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Purpose: In this in vitro study, we investigated the effects of polychlorinated biphenyls (PCBs) on human thyrocytes, with a focus on the involvement of AhR, a key player in xenobiotic response, and the anti-oxidant Nrf-2/HO-1 pathway. Methods: Primary cultured thyrocytes were exposed to the dioxin-like congeners PCB118 and PCB126 at 2.5 and 5 µM concentrations. mRNA expression was assessed by real-time PCR, and protein expression by Western Blot and ELISA, while protein quantification was assessed by densitometric analysis. Results: In cultured thyrocytes, PCB118 and PCB126 induced a significant (P< 0.01) increase of mRNA and protein levels of the pro-inflammatory cytokines IL-1beta and IL-6, while reducing those of thyroglobulin (TG) and NIS (p< 0.05), indicating down-regulation of these thyroid-specific genes in PCB-induced inflammation. ROS production also increased (p< 0.001). mRNA levels of AhR and the downstream molecules cytochrome P4501A, Nrf-2/HO-1 increased (p< 0.001), as well as related protein levels (p< 0.01), suggesting the activation of AhR and Nrf-2 pathways in response to PCBs exposure. AhR silencing decreased AhR-related gene expression and restored NIS and TG expression, while reducing inflammatory cytokines and oxidative stress markers (p< 0.05). Conclusions: Dioxin-like PCBs (PCB118 and PCB126) may promote inflammation and oxidative stress in thyrocytes, impairing the expression of genes that are key players of thyroid function. These effects can be partially attributed to the activation of the AhR and Nrf-2 pathways. These data may contribute to explain the mechanisms underlying thyroid toxicity of PCBs, highlighting the potential role of these pollutants as a trigger of autoimmune thyroid inflammation and damage.

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AbstractThirty-six multiparous Holstein mid-lactating cows were housed in 6 pens (6 cows/pen) and allocated in two groups (3 pens/group), receiving a control total mixed ration (CTR), or the same diet supplemented with a feed additive (TRT). Between 15 and 35 days from enrolment (DFE) the dry matter intake (DMI) of each pen, and the individual milk yield (MY), rumination time (RT), the compositions of milk and rumen fluid and the metabolic profile of plasma were monitored regularly. At 35 DFE, cows started a 1-week wash-up period prior to the changeover. Data were analysed with a mixed model using repeated measures. Cows receiving the additive had higher DMI and MY (p < .01), a longer RT between 22 and 29 DFE (p < .05), a higher total VFA concentration and a lower pH in the rumen fluid (p < .01 and p = .04, respectively). At 15 DFE, TRT cows had a higher concentration of lactose in their milk, and lower concentrations of BHB, ceruloplasmin and haptoglobin, paired with higher concentrations of albumin, paraoxonase and aspartate aminotransferase in their plasma (p < .01). These outcomes suggest a positive effect of the additive on increasing DMI and MY, possibly reflecting that it had a combined action on the rumen and the liver.HighlightsThe additive increased feed intake, rumination time and milk yield.It improved rumen fermentations and liver activity, and mitigated ketogenesis and inflammatory conditions.Beneficial actions of the active components on rumen and liver functions could be hypothesised.

We report a case of syphilitic balanitis of Follmann arising in a man with a history of prior infection with syphilis. Few cases have been described in the literature. In our case, a man with history of multiple unprotected sexual contacts presented with erosive balanitis and painless inguinal bilateral lymphadenopathy. All tests for sexually transmitted infections (STIs) performed were negative with the exception of serology for syphilis. We made the diagnosis of syphilitic balanitis of Follmann that was confirmed by prompt resolution after treatment.

(Abstracted from Prenat Diagn2022;42:1575–1586Methods for diagnosis of genetic abnormalities have recently undergone substantial improvement. Noninvasive prenatal testing (NIPT) is performed early in pregnancy, typically at the end of the first trimester using cell-free DNA (cfDNA) to identify 3 commonly occurring trisomies (13, 18, and 21).

