Tissue chips as headway model and incitement technology.

Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in-vitro cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals. This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology.

Development and characterization of sodium alginate and ß-cyclodextrin nanoemulsions encapsulating betel leaf (Piper betle L.) extract for enhanced antimicrobial efficacy against foodborne pathogen.

This study aims to investigate the physical stability, droplet size, zeta potential, and antimicrobial properties of nanoemulsions formulated with betel leaf extract using ß-cyclodextrin (CD) and sodium alginate (SA) biopolymers. Nanoemulsions with ß-cyclodextrin exhibit superior stability at lower temperatures, with limited droplet size, and strong electrostatic repulsion. Morphological images demonstrate the successful encapsulation of betel leaf extract within both biopolymers, highlighting their potential for antimicrobial applications. Both CD and SA nanoemulsions display inhibitory effects on bacterial strains (E. coli, P. aeruginosa, L. monocytogenes, S. aureus, and B. cereus) and fungal growth (A. brasiliensis, R. stolonifer, F. oxysporum, and C. albicans). SA nanoemulsions show higher antimicrobial activity due to H+ ion release, particularly against A. brasiliensis and C. albicans. These findings underscore the potential of betel leaf extract nanoemulsions, especially those with SA, for various antimicrobial applications for sustainable food packaging, highlighting their significance in addressing microbial challenges.

Therapeutic Applications of Engineered Mesenchymal Stromal Cells for Enhanced Angiogenesis in Cardiac and Cerebral Ischemia.

Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed.

Comparison of reactivation between ranibizumab and bevacizumab in aggressive retinopathy of prematurity: A retrospective case series.

PURPOSE: To compare the incidence, type, interval for reactivation, and structural outcomes in infants with aggressive retinopathy of prematurity (A-ROP) treated with ranibizumab or bevacizumab. METHOD: It is a single-center, retrospective, consecutive, case series. We included infants with A-ROP which were initially treated with either intravitreal ranibizumab (IVR, 0.25 mg) or intravitreal bevacizumab (IVB, 0.625 mg) between January 2017 and December 2023. The infants were followed up for reactivation. The demographic and clinical data were collected. The time, zone, type of reactivation, its treatment, type of final structural outcome, and factors associated with reactivation were analyzed. RESULTS: One hundred eight among the 322 infants with A-ROP were included in the study. Fifty-five received IVR, while 53 received IVB. Infants treated with IVR had higher incidence of reactivation (92.7% vs 52.8%, P < 0.001) at an earlier interval than IVB (7.7 weeks vs 12.8 weeks, P < 0.001). Infants treated with IVR had approximately 3.3 times higher possibility of reactivation than those treated with IVB. Three infants (5.9%) in the IVR group and five (9.4%) in the IVB group attained complete vascularization of the retina (P = 0.72). More infants treated with IVB had regression with a persistent avascular retina (PAR) than IVR (52.8% vs 15.7%, P < 0.001). Infants in the IVB group had 10 times higher possibility of regression with PAR. CONCLUSION: Infants of A-ROP treated with IVR have a higher incidence and earlier reactivation, while those treated with IVB have less incidence and delayed reactivation, albeit with a higher possibility of regression with a PAR.

A squalene oil emulsified MPL-A and anti-CD200/CD300a antibodies adjuvanted whole-killed Leishmania vaccine provides durable immunity against L. donovani parasites.

