Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The mai...Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.展开更多
Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determ...Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.Results: Of the total sample, 81% met the hydration criteria(urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria(urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status(score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs.(80.5±10.2) kg], body mass index [(26.3±3.1) kg/m;vs.(25.2±2.8) kg/m;], body fat [(22.3±5.6)% vs.(18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat(P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water(r=0.357, P=0.000) and negatively with body fat(kg)(r=–0.427, P=0.000), percentage of body fat(r=–0.405, P=0.000), and waist/hip ratio(r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat(P=0.001) and percentage of body water content(P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.Conclusions: These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.展开更多
Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and ...Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.展开更多
Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and...Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.展开更多
Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potentia...Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potential insecticidal compounds,thus increasingly attracting research interest.Commiphora myrrha(T.Nees)Engl.(Burseraceae)is a medicinal plant whose oleo-gum resin is used in food,cosmetics,fragrances,and pharmaceuticals.Herein,the larvicidal potential of its essential oil(EO)was assessed on four mosquito species(Aedes albopictus Skuse,Ae.aegypti L.,Anopheles gambiae Giles and An.stephensi Liston),with LC_(50) values ranging from 4.42 to 16.80 μg/mL.The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds.A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae.The EO non-target toxicity on Daphnia magna Straus(LC_(50)=4.51 μL/L)and its cytotoxicity on a human kidney cell line(HEK293)(IC50 of 14.38 μg/mL)were also assessed.This study shows the potential of plant products as innovative insecticidal agents and lays the ground-work for the possible exploitation of C.myrrha EO in the sustainable approaches for mosquito management.展开更多
Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium betw...Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium between variants.Here we describe the development of two MAGIC populations derived from a cross of 11 founder lines from the INTA(National Institute for Agricultural Technology in Argentina)sunflower breeding program.The founder lines are fertility maintainer inbred lines that exhibit genetic diversity in several traits,including flowering cycle,plant architecture,disease resistance,oil content and oil quality.The crossing scheme applied follows the design of two-way,four-way and eight-way crosses with a modification to increase the number of recombinations and shorten the linkage disequilibrium.Phenotyping a subset of F_(2)families and F_5 lines for different traits shows an increase in the diversity of the analyzed traits compared to the parental lines.In addition,we identified lines with transgressive segregation for Sunflower Verticillium Wilt resistance.These results confirm that the MAGIC populations will serve as unique genetic and genomic resources to better characterize the genetics of complex traits and identify potentially superior alleles for sunflower breeding.It will also enrich the gene pool of fertility maintainers(A/B line)of the sunflower germplasm and facilitate the introduction of new breeding methods to select female parents for use in AxR combinations to obtain superior sunflower hybrids.展开更多
The Brown-Preston-Singleton(BPS)stopping power model is added to our previously developed hybrid code to model ion beam-plasma interaction.Hybrid simulations show that both resistive field and ion scattering effects a...The Brown-Preston-Singleton(BPS)stopping power model is added to our previously developed hybrid code to model ion beam-plasma interaction.Hybrid simulations show that both resistive field and ion scattering effects are important for proton beam transport in a solid target,in which they compete with each other.When the target is not completely ionized,the self-generated resistive field effect dominates over the ion scattering effect.However,when the target is completely ionized,this situation is reversed.Moreover,it is found that Ohmic heating is important for higher current densities and materials with high resistivity.The energy fraction deposited as Ohmic heating can be as high as 20%-30%.Typical ion divergences with half-angles of about 5°-10°will modify the proton energy deposition substantially and should be taken into account.展开更多
