Modulation Engineering of Electromagnetic Wave Absorption Performance of Layered Double Hydroxides Derived Hollow Metal Carbides Integrating Corrosion Protection.

Layered double hydroxides (LDHs) with unique layered structure and atomic composition are limited in the field of electromagnetic wave absorption (EMA) due to their poor electrical conductivity and lack of dielectric properties. In this study, the EMA performance and anticorrosion of hollow derived LDH composites are improved by temperature control and composition design using ZIF-8 as a sacrifice template. Diverse regulation modes result in different mechanisms for EMA. In the temperature control process, chemical reactions tune the composition of the products and construct a refined structure to optimize the LDHs conductivity loss. Additionally, the different phase interfaces generated by the control components optimize the impedance matching and enhance the interfacial polarization. The results show that the prepared NCZ (Ni3ZnC0.7/Co3ZnC@C) has a minimum reflection loss (RLmin ) of -58.92 dB with a thickness of 2.4 mm and a maximum effective absorption bandwidth (EABmax ) of 7.36 GHz with a thickness of 2.4 mm. Finally, due to its special structure and composition, the sample exhibits excellent anticorrosion properties. This work offers essential knowledge for designing engineering materials derived from metal organic framework (MOF) with cutting-edge components and nanostructures.

Pseudotyped Viruses.

Pseudotyped viruses have been constructed for many viruses. They can mimic the authentic virus and have many advantages compared to authentic viruses. Thus, they have been widely used as a surrogate of authentic virus for viral function analysis, detection of neutralizing antibodies, screening viral entry inhibitors, and others. This chapter reviewed the progress in the field of pseudotyped viruses in general, including the definition and the advantages of pseudotyped viruses, their potential usage, different strategies or vectors used for the construction of pseudotyped viruses, and factors that affect the construction of pseudotyped viruses.

Distinct Function of Mediator Subunits in Fungal Development, Stress Response, and Secondary Metabolism in Maize Pathogen Fusarium verticillioides.

Mediator is a nucleus-localized, multisubunit protein complex highly conserved across eukaryotes. It interacts with RNA polymerase II transcription machinery as well as various transcription factors to regulate gene expression. However, systematic characterization of the Mediator complex has not been performed in filamentous fungi. In our study, the goal was to investigate key biological functions of Mediator subunits in a mycotoxigenic plant pathogen Fusarium verticillioides. Although there is some level of divergence in the constituent subunits, the overall structure was conserved between Saccharomyces cerevisiae and F. verticillioides. We generated 11 Mediator subunit deletion mutants and characterized vegetative growth, conidia formation, environmental stress response, carbon and fatty acid use, virulence, and fumonisin B1 (FB1) biosynthesis. Each Mediator subunit deletion mutant showed deficiencies in at least three of the phenotypes tested, suggesting that each subunit has different principal functions in F. verticillioides development, metabolism, and virulence. The deletion of FvMed1 led to increased FB1 production, and we confirmed that FvMed1 is transported from the nucleus to the cytoplasm under fumonisin-producing conditions. Taken together, our study characterized various important functional roles for Mediator subunits in F. verticillioides and suggests that select subunits can perform unique cytoplasmic functions independent of the core Mediator in fungal nucleus.

Comparative pharmacokinetics of four major flavonoids in normal and chronic gastritis rats after oral administration of different combinations of Banxia Xiexin decoction.

Chronic gastritis (CG) has become a major threat to human health. Banxia Xiexin Decoction (BXXXD) has been used clinically to treat gastritis by acting on the spleen and stomach for thousands of years. Baicalin, wogonoside, liquiritin and liquiritigenin are the main bioactive flavonoids of BXXXD. A rapid, sensitive and selective HPLC-triple quadrupole (TQ)-MS/MS method was developed to simultaneously quantify the four flavonoids in rat plasma in this study. With salidroside as internal standard (IS), plasma samples were extracted and separated on a Welch HPLC XB-C18 column (2.1 × 50 mm, 1.8 µm) using gradient elution. The optimized gradient of the mobile phase consisted of water (containing 0.1% formic acid) (A) and methanol (B) was used. Detection was implemented in multiple reaction monitoring mode with an electrospray negative ionization source. The comparative pharmacokinetics of four analytes in normal and CG rats after oral administration of BXXXD or its different compatibilities were first investigated. The results indicated that the pharmacokinetic behaviors of analytes were obviously changed in CG rats. From the comparison between the whole prescription group and the compatibility groups, it was found that the pharmacokinetic behavior of analytes also changed to some extent. The pharmacokinetic alterations of analytes might be due to the pathological conditions of CG.