Antigenic inefficacy to induce robust immune responses and durable memory are major causes of constantly failing prophylactic approaches in leishmaniasis. Here, we determine the potential of a standardized whole-killed Leishmania vaccine (Leishvacc) adjuvanted with anti-CD200 and anti-CD300a antibodies, either alone or with monophosphoryl lipid A (MPL-SE) emulsified in squalene oil, in restoring the compromised antigen presenting abilities of dendritic cells (DCs), effector properties of CD4+T cells and providing protection against Leishmania donovani parasites. In animals vaccinated with antibodies adjuvanted vaccines, either alone or with MPL-SE, the antigen presenting abilities of CD11c+ DCs against Leishmania antigens, measured in terms of CD80, CD86, MHC-I, and MHC-II surface receptors and intracellular IL-12 were found enhanced than non-adjuvanted vaccine. We observed more proliferative and pro-inflammatory cytokines i.e. IL-2, IFN-γ, IL-23, and IL-12 producing CD4+T cells in antibodies/MPL-SE adjuvanted vaccinated animals further suggesting that this approach helps antigen activated CD4+T cells to acquire pro-inflammatory cytokines producing abilities. In antibodies, either alone or with MPL-SE, vaccinated animals, the number of CD4+ central memory T cells and their longevity were found significantly enhanced that further evidenced the impact of this vaccination approach in inducing long term protective immunity. The animals, receiving antibodies adjuvanted vaccines, either alone or with MPL-SE, exhibited excellent protection against virulent parasites by restricting their growth, which correlated with the significantly reduced parasitemia, splenomegaly, and hepatomegaly, along with fewer numbers of liver granulomas. Our findings provide an insight to a new immunoprophylactic approach against visceral leishmaniasis, which not only satisfies the safety criteria, but also provides a robust immunogenic response with remarkable potential for parasites control. However, further in-depth investigations are needed to ascertain its ability in inducing long-lasting immunity.

Role of phonon scattering and bonding in resolving lattice thermal conductivity ambiguities of ß-Ga2O3.

Understanding the lattice thermal conductivity (κl) of ß-Ga2O3 is very intriguing owing to its advantages in high-voltage and high-temperature applications. Despite several attempts, the underlying mechanism and causes of the notable discrepancies found in the κl values of ß-Ga2O3 along [100] and [001] directions calculated using first principles remained unresolved. We demonstrate that the understanding of the nature of chemical bonding is crucial to overcome the inconsistency in theoretically reported κl values. In low-symmetry structures such as ß-Ga2O3, the nature of the interactions is primarily long-range; therefore, a sufficiently large supercell inclusive of various bonding characteristics is required to capture relevant phonon wavelengths. Bonding nature-aware structure modeling allows precise estimation of acoustic and optical mode contributions towards κl. Additionally, phonon mean free path analysis confirms that considering only third-order interaction terms is adequate to determine the κl of ß-Ga2O3. The calculated κl values are in excellent agreement with experimentally reported values in all three directions. Our results establish that the bonding nature and its influence on phonon scattering are essential to consider in calculating κl accurately.

Correlation of Pseudocholinesterase Level with Clinical, Biochemical Parameters Including Cardiac Profile and the Outcome in Organophosphorus Poisoning.

BACKGROUND: Poisoning is a significant health hazard and a leading cause of morbidity and mortality worldwide. India, being a predominantly agrarian country, routinely employs organophosphate (OP) pesticides in farming, and they are readily available "over the counter." OPs exert their toxicity by interfering with the normal function of acetylcholine, an essential neurotransmitter throughout the autonomic and central nervous systems. Due to the limited availability of facilities and resources in health-care systems, and economically restraining patients, it is necessary to rely more on clinical features to assess the severity of poisoning and manage the condition properly. METHODOLOGY: It was a hospital-based prospective observational study that included patients aged >13 years in a tertiary care hospital. All patients were clinically evaluated based on their history and examination. The diagnosis was made based on characteristic clinical manifestations or evidence of exposure to organophosphorus compounds (corroborative evidence such as empty containers and the odor of gastric aspirates). Clinical severity was assessed and categorized according to the Peradeniya Organophosphorus Poisoning Scale (POP scale). A score of 0-3 is considered mild poisoning, 4-7 as moderate poisoning, and 8-11 as severe poisoning. RESULTS: Out of the 50 patients enrolled in the study, 17 (34.00%) were aged <20 years, 19 (38%) were in the 20-30 years age group, and 14 (28%) were aged >30 years. Ingestion is the only mode of exposure to poisoning. None of the patients had history of contact or inhalational exposure. Of the 50 cases, 12 (24.0%) were in the mild category, 26 (52.0%) in the moderate category, and 12 (24%) in the severe category on the POP grading. A comparison of the mean serum pseudocholinesterase, troponin-T, and pro-BNP levels with severity was performed. In mild OP poisoning, the mean serum PChE level was 2766.58 ± 1120.44; in moderate, it was 1969.35 ± 1330.07, and in severe, it was 701.83 ± 961.17. Pseudocholinesterase levels decreased progressively with increasing clinical severity from mild-to-severe cases, and this association was statistically significant (P < 0.001). Two-dimensional echocardiography screening done in all patients did not show any significant abnormalities. CONCLUSION: This study shows that serum PCE is reduced in OP poisoning and correlates with the clinical severity grading done by the POP scale and is also associated with an increase in the duration of intensive care unit stay. No significant evidence of direct cardiac injury was observed in this study. A low Glasgow Coma Scale score and an increased respiratory rate at presentation are associated with poor outcomes.

