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Defective brain hormonal signaling has been associated with Alzheimer’s disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD. Expression of the exercise-induced myokine irisin (FNDC5) is lower in patients with AD. Whereas knockdown of FNDC5/irisin is sufficient to induce learning and memory deficits, restoration of its expression can ameliorate these phenotypes in rodent models.

The century-old maize (Zea mays) salmon silks mutation has been linked to the absence of maysin. Maysin is a C-glycosyl flavone that, when present in silks, confers natural resistance to the maize earworm (Helicoverpa zea), which is one of the most damaging pests of maize in America. Previous genetic analyses predicted Pericarp Color1 (P1; R2R3-MYB transcription factor) to be epistatic to the sm mutation. Subsequent studies identified two loci as being capable of conferring salmon silks phenotypes, salmon silks1 (sm1) and sm2. Benefitting from available sm1 and sm2 mapping information and from knowledge of the genes regulated by P1, we describe here the molecular identification of the Sm1 and Sm2 gene products. Sm2 encodes a rhamnosyl transferase (UGT91L1) that uses isoorientin and UDP-rhamnose as substrates and converts them to rhamnosylisoorientin. Sm1 encodes a multidomain UDP-rhamnose synthase (RHS1) that converts UDP-glucose into UDP-l-rhamnose. Here, we demonstrate that RHS1 shows unexpected substrate plasticity in converting the glucose moiety in rhamnosylisoorientin to 4-keto-6-deoxy glucose, resulting in maysin. Both Sm1 and Sm2 are direct targets of P1, as demonstrated by chromatin immunoprecipitation experiments. The molecular characterization of Sm1 and Sm2 described here completes the maysin biosynthetic pathway, providing powerful tools for engineering tolerance to maize earworm in maize and other plants.

Ayahuasca is a psychoactive brew traditionally used in indigenous and religious rituals and ceremonies in South America for its therapeutic, psychedelic, and entheogenic effects. It is usually prepared by lengthy boiling of the leaves of the bush Psychotria viridis and the mashed stalks of the vine Banisteriopsis caapi in water. The former contains the classical psychedelic N,N-dimethyltryptamine (DMT), which is thought to be the main psychoactive alkaloid present in the brew. The latter serves as a source for β-carbolines, known for their monoamine oxidase-inhibiting (MAOI) properties. Recent preliminary research has provided encouraging results investigating ayahuasca’s therapeutic potential, especially regarding its antidepressant effects. On a molecular level, pre-clinical and clinical evidence points to a complex pharmacological profile conveyed by the brew, including modulation of serotoninergic, glutamatergic, dopaminergic, and endocannabinoid systems. Its substances also interact with the vesicular monoamine transporter (VMAT), trace amine-associated receptor 1 (TAAR1), and sigma-1 receptors. Furthermore, ayahuasca’s components also seem to modulate levels of inflammatory and neurotrophic factors beneficially. On a biological level, this translates into neuroprotective and neuroplastic effects. Here we review the current knowledge regarding these molecular interactions and how they relate to the possible antidepressant effects ayahuasca seems to produce.

Pericarp Color1 (P1) encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize (Zea mays) silks and red phlobaphene pigments in pericarps and other floral tissues, which makes P1 an important visual marker. Using genome-wide expression analyses (RNA sequencing) in pericarps and silks of plants with contrasting P1 alleles combined with chromatin immunoprecipitation coupled with high-throughput sequencing, we show here that the regulatory functions of P1 are much broader than the activation of genes corresponding to enzymes in a branch of flavonoid biosynthesis. P1 modulates the expression of several thousand genes, and ∼1500 of them were identified as putative direct targets of P1. Among them, we identified F2H1, corresponding to a P450 enzyme that converts naringenin into 2-hydroxynaringenin, a key branch point in the P1-controlled pathway and the first step in the formation of insecticidal C-glycosyl flavones. Unexpectedly, the binding of P1 to gene regulatory regions can result in both gene activation and repression. Our results indicate that P1 is the major regulator for a set of genes involved in flavonoid biosynthesis and a minor modulator of the expression of a much larger gene set that includes genes involved in primary metabolism and production of other specialized compounds.