AbstractAn unsupervised machine learning approach (ML) of rumination time (RT) data was used to evaluate metabolic and lactation performance in a cohort of Simmental dairy cows (29) around parturition. The k-means clustering (unsupervised ML) was used to generate clusters based on RT (Hr-Tags; SCR by Allflex) over 24 h from 1 to 7-d post-calving. Two large clusters were obtained: high (High-RT, n = 13) and low (Low-RT, n = 12). Milk production was recorded until 42 d in lactation and milk samples collected weekly. Blood samples were collected from −21 to +28 d relative to calving. Data were subjected to PROC MIXED of SAS. Compared with Low-RT, High-RT cows had lower plasma BHB (3, 7, and 14 d), haptoglobin (3 and 7 d), and non-esterified fatty acids (1 and 3 d). High-RT cows had greater tocopherol from 3 to 28 d, fructosamine and albumin at 7 d, and retinol at 3 and 7 d after calving than Low-RT cows. Compared with multiparous Low-RT, milk production was greater in multiparous High-RT cows, but no differences were detected for primiparous. Only for multiparous, High-RT cows displayed a greater LFI than Low-Rt cows. The close relationship between RT and the physiological state at the onset of lactation supports the use of RT as an indicator of metabolic and inflammatory adaptations to the negative energy balance of cows after parturition. At the farm level, these outcomes provide information to farmers that can be helpful in management decisions for cow health, complementing traditional methods.HIGHLIGHTSThe unsupervised ML applied was able to group cows with different RT increase rates after calving based on differences in plasma biomarkers of energy metabolism, inflammatory response, and liver functionality, particularly in multiparous cows.A quicker increase in RT after calving was associated with a lower inflammatory response, lower lipid mobilisation, and greater milk production.At the farm level, the fine-tuning of specific algorithm in the actual sensors considering the rate of increase of RT after calving can be helpful in management decisions for cow health, complementing traditional methods to better monitor early lactation dairy cows.

AbstractOur study investigates metabolic changes occurring at dry-off and the contribution of milk yield (MY) in such alterations. Thirteen Holsteins were dried off at 55 days from expected calving day (assumed as 0 days from dry-off, DFD) and divided in two groups according to their average daily MY in the last week of lactation, assuming a cut-off of 15 kg·d−1: low MY (7 cows) and high MY (6 cows). From −7 to 34 DFD dry matter intake (DMI) and rumination time were measured. Blood samples were collected at −7, 2, 7, 27 and 34 DFD to assess an haematological and metabolic profile and at −7, 7 and 34 DFD to test functions of circulating white blood cell (WBC) through ex vivochallenges. Data were included in a mixed model for repeated measures assuming MY at dry-off, time and their interaction as fixed effects. After dry-off, DMI was reduced and rumination time was increased in all the animals. High MY cows had greater DMI and rumination time than low MY cows. In blood, WBC counts decreased at 7 DFD and increased the production of pro-inflammatory cytokines at 7 and 34 DFD. Plasmatic concentrations of liver enzymes indicators, positive acute phase proteins (APPs); and nitrogen species increased after dry-off. Conversely, negative APPs and antioxidant species decreased. Those alterations were more marked in high MY animals. This study suggests that dry-off decreased liver function, triggered a systemic inflammation and depleted antioxidant systems, especially in the group of cows with high MY at dry-off.HighlightsInflammation, liver dysfunctions and altered redox balance has been detected after dry-off in all the animals.Cows with highest milk yield before halting of milk removal faced the most severe metabolic challenges.Such founding indicates the management of dry-off as a key point for dairy cows health.

In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources. The paper provides a detailed description of: (1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload; (2) the elements and functions of the mission, from the spacecraft to the ground segment.

AbstractThe increased resistance to disease observed after monensin treatment could reflect a reduction of inflammation and oxidative stress. We hypothesised that if monensin supplementation was given before calving, it would help in controlling inflammation, reduce the susceptibility to disease and increase the performance. Fourteen pregnant heifers (PR) and 24 multiparous cows (ML) were randomly assigned to a treated group (Mon) or a control group (Ctr). The Mon group received 32.4 g of monensin in a controlled-release capsule 21 days before calving (expected release rate, 335 mg/d for 95 days). Their health status, rumination activity, and plasma parameters were monitored from –28 to 56 days from calving. The milk yield (MY), milk composition, and cheese-making properties were also monitored. Rumen samples were collected at 30 days from calving to assess the volatile fatty acids composition and investigate immunological parameters. After calving, the Mon group had fewer clinical diseases, an increased rumination time, and a higher MY. Monensin reduced the infiltration of both T and B cells in rumen fluid. In ML, the Mon group had lower levels of β-hydroxybutyrate in the early postpartum period and a lower level of total reactive oxygen species. Of PR, the Mon group had a tendency for lower levels of nonesterified fatty acids, higher levels of ceruloplasmin after the first month of lactation, a tendency for lower levels of paraoxonase, higher levels of γ-glutamyl transferase and higher levels of total reactive oxygen species. Monensin treatment decreased the cheese-making properties in the milk of PR.HighlightsMonensin improved the performance of all the animals and decreased the disease incidence in all of them.Monensin heightened the inflammatory and oxidative stress status and reduced the cheese-making properties in pregnant heifers.Although different effects were seen in cows with different parity, dairy cows generally beneficed of monensin administration.

