Impact of intravascular hemolysis on functional and molecular alterations in the urinary bladder: implications for an overactive bladder in sickle cell disease.

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-ß-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD.

[1-7-NαC]-Crocaorb A1 and A2, orbitides from the latex of Croton campanulatus.

Two new heptapeptides, [1-7-NαC]-crocaorbs A1 (1) and A2 (2), were isolated from the latex of Croton campanulatus. Their structures were determined using NMR spectroscopic techniques, ESI-HRMS data, Marfey's method, and further refined using molecular dynamics with simulated annealing (MD/SA). Molecular dynamics calculations of peptides 1 and 2 demonstrated greater stability in simulations using a biological solvent compared to those using DMSO. Compound 1, the most abundant peptide in latex, was assessed for NO production, antiplasmodial and cytotoxicity activities. The peptide significantly increased nitric oxide (NO) production at concentrations of 40, 20 or 10 µM (17.932 ± 1.1, 18.270 ± 0.9, 18.499 ± 0.7, respectively). Its antiplasmodial activity exhibited limited efficacy, with only 5% inhibition of Plasmodium falciparum 3D7 growth at a concentration of 50 µM. Also, it exhibited no cytotoxic effects in the J774A.1 murine macrophages cell line. This study represents the first report of a phytochemical investigation of the species C. campanulatus, which showed orbitides with distinctive sequences in contrast to other peptides described for the genus Croton and contributes to the study of structural diversity within this particular class of compounds.

Lipidomic Analysis Reveals Branched-Chain and Cyclic Fatty Acids from Angomonas deanei Grown under Different Nutritional and Physiological Conditions.

Angomonas deanei belongs to Trypanosomatidae family, a family of parasites that only infect insects. It hosts a bacterial endosymbiont in a mutualistic relationship, constituting an excellent model for studying organelle origin and cellular evolution. A lipidomic approach, which allows for a comprehensive analysis of all lipids in a biological system (lipidome), is a useful tool for identifying and measuring different expression patterns of lipid classes. The present study applied GC-MS and NMR techniques, coupled with principal component analysis (PCA), in order to perform a comparative lipidomic study of wild and aposymbiotic A. deanei grown in the presence or absence of FBS. Unusual contents of branched-chain iso C17:0 and C19:0-cis-9,10 and-11,12 fatty acids were identified in A. deanei cultures, and it was interesting to note that their content slightly decreased at the log phase culture, indicating that in the latter growth stages the cell must promote the remodeling of lipid synthesis in order to maintain the fluidity of the membrane. The combination of analytical techniques used in this work allowed for the detection and characterization of lipids and relevant contributors in a variety of A. deanei growth conditions.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

Cyclic vomiting syndrome: From pathophysiology to treatment.

Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent and unpredictable episodes of intense vomiting, interspersed with periods of apparent wellbeing. This disorder, which primarily affects children and adolescents but can persist into adulthood, has recently been the subject of extensive study and analysis in the medical literature. The aim of the present review is to examine the most important aspects of the epidemiology, pathophysiology, subtypes, diagnostic criteria, and current management of CVS. Even though the exact etiology remains unknown, genetic factors (polymorphisms), nervous system alterations and autonomic dysregulation, and environmental factors (use and abuse of cannabinoids) are postulated as possible triggers. CVS has significant diagnostic challenges, given that there is no specific test for confirming its presence. Thorough evaluation of symptoms and the ruling out of other possible causes of recurrent vomiting are required. Management of CVS typically involves a multidisciplinary approach. Pharmacologic options are explored, such as antiemetics and preventive medications, as well as behavioral and psychologic support therapies. Treatment personalization is essential, adapting it to the individual needs of each patient. Despite advances in the understanding of CVS, it remains a significant clinical challenge. This disorder impacts the quality of life of those affected and their families, underscoring the ongoing need for research and the development of more effective treatment strategies.