The generation of chemically engineered essential oils(CEEOs)prepared from bi-heteroatomic reactions using ammonium thiocyanate as a source of bioactive compounds is described.The impact of the reaction on the chemica...The generation of chemically engineered essential oils(CEEOs)prepared from bi-heteroatomic reactions using ammonium thiocyanate as a source of bioactive compounds is described.The impact of the reaction on the chemical composition of the mixtures was qualitatively demonstrated through GC-MS,utilizing univariate and multivariate analysis.The reaction transformed most of the components in the natural mixtures,thereby expanding the chemical diversity of the mixtures.Changes in inhibition properties between natural and CEEOs were demonstrated through acetylcholinesterase TLC autography,resulting in a threefold increase in the number of positive events due to the modification process.The chemically engineered Origanum vulgare L.essential oil was subjected to bioguided fractionation,leading to the discovery of four new active compounds with similar or higher potency than eserine against the enzyme.The results suggest that the directed chemical transformation of essential oils can be a valuable strategy for discovering new acetylcholinesterase(AChE)inhibitors.展开更多
BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biologica...BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biological factor for bone remodeling,and growth factors may enhance the repair process.AIM To evaluate the gene expression of cytokines(IL-1β,IL-6,IL-10 and TNF-α),markers of osteoclastogenesis(RANK,RANKL and OPG)and MMPs(MMP-1,MMP-2,MMP-8 and MMP-13)from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.METHODS Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion,which varied between the combination of 1,10 and 100μmol/L of melatonin.Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.RESULTS There were differences between groups when compared with clot or scaffold control,and improvement with a higher concentration of melatonin or rhBMP-2.The combination melatonin(1μg)with 5μg of rhBMP-2,using the guided bone regeneration technique,demonstrated some effects,albeit mild,on bone repair of critical bone defects.CONCLUSION This indicates that the approach for administering these substances needs to be reassessed,with the goal of ensuring their direct application to the affected area.Therefore,future research must be carried out,seeking to produce materials with these ideal characteristics.展开更多
In conventional absorption refrigeration systems(ARS),the heat from the condenser is usually rejected by the environment in place to be used in the system,so recuperating this is a good alternative to enhance the sys...In conventional absorption refrigeration systems(ARS),the heat from the condenser is usually rejected by the environment in place to be used in the system,so recuperating this is a good alternative to enhance the system’s performance.For instance,in this paper,an alternative ARS in which LiBr/Water is used as a refrigerant mixture,where part of condensing heat is recovered via the solution heat recovery generator absorption cycle(HR-ARS)was energy and exergy evaluated.The influence of generator,condenser and evaporator temperatures,as well as the efficiency of the solution heat exchanger on the coefficient of performance,exergy performance and exergy destroyed of the HR-ARS system,were analyzed and compared with the traditional ARS system at the same working conditions.The results showed an increase between 5.8%–6.3%on the COP and 3.7%–9.5%in the exergy efficiency when condenser/absorber temperature was reduced from 40℃ to 30℃.However,when the evaporation temperature rose from 5℃ to 15℃,the COP(coefficient of performance)increased by around 8%,although this could be increased by 2.3%–6.3%if the generator temperature decreases from 100℃ to 80℃.Moreover,the COP and exergetic performance for the HR-ARS is more significant at the lowest generator,condenser and evaporator temperatures,as well as at high efficiency in the solution heat exchanger,in comparison to ARS system.Furthermore,the COP and exergy performance for the HR-ARS system was improved by 2.57%to 3.11%and 0.22%to 0.7%,respectively,while the recovering condensation heat for generation is around 1.51%–3.76%lower than with the ARS.It also was found that for all ranges of evaporator and condenser temperatures,the COP for the HR-ARS system is around 3%higher than that obtained with the ARS at the three different generator temperatures here analyzed,while when the solution heat exchanger effectiveness was increased from 0.7–1.0,the total exergy destruction for the HR-ARS resulted be 3.24%–5.01%smaller than the ARS system.Finally,it can be concluded that the components with the most exergy destroyed in the systems(80%to 94%)are the generator and absorber.展开更多
