Interfacial Phenomena Governing Performance of Graphene Electrodes in Aqueous Electrolyte.

There is evidence of the presence of intercalated water between graphene and the substrate in electronic devices. However, a proper understanding of the impact of this phenomenon, which causes important limitations for the optimization of graphene-based devices operating in aqueous electrolytes, is missing. We used graphene-based electrodes on insulating and conducting substrates to evaluate the impact of intercalated water by combining experimental techniques with numerical simulations. Results show that the capacitance of the conductive substrate/graphene electrodes is significantly higher than that of the insulating substrate/graphene ones. Meanwhile, Raman spectroscopy demonstrates that graphene charge modulation with the applied potential is independent of the substrate conductivity. We found that this intriguing behavior is influenced by the water intercalation phenomena and governed by the substrate conductive nature. This work contributes to the understanding of the electric response of graphene-based devices in an aqueous environment and of the methods to measure and model it.

Accentuated eccentric resistance training: Effects on physical performance in male and female athletes.

This study aimed to compare the effects of an accentuated eccentric training programme on physical performance between men and women. Distributed in two groups by gender, 21 male and 21 female athletes performed four sets of seven repetitions of the half-squat exercise twice per week for 6 weeks. Both groups lifted the same absolute load using a rotary inertial device. To accentuate the eccentric action, the eccentric load was twice as heavy as the concentric load. Vertical jump, sprint, and change of direction (COD) performances were measured pre- and post-intervention. To measure strength gains, vertical ground reaction forces were measured for each repetition of the entire training programme. Vertical jump improved post-intervention (MG: 33.88 ± 4.94 to 35.41 ± 4.86; FG: 20.60 ± 4.62 to 22.12 ± 4.32; p < 0.001; η2p = 0.42), while sprint (MG: 3.08 ± 0.11 to 3.07 ± 0.13; FG: 3.66 ± 0.23 to 3.64 ± 0.23) and COD (MG: 7.77 ± 0.42 to 7.61 ± 0.47; FG: 8.44 ± 0.58 to 8.38 ± 0.57) remained unchanged. Concentric and eccentric forces increased for both groups from session 1 to 4 (p < 0.001; η2p >0.39), while only peak eccentric forces increased until session 12 (p = 0.009; η2p = 0.21). In conclusion, even when men are able to produce greater forces with similar loads, accentuated eccentric RT produces similar strength and strength-related adaptations in male and female athletes.

SAVI catheter digitization impact: A single institution multiuser uncertainty study.

To assess the impact of Strut Adjusted Volume Implant (SAVI) catheter digitization variability on dosimetric evaluation parameters of HDR breast brachytherapy treatment plans. Four clinically approved SAVI cases were chosen for this digitization variability analysis. All patients were implanted with 6-1 SAVI device. Six experienced physicists independently digitized SAVI catheters. Plans utilizing significant peripheral loading were used for this study where SAVI catheters were near the chest wall and/or skin. After digitization was completed for each case by each physicist, the original clinical dwell times were copied over for comparison. This ensured that only variability among plans is the digitization of SAVI catheters by different users. The original plan that went through two physicists' checks and one physician's review was considered the "ground truth" plan to which all other plans were compared. Plans were evaluated on planning parameters for lumpectomy cavity's PTV_Eval D90, V150, V200 and for the OARs (Chest-Wall/Ribs and Skin), on D0.03cc, D0.1cc, D1cc, D2cc. Additionally, a visualization window setting-based uncertainty test was performed on the same 4 cases. Our results showed that the average and maximum dwell positional digitization uncertainties were 0.36 and 0.75 mm, respectively. Average PTV_Eval D90 was 97.11+/-2.93 %, V150 was 23.10+/-4.25 cc, V200 was 11.88+/-1.93 cc. All OAR constraints were met on all plans - Chest-Wall/Ribs (CW/Ribs) and Skin D0.03cc was 103.40+/-9.23 % and 93.60+/-6.14 %, respectively. Aggregate analysis across all plans shows a clinically nonsignificant spread around the mean for all parameters considered. The robustness of SAVI treatment plans to minor variation in catheter digitization was proved through our multiuser study. Our study showed that SAVI planning constraints are stable within reasonable variation of digitization differences. Such uncertainty analysis is useful in standardization of digitization practices in a department and in defining action levels on digitization fixing request during a 2nd check.

The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity.

The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.

