Graphene Oxide Membrane Reactor for Electrochemical Deuteration Reactions.

The deuteration of organic molecules is considerably important in organic and medicinal chemistry. An electrochemical membrane reactor using proton-conducting graphene oxide (GO) nanosheets was developed to synthesize valuable deuterium-labeled products via an efficient hydrogen-to-deuterium (H/D) exchange under mild conditions at ambient temperature and atmospheric pressure. Deuterons (D+) formed by the anodic oxidation of heavy water (D2O) at the Pt/C anode permeate through the GO membrane to the Pt/C cathode, where organic molecules with functional groups (C≡C and C═O) are deuterated with adsorbed atomic D species. Deuteration occurs in outstanding yields with high levels of D incorporation. We also achieved the electrodeuteration of a drug molecule, ibuprofen, demonstrating the promising feasibility of the GO membrane reactor in the pharmaceutical industry.

Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback.

We investigated the role of ligand clustering and density in the activation of natural killer (NK) cells. To that end, we designed reductionist arrays of nanopatterned ligands arranged with different cluster geometries and densities and probed their effects on NK cell activation. We used these arrays as an artificial microenvironment for the stimulation of NK cells and studied the effect of the array geometry on the NK cell immune response. We found that ligand density significantly regulated NK cell activation while ligand clustering had an impact only at a specific density threshold. We also rationalized these findings by introducing a theoretical membrane fluctuation model that considers biomechanical feedback between ligand-receptor bonds and the cell membrane. These findings provide important insight into NK cell mechanobiology, which is fundamentally important and essential for designing immunotherapeutic strategies targeting cancer.

Exploring the Interactions between Obesity and Diabetes: Implications for Understanding Metabolic Dysregulation in a Saudi Arabian Adult Population.

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation's high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18-40 years) were recruited and stratified into four groups: healthy weight (BMI 18.5-24.99 kg/m2) with (n = 57) and without diabetes (n = 58) or overweight/obese (BMI > 24.99 kg/m2) with (n = 102) and without diabetes (n = 72). Distinct plasma metabolic phenotypes associated with high BMI and diabetes were identified using nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography mass spectrometry. Increased plasma glucose and dysregulated lipoproteins were characteristics of obesity in individuals with and without diabetes, but the obesity-associated lipoprotein phenotype was partially masked in individuals with diabetes. Although there was little difference between diabetics and nondiabetics in the global plasma LDL cholesterol and phospholipid concentration, the distribution of lipoprotein particles was altered in diabetics with a shift toward denser and more atherogenic LDL5 and LDL6 particles, which was amplified in the presence of obesity. Further investigation is warranted in larger Middle Eastern populations to explore the dysregulation of metabolism driven by interactions between obesity and diabetes in young adults.

O-GlcNAcylation promotes the cytosolic localization of the m6A reader YTHDF1 and colorectal cancer tumorigenesis.

O-linked GlcNAc (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. The mechanisms underlying the involvement of O-GlcNAc modifications in N6-methyladenosine (m6A) regulation are not fully characterized. Herein, we show that O-GlcNAc modifies the m6A mRNA reader YTH domain family 1 (YTHDF1) and fine-tunes its nuclear translocation by the exportin protein Crm1. First, we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. Then we constructed the O-GlcNAc-deficient YTHDF1-S196A/S197F/S198A (AFA) mutant, which significantly attenuated O-GlcNAc signals. Moreover, we revealed that YTHDF1 is a nucleocytoplasmic protein, whose nuclear export is mediated by Crm1. Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating downstream target (e.g. c-Myc) expression. Molecular dynamics simulations suggest that O-GlcNAcylation at S197 promotes the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. We propose that the OGT-YTHDF1-c-Myc axis underlies colorectal cancer tumorigenesis.

Genetic biofortification: advancing crop nutrition to tackle hidden hunger.

Malnutrition, often termed "hidden hunger," represents a pervasive global issue carrying significant implications for health, development, and socioeconomic conditions. Addressing the challenge of inadequate essential nutrients, despite sufficient caloric intake, is crucial. Biofortification emerges as a promising solution by enhance the presence of vital nutrients like iron, zinc, iodine, and vitamin A in edible parts of different crop plants. Crop biofortification can be attained through either agronomic methods or genetic breeding techniques. Agronomic strategies for biofortification encompass the application of mineral fertilizers through foliar or soil methods, as well as leveraging microbe-mediated mechanisms to enhance nutrient uptake. On the other hand, genetic biofortification involves the strategic crossing of plants to achieve a desired combination of genes, promoting balanced nutrient uptake and bioavailability. Additionally, genetic biofortification encompasses innovative methods such as speed breeding, transgenic approaches, genome editing techniques, and integrated omics approaches. These diverse strategies collectively contribute to enhancing the nutritional profile of crops. This review highlights the above-said genetic biofortification strategies and it also covers the aspect of reduction in antinutritional components in food through genetic biofortification.