Effect of Graphene Oxide Addition on the Properties of Electrochemically Synthesized Polyaniline-Graphene Oxide Films.

In this work, the electrochemical synthesis of PANI and GO-modified PANI was performed using cyclic voltammetry, varying the amount of GO, 1 mg (PG1), 5 mg (PG5), and 10 mg (PG10) to analyze the effect of the amount of GO on the composite. PANI, PG1, PG5, and PG10 materials were characterized using optical microscopy, SEM, UV-vis, FTIR, Raman, and wettability. A stability test was also carried out by putting the materials to 500 oxidation-reduction cycles using cyclic voltammetry. The synthesis method allowed GO in PANI to be added through a chemical interaction between the two compounds. It was also found that the addition of GO led to an improvement in the hydrophilic character of the composite, which would lead to an improvement in the diffusion of reagents/species when the composites are used in aqueous media processes. The results of the stability test showed that the PG10 material presented a lower % loss of specific capacitance and energy compared with the other materials, which indicates that the GO presence (in the amount specified) improves the stability of the PANI. The PG10 material showed favorable and promising conditions for its use in fuel cell and battery processes.

Hexyltrimethylammonium ion enhances potential copper-chelating properties of ammonium thiomolybdate in an in vivo zebrafish model.

Ammonium and hexyltrimethylammonium thiomolybdates (ATM and ATM-C6) and thiotungstates (ATT and ATT-C6) were synthesized. Their toxicity was evaluated using both in vitro and in vivo approaches via the zebrafish embryo acute toxicity assay (ZFET), while the copper-thiometallate interaction was studied using cyclic voltammetry, as well as in an in vivo assay. Cyclic voltammetry suggests that all thiometallates form complexes with copper in a 2:1 Cu:thiometallate ratio. Both in vitro and in vivo assays demonstrated low toxicity in BALB/3T3 cells and in zebrafish embryos, with high IC50 and LC50 values. Furthermore, the hexyltrimethylammonium ion played a crucial role in enhancing viability and reducing toxicity during prolonged treatments for ATM and ATT. In particular, the ZEFT assay uncovered the accumulation of ATM in zebrafish yolk, averted by the incorporation of the hexyltrimethylammonium ion. Notably, the copper-thiometallate interaction assay highlighted the improved viability of embryos when cultured in CuCl2 and ATM-C6, even at high CuCl2 concentrations. The hatching assay further confirmed that copper-ATM-C6 interaction mitigates inhibitory effects induced by thiomolybdates and CuCl2 when administered individually. These results suggest that the incorporation of the hexyltrimethylammonium ion in ATM increase its ability to interact with copper and its potential application as a copper chelator.

Development of a scalable recombinant system for cyclic beta-1,2-glucans production.

BACKGROUND: Cyclic ß-1,2-glucans (CßG) are bacterial cyclic homopolysaccharides with interesting biotechnological applications. These ring-shaped molecules have a hydrophilic surface that confers high solubility and a hydrophobic cavity able to include poorly soluble molecules. Several studies demonstrate that CßG and many derivatives can be applied in drug solubilization and stabilization, enantiomer separation, catalysis, synthesis of nanomaterials and even as immunomodulators, suggesting these molecules have great potential for their industrial and commercial exploitation. Nowadays, there is no method to produce CßG by chemical synthesis and bacteria that synthesize them are slow-growing or even pathogenic, which makes the scaling up of the process difficult and expensive. Therefore, scalable production and purification methods are needed to afford the demand and expand the repertoire of applications of CßG. RESULTS: We present the production of CßG in specially designed E. coli strains by means of the deletion of intrinsic polysaccharide biosynthetic genes and the heterologous expression of enzymes involved in CßG synthesis, transport and succinilation. These strains produce different types of CßG: unsubstituted CßG, anionic CßG and CßG of high size. Unsubstituted CßG with a degree of polymerization of 17 to 24 glucoses were produced and secreted to the culture medium by one of the strains. Through high cell density culture (HCDC) of that strain we were able to produce 4,5 g of pure unsubstituted CßG /L in culture medium within 48 h culture. CONCLUSIONS: We have developed a new recombinant bacterial system for the synthesis of cyclic ß-1,2-glucans, expanding the use of bacteria as a platform for the production of new polysaccharides with biotechnological applications. This new approach allowed us to produce CßG in E. coli with high yields and the highest volumetric productivity reported to date. We expect this new highly scalable system facilitates CßG availability for further research and the widespread use of these promising molecules across many application fields.

