Poly(vinyl alcohol) (PVA) scaffolds are prepared by a cryogenic process that consists of the unidirectional freezing of a PVA solution. The scaffolds exhibit a microchanneled structure, the ...morphology of which (in terms of pore diameter, surface area, and thickness of matter accumulated between adjacent microchannels) can be finely tailored by the averaged molecular weight of PVA, the PVA concentration in the solution, and the freezing rate of the PVA solution. The resulting PVA scaffolds are suitable substrates for drug‐delivery purposes, the drug release being controlled (from tens of minutes up to several days) by the morphology of the microchanneled structure. In vitro experiments reveal the efficiency of PVA scaffolds for controlling the release of ciprofloxacin into a bacteria culture medium.
A unidirectional freezing process, named ISISA (ice segregation induced self‐assembly), is applied for the preparation of monolithic poly(vinyl alcohol) scaffolds with a well‐defined microchanneled structure (see figure; scale bar: 10 μm). The scaffolds can be used for drug delivery purposes: the drug kinetic release being controlled by its structural morphology.
is a worldwide spread fungus that causes the grey mold disease, which is considered the most important factor in postharvest losses in fresh fruit crops. Consequently, the control of gray mold is a ...matter of current and relevant interest for agricultural industries. In this work, a series of phenylpropanoids derived from eugenol were synthesized and characterized. Their effects on the mycelial growth of a virulent and multi-resistant isolate of
(PN2) have been evaluated and IC
values for the most active compounds range between 31⁻95 ppm. The antifungal activity exhibited by these compounds is strongly related to their chemical structure, i.e., increasing activity has been obtained by isomerization of the double bond or introduction of a nitro group on the aromatic ring. Based on the relationship between the fungicide activities and chemical structure, a mechanism of action is proposed. Finally, the activity of these compounds is higher than that reported for the commercial fungicide BC-1000 that is currently employed to combat this disease. Thus, our results suggest that these compounds are potential candidates to be used in the design of new and effective control with inspired natural compounds of this pathogen.
Background: Amelogenesis imperfecta is a hereditary disorder affecting dental enamel. Among its phenotypes, hypocalcified AI is characterized by mineral deficiency, leading to tissue wear and, ...consequently, dental sensitivity. Excessive fluoride intake (through drinking water, fluoride supplements, toothpaste, or by ingesting products such as pesticides or insecticides) can lead to a condition known as dental fluorosis, which manifests as stains and teeth discoloration affecting their structure. Our recent studies have shown that extracts from Colombian native plants, Ilex guayusa and Piper marginatum, deposit mineral ions such as phosphate and orthophosphate into the dental enamel structure; however, it is unknown whether these extracts produce toxic effects on the dental pulp. Objective: To assess cytotoxicity effects on human dental pulp stem cells (hDPSCs) exposed to extracts isolated from I. guayusa and P. marginatum and, hence, their safety for clinical use. Methods: Raman spectroscopy, fluorescence microscopy, and flow cytometry techniques were employed. For Raman spectroscopy, hDPSCs were seeded onto nanobiochips designed to provide surface-enhanced Raman spectroscopy (SERS effect), which enhances their Raman signal by several orders of magnitude. After eight days in culture, I. guayusa and P. marginatum extracts at different concentrations (10, 50, and 100 ppm) were added. Raman measurements were performed at 0, 12, and 24 h following extract application. Fluorescence microscopy was conducted using an OLIMPUS fv1000 microscope, a live–dead assay was performed using a kit employing a BD FACS Canto TM II flow cytometer, and data analysis was determined using a FlowJo program. Results: The Raman spectroscopy results showed spectra consistent with viable cells. These findings were corroborated using fluorescence microscopy and flow cytometry techniques, confirming high cellular viability. Conclusions: The analyzed extracts exhibited low cytotoxicity, suggesting that they could be safely applied on enamel for remineralization purposes. The use of nanobiochips for SERS effect improved the cell viability assessment.
Background
Fever‐7 is a test evaluating host mRNA expression levels of IFI27, JUP, LAX, HK3, TNIP1, GPAA1 and CTSB in blood able to detect viral infections. This test has been validated mostly in ...hospital settings. Here we have evaluated Fever‐7 to identify the presence of respiratory viral infections in a Community Health Center.