Isolated Arthroscopic Partial Meniscectomy Is More Effective at Improving Meniscal Symptoms in Comparison With Mechanical Symptoms in Patients With Concomitant Untreated Chondral Lesions.

PURPOSE: To rank Knee Injury and Osteoarthritis Outcome Score (KOOS) questions from most to least improvement after arthroscopic partial meniscectomy (APM) and compare improvement of meniscal versus mechanical symptoms. METHODS: A secondary analysis of the Chondral Lesions and Meniscus Procedures (ChAMP) Trial was performed. Inclusion criteria were age 30 years or older with degenerative meniscal tear failing nonoperative management, with or without associated unstable chondral lesions. No chondral debridement was performed. Responses to the 42 KOOS questions ranged from 0 (extreme problems) to 4 (no problems), and were answered preoperatively and at 1 year after isolated APM. The 1-year mean change, or delta (Δ), was calculated for each KOOS question and the Δ for meniscal and mechanical symptoms were statistically compared. RESULTS: Greatest improvement in 135 eligible patients was observed for questions about (1) awareness of knee problems (Δ = 1.93, standard deviation [SD] = 1.38), (2) frequency of knee pain (Δ = 1.93, SD = 1.29), (3) degree of difficulty while twisting/pivoting on the injured knee (Δ = 1.88, SD = 1.13), (4) degree of difficulty while running (Δ = 1.67, SD = 1.30), and (5) being troubled by lack of confidence in the knee (Δ = 21.67, SD = 1.11). Least improvement was observed for questions about: (1) degree of difficulty while getting on/off the toilet (Δ = 0.94, SD = 0.96), (2) feel grinding or hear clicking when the knee moves (Δ= 0.90, SD = 1.25), 3) degree of difficulty while getting in/out of the bath (Δ= 0.88, SD = 1.00), (4) knee catches/hangs up during movement (Δ= 0.80, SD = 1.09), and (5) the ability to straighten the knee fully (Δ= 0.54, 1.44). There was greater improvement for the KOOS questions pertaining to meniscal versus mechanical symptoms (P < .00001). CONCLUSIONS: KOOS symptoms as reported by subjects' responses to the questions pertaining to the frequency of knee pain, twisting/pivoting, running, squatting, and jumping showed the most improvement 1 year after isolated APM, whereas those relating to mechanical symptoms improved the least. Focusing on meniscal rather than mechanical symptoms may help surgeons better identify patients expected to benefit from APM. LEVEL OF EVIDENCE: IV, retrospective analysis of prospectively collected data.

Better Outcomes but No Difference in Joint Space Narrowing at Five Years Among Patients Without Unstable Chondral Lesions Versus Those With Unstable Chondral Lesions (Left In Situ) at the Time of Arthroscopic Partial Meniscectomy.

PURPOSE: To compare 5-year outcomes among patients with and without unstable chondral lesions undergoing arthroscopic partial meniscectomy (APM). METHODS: Using data from the Chondral Lesions And Meniscal Procedures (ChAMP) Trial, we compared outcomes for patients with unstable chondral lesions found at the time of APM and left in situ (CL-noDeb, N = 71) versus patients without unstable chondral lesions (NoCL, N = 47) at 5 years after APM. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analog pain scale, Short-form Health Survey (SF-36), physical knee measurements, progressive joint space narrowing on radiographs, and the rate of additional knee surgery. Multivariate linear regression was used to obtain mean differences (MDs) with corresponding 95% confidence intervals (CIs) adjusted for age, body mass index, and preoperative score (for postoperative scores). RESULTS: Compared with CL-noDeb, NoCL subjects had significantly greater improvement at 5 years in the KOOS score for function in sport and recreation (MD = 9.9 [95% CI, 0.7-19.1]), SF-36 pain (MD = 13.9 [95% CI, 5.5-22.3]), knee extension (MD = 0.8 [95% CI, 0.1-1.5]), and decreased quadriceps circumference at the mid-portion of the patella (MD = -1.5 [95% CI, -2.7 to -0.3). A greater proportion of patients in the NoCL group achieved the MCID for all outcome scores except for the WOMAC pain score (89% CL-NoDeb vs 87% NoCL) and SF-36 general (29% CL-NoDeb vs 23% NoCL). There were no significant group differences in measures of progressive radiographic joint space narrowing in any compartments of the operative knee and no significant difference in the rate of additional knee surgery within 5 years of the initial APM. CONCLUSIONS: Patients undergoing APM without unstable chondral lesions had statistically significantly better outcomes than patients with unstable chondral lesions at 5 years after surgery; however, there were no group differences in progressive radiographic joint space narrowing. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Two regulators of G-protein signaling (RGS) proteins FlbA1 and FlbA2 differentially regulate fumonisin B1 biosynthesis in Fusarium verticillioides.