Tetracyclic homoisoflavanoid (+)-brazilin: a natural product inhibits c-di-AMP-producing enzyme and Streptococcus mutans biofilms.

The tenacious biofilms formed by Streptococcus mutans are resistant to conventional antibiotics and current treatments. There is a growing need for novel therapeutics that selectively inhibit S. mutans biofilms while preserving the normal oral microenvironment. Previous studies have shown that increased levels of cyclic di-AMP, an important secondary messenger synthesized by diadenylate cyclase (DAC), favored biofilm formation in S. mutans. Thus, targeting S. mutans DAC is a novel strategy to inhibit S. mutans biofilms. We screened a small NCI library of natural products using a fluorescence detection assay. (+)-Brazilin, a tetracyclic homoisoflavanoid found in the heartwood of Caesalpinia sappan, was identified as one of the 11 "hits," with the greatest reduction (>99%) in fluorescence at 100 µM. The smDAC inhibitory profiles of the 11 "hits" established by a quantitative high-performance liquid chromatography assay revealed that (+)-brazilin had the most enzymatic inhibitory activity (87% at 100 µM) and was further studied to determine its half maximal inhibitory concentration (IC50 = 25.1 ± 0.98 µM). (+)-Brazilin non-competitively inhibits smDAC's enzymatic activity (Ki = 140.0 ± 27.13 µM), as determined by a steady-state Michaelis-Menten kinetics assay. In addition, (+)-brazilin's binding profile with smDAC (Kd = 11.87 µM) was illustrated by a tyrosine intrinsic fluorescence quenching assay. Furthermore, at low micromolar concentrations, (+)-brazilin selectively inhibited the biofilm of S. mutans (IC50 = 21.0 ± 0.60 µM) and other oral bacteria. S. mutans biofilms were inhibited by a factor of 105 in colony-forming units when treated with 50 µM (+)-brazilin. In addition, a significant dose-dependent reduction in extracellular DNA and glucan levels was evident by fluorescence microscopy imaging of S. mutans biofilms exposed to different concentrations of (+)-brazilin. Furthermore, colonization of S. mutans on a representative model of enamel using suspended hydroxyapatite discs showed a >90% reduction with 50 µM (+)-brazilin. In summary, we have identified a drug-like natural product inhibitor of S. mutans biofilm that not only binds to smDAC but can also inhibit the function of smDAC. (+)-Brazilin could be a good candidate for further development as a potent therapeutic for the prevention and treatment of dental caries.IMPORTANCEThis study represents a significant advancement in our understanding of potential therapeutic options for combating cariogenic biofilms produced by Streptococcus mutans. The research delves into the use of (+)-brazilin, a natural product, as a potent inhibitor of Streptococcus mutans' diadenylate cyclase (smDAC), an enzyme crucial in the formation of biofilms. The study establishes (+)-brazilin as a non-competitive inhibitor of smDAC while providing initial insights into its binding mechanism. What makes this finding even more promising is that (+)-brazilin does not limit its inhibitory effects to S. mutans alone. Instead, it demonstrates efficacy in hindering biofilms in other oral bacteria as well. The broader spectrum of anti-biofilm activity suggests that (+)-brazilin could potentially serve as a versatile tool in a natural product-based treatment for combating a range of conditions caused by resilient biofilms.

A Reduced Complexity Acoustic-Based 3D DoA Estimation with Zero Cyclic Sum.