Résumé Contexte:L'empoisonnement est un risque important pour la santé et une cause principale de morbidité et de mortalité dans le monde. L'Inde, étant principalement pays agraire, utilise régulièrement des pesticides organophosphotés (OP) dans l'agriculture, et ils sont facilement disponibles «en vente libre¼. OPS exerce leur toxicité en interférant avec la fonction normale de l'acétylcholine, un neurotransmetteur essentiel à travers l'autonomie et le centre systèmes nerveux. En raison de la disponibilité limitée des installations et des ressources dans les systèmes de soins de santé, et de la contention économique des patients, il est nécessaire pour s'appuyer davantage sur les caractéristiques cliniques pour évaluer la gravité de l'empoisonnement et gérer correctement la condition.Méthodologie:c'était un Étude d'observation prospective basée à l'hôpital qui comprenait des patients âgés de> 13 ans dans un hôpital de soins tertiaires. Tous les patients étaient cliniquement évalué en fonction de leur histoire et de leur examen. Le diagnostic a été posé sur la base de manifestations cliniques caractéristiques ou de preuves de Exposition aux composés organophosphores (preuves corroborantes telles que les conteneurs vides et l'odeur des aspirations gastriques). Gravité clinique a été évalué et classé selon l'échelle d'empoisonnement de Peradeniya organophosphorus (échelle pop). Un score de 0 à 3 est considéré comme doux Empoisonnement, 4­7 comme empoisonnement modéré et 8-11 comme empoisonnement sévère.Résultats:Sur les 50 patients inscrits à l'étude, 17 (34,00%) étaient âgés de <20 ans, 19 ans (38%) dans le groupe d'âge de 20 à 30 ans et 14 (28%) étaient âgés de> 30 ans. L'ingestion est le seul mode d'exposition à empoisonnement. Aucun des patients n'avait des antécédents de contact ou d'inhalation. Sur les 50 cas, 12 (24,0%) étaient dans la catégorie légère, 26 (52,0%) Dans la catégorie modérée, et 12 (24%) dans la catégorie sévère sur le classement POP. Une comparaison de la pseudocholinestérase sérique moyenne, Les niveaux de troponine - T et pro-BNP avec gravité ont été réalisés. Dans l'empoisonnement à l'op léger, le taux de PCHE sérique moyen était de 2766,58 ± 1120,44; dans Modéré, c'était 1969.35 ± 1330,07, et en sévère, il était de 701,83 ± 961,17. Les niveaux de pseudocholinestérase ont diminué progressivement avec l'augmentation Gravité clinique des cas légers à sévère, et cette association était statistiquement significative ( P <0,001). Échocardiographie bidimensionnelle Le dépistage effectué chez tous les patients n'a montré aucune anomalie significative.Conclusion:cette étude montre que le PCE sérique est réduit en op empoisonnement et corréler avec le classement de gravité clinique effectué par l'échelle POP et est également associé à une augmentation de la durée de séjour de l'unité de soins intensifs. Aucune preuve significative de lésion cardiaque directe n'a été observée dans cette étude. Un score d'échelle de coma à faible Glasgow et un Une fréquence respiratoire accrue à la présentation est associée à de mauvais résultats.