Methods
A prospective study was conducted in the “Servicio de Urgencias de Atención Primaria” in Salamanca, Spain. Patients with clinical signs of respiratory infection and at least one point in the National Early Warning Score were recruited. Fever‐7 mRNAs were profiled on a Nanostring nCounter® SPRINT instrument from blood collected upon patient enrolment. Viral diagnosis was performed on nasopharyngeal aspirates (NPAs) using the Biofire‐RP2 panel.
Results
A respiratory virus was detected in the NPAs of 66 of the 100 patients enrolled. Median National Early Warning Score was 7 in the group with no virus detected and 6.5 in the group with a respiratory viral infection (P > .05). The Fever‐7 score yielded an overall AUC of 0.81 to predict a positive viral syndromic test. The optimal operating point for the Fever‐7 score yielded a sensitivity of 82% with a specificity of 71%. Multivariate analysis showed that Fever‐7 was a robust marker of viral infection independently of age, sex, major comorbidities and disease severity at presentation (OR CI95%, 3.73 2.14‐6.51, P < .001).
Conclusions
Fever‐7 is a promising host immune mRNA signature for the early identification of a respiratory viral infection in the community.
Background: Acute myeloid leukemia (AML) is an aggressive disease characterized by uncontrolled clonal proliferation of poorly differentiated myeloid progenitor cells in the bone marrow and blood. ...Deregulated spleen tyrosine kinase (SYK) impairs myeloid differentiation and has been implicated in the pathogenesis of AML driven by FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutation (FLT3-ITD). While SYK is rarely mutated, it is highly activated in FLT3-ITD-mutated AML and directly phosphorylates FLT3-ITD, resulting in aberrant expression of multiple oncogenic pathways. Lanraplenib (LANRA) is a selective, next-generation, SYK inhibitor that has shown favorable PK, PD, and safety in healthy volunteers and patients with autoimmune diseases. LANRA is currently being evaluated in combination with gilteritinib, a FLT3 inhibitor, in patients with relapsed or refractory (R/R) FLT3-mutated AML (NCT05028751). By jointly inhibiting the leukemogenic network created by SYK and mutant FLT3, LANRA and gilteritinib potentially provide a new treatment regimen in a patient population with few treatment options. Method: AML cell viability in response to LANRA, gilteritinib or their combination was assessed by CellTiter Glo (CTG) at 5 days. Apoptosis was evaluated by measuring Annexin V and propidium iodide staining by flow cytometry. Myeloid differentiation was assessed by flow cytometry using CD11b and CD14 cell surface markers and/or immunohistochemistry. In addition, RNA-seq was performed to evaluate differential changes in gene expression in response to LANRA. Gene set enrichment analysis (GSEA) was performed to evaluate perturbation in leukemogenic signaling pathways. In vivo studies were conducted using the MV4;11 cell line-derived xenograft model. LANRA was administered twice daily at a dose of 75 mg/kg via subcutaneous injections, either alone or in combination with gilteritinib at a dose of 2 mg/kg dosed once daily by oral gavage, for 28 days. Results: Treatment of FLT3-ITD mutated AML cells with LANRA results in dose- and time-dependent increase in myeloid differentiation and reductions in leukemic cell viability. RNA-seq analysis of MV4;11 cells revealed that LANRA abrogates multiple downstream FLT3-ITD leukemogenic signaling pathways including JAK/STAT3/5, MAPK, mTOR and OXPHOS. Combined pharmacologic inhibition of SYK with LANRA and FLT3-ITD with gilteritinib results in robust antileukemic effects in preclinical models of FLT3 ITD-driven AML. Additionally, the combination of LANRA and gilteritinib demonstrated increased differentiation and apoptosis induction in vitro. LANRA in combination with gilteritinib showed significant tumor growth inhibition compared to either single agent in a subcutaneous FLT3-ITD AML cell line-derived xenograft mouse model. In line with these observations, a retrospective analysis of bone marrow-engrafted AML cells from a disseminated FLT3-ITD AML patient-derived xenograft mouse model showed evidence of increased myeloid differentiation and inhibition of cell proliferation. Conclusion: In preclinical models, LANRA demonstrates compelling anti-leukemic activity in combination with gilteritinib. By jointly targeting hyperproliferation and differentiation blockade, LANRA and gilteritinib may provide a new therapeutic approach that can be exploited in AML. Additionally, LANRA disrupts downstream signaling of key pathways often associated with resistance to gilteritinib, providing additional mechanistic support for continued testing of LANRA in combination with gilteritinib in FLT3-ITD-mutated AML patients. These studies helped motivate the ongoing clinical combination with gilteritinib in patients with (R/R) FLT3-mutated AML (NCT05028751).