Fumonisins are a group of mycotoxins produced by maize pathogen Fusarium verticillioides that pose health concerns to humans and animals. Yet we still lack a clear understanding of the mechanism of fumonisins regulation during pathogenesis. The heterotrimeric G protein complex, which consists of canonical subunits and various regulators of G-protein signaling (RGS) proteins, plays an important role in transducing signals under environmental stress. Earlier studies demonstrated that Gα and Gß subunits are positive regulators of fumonisin B1 (FB1) biosynthesis and that two RGS genes, FvFlbA1 and FvFlbA2, were highly upregulated in Gß deletion mutant ∆Fvgbb1. Notably, FvFlbA2 has a negative role in FB1 regulation. While many fungi contain a single copy of FlbA, F. verticillioides harbors two putative FvFlbA paralogs, FvFlbA1 and FvFlbA2. In this study, we further characterized functional roles of FvFlbA1 and FvFlbA2. While ∆FvflbA1 deletion mutant exhibited no significant defects, ∆FvflbA2 and ∆FvflbA2/A1 mutants showed thinner aerial hyphal growth while promoting FB1 production. FvFlbA2 is required for proper expression of key conidia regulation genes, including putative FvBRLA, FvWETA, and FvABAA, while suppressing FUM21, FUM1, and FUM8 expression. Split luciferase assays determined that FvFlbA paralogs interact with key heterotrimeric G protein components, which in turn will lead altered G-protein-mediated signaling pathways that regulate FB1 production and asexual development in F. verticillioides.

Glucose-6-Phosphate Isomerase FgGPI, a ß2 Tubulin-Interacting Protein, Is Indispensable for Fungal Development and Deoxynivalenol Biosynthesis in Fusarium graminearum.

Glucose-6-phosphate isomerase (GPI) is ubiquitous in most organisms, catalyzing the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. In this study, we investigated biological and genetic functions of FgGPI in the phytopathogen Fusarium graminearum. We found that hyphal growth, conidial germination, and septa formation were significantly inhibited in FgGPI deletion mutant ∆FgGPI. FgGPI was also positively associated with glucose metabolism, ATP biosynthesis, and carbon source utilization. In addition, pyruvate production, deoxynivalenol (DON) biosynthesis, and virulence were reduced in ∆FgGPI. A coimmunoprecipitation assay demonstrated that FgGPI interacts with Fgß2. More importantly, the coimmunoprecipitation assay showed that carbendazim-resistant substitutions in ß2 tubulin could reduce the interaction intensity between FgGPI and Fgß2, thereby increasing FgGPI expression and accelerating DON biosynthesis in carbendazim-resistant strains. Taken together, our work revealed the indispensable role of FgGPI in fungal developmental processes, DON biosynthesis, and pathogenicity in F. graminearum.

Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides.

Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N3)LARLLT and its cyclic analog cyclo(K(N3)larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70-82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm-2) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein.

Carbendazim-resistance associated ß2 -tubulin substitutions increase deoxynivalenol biosynthesis by reducing the interaction between ß2 -tubulin and IDH3 in Fusarium graminearum.

Microtubule is a well-known structural protein participating in cell division, motility and vesicle traffic. In this study, we found that ß2 -tubulin, one of the microtubule components, plays an important role in regulating secondary metabolite deoxynivalenol (DON) biosynthesis in Fusarium graminearum by interacting with isocitrate dehydrogenase subunit 3 (IDH3). We found IDH3 negatively regulate DON biosynthesis by reducing acetyl-CoA accumulation in F. graminearum and DON biosynthesis was stimulated by exogenous acetyl-CoA. In addition, the expression of IDH3 significantly decreased in the carbendazim-resistant mutant nt167 (Fgß2 F167Y ). Furthermore, we found that carbendazim-resistance associated ß2 -tubulin substitutions reducing the interaction intensity between ß2 -tubulin and IDH3. Interestingly, we demonstrated that ß2 -tubulin inhibitor carbendazim can disrupt the interaction between ß2 -tubulin and IDH3. The decreased interaction intensity between ß2 -tubulin and IDH3 resulted in the decreased expression of IDH3, which can cause the accumulation of acetyl-CoA, precursor of DON biosynthesis in F. graminearum. Thus, we revealed that carbendazim-resistance associated ß2 -tubulin substitutions or carbendazim treatment increases DON biosynthesis by reducing the interaction between ß2 -tubulin and IDH3 in F. graminearum. Taken together, the novel findings give the new perspectives of ß2 -tubulin in regulating secondary metabolism in phytopathogenic fungi.