The modification of catalytic activity through the use of metallic promoters is a key strategy for optimizing performance, as electronic factors play a crucial role in regulating catalytic behavior. This study explores the electronic factors behind the adsorption of glycerol (Gly) on bimetallic nickel-based compounds (Ni3X) using density functional theory (DFT) calculations; incorporating Mn, Fe, Co, Cu, and Zn as promoters effectively tunes the d-band center of these systems, directly influencing their magnetic, adsorption, and catalytic properties. A good correlation between the calculated glycerol adsorption energy and the d-band filling of the studied bimetallic surfaces was identified. Interestingly, this correlation can be rationalized using the celebrated Newns–Anderson model based on the calculated d-band fillings and centers of the systems under study. Additionally, the adsorption energies and relative stability of other electro-oxidation intermediates toward dihydroxyacetone (DHA) were calculated. Notably, the Ni3Co and Ni3Cu systems exhibit an optimal balance between glycerol adsorption and DHA desorption, making them promising candidates for glycerol electro-oxidation. These theoretical insights address fundamental aspects of developing glycerol valorization processes and advancing alcohol electro-oxidation technologies in fuel cells with noble-metal-free catalysts.

Social Capital on health has been studied widely, to date there is no valid and reliable questionnaire that measure it in Chronic Kidney Disease (CKD). To develop, validate and assess the reliability of Social Capital related to CKD questionnaire for Mexican adolescents. An instrumental study was employed to validate a questionnaire that assesses the cognitive and structural domains of Social Capital related to CKD. The questionnaire was generated by operationalization of the constructs and validated by assessing the content, face validity, criteria and construct validity. Reliability was assessed through the Cronbach´s alpha. The content validity of the questionnaire was confirmed through Kendall's W of 0.925 (p = 0.01) and its face validity was evaluated by four focus groups. A principal component analysis on a sample of 281 adolescents indicated that 72.78% of the variance was explained by the cognitive domain and 83.20% by the structural domain. A confirmatory analysis returned a chi-squared value of 142.99 (p = 0.05), a CFI of 0.97, a TLI of 0.96, a RMSEA of 0.040 and a SRMR of 0.07 for the cognitive domain. Similarly, a chi-squared of 408.296 (p < 0.001), a CFI of 0.98, a TLI of 0.97, a RMSEA 0.03 and a SRMR of 0.06 were returned for the structural domain. The validity of the criteria was assessed through a Pearson's correlation for both the cognitive and structural domains. There was a mild-to-strongly significant correlation (p ≤ 0.001) among items and dimensions within each domain, with correlation coefficients ranging from 0.23 to 0.83. As a determinant of the reliability of the questionnaire, the Cronbach's alpha was 0.84 and 0.94 for the cognitive and structural domain, respectively. A valid and reliable questionnaire has been developed to measure the influence of Social Capital on health in relation to CKD among Mexican adolescents.

Background and Objectives: Pelvic organ prolapse (POP) is a prevalent condition that negatively impacts women’s quality of life. Uterine-preserving procedures are increasingly demanded by patients with uterine prolapse, particularly when associated with true cervical elongation. The Manchester procedure, historically used for uterine preservation, has regained interest due to its effectiveness and low morbidity. This study aims to evaluate the anatomical and functional outcomes of the Manchester procedure in women with uterine prolapse due to cervical elongation, assessing patient satisfaction and associated clinical factors. Materials and Methods: We conducted a retrospective, observational, single-center study at the Regional University Hospital of Málaga, Spain, including patients undergoing the Manchester procedure between January 2017 and December 2022. Inclusion criteria required a diagnosis of uterine prolapse due to clinically confirmed true cervical elongation. Surgical details, complications, and postoperative outcomes were recorded. Patient satisfaction was assessed using a Likert scale during follow-up visits. Results: A total of 38 patients were included, with a mean age of 48.7 years. All presented with symptomatic uterine prolapse and elongated cervix (>5 cm). The anatomical success rate was 97%, with only one case of symptomatic recurrence. The most common early postoperative complication was urinary tract infection (10.5%). The average follow-up duration was 18.6 months. A high level of satisfaction was recorded: 94.8% of patients were either “very satisfied” (73.7%) or “satisfied” (21.1%), and only 5.3% reported dissatisfaction. Multicompartmental repair (anterior and/or posterior colporrhaphy) improved satisfaction outcomes. Conclusions: The Manchester procedure is a safe, effective uterine-sparing surgical option for patients with cervical elongation-related uterine prolapse. It demonstrates a high anatomical success rate and low morbidity, with excellent patient satisfaction. Comprehensive preoperative assessment and addressing modifiable risk factors such as obesity and smoking are key to optimizing results. Further prospective studies are needed to assess long-term durability and quality-of-life outcomes.