Alleviating salinity stress in canola (Brassica napus L.) through exogenous application of salicylic acid.

Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61-65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na+ ions and concomitantly decreased the K+ and Ca2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.

Evolution of Metal Tellurides for Energy Storage/Conversion: From Synthesis to Applications.

Metal telluride (MTe)-based nanomaterials have emerged as a potential alternative for efficient, highly conductive, robust, and durable electrodes in energy storage/conversion applications. Significant progress in the material development of MTe-based electrodes is well-sought, from the synthesis of its nanostructures, integration of MTes with supporting materials, synthesis of their hybrid morphologies, and their implications in energy storage/conversion systems. Herein, an extensive exploration of the recent advancements and progress in MTes-based nanomaterials is reviewed. This review emphasizes elucidating the fundamental properties of MTes and providing a systematic compilation of its wet and dry synthesis methods. The applications of MTes are extensively summarized and discussed, particularly, in energy storage and conversion systems including batteries (Li-ion, Zn-ion, Li-S, Na-ion, K-ion), supercapacitor, hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and CO2 reduction. The review also emphasizes the future prospects and urgent challenges to be addressed in the development of MTes, providing knowledge for researchers in utilizing MTes in energy storage and conversion technologies.

Malignant Left Ventricular Hypertrophy and Risk of Cognitive Impairment in SPRINT MIND Trial.

BACKGROUND: The association of malignant left ventricular hypertrophy (LVH), a specific subphenotype of LVH characterized by elevated levels of high-sensitivity cardiac troponin (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), with cognitive decline remains understudied. METHODS: This post-hoc analysis included a total of 8,027 (67.9±9.3 years) SPRINT MIND trial participants who had with at least one follow-up cognitive assessment. Participants were classified into six groups on the basis of LVH status on electrocardiogram (ECG), and elevations in levels of hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline visit. Multivariate Cox proportional hazard models were used to examine the association of LVH/biomarker groups with incident probable dementia, mild cognitive impairment (MCI) and a composite of MCI/probable dementia. RESULTS: Over a median follow-up period of 5 years, there were 306, 597 and 818 incidents of MCI, probable dementia and a composite of MCI/probable dementia, respectively. Compared with participants without LVH and normal biomarker levels, those with concomitant LVH and elevated levels of both biomarkers were associated with a higher risk of probable dementia (HR, 2.50; 95% CI (1.26 - 4.95), MCI (HR, 1.78; 95% CI (0.99 - 3.23) and the composite of MCI/ probable dementia (HR, 1.89; 95% CI, 1.16 - 3.10). CONCLUSIONS: Among SPRINT participants, malignant LVH is associated with incident probable dementia and mild cognitive impairment. These findings underscore the potential utility of measuring hs-cTnT and NT-proBNP levels when LVH is detected on ECG, aiding in the differentiation of individuals with a favorable risk for cognitive impairment from those with a higher risk.

Leveraging shape screening and molecular dynamics simulations to optimize PARP1-Specific chemo/radio-potentiators for antitumor drug design.

PARP1 plays a pivotal role in DNA repair within the base excision pathway, making it a promising therapeutic target for cancers involving BRCA mutations. Current study is focused on the discovery of PARP inhibitors with enhanced selectivity for PARP1. Concurrent inhibition of PARP1 with PARP2 and PARP3 affects cellular functions, potentially causing DNA damage accumulation and disrupting immune responses. In step 1, a virtual library of 593 million compounds has been screened using a shape-based screening approach to narrow down the promising scaffolds. In step 2, hierarchical docking approach embedded in Schrödinger suite was employed to select compounds with good dock score, drug-likeness and MMGBSA score. Analysis supplemented with decomposition energy, molecular dynamics (MD) simulations and hydrogen bond frequency analysis, pinpointed that active site residues; H862, G863, R878, M890, Y896 and F897 are crucial for specific binding of ZINC001258189808 and ZINC000092332196 with PARP1 as compared to PARP2 and PARP3. The binding of ZINC000656130962, ZINC000762230673, ZINC001332491123, and ZINC000579446675 also revealed interaction involving two additional active site residues of PARP1, namely N767 and E988. Weaker or no interaction was observed for these residues with PARP2 and PARP3. This approach advances our understanding of PARP-1 specific inhibitors and their mechanisms of action, facilitating the development of targeted therapeutics.

