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Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.
Assuntos
Hipertensão , Apneia Obstrutiva do Sono , Rigidez Vascular , Lesões do Sistema Vascular , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Espessura Intima-Media Carotídea , Estudos Transversais , Hipertensão/complicações , Apneia Obstrutiva do Sono/complicações , Artérias CarótidasRESUMO
Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Irinotecano/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Fluoruracila , Neoplasias do Colo/induzido quimicamente , Neoplasias Retais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversosRESUMO
Objective: To investigate the effect of oral administration of branched-chain amino acids (BCAA) supplementation on the mortality of patients with hepatocellular carcinoma (HCC) after treatment. Methods: Computer searching of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database was conducted to search for clinical controlled trials and randomized controlled trials (RCTs) on the effect of oral administration of BCAA on the mortality of patients with HCC. The retrieval time limit was from the time of the establishment of each database to December 30, 2019. Two researchers independently screened the literature and extracted the data. Another researcher assessed the risk of bias in the included studies and then used RevMan 5.3 software for meta-analysis. Results: A total of 14 studies were included with 1 179 patients. The overall results showed that oral administration of BCAA had no significant effect on the mortality of HCC patients at 1 year after treatment (RR=0.85, 95%CI:0.68-1.06, P=0.16), while the mortalities of patients at 3 years (RR=0.73, 95%CI: 0.61-0.88, P=0.000 7) and 5 years (RR=0.57, 95%CI:0.34-0.96, P=0.03) after treatment were significantly lower than those of the control group. The subgroup analysis showed that for radiofrequency ablation (RFA) patients, there was no significant difference in 1-year mortality between the BCAA group and the control group (RR=0.96, 95%CI:0.14-6.5, P=0.97), while 3-year mortality was significantly reduced (RR=0.59, 95%CI:0.43-0.81, P=0.001); for hepatectomy patients, there was no significant differences in 1 -and 3-year mortality between the two groups (RR=0.90, 95%CI:0.44-1.88, P=0.79; RR=0.97, 95%CI:0.71-1.33, P=0.85, respectively). In addition, as for albumin levels, BCAA supplementation significantly increased albumin levels without considering the treatment of HCC (SD=0.45, 95%CI: 0.29-0.90; P=0.000 1), but had no significant effect on hepatectomy patients (SD=0, 95%CI: -0.41-0.41, P=0.99). Conclusion: BCAA supplementation might improve liver reserve function and long-term prognosis of HCC patients, which was related to the surgical method. Supplementing BCAA reduced the long-term mortality of RFA patients, but had no significant effect on hepatectomy patients.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Administração Oral , Aminoácidos de Cadeia Ramificada , China , Suplementos Nutricionais , HumanosRESUMO
Cysteine protease Cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. Spinal delivery of irreversible CatS inhibitor LHVS reduced hyperalgesia, attenuated activation of spinal microglia and blocked phosphorylation of NMDA receptor NR1 subunit induced by remifentanil. Furthermore, inhibition of microglia by minocycline effectively suppressed remifentanil-induced hyperalgesia, as well as CatS upregulation. In addition, remifentanil infusion also induced an increase in reactive oxygen species (ROS) levels in spinal neurons. Systemic administration of ROS scavenger PBN was sufficient to suppress remifentanil-induced painful hypersensitivity. Removal of ROS by PBN prevented upregulation of mature CatS in spinal microglia. However, increased protein level of premature form of CatS was not affected by PBN. Altogether, our findings demonstrate that neuronal ROS promote maturation of microglial CatS which facilitates activation of NMDA in the spinal dorsal horn. Therefore, such mechanism is involved in neuron-microglia positive feedback and contributes to remifentanil-induced hyperalgesia.