AbstractThe aim of this study was to evaluate the use of Fourier transform mid-infra-red (FT-MIR) spectrometry to analyse blood biochemical parameters of the horse. For this purpose, mid infrared transmission spectra were acquired from plasma samples from 72 healthy horses. Each sample was also analysed using reference clinical chemical methods, and these results were used as calibrating values to develop predictive models by partial least squares method. The validation was carried out using external validation method. The coefficient of determination (R2) and the ratio of prediction to deviation (RPD) showed high values for parameters regarding energy and protein metabolism. Among energy parameters, an excellent prediction model was developed for total cholesterol (R2 = 0.94; RPD = 4.40) and triglycerides (R2 = 0.96; RPD = 5.0) while fair results were obtained for cholesterol fractions (R2range: 0.75–0.80; RPD range: 2.0–2.3). Among protein metabolism parameters, excellent prediction models were developed for total protein, albumin, globulin (R2range: 0.96–0.99; RPD range: 5.40–9.30) and good prediction model for urea (R2 = 0.90; RPD = 3.2), confirming previous results with the plasma of dairy cows. Our results highlight that FT-MIR spectrometry offers an accurate measurement of important plasma biomarkers for the evaluation of energy (cholesterol and triglycerides) and protein metabolism (urea), as well as for health status (albumin/globulin ratio). Our results may open an interesting perspective of a more cost-effective approach to monitoring the metabolic status and health conditions of the horse, with the future possibility to predict some blood biomarkers by the practitioner in field.HighlightsFT-MIR potential to measure blood parameters in horses was explored;Infra-red spectrometry can be used in horse’s clinical chemistry;Fast and cost-effective metabolic status evaluation in horses;Accurate FT-MIR predictions for plasma protein and lipid fractions in horses.

AbstractForages dry matter (DM) could vary among batches and in particular when silages are fed. These variations could modify nutrients composition of total mixed ration and affect cows performance. The aim of this study was to evaluate the effect of application of a precision feeding system (PFS) based on a near infra-red scanner, on metabolic conditions and milk yield in lactating dairy cows. The study was performed in 7 farms where PFS was installed on feed mixer to perform a weight-adjustment of DM measured in real time on feeds. A cross-over (14 weeks periods) was applied, PFS was switched on (PF-ON) in three herds and off in the other four (PF-OFF) during 1st period, and vice versain 2nd period. At the end of two periods, in each herd 7 early and 7 mid lactation cows, for a total of 196 cows, were checked for: blood parameters, milk yield and composition. During the study deviation of DM of target diet (calculated on amount of feed in recipe and applying the DM determined in laboratory) and diets really distributed to cows tended to be lower with PF-ON vs. PF-OFF (0.06 vs 0.12 kg, p = .12). In early lactating cows, lower blood urea (4.63 vs 4.88 mmol/L, p = .115) indicated a better feed protein utilisation in PF-ON vs. PF-OFF. Milk yield and composition were not affected. The use of PFS meliorated the consistency of TMR, which could determine a better efficiency of nutrients utilisation and a reduction of production costs.HighlightsNear infra-red (NIR) technology can be advantageously applied at farm level within a precision feeding system for dairy cows.The system allowed a more constant daily supply of nutrients with a reduction of metabolic alterations and a higher efficiency of feed protein utilisation.Utilization of NIR technology at farm level can be economically sustainable.

Oncogene-addicted non-small cell lung cancer (NSCLC) inevitably becomes resistant to targeted therapy, by developing acquired resistance (AR), on- or off-target mechanisms, potentially detectable by liquid biopsy (LB). We present the first reported case of a pretreated EGFRdel19/BRAFV600Elung adenocarcinoma patient with symptomatic leptomeningeal metastasis (LM) obtaining durable clinical benefit on Osimertinib, Dabrafenib, and Trametinib treatment.