Energy Application of Graphene Based Membrane: Hydrogen Separation.

Hydrogen gas (H2 ) is a viable energy carrier that has the potential to replace the traditional fossil fuels and contribute to achieving zero net emissions, making it an attractive option for a hydrogen-based society. However, current H2 purification technologies are often limited by high energy consumption, and as a result, there is a growing demand for alternative techniques that offer higher H2 purity and energy efficiency. Membrane separation has emerged as a promising approach for obtaining high-purity H2 gas with low energy consumption. Nevertheless, despite years of development, commercial polymeric membranes have limited performance, prompting researchers to explore alternative materials. In this context, carbon-based membranes, specifically graphene-based nanomaterials, have gained significant attention as potential membrane materials due to their unique properties. In this review, we provide a comprehensive overview of carbon-based membranes for H2 gas separation, fabrication of the membrane, and its characterization, including their advantages and limitations. We also explore the current technological challenges and suggest insights into future research directions, highlighting potential ways to improve graphene-based membranes performance for H2 separations.

Human Oropharyngeal Candidiasis: From Etiology to Current Treatment.

Oral candidiasis is a common but most harmful oral cavity infection caused by yeast-like fungus, this condition is called Oropharyngeal candidiasis. There are various species of candida that are responsible for oral cavity fungal infection including mostly Candida albicans. Different candida infections may be acute and chronic. Cell-mediated immunity, humoral immunity, and granulocytes are the immune factors for the cause of this infection. Different antifungal drugs like nystatin, fluconazole, and amphotericin are used to treat oral cavity fungal infections.

Meta-analysis contrasting freshwater biodiversity in forests and oil palm plantations with and without riparian buffers.

The expansion of oil palm plantations has led to land-use change and deforestation in the tropics, which has affected biodiversity. Although the impacts of the crop on terrestrial biodiversity have been extensively reviewed, its effects on freshwater biodiversity remain relatively unexplored. We reviewed the research assessing the impacts of forest-to-oil palm conversion on freshwater biota and the mitigating effect of riparian buffers on these impacts. We searched for studies comparing taxa richness, species abundance, and community composition of macroinvertebrates, amphibians, and fish in streams in forests (primary and disturbed) and oil palm plantations with and without riparian buffers. Then, we conducted a meta-analysis to quantify the overall effect of the land-use change on the 3 taxonomic groups. Twenty-nine studies fulfilled the inclusion criteria. On average, plantations lacking buffers hosted 44% and 19% fewer stream taxa than primary and disturbed forests, respectively. Stream taxa on plantations with buffers were 24% lower than in primary forest and did not differ significantly from disturbed forest. In contrast, stream community composition differed between forests and plantations regardless of the presence of riparian buffers. These differences were attributed to agrochemical use and altered environmental conditions in the plantations, including temperature changes, worsened water conditions, microhabitat loss, and food and shelter depletion. On aggregate, abundance did not differ significantly among land uses because increases in generalist species offset the population decline of vulnerable forest specialists in the plantation. Our results reveal significant impacts of forest-to-oil palm conversion on freshwater biota, particularly taxa richness and composition (but not aggregate abundance). Although preserving riparian buffers in the plantations can mitigate the loss of various aquatic species, it cannot conserve primary forest communities. Therefore, safeguarding primary forests from the oil palm expansion is crucial, and further research is needed to address riparian buffers as a promising mitigation strategy in agricultural areas.

