently when answering some items.

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne-allenes.

5-(2-Methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene were synthesized by treatment of the corresponding benzannulated enediynes with potassium tert-butoxide in refluxing toluene to give benzannulated enyne-allenes for the subsequent Schmittel cascade cyclization reactions. The structures of these two 5-(1-naphthyl)-11H-benzo[b]fluorenes could be regarded as 2,2'-disubstituted 1,1'-binaphthyls with the newly constructed benzofluorenyl group serving as a naphthyl moiety.

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.