Objective Pharmacopoeias regulate the manufacture of potentised pharmaceutical preparations used in different branches of complementary and integrative medicine.The physicochemical properties and biological activity o...Objective Pharmacopoeias regulate the manufacture of potentised pharmaceutical preparations used in different branches of complementary and integrative medicine.The physicochemical properties and biological activity of these preparations are often investigated in preclinical research,yet no guidelines for experimental research currently exist in this area.The present PrePoP guidelines aim to provide recommendations to promote high-quality,statistically sound,and reproducible preclinical research on potentised preparations.Methods Input was gathered from researchers nominated by the relevant scientific societies using a simplified Delphi consensus approach covering the most relevant aspects of basic research methodology in the field including appropriate controls,sample preparation and handling,and statistics.After three rounds of feedback,a consensus was finally reached on the most important aspects and considerations for conducting high-quality research on potentised preparations.Results We present a series of recommendations on a range of topics including experimental controls,system stability,blinding and randomisation,environmental influences,and procedures for the preparation of potentised samples and controls,and we address some specific challenges of this research field.Conclusion This expert consensus process resulted in a robust set of methodological guidelines for research on potentised preparations and provides a valuable framework that will inform and improve the quality of subsequent research in this emerging field.展开更多
The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular t...The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.展开更多
This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transpo...This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.展开更多
The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this p...The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this paper, handicap is defined as the difficulty to survive and reproduce independently. Kin sociality is derived from the childhood handicap-care principle where the children are the handicapped children who receive the care from the kin caregivers in the inclusive kin group to survive. The caregiver gives care for its self-interest to reproduce its gene. The individual’s gene of kin sociality contains the handicapped childhood and the caregiving adulthood. Eusociality is derived from the adulthood handicap-care principle where responsible adults are the handicapped adults who give care and receive care at the same time in the interdependent eusocial group to survive and reproduce its gene. Queen bees reproduce, but must receive care from worker bees that work but must rely on queen bees to reproduce. A caregiver gives care for its self-interest to survive and reproduce its gene. The individual’s gene of eusociality contains the handicapped childhood-adulthood and the caregiving adulthood. The chronological sequence of the sociality evolution is individual sociality without handicap, kin sociality with handicapped childhood, and eusociality with handicapped adulthood. Eusociality in humans is derived from bipedalism and the mixed habitat. The chronological sequence of the eusocial human evolution is 1) the eusocial early hominins with bipedalism and the mixed habitat, 2) the eusocial early Homo species with bipedalism, the larger brain, and the open habitat, 3) the eusocial late Homo species with bipedalism, the largest brain, and the unstable habitat, and 4) extended eusocial Homo sapiens with bipedalism, the shrinking brain, omnipresent imagination, and the harsh habitat. The omnipresence of imagination in human culture converts eusociality into extended eusociality with both perception and omnipresent imagination.展开更多
基金Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Agencia Nacional de Promoción de Ciencia y Tecnología (ANPCyT )Universidad Nacional de Rosario (UNR) for financial support
文摘Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.
基金partially supported by the “Centro de Instrucción Militar Aeroespacial”(CIMA)。
文摘Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.Results: Of the total sample, 81% met the hydration criteria(urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria(urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status(score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs.(80.5±10.2) kg], body mass index [(26.3±3.1) kg/m;vs.(25.2±2.8) kg/m;], body fat [(22.3±5.6)% vs.(18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat(P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water(r=0.357, P=0.000) and negatively with body fat(kg)(r=–0.427, P=0.000), percentage of body fat(r=–0.405, P=0.000), and waist/hip ratio(r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat(P=0.001) and percentage of body water content(P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.Conclusions: These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.
文摘Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.
基金support by Universidad Nacional de Rosario(80020180300114UR and 80020180100128UR)CONICET(PIP No 11220200102423)FONCYT(PICT2019-02232 and PICT2021-1034)for the development of this work.
文摘Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.
基金granted by the project PRIN 2022“Bioformulations for controlled release of botanical pesticides for sustainable agriculture”(prot.202274BK9L)supported by the Italian Ministry of University and Research(MUR)the Technology agency of the Czech Republic for its financial support concerning botanical pesticide(Project No.FW06010376).