Brassinosteroids (BRs) are plant hormones that play an essential role in plant development and have the ability to protect plants against various environmental stresses, such as low and high ...temperature, drought, heat, salinity, heavy metal toxicity, and pesticides. Mitigation of stress effects are produced through independent mechanisms or by interaction with other important phytohormones. However, there are few studies in which this property has been reported for BRs analogs. Thus, in this work, the enhancement of drought stress tolerance of
was assessed for a series of 2-deoxybrassinosteroid analogs. In addition, the growth-promoting activity in the Rice Lamina Inclination Test (RLIT) was also evaluated. The results show that analog 1 exhibits similar growth activity as brassinolide (BL; used as positive control) in the RLIT bioassay. Interestingly, both compounds increase their activities by a factor of 1.2-1.5 when they are incorporated to polymer micelles formed by Pluronic F-127. On the other hand, tolerance to water deficit stress of
seedlings was evaluated by determining survival rate and dry weight of seedlings after the recovery period. In both cases, the effect of analog 1 is higher than that exhibited by BL. Additionally, the expression of a subset of drought stress marker genes was evaluated in presence and absence of exogenous applied BRs. Results obtained by qRT-PCR analysis, indicate that transcriptional changes of At
A and
genes were more significant in
treated with analog 1 in homogeneous solution than in that treated with BL. These changes suggest the activation of alternative pathway in response to water stress deficit. Thus, exogenous application of BRs synthetic analogs could be a potential tool for improvement of crop production under stress conditions.
Studying the variables that describe the spatial ecology of threatened species allows us to identify and prioritize areas that are critical for species conservation. To estimate the home range and ...core area of the Endangered (EN) Amazon river dolphin
Inia geoffrensis
, 23 individuals (6 , 17 ) were tagged during the rising water period in the Amazon and Orinoco river basins between 2017 and 2018. The satellite tracking period ranged from 24 to 336 d (mean ± SE = 107 ± 15.7 d), and river dolphin movements ranged from 7.5 to 298 km (58 ± 13.4 km). Kernel density estimates were used to determine minimum home ranges at 95% (K
95
= 6.2 to 233.9 km
2
; mean = 59 ± 13.5 km
2
) and core areas at 50% (K
50
= 0.6 to 54.9 km
2
; mean = 9 ± 2.6 km
2
). Protected areas accounted for 45% of the K
50
estimated core area. We observed dolphin individuals crossing country borders between Colombia and Peru in the Amazon basin, and between Colombia and Venezuela in the Orinoco basin. Satellite tracking allowed us to determine the different uses of riverine habitat types: main rivers (channels and bays, 52% of recorded locations), confluences (32%), lagoons (9.6%), and tributaries (6.2%). Satellite monitoring allowed us to better understand the ecological preferences of the species and demonstrated the importance of maintaining aquatic landscape heterogeneity and spatial connectivity for effective river dolphin conservation.
The probiotic potential of a designed bacterial consortia isolated from a competitive exclusion culture originally obtained from the intestinal contents of tilapia juveniles were evaluated on Nile ...tilapia alevins. The growth performance, intestinal histology, microbiota effects, resistance to Streptococcus agalactiae challenge, and immune response were assessed. In addition, the following treatments were included in a commercial feed: A12+M4+M10 (Lactococcus lactis A12, Priestia megaterium M4, and Priestia sp. M10), M4+M10 (P. megaterium M4, and Priestia sp. M10) and the single bacteria as controls; A12 (L. lactis A12), M4 (P. megaterium M4), M10 (Priestia sp. M10), also a commercial feed without any probiotic addition was included as a control. The results showed that all probiotic treatments improved the growth performance, intestinal histology, and resistance during experimental infection with S. agalactiae in comparison to the control fish. Also, the administration of probiotics resulted in the modulation of genes associated with the innate and adaptive immune systems that were non-dependent on microbial colonization. Surprisingly, L. lactis A12 alone induced benefits in fish compared to the microbial consortia, showing the highest increase in growth rate, survival during experimental infection with S. agalactiae, increased intestinal fold length, and the number of differentially expressed genes. Lastly, we conclude that a competitive exclusion culture is a reliable source of probiotics, and monostrain L. lactis A12 has comparable or even greater probiotic potential than the bacterial consortia.