Hypothyroidism in Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MetS) and hypothyroidism are well-established forerunners of atherogenic cardiovascular disease (CVD). It is possible that patients suffering from both these disease entities may have a compounded risk. This study aimed at determining the prevalence of hypothyroidism in MetS. MATERIALS AND METHODS: This cross-sectional study was conducted from September 2017 to August 2018 in the department of medicine at a tertiary care hospital in Northern India. Ethical approval was obtained from the institutional ethical committee. The study subjects consisted of 157 patients with MetS, the diagnosis of which was based on the International Diabetes Federation criteria. After a detailed history and physical examination, relevant investigations including complete thyroid profile were done. The data were analyzed using appropriate statistical tests (P < 0.05). RESULTS: In our study, the age of subjects ranged between 14 and 92 years, with a mean ± standard deviation of 48.1 ± 17.01 years. There were more females than males with a male-to-female ratio of 1:1.3. The prevalence of hypothyroidism was 46.5%. Hypothyroidism was more common in females (58.9%) as compared to males (41.1%). Patients with hypothyroidism had significantly higher body weight and body mass index (BMI) in comparison to euthyroid patients. The rest of the anthropometric parameters were comparable. Waist circumference and BMI of overt hypothyroid patients were found to be higher as compared to subclinical hypothyroid patients. Total cholesterol and triglyceride were significantly higher (P = 0.001 and P < 0.001, respectively), while high-density lipoprotein levels were significantly lower in patients with hypothyroidism than the euthyroid group (P < 0.001). CONCLUSION: Hypothyroidism, especially subclinical hypothyroidism, is a common endocrine disorder in patients with MetS. As MetS and hypothyroidism are independent risk factors for CVD, hence there is a need for screening for hypothyroidism and the treatment of the same can be beneficial in reducing the cardiovascular morbidity and mortality in patients with MetS.

Résumé Introduction:Le syndrome métabolique (METS) et l'hypothyroïdie sont des précurseurs bien établis d'une maladie cardiovasculaire athérogène (MCV). Il est possible que les patients souffrant de ces deux entités maladie puissent avoir un risque composé. Cette étude visait à déterminer la prévalence de l'hypothyroïdie dans les Mets.Matériaux et méthodes:Cette étude transversale a été menée de septembre 2017 à août 2018 dans le Département de médecine dans un hôpital de soins tertiaires du nord de l'Inde. L'approbation éthique a été obtenue auprès du Comité éthique institutionnel. Les sujets de l'étude étaient composés de 157 patients atteints de MetS, dont le diagnostic était basé sur les critères internationaux de la Fédération du diabète. Après un historique détaillé et un examen physique, des enquêtes pertinentes, y compris un profil thyroïdien complet, ont été effectuées. Les données ont été analysées en utilisant des tests statistiques appropriés ( P <0,05).Résultats:Dans notre étude, l'âge des sujets variait entre 14 et 92 ans, avec une moyenne ± standard déviation de 48,1 ± 17,01 ans. Il y avait plus de femelles que les hommes avec un rapport masculin à féminin de 1: 1,3. La prévalence de l'hypothyroïdie était de 46,5%. L'hypothyroïdie était plus fréquente chez les femmes (58,9%) par rapport aux hommes (41,1%). Les patients atteints d'hypothyroïdie avaient Indice de poids corporel et de masse corporelle significativement plus élevé (IMC) par rapport aux patients euthyroïdiens. Le reste des paramètres anthropométriques étaient comparables. Le tour de taille et l'IMC des patients hypothyroïdiens manifestes se sont révélés plus élevés par rapport à l'hypothyroïde subclinique patients. Le cholestérol total et les triglycérides étaient significativement plus élevés ( P = 0,001 et P <0,001, respectivement), tandis que les lipoprotéines à haute densité Les niveaux étaient significativement plus faibles chez les patients atteints d'hypothyroïdie que le groupe euthyroïdien ( P <0,001).Conclusion:hypothyroïdie, en particulier L'hypothyroïdie subclinique est un trouble endocrinien commun chez les patients atteints de Metts. Comme les Mets et l'hypothyroïdie sont des facteurs de risque indépendants Pour les MCV, il y a donc un besoin de dépistage pour l'hypothyroïdie et le traitement de la même chose peut être bénéfique pour réduire le cardiovasculaire morbidité et mortalité chez les patients atteints de MetS.