•Unimodal TRBC1 pattern correlates with T cell clonality.•A TRBC1-including multiparametric panel improves clonality assessment sensitivity.•Monitoring TRBC1 helps in identifying small T-cell clones of uncertain significance.•TRBC1 represents an opportunity to overcome time-consuming diagnostic strategies.

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS).Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes.Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival.Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

AbstractAloe has long been used as a traditional medicine for its numerous beneficial properties, which are mainly ascribed to β-polysaccharides and phenolic compounds including anthraquinones, anthrones and chromones. However, few studies on large animals are currently available. The effect of whole leaf Aloe arborescenshomogenate on the in vitrorumen fermentative processes was tested using alfalfa hay and barley meal as substrates. The Aloe homogeneate was added at three different concentrations (0.4, 2.0 and 10.0 g L−1of fermentation liquid). The same homogenate was dosed (200 g) orally and through the rumen cannula to three rumen cannulated heifers and orally to six lactating dairy cows to measure the rumen degradation of aloin and the transfer of aloin from the gut into the blood, respectively. The Aloe homogenate did not affect in vitrorumen fermentations and feed digestibility. The administration of Aloe homogenate did not negatively affect animal feed intake and health neither on the cannulated heifers nor on the dairy cows. Aloin underwent a rapid degradation in the rumen milieu, and became undetectable 2 h after oral dosage. However, when Aloe homogenate was administered to dairy cows, aloin appeared in blood as early as 2 h after administration, reached a maximum after 4 h (6.2 ± 5.8 μg L−1) and progressively decreased thereafter. These results suggest that Aloe compounds can be absorbed into the blood and encourage the study of Aloe as a potential nutraceutical in ruminants. Further studies should determine the most effective in vivodosage.

•Non-small-cell lung cancer is the primary cause of cancer-related death. TP53mutations affect patients prognosis, also in oncogene-addicted subgroup. We investigated the role of TP53mutations in predicting response to therapy and prognosis in ALK-rearranged NSCLC patients, finding that specific TP53mutations are able to influence patients prognosis.

Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from –24 to 72 h. After 24 h of fasting (from –24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at –24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P< 0.01) rumen pH and VFA but increased rumen D- and L-lactic acid (P< 0.01). Concurrently, a decrease of fecal pH and VFA occurred in ACID (P< 0.01), together with an abrupt increase (P< 0.01) of lactate and fecal alkaline phosphatase. Blood lactulose was significantly increased in ACID peaking 2 h after lactulose dosage. Blood glucose, β-hydroxybutyrate, Ca, K, Mg, and alkaline phosphatase showed a significant reduction (P< 0.05) at 24 h, whereas urea and NEFA declined (P< 0.05) from 48 to 72 h. A strong inflammatory acute phase response with oxidative stress in ACID group was observed from 24 to 72 h; higher values of haptoglobin (P< 0.01) were measured from 24 to 72 h and of ceruloplasmin from 48 (P< 0.05) to 72 h (P< 0.01). Among the negative acute phase reactants, plasma albumin, cholesterol, paraoxonase, and Zn concentration also decreased (P< 0.05) in ACID at different time points between 24 and 72 h after acidotic challenge start. A rise (P< 0.05) of reactive oxygen metabolites and a drop of vitamin E (P< 0.01) between 24 and 72 h were indicative of oxidative stress in ACID. The perturbation of these blood metabolites suggests that acute acidosis was effectively induced by our model. The increase of lactulose in blood in ACID indicates that gastrointestinal permeability for the marker increased and the large increment after 2 h from dosage suggests that most of the passage occurred through the rumen or abomasal walls.

Introduction:Activating mutations of the EGFRand rearrangement of anaplastic lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular characterization in NSCLC patients.Areas covered:For this review article, all published data on the most relevant Phase III trials with tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed.Expert opinion:Eight Phase III trials clearly established EGFR TKIs as the best therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated NSCLC, EGFR TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFRmutations, whereas in the EGFRwild-type population, a similar efficacy to docetaxel or pemetrexed in term of survival has been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the superiority of a multi-target TKI, including ALK, in terms of progression-free survival, response rate and toxicity profile when compared to standard second-line chemotherapy. New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.