Sexual and Urinary Health among Women following Bariatric Surgery.

PURPOSE: Women with obesity are more likely to experience bothersome urinary and sexual symptoms, but the long-term effect of metabolic and bariatric surgery (MBS) on these outcomes is poorly understood. We aimed to describe how MBS longitudinally impacted women's urinary and sexual health. METHODS: Patients who underwent MBS at the University of California, San Francisco Medical Center (UCSF) between 2009 and 2021 participated in a survey examining sexual health, pelvic organ prolapse (POP), and urinary health using three validated questionnaires: a modified version of the Female Sexual Function Index (FSFI), the Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6), and the Urinary Distress Inventory 6 (UDI-6). All questions asked referenced two time points: before surgery and at the time of survey. Logistic regression identified predictors of symptom improvement. RESULTS: Of 162 participants contacted, 118 (73%) had complete survey data. Mean body mass index (BMI) decreased from 52.4 ± 12.6 to 36.3 ± 9.7 kg/m2 (p < 0.01) with an average follow-up of 6 years. The mean UDI-6 score amongst women was 24 ± 24 prior to MBS and 24 ± 26 at the time of survey administration (p = 0.458). Mean modified FSFI scores amongst women were 15 ± 5 prior to surgery and 14 ± 7 at the time of survey administration (p = 0.005). The overall mean POPDI-6 score amongst women was 13 ± 15 prior to surgery and 9 ± 14 at the time of survey administration (p = 0.056). CONCLUSION: Women who underwent MBS reported a high rate of sexual and urological dysfunction that did not improve longitudinally, despite significant weight loss.

Decompressive Hemicraniectomy After Cerebral Fat Embolism.

Fat embolism syndrome is a common occurrence after orthopedic trauma and surgery. Cerebral fat embolism (CFE) may arise after fat globules enter the arterial circulation. The neurological manifestations of CFE vary and generally carries a favorable outcome. A small number of reports exist regarding patients with CFE who experienced severe neurological deficits and significant edema on radiographic studies, and subsequently underwent decompressive hemicraniectomy (DHC), some of which had full neurological recoveries. Here, we present the case of a 21-year-old male who presented after a motorcycle accident with multiple orthopedic injuries, who after fixation did not awake from anesthesia. The patient was ultimately found to have cerebral fat emboli, and developed significant edema and swelling. The patient underwent DHC with subsequent cranioplasty and returned to his neurological baseline seven months after his initial injury. DHC for CFE has been described in a few cases with some patients have had substantive recoveries, including the present case. This case emphasizes the importance of promptly recognizing and reversing elevated intracranial pressures and the possibility of promising recoveries.

Patterns of morphological evolution in the raptorial appendages of praying mantises.

Mantodea (praying mantises) is a group of exclusively predatory insects, which, together with nonraptorial blattodeans (cockroaches and termites) and groups exclusively found in the fossil record, form the group Dictyoptera. A central characteristic of Mantodea is the specialization of their first pair of legs as raptorial grasping appendages, but the evolution from walking to raptorial legs is not yet fully understood. Here, we trace the evolution of the raptorial appendages in Dictyoptera through time using a morphometric (morphospaces) approach. We also describe two new mantodean nymphs preserved in amber from the Cretaceous and Eocene, which expand the scarce mantodean fossil record. Blattodean and mantodean appendages appear distinct in morphospace, but several appendages of fossil non-mantodeans can be considered raptorial, providing a potential transitional link between walking and raptorial morphotypes. Therefore, we discuss potential mantodean affinities for other predatory fossil dictyopterans. We examine changes across extant mantodeans, characterized by a straightening of the tibia especially associated with the rise of the diversification of the Mantidea and discuss whether a thickening of the femur could reflect an early adaptation to cursorial hunting.

Reliability of near-infrared spectroscopy in measuring muscle oxygenation during squat exercise.