The critical role of cytochrome c maturation (CCM) system in the tolerance of Xanthomonas campestris pv. campestris to phenazines.

Phenazine-1-carboxylic acid (PCA), a secondary metabolite produced by Pseudomonas spp., exhibits a high inhibitory effect in Xanthomonas oryzae pv. oryzae (Xoo), but less inhibitory effect in Xanthomonas oryzae pv. oryzicola (Xoc), and almost no inhibitory effect in Xanthomonas campestris pv. campestris (Xcc). In our previous study, reactive oxygen species (ROS) scavenging system was reported to be involved in PCA tolerance in Xanthomonas spp. However, the PCA tolerance mechanism of Xanthomonas spp. is unclear. In the current study, we constructed a Tn5-based transposon mutant library in Xcc and four highly PCA-sensitive insertion mutants were obtained. TAIL-PCR further confirmed that the Tn5 transposon was inserted in the cytochrome c maturation (CCM) system (XC_1893, XC_1897) of these mutants. Disruption of the CCM system significantly decreased the growth, motility and tolerance of Xcc to PCA and other phenazines, such as phenazine and 1-OH-phenazine. The CCM system is responsible for the covalent attachment of the apocytochrome and heme. Disruption of the transmembrane thioredox protein (Dsb) pathway (XC_0531), an essential process for the formation of mature apocytochrome, also exhibited a decreased tolerance to PCA, suggesting that the defect of cytochrome c caused decreased tolerance of Xcc to PCA. Meanwhile, disruption of the CCM system or Dsb pathway interfered with the functions of cytochrome c proteins, causing an increased sensitivity to H2O2. Collectively, we concluded that the CCM system and Dsb pathway, regulate the tolerance of Xcc to phenazines by influencing the functions of cytochrome c. Therefore, these results provide important references for revealing the action mechanism of PCA in Xanthomonas spp.

Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.

Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes ß-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1(K38A), partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.

Synthesis and in vitro PDT evaluation of new porphyrins containing meso-epoxymethylaryl cationic groups.

OBJECTIVES: Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT. MATERIALS AND METHODS: New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs. RESULTS: All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35-0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 µM at 1.5 J/cm2 ); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 µM at 1.5 J/cm2 ). The epoxymethyl-containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 µM. The neutral porphyrins showed no phototoxicity up to the 100 µM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes. CONCLUSION: Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl-containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566-575, 2018. © 2018 Wiley Periodicals, Inc.

A new point mutation in ß2-tubulin confers resistance to carbendazim in Fusarium asiaticum.

Resistance to benzimidazole fungicides in many phytopathogenic fungi is caused by specific point mutations in the ß-tubulin gene (ß-tubulin). However, the mutated locus and genotype of ß-tubulin differ among phytopathogenic fungi. To validate the point mutation in Fusarium asiaticum ß2-tubulin that confers resistance to carbendazim and to analyze the molecular interaction between carbendazim and F. asiaticum ß2-tubulin. In this study, a new point mutation (GAG→GCG, E198A) at codon 198 of ß2-tubulin in a wild-type F. asiaticum strain was constructed by site-directed mutagenesis followed by a split marker strategy. The site-directed mutants were verified and exhibited a high level of resistance to carbendazim. In the absence of fungicide treatment, the biological characteristics did not differ between the site-directed mutants and the wild-type strain. Molecular docking between carbendazim and ß2-tubulin was carried out using the Surflex-Dock program in Sybyl X-2.0 version and the results indicated that the E198A mutation altered the configuration of ß2-tubulin, resulting in the change of the bonding sites and docking scores. We concluded that the point mutation of F. asiaticum ß2-tubulin conferring carbendazim resistance may not always be the bonding site for carbendazim.