The aim of the study was to assess the small intestine permeability by using lactulose as a sugar probe and blood metabolites in sheep after a challenge with repeated indomethacin injections. According to a changeover design, 7 adult sheep (4 males and 3 females) were subjected to 4 intramuscular injections (every 12 h) of saline [control (CRT); 7 animals] or indomethacin (INDO; 7 animals). Two hours after the last injection, 30 g of lactulose were administered orally to both CTR and INDO. Blood samples were collected daily for the analysis of the metabolic profile and 5 samples were collected at 2-h intervals following lactulose ingestion to monitor changes in blood levels of lactulose as an index of intestinal permeability. The INDO challenge induced clinical symptoms such as lack of appetite, dullness, weakness, depression, and diarrhea with traces of blood in the feces. In INDO group, haptoglobin and ceruloplasmin increased (P< 0.01) after INDO challenge whereas a decrease (P< 0.05) of negative acute phase reactants (e.g., cholesterol, albumin, and paraoxonase) was observed. Reactive oxygen metabolites increased (P< 0.01) from 60 to 204 h after the INDO challenge start, with a decrease of vitamin E concentration from 12 (P< 0.01) to 132 h (P< 0.05). Blood lactulose concentrations were increased (P< 0.05) in INDO animals and the highest mean values (17.67 µg/mL in INDO vs. 0.17 µg/mL in CRT; P< 0.01) were observed 6 h after oral dosage of lactulose. These changes indicate that the INDO challenge led to severe inflammatory responses with oxidative stress by enhancing small intestinal permeability in sheep that allowed lactulose to enter in blood. The results of this experiment demonstrate that lactulose can be used as a probe to assess gastrointestinal permeability in adult ruminants to test the consequences of stressing conditions on animal welfare. For this purpose, the most suitable time for blood sampling is between 2 and 8 h after the oral dosage of lactulose.

Introduction:Activating mutations of the epidermal growth factor receptor (EGFR) gene and rearrangement of anaplastic lymphoma kinase (ALK) gene best illustrate the therapeutic relevance of molecular characterization in non-small cell lung cancer (NSCLC) patients. Several genetic aberrations with a potential prognostic or predictive role have been identified, mainly in adenocarcinoma subtype, including ROS1,RET,MET,HER2,BRAFand KRAS.More recently oncogenic drivers, such as DDR2,FGFR1and PI3KCA,have been characterized in squamous cell lung carcinoma (SCC) and target agents are currently under evaluation. The aim of this review is to summarize the growing scenario of new targetable oncogenes in NSCLC.Areas covered:For this review article all published data on NSCLC genomic alterations, including the techniques employed for oncogenic drivers identification, the prevalence of each one in lung cancer subtypes, the preclinical data corroborating their role in tumorigenesis and the potential biological tailored agents tested and under evaluation were collected and analyzed using PubMed.Expert opinion:Oncogenic products represent reliable targets for drug therapy and the expanding knowledge of molecular pathways involved in lung tumorigenesis is resulting in a dramatic change of treatment strategies leading to an improvement in disease and symptom control, extending life duration and improving quality of life.

Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions.

The mesenchymal–epidermal transition (c-MET) receptor tyrosine kinase has a central role in the cancer cell's survival. MET and its ligand, hepatocyte growth factor (HGF), have recently been identified as promising targets in solid tumors, including nonsmall-cell lung cancer (NSCLC).

The synthesis and photoelectrical properties of 2.2paracyclophanes, containing conjugated acetylenic triple bonds in the linear side-chain, are described. These compounds were incorporated as an electroactive component within a conductive polymer, i.e.poly3-butylthiophene. The blend showed a photoelectrical response higher than that of the neat polymer. Surprisingly, it was found that the application of an electric bias during the preparation of the blend led to an increase in the photocurrent.

Our ongoing study on cycloaddition reactions of dienes with different dienophiles afforded a great variety of derivatives with interesting molecular structures and electronic behavior. A new type of angularly annelated [2.2]paracyclophane (3) has been synthesize by the Diels–Alder reaction of 4-(2-propenyl[2.2]paracyclophane (1) and 1,4-benzoquinone (2) under high pressure conditions. The structure determination of this compound has been achieved by NMR measurements and semiempirical calculations.

In the course of our on-going investigation to develop synthetic methods for helical cyclophanes using Diels–Alder methodology, a great variety of polycyclic aromatic compounds have been formed. In some cases, the cycloaddition reactions, in addition to the target compounds, gave rise to unexpected products, which were identified by spectroscopic methods. The structure determination based on NMR measurements and semiempirical calculations of two such new compounds are presented in this paper.