Interlocking G-Quadruplexes Using a G-Triad•G Connection: Implications for G-Wire Assembly.

G-quadruplexes are noncanonical structures of nucleic acids formed mainly by G-rich sequences and play crucial roles in important cellular processes. They are also increasingly used in nanotechnology for their valuable properties. Various unexpected structures of G-quadruplexes have been solved recently, including a stable G-quadruplex lacking one guanine in the G-tetrad core, harboring a vacant site. In this study, we demonstrate the interlocking of two intramolecular G-quadruplexes: one containing a vacant site (4n - 1) and the other with an unbound guanine (4n + 1). These G-quadruplexes interact through a G-triad-G connection with unprecedented 5'-3' stacking. Using these interconnection properties, we have identified a sequence capable of self-assembling into G-wires in K+ solutions with potential nanotechnological applications.

Differential culprit plaque morphology in acute coronary syndrome: a comparison between very young patients (≤35 years) and older counterparts using optical coherence tomography.

Aims: Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT. Methods and results: This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P < 0.001) groups. Conclusion: Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.

Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders.

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.

Comparative study of thulium fiber laser versus holmium:yttrium-aluminum-garnet laser for ureteric stone management with semi-rigid ureteroscopy: A prospective, single-center study.

Objective: To compare the efficacy and safety of thulium fiber laser (TFL) and holmium:yttrium-aluminum-garnet (Ho:YAG) laser for ureteric stone management with semi-rigid ureteroscopy. Methods: In a prospective study from January 2020 to December 2021, we compared 40 patients in each group who underwent semi-rigid ureteroscopic lithotripsy with TFL and that with Ho:YAG laser. Stone volume, stone density, stone fragmentation rates, total lasing time, total operative time, endoscopic vision, retropulsion and stone free rates were analyzed in both groups and compared. Results: Mean stone volume was comparable in the TFL group and the Ho:YAG laser group (282.45 [standard deviation, SD 139.79] mm3 vs. 279.49 [SD 312.52] mm3; p=0.964). Mean stone density was also comparable in the TFL group and the Ho:YAG laser group (1135.30 [SD 317.04] Hounsfield unit vs. 1131.75 [SD 283.03] Hounsfield unit; p=0.959). The mean stone fragmentation rates calculated as stone volume divided by lasing time were 25.85 (SD 10.61) mm3/min and 21.37 (SD 14.13) mm3/min in the TFL group and the Ho:YAG laser group, respectively (p=0.113). The mean total lasing time (10.15 [SD] 4.69 min vs. 11.43 [SD 4.56] min; p=0.222), mean operative time (25.13 [SD 9.51] min vs. 25.54 [SD 10.32] min; p=0.866), and mean total hospital stay (2.62 [SD 0.77] days vs. 2.61 [SD 0.84] days; p=0.893) were comparable in the TFL group and in the Ho:YAG group. The vision was better and retropulsion was less in the TFL group. The stone-free rate at 1 month postoperatively was slightly better in the TFL group (100% vs. 90%; p=0.095). Conclusion: TFL technology was associated with the comparable total surgical time, total lasing time, and stone fragmentation rate with Ho:YAG laser. However, TFL had better endoscopic vision, lesser stone retropulsion, and slightly better stone-free rates.