Accurate direction of arrival (DoA) estimation is paramount in various fields, from surveillance and security to spatial audio processing. This work introduces an innovative approach that refines the DoA estimation process and demonstrates its applicability in diverse and critical domains. We propose a two-stage method that capitalizes on the often-overlooked secondary peaks of the cross-correlation function by introducing a reduced complexity DoA estimation method. In the first stage, a low complexity cost function based on the zero cyclic sum (ZCS) condition is used to allow for an exhaustive search of all combinations of time delays between pairs of microphones, including primary peak and secondary peaks of each cross-correlation. For the second stage, only a subset of the time delay combinations with the lowest ZCS cost function need to be tested using a least-squares (LS) solution, which requires more computational effort. To showcase the versatility and effectiveness of our method, we apply it to the challenging acoustic-based drone DoA estimation scenario using an array of four microphones. Through rigorous experimentation with simulated and actual data, our research underscores the potential of our proposed DoA estimation method as an alternative for handling complex acoustic scenarios. The ZCS method demonstrates an accuracy of 89.4%±2.7%, whereas the ZCS with the LS method exhibits a notably higher accuracy of 94.0%±3.1%, showcasing the superior performance of the latter.

Sources and profiles of toxins in shellfish from the south-central coast of Chile (36°â€’ 43° S).

The study of marine toxins in shellfish is of the utmost importance to ensure people's food safety. Marine toxins in shellfish and microalgae in the water column off the south-central coast of Chile (36°â€’43° S) were studied in a network of 64 stations over a 14-month period. The relative abundance of harmful species Alexandrium catenella, Alexandrium ostenfeldii, Protoceratium reticulatum, Dinophysis acuminata, Dinophysis acuta, Pseudo-nitzschia seriata group and P. delicatissima group was analyzed. The detection and quantification of lipophilic toxins and domoic acid (DA) in shellfish was determined by UHPLC-MS/MS, and for Paralytic Shellfish Toxins (PSTs) by HPLC-FD with post-column oxidation, while for a culture of A. ostenfeldii a Hylic-UHPLC-MS/MS was used. Results showed that DA, gonyautoxin (GTX)-2, GTX-3 and pectenotoxin (PTX)-2 were detected below the permitted limits, while Gymnodimine (GYM)-A and 13-desmethylespirolide C (SPX-1) were below the limit of quantitation. According to the distribution and abundance record of microalgae, DA would be associated to P. seriata and P. delicatissima-groups, PTX-2 to D. acuminata, and GTX-2, GTX-3, GYM-A, and SPX-1 to A. ostenfeldii. However, the toxin analysis of an A. ostenfeldii culture from the Biobío region only showed the presence of the paralytic toxins C2, GTX-2, GTX-3, GTX-5 and saxitoxin, therefore, the source of production of GYM and SPX is still undetermined.

Clinical, Immunological and Inflammatory Characteristics among Mexican Children with Different Subtypes of Juvenile Idiopathic Arthritis: Exploring the Correlation between Anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF).

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood, affecting one to four of every 1000 children worldwide. It is characterized by joint inflammation lasting more than six weeks in children under 16 years. The aim of this study was to estimate the frequency of JIA subtypes in the Mexican patient population; compare clinical, immunological and inflammation markers by JIA subtype; and examine the correlation between these variables. METHODS: We conducted a cross-sectional study of 50 patients with JIA (2-15 years). We estimated the frequency of each JIA subtype, assessed and compared the immunological characteristics (RF, ANA and anti-CCP) by JIA subtype at the time of diagnosis using Kruskal-Wallis or chi-square tests, and calculated Spearman correlation coefficients between the assessments. RESULTS: Our analysis included 50 patients, 29 (58%) girls and 21 (42%) boys, aged at the time of diagnosis 10.56 ± 3.99 years. The frequencies of JIA subtypes were RF-seropositive polyarthritis (34%), RF-seronegative polyarthritis (28%), systemic arthritis (16%), oligoarthritis (14%) and arthritis-related enthesitis (8%). We found a significant association between sex and JIA subtype (p = 0.014). There was a significant difference in anti-CCP levels by JIA subtype (p < 0.001). We also detected positive correlations between RF and anti-CCP (r = 0.63, p < 0.001) and between age and anti-CCP (r = 0.29, p = 0.041). CONCLUSIONS: Our study suggests that the frequency of the polyarticular subtypes of JIA is higher in Mexican children compared to other populations. Our findings highlight the importance of considering the presence of anti-CCP and RF as important criteria when deciding on treatment for JIA patients as elevated levels of these antibodies may indicate early forms of adult rheumatoid arthritis.