文摘Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potential insecticidal compounds,thus increasingly attracting research interest.Commiphora myrrha(T.Nees)Engl.(Burseraceae)is a medicinal plant whose oleo-gum resin is used in food,cosmetics,fragrances,and pharmaceuticals.Herein,the larvicidal potential of its essential oil(EO)was assessed on four mosquito species(Aedes albopictus Skuse,Ae.aegypti L.,Anopheles gambiae Giles and An.stephensi Liston),with LC_(50) values ranging from 4.42 to 16.80 μg/mL.The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds.A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae.The EO non-target toxicity on Daphnia magna Straus(LC_(50)=4.51 μL/L)and its cytotoxicity on a human kidney cell line(HEK293)(IC50 of 14.38 μg/mL)were also assessed.This study shows the potential of plant products as innovative insecticidal agents and lays the ground-work for the possible exploitation of C.myrrha EO in the sustainable approaches for mosquito management.
基金supported by a doctoral grant from the National Scientific and Technical Research Council(Consejo Nacional de Investigaciones Científicas y T ecnicas,CONICET)the National Institute of Agricultural Technology(INTA)+1 种基金by projects funded by INTA(CP_2019–2023 I-114,I-127,I-090/2023–2025 I-111,I-87)Agencia Nacional de Promocio n Científica y T ecnica(PICT 2017N?2523)。
文摘Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium between variants.Here we describe the development of two MAGIC populations derived from a cross of 11 founder lines from the INTA(National Institute for Agricultural Technology in Argentina)sunflower breeding program.The founder lines are fertility maintainer inbred lines that exhibit genetic diversity in several traits,including flowering cycle,plant architecture,disease resistance,oil content and oil quality.The crossing scheme applied follows the design of two-way,four-way and eight-way crosses with a modification to increase the number of recombinations and shorten the linkage disequilibrium.Phenotyping a subset of F_(2)families and F_5 lines for different traits shows an increase in the diversity of the analyzed traits compared to the parental lines.In addition,we identified lines with transgressive segregation for Sunflower Verticillium Wilt resistance.These results confirm that the MAGIC populations will serve as unique genetic and genomic resources to better characterize the genetics of complex traits and identify potentially superior alleles for sunflower breeding.It will also enrich the gene pool of fertility maintainers(A/B line)of the sunflower germplasm and facilitate the introduction of new breeding methods to select female parents for use in AxR combinations to obtain superior sunflower hybrids.
基金supported by the National Natural Sci-ence Foundation of China(Grant Nos.12005298,12275356,11774430,U2241281,and 12175309)Research Grant No.PID2022-137339OB-C22 of the Spanish Ministry of Education and Research+1 种基金the Natural Science Foundation of Hunan Province(Grant Nos.2021JJ40661 and 2022JJ30656)a research project of the NUDT(Contract No.ZK19-25).
文摘The Brown-Preston-Singleton(BPS)stopping power model is added to our previously developed hybrid code to model ion beam-plasma interaction.Hybrid simulations show that both resistive field and ion scattering effects are important for proton beam transport in a solid target,in which they compete with each other.When the target is not completely ionized,the self-generated resistive field effect dominates over the ion scattering effect.However,when the target is completely ionized,this situation is reversed.Moreover,it is found that Ohmic heating is important for higher current densities and materials with high resistivity.The energy fraction deposited as Ohmic heating can be as high as 20%-30%.Typical ion divergences with half-angles of about 5°-10°will modify the proton energy deposition substantially and should be taken into account.
基金support by Universidad Nacional de Rosario(80020180300114UR and 80020180100128UR)CONICET(PIP No 11220200102423)and FONCYT(PICT2015-3574 and PICT2018-01554)for the development of this work.