Assuntos
Catepsinas/metabolismo , Hiperalgesia/induzido quimicamente , Microglia/efeitos dos fármacos , Piperidinas/toxicidade , Medula Espinal/efeitos dos fármacos , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Sequestradores de Radicais Livres/farmacologia , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Microglia/metabolismo , Microglia/patologia , Minociclina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Remifentanil , Medula Espinal/metabolismo , Medula Espinal/patologia , Tato , Regulação para Cima/efeitos dos fármacosRESUMO
Oobius agrili Zhang and Huang (Hymenoptera: Encyrtidae) is a solitary egg parasitoid of the invasive emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), and has been introduced to the United States for classical biological control. We characterized the weekly survivorship, fecundity, and diapause patterns of both diapaused and nondiapaused populations of O. agrili under four different temperature-photophase combinations: 30°C (warm) and 20°C (cold) temperatures with both long-day (16 h) and short-day (8 h) photophase. Results of this study showed that regardless of the length of photophase, parental parasitoids of both diapaused and nondiapaused O. agrili survived significantly longer at 20°C than at 30°C. Both populations also laid their eggs faster at 30°C compared with those at 20°C. Higher proportions of the progeny produced by both populations of O. agrili were induced into diapause by short-day (8 h) photophase, regardless of rearing temperature. In addition, the diapaused parasitoids in the short-day photophase treatment at both warm and cold temperatures produced increasing proportions of diapaused progeny over time, whereas no significant differences were observed in the proportions of diapaused progeny by the nondiapaused parasitoids over different sampling times. These findings suggest that O. agrili should be continuously reared under warm temperature and long-day photoperiod (to avoid diapause for increased reproduction). In addition, we recommend that diapaused adults be used for field releases in early summer when temperatures are still relatively low (â¼20°C) and host eggs are available so that they can produce multiple generations prior to overwintering.
RESUMO
Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.
Assuntos
Besouros/fisiologia , Fraxinus/fisiologia , Estágios do Ciclo de Vida/fisiologia , Animais , Larva/fisiologia , Dinâmica PopulacionalRESUMO
OBJECTIVES: Efficacy and toxicity of the drug are mainly determined by physicochemical properties and pharmacological effects of its own. In addition, they are also affected by other factors, such as gender, age, genetic character, pathophysiological status, mood states and so on. The paper aims to study whether mood disorder alters drug metabolism process through the pharmacokinetic research on some clinically important anticancer drugs in depression model rats. MATERIALS AND METHODS: The depression model rats were built by exposing to chronic unpredicted mild stresses (CUMS) for 8 weeks. 36 female Sprague-Dawley (SD) rats were randomized into model group and control group. In each group, 18 rats were randomized into 2 subgroups: 5-fluorouracil (5-FU) subgroup and cyclophosphamide (CP) subgroup which were given a certain doses of 5-FU and CP. The blood samples were collected at different time points and plasma drug concentration were respectively assayed by high performance liquid chromatography (HPLC) for 5-FU and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for CP. Pharmacokinetic parameters were processed with DAS software. RESULTS: There were significant differences in the pharmacokinetic parameters of 5-FU and CP between in depression model rats group and in the normal control group (p < 0.05), except t1/2alpha (p > 0.05) for CP pharmacokinetics in depression model rats group and in the normal control rats group, with the value of those was 0.07 and 0.09 h. CONCLUSIONS: Depression mood disorder might alter drug metabolism process.
Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Antineoplásicos Alquilantes/farmacocinética , Ciclofosfamida/farmacocinética , Depressão/metabolismo , Fluoruracila/farmacocinética , Afeto , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/sangue , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/sangue , Comportamento Animal , Cromatografia Líquida de Alta Pressão , Ciclofosfamida/administração & dosagem , Ciclofosfamida/sangue , Sistema Enzimático do Citocromo P-450/metabolismo , Depressão/sangue , Depressão/etiologia , Depressão/psicologia , Modelos Animais de Doenças , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/sangue , Fígado/enzimologia , Atividade Motora , Ratos , Ratos Sprague-Dawley , Serotonina/sangue , Estresse Fisiológico , Estresse Psicológico/complicações , Espectrometria de Massas em TandemRESUMO
L-Tryptophan (L-Trp) is an essential amino acid. It is widely used in medical, health and food products, so a low-cost supply is needed. There are 4 methods for L-Trp production: chemical synthesis, extraction, enzymatic synthesis, and fermentation. In this study, we produced a recombinant bacterial strain pET-tnaA of Escherichia coli which has the L-tryptophanase gene. Using the pET-tnaA E. coli and the strain TS1138 of Pseudomonas sp., a one-pot enzymatic synthesis of L-Trp was developed. Pseudomonas sp. TS1138 was added to a solution of D,L-2-amino-delta2-thiazoline-4-carboxylic acid (DL-ATC) to convert it to L-cysteine (L-Cys). After concentration, E. coli BL21 (DE 3) cells including plasmid pET-tnaA, indole, and pyridoxal 5'-phosphate were added. At the optimum conditions, the conversion rates of DL-ATC and L-Cys were 95.4% and 92.1%, respectively. After purifying using macroporous resin S8 and NKA-II, 10.32 g of L-Trp of 98.3% purity was obtained. This study established methods for one-pot enzymatic synthesis and separation of L-Trp. This method of producing L-Trp is more environmentally sound than methods using chemical synthesis, and it lays the foundations for industrial production of L-Trp from DL-ATC and indole.
Assuntos
Ácidos Carboxílicos/metabolismo , Escherichia coli/enzimologia , Engenharia Genética/métodos , Indóis/metabolismo , Microbiologia Industrial/métodos , Pseudomonas/enzimologia , Triptofano , Amidoidrolases , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Cisteína/análogos & derivados , Cisteína/biossíntese , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Plasmídeos , Pseudomonas/genética , Tiazóis/metabolismo , Triptofano/biossíntese , Triptofanase/metabolismoRESUMO
The aim of this study was to explore the impact of depression mood disorder on the incidence of adverse drug reactions of anticancer drugs in cancer patients. The Hamilton Depression Scale 17 was used to evaluate the depression mood disorder level in 73 cancer patients before chemotherapy. Pharmacists monitored adverse drug reactions during the chemotherapy period. The relationship between depression mood disorder level and the incidence of adverse drug reactions was analysed. The frequency and extent of total adverse drug reactions were not related to depression mood disorder level. The frequency and extent of subjectively experienced adverse drug reactions such as anorexia, nausea and fatigue were related to depression mood disorder level. In conclusion, psychological support and intervention should be provided to cancer patients in order to improve patient adherence and cancer chemotherapy effectiveness, and to decrease the incidence of adverse drug reactions.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Transtorno Depressivo/complicações , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Transtorno Depressivo/etiologia , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Adulto JovemRESUMO
One of the possible adverse effects of transgenic insecticidal crops is the unintended decline in the abundance of nontarget arthropods. Field trials designed to evaluate potential nontarget effects can be more complex than expected because decisions to conduct field trials and the selection of taxa to include are not always guided by the results of laboratory tests. Also, recent studies emphasize the potential for indirect effects (adverse impacts to nontarget arthropods without feeding directly on plant tissues), which are difficult to predict because of interactions among nontarget arthropods, target pests, and transgenic crops. As a consequence, field studies may attempt to monitor expansive lists of arthropod taxa, making the design of such broad studies more difficult and reducing the likelihood of detecting any negative effects that might be present. To improve the taxonomic focus and statistical rigor of future studies, existing field data and corresponding power analysis may provide useful guidance. Analysis of control data from several nontarget field trials using repeated-measures designs suggests that while detection of small effects may require considerable increases in replication, there are taxa from different ecological roles that are sampled effectively using standard methods. The use of statistical power to guide selection of taxa for nontarget trials reflects scientists' inability to predict the complex interactions among arthropod taxa, particularly when laboratory trials fail to provide guidance on which groups are more likely to be affected. However, scientists still may exercise judgment, including taxa that are not included in or supported by power analyses.