Novel 2,5-Diketopiperazines with In Vitro Activities against Protozoan Parasites of Tropical Diseases.

Malaria, Chagas disease, and leishmaniasis are tropical diseases caused by protozoan parasites of the genera Plasmodium, Trypanosoma and Leishmania, respectively. These diseases constitute a major burden on public health in several regions worldwide, mainly affecting low-income populations in economically poor countries. Severe side effects of currently available drug treatments and the emergence of resistant parasites need to be addressed by the development of novel drug candidates. Natural 2,5-Diketopiperazines (2,5-DKPs) constitute N-heterocyclic secondary metabolites with a wide range of biological activities of medicinal interest. Its structural and physicochemical properties make the 2,5-DKP ring a versatile, peptide-like, and stable pharmacophore attractive for synthetic drug design. In the present work, twenty-three novel synthetic 2,5-DKPs, previously synthesized through the versatile Ugi multicomponent reaction, were assayed for their anti-protozoal activities against P. falciparum, T. cruzi, and L. infantum. Some of the 2,5-DKPs have shown promising activities against the target protozoans, with inhibitory concentrations (IC50) ranging from 5.4 to 9.5 µg/mL. The most active compounds also show low cytotoxicity (CC50), affording selectivity indices ≥ 15. Results allowed for observing a clear relationship between the substitution pattern at the aromatic rings of the 2,5-DKPs and their corresponding anti-Plasmodium activity. Finally, calculated drug-like properties of the compounds revealed points for further structure optimization of promising drug candidates.

Repair of monolithic zirconia restorations with different direct resin composites: effect on the fatigue bonding and mechanical performance.

OBJECTIVE: The study aims to evaluate the shear bond and flexural strength fatigue behavior of yttrium-stabilized zirconia (4YSZ) repaired using different resin composites. MATERIALS AND METHODS: Cylindric specimens of 4YSZ were obtained for the bond strength (Ø = 6 mm, 1.5 mm of thickness) and biaxial flexural strength (Ø = 15 mm, 1 mm of thickness) fatigue tests and divided into 3 groups according to the repair resin composite: EVO (nanohybrid), BULK (bulk-fill), and FLOW (flowable). The zirconia surface was air-abraded with alumina particles, a 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) primer was applied, and the resin composite was build-up over the zirconia. Fatigue shear bond strength and flexural fatigue strength tests were performed (n = 15). One-way ANOVA and Tukey post hoc tests were carried out for both outcomes, besides scanning electron microscopy and finite element analysis. RESULTS: The repair material affected the fatigue shear bond strength of zirconia ceramic. The BULK group (18.9 MPa) depicted higher bond strength values than FLOW (14.8 MPa) (p = 0.04), while EVO (18.0 MPa) showed similar results to both groups. No effect was observed for the mechanical behavior (p = 0.53). The stress distribution was similar for all groups. CONCLUSION: The repair of yttrium-stabilized zirconia (4YSZ) ceramics with bulk-fill resin composites was the best option for high fatigue bond strength. However, the fatigue mechanical performance was similar regardless of the applied repair material. CLINICAL RELEVANCE: The repair of yttrium-stabilized zirconia (4YSZ) monolithic restorations may be performed with nanohybrid and bulk-fill resin composites in order to promote longevity in the treatment.