文摘The generation of chemically engineered essential oils(CEEOs)prepared from bi-heteroatomic reactions using ammonium thiocyanate as a source of bioactive compounds is described.The impact of the reaction on the chemical composition of the mixtures was qualitatively demonstrated through GC-MS,utilizing univariate and multivariate analysis.The reaction transformed most of the components in the natural mixtures,thereby expanding the chemical diversity of the mixtures.Changes in inhibition properties between natural and CEEOs were demonstrated through acetylcholinesterase TLC autography,resulting in a threefold increase in the number of positive events due to the modification process.The chemically engineered Origanum vulgare L.essential oil was subjected to bioguided fractionation,leading to the discovery of four new active compounds with similar or higher potency than eserine against the enzyme.The results suggest that the directed chemical transformation of essential oils can be a valuable strategy for discovering new acetylcholinesterase(AChE)inhibitors.
文摘BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biological factor for bone remodeling,and growth factors may enhance the repair process.AIM To evaluate the gene expression of cytokines(IL-1β,IL-6,IL-10 and TNF-α),markers of osteoclastogenesis(RANK,RANKL and OPG)and MMPs(MMP-1,MMP-2,MMP-8 and MMP-13)from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.METHODS Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion,which varied between the combination of 1,10 and 100μmol/L of melatonin.Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.RESULTS There were differences between groups when compared with clot or scaffold control,and improvement with a higher concentration of melatonin or rhBMP-2.The combination melatonin(1μg)with 5μg of rhBMP-2,using the guided bone regeneration technique,demonstrated some effects,albeit mild,on bone repair of critical bone defects.CONCLUSION This indicates that the approach for administering these substances needs to be reassessed,with the goal of ensuring their direct application to the affected area.Therefore,future research must be carried out,seeking to produce materials with these ideal characteristics.
文摘In conventional absorption refrigeration systems(ARS),the heat from the condenser is usually rejected by the environment in place to be used in the system,so recuperating this is a good alternative to enhance the system’s performance.For instance,in this paper,an alternative ARS in which LiBr/Water is used as a refrigerant mixture,where part of condensing heat is recovered via the solution heat recovery generator absorption cycle(HR-ARS)was energy and exergy evaluated.The influence of generator,condenser and evaporator temperatures,as well as the efficiency of the solution heat exchanger on the coefficient of performance,exergy performance and exergy destroyed of the HR-ARS system,were analyzed and compared with the traditional ARS system at the same working conditions.The results showed an increase between 5.8%–6.3%on the COP and 3.7%–9.5%in the exergy efficiency when condenser/absorber temperature was reduced from 40℃ to 30℃.However,when the evaporation temperature rose from 5℃ to 15℃,the COP(coefficient of performance)increased by around 8%,although this could be increased by 2.3%–6.3%if the generator temperature decreases from 100℃ to 80℃.Moreover,the COP and exergetic performance for the HR-ARS is more significant at the lowest generator,condenser and evaporator temperatures,as well as at high efficiency in the solution heat exchanger,in comparison to ARS system.Furthermore,the COP and exergy performance for the HR-ARS system was improved by 2.57%to 3.11%and 0.22%to 0.7%,respectively,while the recovering condensation heat for generation is around 1.51%–3.76%lower than with the ARS.It also was found that for all ranges of evaporator and condenser temperatures,the COP for the HR-ARS system is around 3%higher than that obtained with the ARS at the three different generator temperatures here analyzed,while when the solution heat exchanger effectiveness was increased from 0.7–1.0,the total exergy destruction for the HR-ARS resulted be 3.24%–5.01%smaller than the ARS system.Finally,it can be concluded that the components with the most exergy destroyed in the systems(80%to 94%)are the generator and absorber.