Long-term outcomes of urethral balloon dilation for anterior urethral stricture: A prospective cohort study.

Objective: To prospectively follow up a cohort of anterior urethral stricture disease patients managed with balloon dilation (BD) for 3 years to evaluate the long-term outcomes and to study factors that contribute to recurrence. Methods: This study included men who had urethral BD for significant anterior urethral stricture disease between January 2017 and March 2019. Data about the patient age, stricture characteristics, and recurrence date were recorded, along with information on postoperative indwelling catheter use and operative complications. Furthermore, information about the self-calibration procedure was collected and where available, free flow (FF) measurements during the follow-up period were recorded and analyzed. Success was defined as a lack of symptoms and acceptable FF rates (maximum flow rate>12 mL/s). Results: The final analysis was conducted on 187 patients. The mean follow-up period was 37 months. The long-term overall success rate at the end of our study was 66.8%. Our recurrence rate was 7.4% at 12 months, 24.7% at 24 months, and reached 33.2% at the end of our study. The time to recurrence ranged from 91 days to 1635 days, with a mean of 670 days. The stricture-free survival was significantly shorter with lengthy peno-bulbar (p=0.031) and multiple strictures (p=0.015), and in the group of patients who were not committed to self-calibration protocol (p<0.011). However, post-procedural self-calibration was the most important factor that may have decreased the incidence of recurrence (odds ratio=5.85). Adjuvant self-calibration after BD not only reduced the recurrence rate from 85.4% in the non-self-calibration group to 15.1% in the self-calibration one (p<0.001), but also improved the overall stricture-free survival and FF parameters. Conclusion: Urethral BD has a high recurrence rate in the long-term, especially with long and multiple strictures. Adjuvant self-calibration has proven to reduce the recurrence risk and the need for re-intervention.

Primary Ewing sarcoma/primitive neuroectodermal tumors of the kidney: Case series of eight cases from a single center with follow-up details.

Introduction: We aim to share the experience of a single center in the management of eight cases of renal primitive neuroectodermal tumor (PNET) which are uncommon, aggressive tumors. The objectives were to study the presentation of the disease, the treatment offered and its outcomes, and the comparison of the treatment with published literature. Methods: The single-center renal PNET data of all patients were retrospectively reviewed from 2011 to 2022. Renal PNET was seen in eight patients. Minimum follow-up period of 1 year was required. Results: Male-to-female ratio was 7:1. The mean age was 26.5 years. All were locally advanced tumors on presentation. One patient had an inferior vena cava thrombus, one patient had metastases on presentation, and two patients had tumor extending to paranephric space. The diagnosis was made by histopathology supported by immunohistochemistry showing CD99 positivity. All patients were treated with radical nephrectomy, followed by chemotherapy in all and radiotherapy in three patients. Two patients expired at 3½ and 6 years after surgery, the remaining six are alive at a median follow-up period of 34.5 months. Conclusion: Renal PNET is an uncommon renal tumor which is aggressive and requires multimodal therapy for prolonged survival.

Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer's disease-related amyloid pathology.

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-ß (Aß) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes. Yet, sustained manipulation of dLVs did not significantly alter the overall brain Aß plaque load. Moreover, dLV atrophy did not alter the behavioral phenotypes of the AD mice, but it improved CSF-to-blood drainage. Our results indicate that sustained dLV manipulation does not affect Aß deposition in the brain and that compensatory mechanisms promote CSF clearance.

Carbon Nanodot-Microbe-Plant Nexus in Agroecosystem and Antimicrobial Applications.