Measures of contextuality in cyclic systems and the negative probabilities measure CNT3.

Several principled measures of contextuality have been proposed for general systems of random variables (i.e. inconsistently connected systems). One such measure is based on quasi-couplings using negative probabilities (here denoted by [Formula: see text], Dzhafarov & Kujala, 2016 Quantum interaction). Dzhafarov & Kujala (Dzhafarov & Kujala 2019 Phil. Trans. R. Soc. A 377, 20190149. (doi:10.1098/rsta.2019.0149)) introduced a measure of contextuality, [Formula: see text], that naturally generalizes to a measure of non-contextuality. Dzhafarov & Kujala (Dzhafarov & Kujala 2019 Phil. Trans. R. Soc. A 377, 20190149. (doi:10.1098/rsta.2019.0149)) additionally conjectured that in the class of cyclic systems these two measures are proportional. Here we prove that conjecture is correct. Recently, Cervantes (Cervantes 2023 J. Math. Psychol. 112, 102726. (doi:10.1016/j.jmp.2022.102726)) showed the proportionality of [Formula: see text] and the Contextual Fraction measure introduced by Abramsky & Brandenburger (Abramsky & Brandenburger 2011 New J. Phys. 13, 113036. (doi:10.1088/1367-2630/13/11/113036)). The present proof completes the description of the interrelations of all contextuality measures proposed within or translated into the Contextuality-by-Default framework so far as they pertain to cyclic systems. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

cAMP regulates the progesterone receptor gene expression through the protein kinase A pathway during decidualization in human immortalized endometrial stromal cells.

Decidualization, a crucial process for successful pregnancy establishment and maintenance, involves endometrial stromal cell differentiation. This process is orchestrated by estradiol (E2), progesterone, and other stimuli that increase intracellular cyclic adenosine monophosphate (cAMP) levels. The intracellular progesterone receptor (PR), encoded by the PGR gene, has a key role in decidualization. This study aimed to understand the role of sex steroids and cAMP in regulating PGR expression during the in vitro decidualization of the human immortalized endometrial stromal cell line, T-HESC. We subjected the cells to individual and combined treatments of E2, medroxyprogesterone (MPA), and cAMP. Additionally, we treated cells with PR and estrogen receptor antagonists and a protein kinase A (PKA) inhibitor. We evaluated the expression of PGR isoforms and decidualization-associated genes by RT-qPCR. Our findings revealed that cAMP induced PGR-B and PGR-AB expression by activating the PKA signaling pathway, while MPA downregulated their expression through the PR. Furthermore, downstream genes involved in decidualization, such as those coding for prolactin (PRL), insulin-like growth factor-binding protein-1 (IGFBP1), and Dickkopf-1 (DKK1), exhibited positive regulation via the cAMP-PKA pathway. Remarkably, MPA-activated PR signaling induced the expression of IGFBP1 and DKK1 but inhibited that of PRL. In conclusion, we have demonstrated that the PKA signaling pathway induces PGR gene expression during in vitro decidualization of the T-HESC human endometrial stromal cell line. This study has unraveled some of the intricate regulatory mechanisms governing PGR expression during this fundamental process for implantation and pregnancy maintenance.

Access to carbonyl compounds via the electroreduction of N-benzyloxyphthalimides: Mechanism confirmation and preparative applications.

A method to access carbonyl compounds using reductive conditions was evaluated via electrochemical reduction of their corresponding N-benzyloxyphthalimide derivatives (NBOPIs). The mechanism of this originally reported electrochemical reaction was proposed based on DFT calculation and is experimentally confirmed herein, contrasting simulated and experimental cyclic voltammetry data. The reaction scope studied in a preparative scale and using redox sensitive functional groups showed good selectivity and tolerance toward oxidation under the reaction conditions with a moderate to good yield (50-71%). Nevertheless, some restrictions with reducible functional groups, like benzyl-brominated and nitro-aromatic derivatives, were observed. The present approach can be considered a self-sustainable electrochemical catalysis for the synthesis of aromatic carbonylic compounds passing through anion radical intermediates produced by a cathodic reaction.