Synthesis of BODIPY-Peptide Conjugates for Fluorescence Labeling of EGFR Overexpressing Cells.

Regioselective functionalization of 2,3,5,6,8-pentachloro-BODIPY 1 produced unsymmetric BODIPY 5, bearing an isothiocyanate group suitable for conjugation, in only four steps. The X-ray structure of 5 reveals a nearly planar BODIPY core with aryl dihedral angles in the range 47.4-62.9°. Conjugation of 5 to two EGFR-targeting pegylated peptides, 3PEG-LARLLT (6) and 3PEG-GYHWYGYTPQNVI (7), under mild conditions (30 min at room temperature), afforded BODIPY conjugates 8 and 9 in 50-80% isolated yields. These conjugates showed red-shifted absorption and emission spectra compared with 5, in the near-IR region, and were evaluated as potential fluorescence imaging agents for EGFR overexpressing cells. SPR and docking investigations suggested that conjugate 8 bearing the LARLLT sequence binds to EGFR more effectively than 9 bearing the GYHWYGYTPQNVI peptide, in part due to the lower solubility of 9, and its tendency for aggregation at concentrations above 10 µM. Studies in human carcinoma HEp2 cells overexpressing EGFR demonstrated low dark and photo cytotoxicities for BODIPY 5 and the two peptide conjugates, and remarkably high cellular uptake for both conjugates 8 and 9, up to 90-fold compared with BODIPY 5 after 1 h. Fluorescence imaging studies in HEp2 cells revealed subcellular localization of the BODIPY-peptide conjugates mainly in the Golgi apparatus and the cell lysosomes. The low cytotoxicity of the new conjugates and their remarkably high uptake into EGFR overexpressing cells renders them promising imaging agents for cancers overexpressing EGFR.

Synthesis and Spectroscopic and Cellular Properties of Near-IR [a]Phenanthrene-Fused 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes.

A new synthetic method to build aryl-fused 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) is reported. The intramolecular cyclization step was completed in a short time (1-2 h) and in high yields (>90%), due to the intrinsic rigid structural conformation of the precursor BODIPY and the high reactivity of its 1,7-bromo groups. The [a]phenanthrene-fused BODIPYs 4a-c were characterized by NMR spectroscopy, HRMS, DFT calculations, and, in the case of 4a, by X-ray crystallography. Spectroscopic studies show that 4a-c strongly absorb and emit in the NIR spectral region, in the range 642-701 nm. In addition, BODIPYs 4b and 4c exhibit no toxicity in the light or dark in HEp2 cells and accumulate intracellularly in a time-dependent manner, mainly in the cell endoplasmic reticulum. These results suggest the potential use of [a]phenanthrene-fused BODIPYs as NIR bioimaging probes.

Synthesis and Spectroscopic Investigation of a Series of Push-Pull Boron Dipyrromethenes (BODIPYs).

A series of push-pull BODIPYs bearing multiple electron-donating and electron-acceptor groups were synthesized regioselectively from 2,3,5,6,8-pentachloro-BODIPY, and characterized by NMR spectroscopy, HRMS, and X-ray crystallography. The influence of the push-pull substituents on the spectroscopic and electrochemical properties of BODIPYs was investigated. Bathochromic shifts were observed for both absorbance (up to 37 nm) and emission (up to 60 nm) in different solvents upon introduction of the push-pull moieties. DFT calculations, consistent with the spectroscopic and cyclic voltammetry studies, show decreased HOMO-LUMO energy gaps upon the installation of the push-pull moieties. BODIPY 7 bearing thienyl groups on the 2 and 6 positions showed the largest λmax for both absorption (635-653 nm) and emission (706-707 nm), but also the lowest fluorescence quantum yields. All BODIPYs were nontoxic in the dark (IC50 > 200 µM) and showed low phototoxicity (IC50 > 100 µM, 1.5 J/cm2) toward human HEp2 cells. Despite the relatively low fluorescence quantum yields, the push-pull BODIPYS were effective for cell imaging, readily accumulating within cells and localizing mainly in the ER and Golgi. Our structure-property studies can guide future design of functionalized BODIPYs for various applications, including bioimaging and in dye-sensitized solar cells.

The Effect of Body Mass Index on Clinical Outcomes in Patients Without Radiographic Evidence of Degenerative Joint Disease After Arthroscopic Partial Meniscectomy.