Background Cervical cancer screening is a cost-effective method responsible for reducing cervical cancer-related mortality by 70% in countries that have achieved high coverage through nationwide screening strategies. However, there are disparities in access to screening. In Ecuador, although cervical cancer is the second most common cancer in women, only 58.4% of women of reproductive age have ever been screened for cervical cancer. Methodology A qualitative study was performed to understand the current barriers to screening and to identify strategies that could increase uptake in Azuay province, Ecuador . Seven focus group discussions (FGDs) were conducted with under-screened women and health professionals (HPs). The FGDs were recorded and transcribed. Content analysis was done using the socio-ecological framework to categorize and analyse the data. Results Overall, 28 women and 27 HPs participated in the study. The two groups perceived different barriers to cervical cancer screening. The HPs considered barriers to be mainly at the policy level (lack of a structured screening plan; lack of health promotion) and the individual level (lack of risk perception; personal beliefs). The women identified barriers mainly at organizational level, such as long waiting times, lack of access to health centres, and inadequate patient–physician communication. Both groups mentioned facilitators at policy level, such as national campaigns promoting cervical cancer screening, and at community and individual level, including health literacy and women’s empowerment. Conclusions The women considered access to health services the main barrier to screening, while the HPs identified a lack of investment in screening programmes and cultural patterns at the community level as major obstacles. To take an integrated approach to cervical cancer prevention, the perspectives of both groups should be taken into account. Additionally, new strategies and technologies, such as self-administered human papillomavirus (HPV) testing and community participation, should be implemented to increase access to cervical cancer screening.

Creatinine is one of the most important biomarkers to detect renal failures. The electrochemical detection of creatinine has been performed using complex enzymatic and non-enzymatic electrode arrays hindering their commercialization. In this work, a new and practical non-enzymatic electrochemical sensor was fabricated depositing copper on carbon paper electrodes by physical vapor deposition (namely Cu/CP). Surface and cross-sectional SEM images demonstrated the deposition of copper over the 3D structure of carbon paper. A thin film was found on the surface, while Cu nanowires with diameters of 180 ± 30 nm were found inside the 3D structure of CP. The thickness of the Cu film on the tubular structures of CP was of 390 ± 40 nm. High-resolution TEM images indicated that the Cu film was integrated by hierarchical structures containing terminal Cu hemispheres of 17.6 ± 2.2 nm. Additionally, interplanar distances from the selected-area electron diffraction pattern demonstrated the presence of Cu 0 , while Cu 2 O was also found. Creatinine concentrations in saliva between 16 and 400 µM indicate kidney failure. The Cu/CP electrochemical sensor detected creatinine with linear concentration ranges from 0 to 1000 µM with a r 2  = 0.9936. Outstandingly, this sensor presented good reproducibility ( RSD  = 7.3%), and selectivity to detect creatinine in artificial saliva using interferents like urea, glucose, glycine, ascorbic and uric acids. Graphical abstract

Background Mycobacterium avium complex (MAC) is the most common non-tuberculous mycobacteria (NTM) causing disease in immunosuppressed patients. People living with human immunodeficiency virus (PLHIV) typically present with disseminated infections characterized by non-specific constitutional symptoms such as fever, night sweats, and weight loss. Cutaneous lesions in disseminated MAC are rare and include panniculitis, granulomas, pustules, papules, nodules, abscesses and ulcerations, and ulcers. Here, we present two HIV patients who developed a disseminated MAC infection with skin lesions. Case presentation A 40-year-old woman with a 10-year history of untreated HIV infection and a 47-year-old woman recently diagnosed with HIV both presented with constitutional symptoms. After routine screening for opportunistic infections and exclusion of active infection, they were started on antiretroviral therapy (ART) with tenofovir, lamivudine, and dolutegravir. One month later, both presented inflammatory skin lesions that evolved into ulcers. Case 1 presented with painful nodules of variable size on the upper and lower extremities that subsequently suppurated and ulcerated. Case 2 presented with erythematous-violaceous nodules on the trunk and limbs that progressed to ulceration with irregular borders, well defined, infiltrated, with necrotic background and fine perilesional desquamation. The secretion of the lesions was analyzed in both cases. Ziehl-Neelsen stain showed the presence of acid-fast bacilli only in case 1, while the GeneXpert MTB/RIF assay was negative in both cases. The biopsy of case 2 documented panniculitis. Non-pigmented colony growth was observed after 42 and 38 days of incubation, respectively. PCR restriction enzyme pattern analysis demonstrated the presence of MAC in both cases. Clarithromycin and ethambutol were started in both cases, and clofazimine was added in case 1, resulting in a satisfactory clinical course in both patients, as evidenced by the healing of the ulcers. Conclusions These cases of disseminated MAC infection highlight that unmasking immune reconstitution inflammatory syndrome can present with severe cutaneous lesions shortly after the initiation of modern ART. Our report underscores the need for a high index of suspicion for NTM infections in patients with advanced HIV who develop new inflammatory syndromes, particularly in resource-limited settings where diagnostic delays for mycobacterial diseases are common.