Accelerated Cr (VI) removal by a three-dimensional electro-Fenton system using green iron nanoparticles.

Green-synthesized iron nanoparticles (GAP-FeNP) were used as particle electrodes in a three-dimensional electro-Fenton (3DEF) process to accelerate the removal of hexavalent chromium [Cr (VI)]. Removal was evaluated by varying the pH (3.0, 6.0, and 9.0) and initial Cr (VI) concentrations (10, 30, and 50 mg/L) at 5 and 25 min. These results demonstrated that GAP-FeNP/3DEF treatment achieved more than 94% Cr (VI) removal under all tested conditions. Furthermore, it was observed that Cr (VI) removal exceeded 98% under pH 9.0 in all experimental parameters tested. The results of the response surface methodology (RSM) determined two optimal conditions: the first, characterized by a pH of 3.0, Cr (VI) concentration at 50 mg/L, and 25 min, yielded a Cr (VI) removal of 99.7%. The second optimal condition emerged at pH 9.0, with Cr (VI) concentrations of 10 mg/L and 5 min, achieving a Cr (VI) removal of 99.5%. This study highlights the potential of the GAP-FeNP to synergistically accelerate Cr (VI) removal by the 3DEF process, allowing faster elimination and expansion of the alkaline (pH 9.0) applicability. PRACTITIONER POINTS: The required time for >99% of Cr (VI) removal by the GAP-FeNP/3DEF process was shortened from 25 to 5 min. EF process with GAP-FeNP reduces the time necessary for Cr (VI) removal, which is 67% faster than conventional methods. EF process using GAP-FeNP removed >94% of Cr (VI) after 25 min for all initial Cr (VI) concentrations and pH treatments. Cr (VI) removal by the GAP-FeNP/3DEF process was >98% at a pH of 9.0, widening the solution pH applicability.

Nucleotides as Bacterial Second Messengers.

In addition to comprising monomers of nucleic acids, nucleotides have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells. The most common example is cyclic AMP (cAMP). Nucleotide signaling is a focus of great interest in bacteria. Cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, and virulence. Moreover, the cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells to allow for infection. On the other hand, non-cyclic nucleotide molecules pppGpp and ppGpp are alarmones involved in regulating the bacterial response to nutritional stress; they are also considered second messengers. These second messengers can potentially be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, the role of c-di-nucleotides and cAMP as second messengers in different bacterial processes is addressed.

Influence of Pulsed Arc Parameters on the Tig Welding Process for the Stainless Steel Duplex UNS S31803.

The influence of parameters involved in the pulsed electric arc, used as an energy source in the tungsten inert gas (TIG)-mediated welding of Duplex UNS S31803 stainless steel, to attend the manufacture of flexible pipes for the extraction of oil and gas is presented. A fundamental part in the manufacturing process of flexible pipelines is the welding of these strips so that corresponding TIG welds will be subjected to the same process and work conditions. Therefore, it is necessary to maintain the same properties in the welded regions. Covering the effects of each parameter of the pulsed electric arc such as peak and base current as welds, cyclic ratio, and pulsation frequency is a desirable endeavor. The final objective is the mitigation of problems that have a great impact on production, such as weld breakage during the conformation of the strip in the process and test failures. With this, tensile, bending, and ferrite percentage tests were performed on 12 samples that qualified as satisfactory in the visual aspect. A minimum tensile strength of 734.57 MPa and a maximum of 775.77 MPa were obtained where all values found are above the tensile strength limit of the base material of 620 MPa. With the completion of the study, it is possible to understand not only the response of the process to each parameter but also the tendency when changing them. Moreover, it is possible to explore the possibility of guiding the changes to achieve results about the visual aspect and the mechanical properties of the welded material.