•A competitive exclusion culture is a good source of potential probiotic bacteria.•Probiotic enhances growth performance, fold length, and resistance after infection.•Tilapia-isolated bacteria regulate innate and adaptive immune system pathways.•Monostrain probiotics offer higher benefits compared with multistrain probiotics.
Evidences of climate change in Colombia: trends and phase an amplitude changes of annual and semiannual cycles
Several statistical techniques and tests are performed trying to detect signals of ...climatic change in hydroclimatic records of Colombia, including identifying possible changes in the mean and the variance of the records, as well as detection of trends and non-homogeneities of the records. Results confirm positive trends in minimum and mean temperature records throughout Colombia. Precipitation series exhibit no clear spatial signal. Most important rivers basins appear to exhibit decresing trends in discharge. Deforestation and changes in evapotranspiration could account for the observed trends. Complex Demodulation (CD) is used to examine the evolution of amplitude and phase of climatic records. CD confirms shifts in phase and amplitude of annual and semi-annual cycles. These results have tremendous impact on water resources availability and their planning and operation.
Évidences de changement climatique en Colombie : tendances, changements de phase et amplitude des cycles annuels et semi-annuels
On a utilisé plusieurs techniques d’analyse pour mettre en évidence des changements climatiques en Colombie. On a montré une nette tendance au réchauffement des températures minimales et moyennes. Les chroniques de points de rosée et de pression de vapeur d’eau indiquent une augmentation de l’humidité de l’atmosphère qui va de pair avec un réchauffement. Par contre les séries de précipitations ne montrent pas de tendance bien définie. Les débits des principaux bassins ont tendance à diminuer, ce qui pourrait être relié aux variations de l’évapotranspiration. Une analyse par démodulation complexe confirme ces tendances dans plusieurs parties de la Colombie. Ces résultats pourraient être d’une grande utilité pour l’estimation des ressources hydriques, la planification et la gestion des systèmes hydrauliques.
Se implementan varias técnicas estadísticas de análisis para identificar señales de cambio climático en registros hidrológicos y climáticos de Colombia. Hay clara tendencia de calentamiento que se observa en las series de temperaturas mínimas y que concuerda con las series de temperaturas medias. Las series de punto de rocío y presión de vapor indican un aumento en la humedad atmosférica. Esta tendencia coincide con el calentamiento. Las series de precipitación no muestran señal clara de cambio climático. Las principales cuencas presentan tendencia decreciente en los caudales. Los resultados de Demodulación Compleja ratifican los resultados descritos anteriormente y permiten establecer corrimientos en las fases de los ciclos anual y semianual de diversas variables climáticas en Colombia. Estos resultados tienen implicaciones fundamentales para la disponibilidad del recurso hídrico y para el planeamiento y manejo de sistemas hidráulicos.
Pérez Carlos A., Poveda Germán, Mesa Oscar J., Ochoa Andrés, Carvajal Luis F. Evidencias de cambio climático en Colombia: tendencias y cambios de fase y amplitud de los ciclos anual y semianual. In: Bulletin de l'Institut Français d'Études Andines, tome 27, N°3, 1998. Variations climatiques et ressources en eau en Amérique du Sud. Importance et conséquences des événements El Niño. pp. 537-546.
is a phytopathogenic fungus that causes serious damage to the agricultural industry by infecting various important crops. 2-allylphenol has been used in China as a fungicide for more than a decade, ...and it has been shown that is a respiration inhibitor. A series of derivatives of 2-allylphenol were synthesized and their activity against
was evaluated by measuring mycelial growth inhibition. Results indicate that small changes in the chemical structure or the addition of substituent groups in the aromatic ring induce important variations in activity. For example, changing the hydroxyl group by methoxy or acetyl groups produces dramatic increases in mycelial growth inhibition, i.e., the IC
value of 2-allylphenol decreases from 68 to 2 and 1 μg mL
. In addition, it was found that the most active derivatives induce the inhibition of
expression in the early stages of
conidia germination. This gene is associated with the activation of the alternative oxidase enzyme (AOX), which allows fungus respiration to continue in the presence of respiratory inhibitors. Thus, it seems that 2-allylphenol derivatives can inhibit the normal and alternative respiratory pathway of
. Therefore, we believe that these compounds are a very attractive platform for the development of antifungal agents against
.
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