Monitoring of changes in skeletal muscle oxygenation during exercise has increased in recent years. Tissue oxygenation, which is related to fatigue and muscle hypertrophy, is often measured using near-infrared spectroscopy (NIRS). OBJECTIVES: This study aimed to determine the test-retest reliability of a non-portable NIRS (NIRO200Nx) during the full-squat exercise and recovery in young healthy men. DESIGN: Twenty-five male participants (21.8 ±â€¯2.6 years) were recruited for this original research. Each participant completed an 8-repetition test with a load that elicited a velocity of 1 m·s-1. The test was conducted twice, with a 48-hour washout period between sessions. METHODS: The NIRS measured the changes of oxygenated-Hemoglobin (O2Hb), deoxygenated-Hemoglobin (HHb) and Tissue Oxygenation Index (TOI) in both Vastus Lateralis and Vastus Medialis during rest, exercise, and recovery. Coefficient of Variation (CV), Standard Error Measurement (SEM) and Intraclass Correlation Coefficient (ICC) were used to evaluate the reliability of the data. Significance was set at p < 0.05. RESULTS: The results indicated that TOI had good to acceptable absolute reliability (CVTOI = 2.7-10.2 %). A good relative relativity for the overall test was found for Vastus Medialis O2Hb (ICC = 0.851), HHb (ICC = 0.852), and TOI (ICC = 0.864), and Vastus Lateralis O2Hb (ICC = 0.898), HHb (ICC = 0.899), and TOI (ICC = 0.897). CONCLUSIONS: We conclude that NIRO200Nx is a reliable instrument for measuring muscle oxygen saturation through the TOI parameter in not-to-failure dynamic resistance exercises (1 set of 8 reps against ∼40 % 1 repetition maximum). Tissue oxygenation assessment could be a new way of individualizing exercise through dynamic resistance exercises.

Sunflower Oil and Cholesterol Nanoemulsion: A Novel Carrier for Micafungin to Combat Multi-Resistant Candida auris.

Candida auris is an emerging, multidrug-resistant yeast that causes systemic infections, mainly in hospitalized or immunosuppressed patients. This pathogen has a high mortality and morbidity rate. This study aims to evaluate the antifungal potential of micafungin (MICA) encapsulated in a nanoemulsion (NEM) against four clades of C. auris and other non-C. auris species. The antifungal potential of MICA and NEM was evaluated by determining mature biofilm inhibition (0.78-50 µg/mL). The antifungal activities of MICA and NEM (5.92 mg/Kg) were evaluated using an in vivo model of Galleria mellonella. The results showed that NEM intensified the antibiofilm action of MICA, especially in 48 h mature biofilms. In vivo results displayed a higher effectiveness of NEM against all clades of C. auris tested, inhibiting the fungal load in the hemolymph and tissues of G. mellonella with a difference of 3 log10. In addition, C. auris infection caused granulomas surrounded by hemocytes, mainly at the lower and upper ends. Conversely, C. albicans developed pseudohyphae, biofilms, filaments, and chlamydospores. In conclusion, encapsulation of MICA in a nanoemulsion enhances its antifungal activity against mature biofilms of C. auris. This strategy may be considered a therapeutic approach for the control of infections and the dissemination of this new global health threat.

A voice and speech corpus of patients who underwent upper airway surgery in pre- and post-operative states.

Many research articles have explored the impact of surgical interventions on voice and speech evaluations, but advances are limited by the lack of publicly accessible datasets. To address this, a comprehensive corpus of 107 Spanish Castilian speakers was recorded, including control speakers and patients who underwent upper airway surgeries such as Tonsillectomy, Functional Endoscopic Sinus Surgery, and Septoplasty. The dataset contains 3,800 audio files, averaging 35.51 ± 5.91 recordings per patient. This resource enables systematic investigation of the effects of upper respiratory tract surgery on voice and speech. Previous studies using this corpus have shown no relevant changes in key acoustic parameters for sustained vowel phonation, consistent with initial hypotheses. However, the analysis of speech recordings, particularly nasalised segments, remains open for further research. Additionally, this dataset facilitates the study of the impact of upper airway surgery on speaker recognition and identification methods, and testing of anti-spoofing methodologies for improved robustness.

The Cambrian Odaraia alata and the colonization of nektonic suspension-feeding niches by early mandibulates.