Cycloadditions between the indenone derivatives prepared in situ from the bromides 12a and 12b and 4-vinyl[2.2]paracyclophane (11) yielded the Diels−Alder adducts 13a and 13b in acceptable yields. When these were heated in the presence of DDQ in toluene, the fluorenophanes 14a and 14b were produced in good yields. The diol 17 obtained from the tetralonophane 15 on treatment with POCl3/pyridine was dehydrated to the diene 18, which could be trapped by p-benzoquinone (19) to provide the cycloadducts 20 and 21; the former was oxidized to the latter by DDQ treatment. Although the even more highly annelated helical phane system 22 could be prepared from 17 and 12a, its aromatization to the ketone 24 or the hydrocarbon 25 failed. All new compounds were characterized by their spectroscopic data, in particular by extensive NMR investigations. A single-crystal X-ray structure analysis for the parent hydrocarbon phenanthreno[2.2]paracyclophane (5) is reported.

AbstractThe synthesis of two aromatic ketones 7(H)-indeno[2,1-a]phenanthren-7-one and 11(H)-indeno[1,2-a]phenanthren-11-one by Diels-Alder cycloaddition of 1-vinyl-3,4-dihydronaphthalene with inden-1-one generated in situ from 3-bromo-indan-1-one and triethylamine, followed by dehydrogenation-aromatization reaction of the cycloadducts, is reported. Further the synthesis of 7(H)-indeno[2,1-a]phenanthrene, 11(H)-indeno[1,2-a]phenanthrene, 9(H)-benzo[g]indeno[2,1-a]phenanthrene and 13(H)-benzo[g]indeno[1,2-a]phenanthrene by a procedure based on the reduction of the corresponding cycloadducts followed by a dehydration-aromatization reaction is presented. The assignments of the structure by 1H- and 13C-NMR spectroscopy is discussed. Estimates of the mutagenic activity of the compounds in Salmonella typhymuriundetermined by Ames' test show that three compounds are mutagenic for TA 98 strain and four for TA 100 strain. The mutagenic activities exhibited by these compounds are compared with those shown by cyclopeta[a]phenanthrenes. The effect of benzoannulation on cyclopenta[a]phenanthrenes and related cyclopenta[a]phenanthrenones is discussed.

A two-step synthetic approach to penta- and hexahelicenes substituted at the terminal aromatic rings has been studied. This approach is based on the Diels–Alder reaction of 5,5',8,8'-tetramethyl-3,3',4,4'-tetrahydro-[1,1']-binaphthalene (2b), 3-vinyl-1,2-dihydronaphthalene (5a), 5,8-dimethyl-3-vinyl-1,2-dihydronaphthalene (5b) and 3-vinyl-1,2-dihydrophenanthrene (15) followed by the aromatization of the cycloadducts. This method is flexible, efficient and of wide application to the synthesis of several benzenoid and nonbenzenoid penta- and hexahelicenes. The racemization energy barriers of helicenes 3, 9, 10, 13, 14, 17 and 18 were computed with the semiempirical quantum method AM1. The computed values show that, when methyl groups are introduced at the inner position of the terminal aromatic rings, the racemization barriers increase markedly. A structure analysis of the reaction products by ¹H- and ¹³C-NMR spectroscopy is also presented.

Diels-Alder reactions of 2-methyl-2-cyclopenten-l-one with l-ethenylhydronaphthalenes are described. The structure analysis of the reaction products by NMR spectroscopy is reported. The regioselectivity as well as the diastereoselectivity of the cycloadditions are discussed.

A new strategy for the fluorometric determination of glycosyltransferase activities is reported. The method involves dansyl chloride derivatization of the reduced form (pNH2phenyl) of a hydrophobic, aglycon moiety covalently linked to a number of acceptor substrates (pNO2phenyl). Focusing on the Golgi enzyme core 2N-acetylglucosaminyltransferase, we found that synthesis and fractionation of the dansylated substrate derivative were rapid, easy and inexpensive. Additionally, the corresponding enzyme assay proved reproducible and very sensitive, as 0.4 pmol of reaction product were readily detected. This fluorometric approach appears therefore to be a valid tool for investigating the monitoring differential expression of glycosyltransferases exhibiting low levels of enzyme activity.

AbstractAs the 21st century approaches, library/information services are rapidly embracing the concept of the virtual library as the vehicle to ensure equal information services to all citizens. This is the latest manifestation of an idea with deep roots in American librarianship. A pioneer in the development of this concept was Carleton Joeckel. This paper outlines his contributions to the evolution of the virtual library.