文摘Objective Pharmacopoeias regulate the manufacture of potentised pharmaceutical preparations used in different branches of complementary and integrative medicine.The physicochemical properties and biological activity of these preparations are often investigated in preclinical research,yet no guidelines for experimental research currently exist in this area.The present PrePoP guidelines aim to provide recommendations to promote high-quality,statistically sound,and reproducible preclinical research on potentised preparations.Methods Input was gathered from researchers nominated by the relevant scientific societies using a simplified Delphi consensus approach covering the most relevant aspects of basic research methodology in the field including appropriate controls,sample preparation and handling,and statistics.After three rounds of feedback,a consensus was finally reached on the most important aspects and considerations for conducting high-quality research on potentised preparations.Results We present a series of recommendations on a range of topics including experimental controls,system stability,blinding and randomisation,environmental influences,and procedures for the preparation of potentised samples and controls,and we address some specific challenges of this research field.Conclusion This expert consensus process resulted in a robust set of methodological guidelines for research on potentised preparations and provides a valuable framework that will inform and improve the quality of subsequent research in this emerging field.
文摘先天性长QT综合征(LQTS)是发病率在1/2 500左右的恶性遗传性心脏疾病。LQTS的典型心脏表现包括可导致心脏骤停和心脏猝死的晕厥发作,以及包括QT间期延长和T波异常在内的心电图异常。90年代中期,LQTS的治病基因被首次发现,至今已有13型被确认。致病基因主要是离子通道和转运相关蛋白。对于具有典型特征的患者,医生并无诊断困难。对于模棱两可的病例,需要参照特殊诊断标准,比如心电图,病史和家族史等等。此外,基因扫描正日益成为诊断过程的一部分。除非有明确的禁忌证,治疗上还是要首选β受体阻滞剂。若在接受足量β受体阻滞剂期间,还有1次以上的晕厥,需立即采取左侧交感神经切除术,并根据病人特征(年龄、性别、临床病史、24 h Holter在内的心电图特征、基因表型等)考虑安装埋藏式心脏转复除颤器。病人接受适当治疗后,一般预后较好。但是LQTS8(Timothy综合征)病人,携带KCNQ1突变的Jervel Lange-Nielsen综合征患者,以及伴有2∶1房室传导阻滞,病窦综合征或Brugada综合征的LQT3病患的预后极其不容乐观。
基金Grants from Agencia Nacional de Promoción Científicay Tecnológica (PICT N° 05-26306)Consejo Nacional de Investigaciones Científicasy Técnicas (PIP N° 6442)Universidad Nacional de Rosario,Argentina
文摘The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.
基金Grant PICT 05-31670(R.A.Marinelli) from Agencia Nacional de Promoción Científica y Tecnológicaby Grant PIP 6440 from Consejo Nacional de Investigaciones Científicas y Técnicas
文摘This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.
文摘The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this paper, handicap is defined as the difficulty to survive and reproduce independently. Kin sociality is derived from the childhood handicap-care principle where the children are the handicapped children who receive the care from the kin caregivers in the inclusive kin group to survive. The caregiver gives care for its self-interest to reproduce its gene. The individual’s gene of kin sociality contains the handicapped childhood and the caregiving adulthood. Eusociality is derived from the adulthood handicap-care principle where responsible adults are the handicapped adults who give care and receive care at the same time in the interdependent eusocial group to survive and reproduce its gene. Queen bees reproduce, but must receive care from worker bees that work but must rely on queen bees to reproduce. A caregiver gives care for its self-interest to survive and reproduce its gene. The individual’s gene of eusociality contains the handicapped childhood-adulthood and the caregiving adulthood. The chronological sequence of the sociality evolution is individual sociality without handicap, kin sociality with handicapped childhood, and eusociality with handicapped adulthood. Eusociality in humans is derived from bipedalism and the mixed habitat. The chronological sequence of the eusocial human evolution is 1) the eusocial early hominins with bipedalism and the mixed habitat, 2) the eusocial early Homo species with bipedalism, the larger brain, and the open habitat, 3) the eusocial late Homo species with bipedalism, the largest brain, and the unstable habitat, and 4) extended eusocial Homo sapiens with bipedalism, the shrinking brain, omnipresent imagination, and the harsh habitat. The omnipresence of imagination in human culture converts eusociality into extended eusociality with both perception and omnipresent imagination.