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Artrópodes/fisiologia , Produtos Agrícolas/genética , Interpretação Estatística de Dados , Projetos de Pesquisa , Animais , Bacillus thuringiensis/genética , Ecologia/métodos , Inseticidas , Controle Biológico de Vetores/métodos , Plantas Geneticamente Modificadas , Densidade Demográfica , Zea maysRESUMO
To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the P1 and P2' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2' linkers. With an N-methylamide at P3', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3'-P4' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC(50) values of =0.2 microM in whole blood assay (WBA). Although the P3' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3', an N-methylamide at P4' provided the best cyclophane analogue, SL422 (WBA IC(50) = 0.22 microM, LPS-mouse ED(50) = 15 mg/kg, po), whereas a morpholinylamide at P4' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC(50) = 0.067 microM, LPS-mouse ED(50) = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K(i) values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.
Assuntos
Inibidores Enzimáticos/síntese química , Ácidos Hidroxâmicos/síntese química , Lactamas/síntese química , Metaloendopeptidases/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Proteínas ADAM , Proteína ADAM17 , Administração Oral , Animais , Disponibilidade Biológica , Carbamatos/síntese química , Carbamatos/química , Carbamatos/farmacocinética , Carbamatos/farmacologia , Cães , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Humanos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacocinética , Ácidos Hidroxâmicos/farmacologia , Técnicas In Vitro , Lactamas/química , Lactamas/farmacocinética , Lactamas/farmacologia , Masculino , Camundongos , Estereoisomerismo , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/análiseRESUMO
[reaction: see text] A pyrrolinone-based hydroxamate matrix metalloprotease inhibitor, (-)-1, has been designed and synthesized. Enzymatic assay revealed that (-)-1 inhibited three of the ten matrix metalloprotease enzymes examined and as such represents a new, potentially important lead structure.
Assuntos
Metaloendopeptidases/antagonistas & inibidores , Inibidores de Proteases/síntese química , Pirróis/síntese química , Aldeídos , Desenho de Fármacos , Isoenzimas/antagonistas & inibidores , Metaloendopeptidases/química , Modelos Moleculares , Inibidores de Proteases/química , Pirróis/químicaRESUMO
An effective lure-and-kill trap is a potentially important instrument in monitoring and controlling oriental fruit flies, Bactrocera dorsalis (Hendel). A number of experiments were performed in an orchard of commercial guava, Psydium guajava L., to determine how fly captures are affected by combining visual and olfactory stimuli, and by the timing of trap deployment relative to host phenology. Baiting sticky Ladd traps with hydrolyzed liquid protein significantly increased the number of captured flies. Mostly male flies were caught in the absence of mature guava fruit, whereas mostly female flies were caught when ripe fruit was abundant. These results suggest that an effective oriental fruit fly trap should include both visual and olfactory lures, and that proper timing of trap deployment can be an important factor in monitoring female abundance in oriental fruit fly populations.
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Dípteros/fisiologia , Controle de Insetos/métodos , Animais , Comportamento Alimentar , Feminino , Masculino , Estimulação Luminosa , OlfatoRESUMO
We examined the responses of oriental fruit flies, Bactrocera dorsalis Hendel, to the odors of different stages and types of fruit presented on potted trees in a field cage. Females were most attracted to odors of soft, ripe fruit. Odors of common guava were more attractive to females than papaya and starfruit, and equally as attractive as strawberry guava, orange, and mango. In field tests, McPhail traps baited with mango, common guava, and orange captured equal numbers of females. Traps baited with mango were compared with 2 commercially available fruit fly traps. McPhail traps baited with mango captured more females than visual fruit-mimicking sticky traps (Ladd traps) and equal numbers of females as McPhail traps baited with protein odors. Results from this study indicate that host fruit volatiles could be used as lures for capturing oriental fruit flies in orchards.
Assuntos
Frutas/química , Odorantes , Feromônios , Tephritidae/fisiologia , Animais , Citrus sinensis , Feminino , Mangifera , PsidiumRESUMO
A novel series of 13- and 14-membered macrocyclic amines was developed by linking the P1 and P2' groups. The synthesis entails stereoselective Frater alkylation to install the anti-succinate configuration and macrocyclic amination via nucleophilic displacement. This strategy resulted in a new class of conformationally constrained inhibitors that are potent and selective for MMP-8 and 9 over MMP-1 and 3.