The intensive applications of nanomaterials in the agroecosystem led to the creation of several environmental problems. More efforts are needed to discover new insights in the nanomaterial-microbe-plant nexus. This relationship has several dimensions, which may include the transport of nanomaterials to different plant organs, the nanotoxicity to soil microbes and plants, and different possible regulations. This review focuses on the challenges and prospects of the nanomaterial-microbe-plant nexus under agroecosystem conditions. The previous nano-forms were selected in this study because of the rare, published articles on such nanomaterials. Under the study's nexus, more insights on the carbon nanodot-microbe-plant nexus were discussed along with the role of the new frontier in nano-tellurium-microbe nexus. Transport of nanomaterials to different plant organs under possible applications, and translocation of these nanoparticles besides their expected nanotoxicity to soil microbes will be also reported in the current study. Nanotoxicity to soil microbes and plants was investigated by taking account of morpho-physiological, molecular, and biochemical concerns. This study highlights the regulations of nanotoxicity with a focus on risk and challenges at the ecological level and their risks to human health, along with the scientific and organizational levels. This study opens many windows in such studies nexus which are needed in the near future.

Mechanistic insights into how mixing factors govern polyelectrolyte-surfactant complexation in RNA lipid nanoparticle formulation.

HYPOTHESIS: Lipid nanoparticle self-assembly is a complex process that relies on ion pairing between nucleic acids and hydrophobic cationic lipid counterions for encapsulation. The chemical factors influencing this process, such as formulation composition, have been the focus of recent research. However, the physical factors, particularly the mixing protocol, which directly modulates these chemical factors, have yet to be mechanistically examined using a reproducible mixing platform comparable to the industry standard. We here utilize Flash NanoPrecipitation (FNP), a scalable rapid mixing platform, to isolate and systematically investigate how mixing factors influence this complexation step, first by using a model polyelectrolyte-surfactant system and then generalizing to a typical RNA lipid nanoparticle formulation. EXPERIMENTS: Aqueous polystyrene sulfonate (PSS) and cetrimonium bromide (CTAB) solutions are rapidly homogenized using reproducible FNP mixing and controlled flow rates at different stoichiometric ratios and total solids concentrations to form polyelectrolyte-surfactant complexes (PESCs). Then, key mixing factors such as total flow rate, inlet stream relative volumetric flow rate, and magnitude of flow fluctuation are studied using both this PESC system and an RNA lipid nanoparticle formulation. FINDINGS: Fluctuations in flow as low as ± 5 % of the total flow rate are found to severely compromise PESC formation. This result is replicated in the RNA lipid nanoparticle system, which exhibited significant differences in size (132.7 nm vs. 75.6 nm) and RNA encapsulation efficiency (34.0 % vs. 82.8 %) under fluctuating vs. steady flow. We explain these results in light of the chemical variables isolated and studied; slow or nonuniform mixing generates localized concentration gradients that disrupt the balance between the hydrophobic and electrostatic forces that drive complex formation. These experiments contribute to our understanding of the complexation stage of lipid nanoparticle formation and provide practical insights into the importance of developing controlled mixing protocols in industry.

Non-equilibrium self-assembly for living matter-like properties.

The soft and wet machines of life emerged as the spatially enclosed ensemble of biomolecules with replicating capabilities integrated with metabolic reaction cycles that operate at far-from-equilibrium. A thorough step-by-step synthetic integration of these elements, namely metabolic and replicative properties all confined and operating far-from-equilibrium, can set the stage from which we can ask questions related to the construction of chemical-based evolving systems with living matter-like properties - a monumental endeavour of systems chemistry. The overarching concept of this Review maps the discoveries on this possible integration of reaction networks, self-reproduction and compartmentalization under non-equilibrium conditions. We deconvolute the events of reaction networks and transient compartmentalization and extend the discussion towards self-reproducing systems that can be sustained under non-equilibrium conditions. Although enormous challenges lie ahead in terms of molecular diversity, information transfer, adaptation and selection that are required for open-ended evolution, emerging strategies to generate minimal metabolic cycles can extend our growing understanding of the chemical emergence of the biosphere of Earth.