The diversity of cephalic morphologies in mandibulates (myriapods and pancrustaceans) was key to their evolutionary success. A group of Cambrian bivalved arthropods called hymenocarines exhibit diagnostic mandibulate traits that illustrate this diversity, but many forms are still poorly known. These include the odaraiids, typified by Odaraia alata from the Burgess Shale (Wuliuan), characterized by its unique tubular carapace and rudder-like tail fan, and one of the largest Cambrian euarthropods at nearly 20 cm in length. Unfortunately, odaraiid cephalic anatomy has been largely unknown, limiting evolutionary scenarios and putting their mandibulate affinities into question. Here, we reinvestigate Odaraia based on new specimens from the Burgess Shale and describe exquisitely preserved mandibles with teeth and adjacent structures: a hypostome, maxillae and potential paragnaths. These structures can be homologized with those of Cambrian fuxianhuiids and extant mandibulates, and suggest that the ancestral mandibulate head could have had a limbless segment but retained its plasticity, allowing for limb re-expression within Pancrustacea. Furthermore, we show the presence of limbs with spinose endites which created a suspension-feeding structure. This discovery provides morphological evidence for suspension feeding among large Cambrian euarthropods and evinces the increasing exploitation of planktonic resources in Cambrian pelagic food webs.

Nutritional Strategies for Optimizing Health, Sports Performance, and Recovery for Female Athletes and Other Physically Active Women: A Systematic Review.

CONTEXT: Despite the progress toward gender equality in events like the Olympic Games and other institutionalized competitions, and the rising number of women engaging in physical exercise programs, scientific studies focused on establishing specific nutritional recommendations for female athletes and other physically active women are scarce. OBJECTIVE: This systematic review aimed to compile the scientific evidence available for addressing the question "What dietary strategies, including dietary and supplementation approaches, can improve sports performance, recovery, and health status in female athletes and other physically active women?" DATA SOURCES: The Pubmed, Web of Science, and Scopus databases were searched. DATA EXTRACTION: The review process involved a comprehensive search strategy using keywords connected by Boolean connectors. Data extracted from the selected studies included information on the number of participants and their characteristics related to sport practice, age, and menstrual function. DATA ANALYSIS: A total of 71 studies were included in this review: 17 focused on the analysis of dietary manipulation, and 54 focused on the effects of dietary supplementation. The total sample size was 1654 participants (32.5% categorized as competitive athletes, 30.7% as highly/moderately trained, and 37.2% as physically active/recreational athletes). The risk of bias was considered moderate, mainly for reasons such as a lack of access to the study protocol, insufficient description of how the hormonal phase during the menstrual cycle was controlled for, inadequate dietary control during the intervention, or a lack of blinding of the researchers. CONCLUSION: Diets with high carbohydrate (CHO) content enhance performance in activities that induce muscle glycogen depletion. In addition, pre-exercise meals with a high glycemic index or rich in CHOs increase CHO metabolism. Ingestion of 5-6 protein meals interspersed throughout the day, with each intake exceeding 25 g of protein favors anabolism of muscle proteins. Dietary supplements taken to enhance performance, such as caffeine, nitric oxide precursors, ß-alanine, and certain sport foods supplements (such as CHOs, proteins, or their combination, and micronutrients in cases of nutritional deficiencies), may positively influence sports performance and/or the health status of female athletes and other physically active women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD480674.

Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut.

The Aedes aegypti midgut is crucial for blood digestion, nutrition, reproduction, and pathogen interaction. Using single-cell RNA sequencing, we explored virus infection and transcriptomic changes at the cellular level. We identified 12 distinct cell clusters in the Ae. aegypti midgut post-Zika virus infection, including intestinal stem cells, enteroblasts, enteroendocrine cells (EE), and enterocytes (ECs). The virus was found mainly in specific subsets of ECs and EE. Infection altered transcriptional profiles related to metabolism, signaling, and immune responses. Functional studies highlighted three significantly differentially expressed genes in infected cells. Notably, silencing apolipophorin III reduced virus RNA copy number in the midgut, emphasizing the role of specific genes in viral infection. These findings enhance our understanding of mosquito midgut cell processes during Zika virus infection and suggest potential targets for vector control.

Co-expression of VP2, NS1 and NS2-Nt proteins by an MVA viral vector induces complete protection against bluetongue virus.