PURPOSE: To examine the effect of obesity on clinical outcomes at 1 year after arthroscopic partial meniscectomy. METHODS: We conducted a secondary analysis of the ChAMP (Chondral Lesions and Meniscus Procedures) randomized controlled trial (N = 256). The visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), range of motion, and presence of effusion were assessed preoperatively and at 1 year after arthroscopic partial meniscectomy. Body mass index was categorized as normal weight, 24.99 or less; overweight, 25 to 29.99; or obese, 30 or greater. Analysis of variance or the Cochran-Mantel-Haenszel test was used to examine differences in clinical outcomes between body mass index categories, and mean ± standard deviation or number (percentage) is reported. RESULTS: Preoperatively, obese patients had worse WOMAC pain (56.2 ± 17.2 vs 61.3 ± 17.2, P = .02), WOMAC physical function (55.8 ± 17.1 vs 62.8 ± 17.1, P = .004), pain visual analog scale (4.9 ± 2.1 vs 4.2 ± 1.9, P = .01), KOOS pain (49.5 ± 14.9 vs 54.0 ± 15.1, P = .02), and KOOS quality-of-life (27.9 ± 18.3 vs 36.9 ± 17.0, P = .001) scores, as well as decreased flexion (121.8° ± 22.6° vs 132.3° ± 16.5°, P = .003), compared with normal-weight patients. Overweight patients (n = 51 [51.5%], P = .03) and obese patients (n = 56 [52.8%], P = .002) were more likely to have knee effusion before surgery than normal-weight patients (n = 17 [34%]). At 1 year after surgery, overweight (130.2° ± 7.7°, P = .03) and obese (128.1° ± 7.1°, P = .003) patients had decreased flexion compared with normal-weight patients (134.5° ± 8.3°). CONCLUSIONS: Obese patients had worse pain, physical functioning, and quality-of-life scores, as well as decreased flexion, compared with normal-weight patients before arthroscopic partial meniscectomy. At 1 year after arthroscopic partial meniscectomy, there were no statistically significant differences in clinical outcomes but obesity was associated with decreased knee flexion. LEVEL OF EVIDENCE: Level II, prospective comparative trial.

Syntheses and cellular investigations of di-aspartate and aspartate-lysine chlorin e(6) conjugates.

Chlorin e6 is a tricarboxylic acid degradation product of chlorophyll a. Four chlorin e6 bis(amino acid) conjugates were regioselectively synthesized bearing two aspartate conjugates in the 13(1),17(3)- and 15(2),17(3)-positions, or at the 13(1),15(2)via an ethylene diamine linker. One additional conjugate bearing two different amino acids, lysine at 13(1)via an ethylene diamine linker and an aspartate at 15(2)via a ß-alanine linker was also synthesized. The cytotoxicity and uptake of four di(amino acid) chlorin e6 conjugates were investigated in human HEp2 cells, and compared with chlorin e6. The most cytotoxic and most taken up conjugates were the zwitterionic 13(1),15(2)-disubstituted conjugates 28 and 33; these also localized in multiple organelles. In contrast, the anionic 13(1),17(3)- and 15(2),17(3)-di-aspartyl chlorin e6 conjugates 12 and 13 showed low dark cytoxicity and lower phototoxicity compared with chlorin e6.

Effects of phenazine-1-carboxylic acid on the biology of the plant-pathogenic bacterium Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae (Xoo) is the casual agent of bacterial blight, which is one of the most serious diseases of rice. The antibiotic phenazine-1-carboxylic acid (PCA), which is primarily produced by Pseudomonas spp., was found and previously reported very effective against Xoo. However, the biological effects of PCA on Xoo remain unclear. In this study, we found that PCA increased the accumulation of reactive oxygen species (ROS) and reduced the activities of catalase (CAT) and superoxide dismutase (SOD) in Xoo. Xoo was more sensitive to H2O2 than Xanthomonas oryzae pv. oryzicola (Xoc), and had a much lower expression of CAT genes. In addition, proteomic analysis indicated that PCA inhibited carbohydrate metabolism and nutrient uptake in Xoo, and analysis of carbon source utilization further confirmed that carbohydrate metabolism in Xoo was repressed by PCA. In conclusion, PCA acted as a redox-cycling agent that disturbed the redox balance in Xoo and reduced CAT and SOD activities, resulting in higher accumulation of ROS, altered carbohydrate metabolism, and lower energy production and nutrient uptake. Moreover, a deficient antioxidant system in Xoo made it very sensitive to PCA.