Introduction: Bluetongue (BT), caused by bluetongue virus (BTV), is an important arthropod-borne livestock disease listed by the World Organization for Animal Health. Live-attenuated and inactivated vaccines have permitted to control BT but they do not simultaneously protect against the myriad of BTV serotypes. Recently, we identified the highly conserved BTV nonstructural protein NS1 and the N-terminal region of NS2 as antigens capable of conferring multiserotype protection against BTV. Methods: Here, we designed Modified Vaccinia Ankara (MVA) viral vectors that expressed BTV-4 proteins VP2 or VP7 along with NS1 and NS2-Nt as well as MVAs that expressed proteins VP2, VP7 or NS1 and NS2-Nt. Results: Immunization of IFNAR(-/-) mice with two doses of MVA-NS1-2A-NS2-Nt protected mice from BTV-4M infection by the induction of an antigen-specific T cell immune response. Despite rMVA expressing VP7 alone were not protective in the IFNAR(-/-) mouse model, inclusion of VP7 in the vaccine formulation amplified the cell-mediated response induced by NS1 and NS2-Nt. Expression of VP2 elicited protective non-cross-reactive neutralizing antibodies (nAbs) in immunized animals and improved the protection observed in the MVA-NS1-2A-NS2-Nt immunized mice when these three BTV antigens were co-expressed. Moreover, vaccines candidates co-expressing VP2 or VP7 along with NS1 and NS2-Nt provided multiserotype protection. We assessed protective efficacy of both vaccine candidates in sheep against virulent challenge with BTV-4M. Discussion: Immunization with MVA-VP7-NS1-2A-NS2-Nt partially dumped viral replication and clinical disease whereas administration of MVA-VP2-NS1-2A-NS2-Nt promoted a complete protection, preventing viraemia and the pathology produced by BTV infection.

Infection by Crithidia bombi increases relative abundance of Lactobacillus spp. in the gut of Bombus terrestris.

Gut microbial communities confer protection against natural pathogens in important pollinators from the genera Bombus and Apis. In commercial species B. terrestris and B. impatiens, the microbiota increases their resistance to the common and virulent trypanosomatid parasite Crithidia bombi. However, the mechanisms by which gut microorganisms protect the host are still unknown. Here, we test two hypotheses: microbiota protect the host (1) through stimulation of its immune response or protection of the gut epithelium and (2) by competing for resources with the parasite inside the gut. To test them, we reduced the microbiota of workers and then rescued the microbial community by feeding them with microbiota supplements. We then exposed them to an infectious dose of C. bombi and characterised gene expression and gut microbiota composition. We examined the expression of three antimicrobial peptide genes and Mucin-5AC, a gene with a putative role in gut epithelium protection, using qPCR. Although a protective effect against C. bombi was observed in bumblebees with supplemented microbiota, we did not observe an effect of the microbiota on gene expression that could explain alone the protective effect observed. On the other hand, we found an increased relative abundance of Lactobacillus bacteria within the gut of infected workers and a negative correlation of this genus with Gilliamella and Snodgrassella genera. Therefore, our results point to a displacement of bumblebee endosymbionts by C. bombi that might be caused by competition for space and nutrients between the parasite and the microbiota within the gut.

La microbiota intestinal confiere protección frente a los patógenos naturales en polinizadores importantes de los géneros Bombus y Apis. En concreto, la microbiota de las especies comerciales B. terrestris y B. impatients, incrementa su resistencia frente al parásito tripanosomátido común y virulento Crithidia bombi. Sin embargo, los mecanismos por los cuales los microorganismos protegen al hospedador todavía se desconocen. Aquí probamos dos hipótesis: la microbiota protege al hospedador (1) a través de la estimulación de la respuesta inmunitaria o la protección del epitelio y (2) por competición por los recursos con el parásito dentro del intestino. Para probar estas hipótesis, redujimos la microbiota de obreras y dimos suplementos de microbiota a una parte de ellas. Las expusimos a una dosis infecciosa de C. bombi y caracterizamos la expresión génica y la composición de la microbiota intestinal. Examinamos la expresión de los genes de tres péptidos antimicrobianos (AMPs) y de Mucin­5AC, un gen con un rol putativo en la protección del epitelio intestinal, usando la qPCR. Aunque observamos un efecto protector contra C. bombi en los abejorros suplementados con microbiota, no vimos un efecto en la expresión génica que pudiese explicar por sí solo la protección observada. Por otro lado, encontramos un incremento en la abundancia relativa de bacterias del género Lactobacillus en el intestino de obreras infectadas y una correlación negativa de este género con los géneros Gilliamella y Snodgrassella. Por tanto, nuestros resultados apuntan a un desplazamiento de los endosimbiontes por parte de C. bombi, que podría estar causado por la competición por espacio y nutrientes entre el parásito y la microbiota dentro del intestino.

Optimizing Antimony Speciation Analysis via Frontal Chromatography-ICP-MS to Explore the Release of PET Additives.

Antimony (Sb) contamination poses significant environmental and health concerns due to its toxic nature and widespread presence, largely from anthropogenic activities. This study addresses the urgent need for an accurate speciation analysis of Sb, particularly in water sources, emphasizing its migration from polyethylene terephthalate (PET) plastic materials. Current methodologies primarily focus on total Sb content, leaving a critical knowledge gap for its speciation. Here, we present a novel analytical approach utilizing frontal chromatography coupled with inductively coupled plasma mass spectrometry (FC-ICP-MS) for the rapid speciation analysis of Sb(III) and Sb(V) in water. Systematic optimization of the FC-ICP-MS method was achieved through multivariate data analysis, resulting in a remarkably short analysis time of 150 s with a limit of detection below 1 ng kg-1. The optimized method was then applied to characterize PET leaching, revealing a marked effect of the plastic aging and manufacturing process not only on the total amount of Sb released but also on the nature of leached Sb species. This evidence demonstrates the effectiveness of the FC-ICP-MS approach in addressing such an environmental concern, benchmarking a new standard for Sb speciation analysis in consideration of its simplicity, cost effectiveness, greenness, and broad applicability in environmental and health monitoring.

Generating universal anti-CD19 CAR T cells with a defined memory phenotype by CRISPR/Cas9 editing and safety evaluation of the transcriptome.

Introduction: Chimeric antigen receptor-expressing T cells (CAR T cells) have revolutionized cancer treatment, particularly in B cell malignancies. However, the use of autologous T cells for CAR T therapy presents several limitations, including high costs, variable efficacy, and adverse effects linked to cell phenotype. Methods: To overcome these challenges, we developed a strategy to generate universal and safe anti-CD19 CAR T cells with a defined memory phenotype. Our approach utilizes CRISPR/Cas9 technology to target and eliminate the B2M and TRAC genes, reducing graft-versus-host and host-versus-graft responses. Additionally, we selected less differentiated T cells to improve the stability and persistence of the universal CAR T cells. The safety of this method was assessed using our CRISPRroots transcriptome analysis pipeline, which ensures successful gene knockout and the absence of unintended off-target effects on gene expression or transcriptome sequence. Results: In vitro experiments demonstrated the successful generation of functional universal CAR T cells. These cells exhibited potent lytic activity against tumor cells and a reduced cytokine secretion profile. The CRISPRroots analysis confirmed effective gene knockout and no unintended off-target effects, validating it as a pioneering tool for on/off-target and transcriptome analysis in genome editing experiments. Discussion: Our findings establish a robust pipeline for manufacturing safe, universal CAR T cells with a favorable memory phenotype. This approach has the potential to address the current limitations of autologous CAR T cell therapy, offering a more stable and persistent treatment option with reduced adverse effects. The use of CRISPRroots enhances the reliability and safety of gene editing in the development of CAR T cell therapies. Conclusion: We have developed a potent and reliable method for producing universal CAR T cells with a defined memory phenotype, demonstrating both efficacy and safety in vitro. This innovative approach could significantly improve the therapeutic landscape for patients with B cell malignancies.

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.

Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works that experimentally verify the role and functionality of T and NK lymphocytes and the generation of CAR-T from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant, and the different sub-populations remain stable. In addition, the expansion and proliferation rates are invariant regardless of mobilization with G-CSF as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Overweight, Obesity, Hypertriglyceridemia, and Insulin Resistance Are Positively Associated with High Serum Copper Levels in Mexican Adults.

Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346 Mexican adults. Serum Cu level was measured by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometrical data were collected, and biochemical parameters were measured. The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Overweight and obesity status was positively associated with the serum Cu level (ß = 19.434 ± 7.309, p = 0.008). Serum Cu level was observed to have a positive association with serum triglycerides level (ß = 0.160 ± 0.045, p < 0.001) and TyG (ß = 0.001 ± 0.001, p < 0.001). Additionally, high serum Cu level was positively associated with overweight and obesity status (odds ratio [OR] = 1.9, 95% confidence interval [95% CI] 1.1-3.4, p = 0.014), hypertriglyceridemia (OR = 3.0, 95% CI 1.7-5.3, p < 0.001), and IR (OR = 2.6, 95% CI 1.4-4.6, p = 0.001). In conclusion, our results suggest that overweight, obesity, hypertriglyceridemia, and IR are positively associated with serum Cu levels in Mexican adults.

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.