Metaanálisis contrastando la biodiversidad de agua dulce en los bosques y las plantaciones de palma de aceite con o sin bosques ribereños Resumen La expansión de las plantaciones de palma de aceite ha derivado en cambios en el uso de suelo y deforestación en los trópicos, afectando a la biodiversidad. Existe una revisión extensa del impacto de este cultivo sobre la biodiversidad terrestre, pero sus efectos sobre la biodiversidad de agua dulce todavía no están muy documentados. Revisamos las investigaciones que han evaluado el impacto de la conversión de bosque a plantación de palma de aceite sobre la biota de agua dulce y el efecto mitigante que tienen los bosques ribereños sobre este impacto. Buscamos estudios que compararan la riqueza de taxones, abundancia de especies y composición comunitaria de los macroinvertebrados, anfibios y peces en los riachuelos de los bosques (primarios y perturbados) y los sembradíos de palma de aceite con y sin bosques ribereños. Después realizamos un metaanálisis para cuantificar el efecto del cambio de uso de suelo en los tres grupos taxonómicos. Veintinueve estudios cumplieron con el criterio de inclusión. En promedio, las plantaciones carentes de bosques ribereños albergaron 44% y 19% menos taxones que los bosques primarios y perturbados. Los taxones en los sembradíos con bosques ribereños fueron 24% menos que en el bosque primario y no difirieron significativamente del bosque perturbado. Como contraste, la composición comunitaria del riachuelo difirió entre los bosques y los sembradíos sin importar la presencia de los bosques ribereños. Atribuimos estas diferencias al uso de agroquímicos y las condiciones ambientales alteradas en las plantaciones, incluidas los cambios térmicos, condiciones hidrológicas alteradas, pérdida de microhábitats y reducción de alimentos y refugios. En general, la abundancia no difirió significativamente entre los usos de suelo porque el incremento de especies generalistas en las plantaciones contrarresta la declinación poblacional de los especialistas de bosque vulnerables. Nuestros resultados revelan un impacto significativo de la conversión de bosque a plantación sobre la biota de agua dulce, particularmente la riqueza de taxones y la composición (pero no la abundancia agregada). Aunque mantener los bosques ribereños en las plantaciones puede mitigar la pérdida de varias especies acuáticas, no puede conservar las comunidades del bosque primario. Por lo tanto, es crucial salvaguardar los bosques primarios de la expansión del aceite de palma, además de que se necesitan más investigaciones para abordar los bosques ribereños como una estrategia prometedora de mitigación en las áreas agrícolas.

Outcomes of dual-chamber implantable cardioverter defibrillator for left bundle branch area pacing: A systematic review of literature.

OBJECTIVE: This systematic review of literature aimed to evaluate the safety and efficacy of dual-chamber ICDs for LBBAP in patients with left bundle branch block (LBBB). METHODS: Digital databases were searched systematically to identify studies reporting the left bundle branch area pacing (LBBAP) with implantable cardioverter defibrillator (ICD) placement in patients with LBBB. Detailed study and patient-level baseline characteristics including the type of study, sample size, follow-up, number of cases, age, gender, and baseline characteristics were abstracted. RESULTS: In a total of three studies, 34 patients were included in this review. There was a significant improvement reported in QRS duration in all studies. The mean QRS duration at baseline was 170 ± 17.4 ms, whereas the follow-up QRS duration at follow-up was 121 ± 17.3 ms. Two studies reported a significant improvement of 50% in LVEF from baseline. No lead-related complications or arrhythmic events were recorded in any study. The findings of the systematic review suggest that dual-chamber ICD for LBBAP is a promising intervention for patients with heart conditions. CONCLUSION: The procedure offers significant improvements in QRS duration and LVEF, and there were no lead-related complications or arrhythmic events recorded in any of the studies.

Electrocardiographic left atrial abnormality and risk of heart failure.

INTRODUCTION: The association and the racial differences of the electrocardiographic markers of left atrial abnormality (ECG-LAA) with heart failure (HF) are unclear. METHODS: We examined the cross-sectional association of ECG-LAA, defined as deep terminal negativity of P wave in V1 (DTNPV1) with HF in 8460 participants (51.5% women, 60.3 ± 13.5 age and 49.8% Whites) from the US Third National Health and Nutrition Examination Survey. We excluded participants without P-wave in their ECG or with ECG findings that interfere with measurements of P-wave. DTNPV1 was automatically measured from ECGs processed at a central lab. Values of DTNPV1 ≥ 100 µV were considered abnormal. Past medical history of HF was identified through health interviews. Multivariable logistic regression analysis was used to examine the associations of DTNPV1 with HF. RESULTS: Abnormal DTNPV1 was detected in 3.2% (n = 271) of the participants. HF was significantly more common in individuals with abnormal, compared to those with normal, DTNPV1 (14.7% vs. 4.8%, respectively; p-value <0.001). In a model adjusted for socio-demographics and cardiovascular risk factors, ECG-LAA was associated with 98% increased odds of HF (OR (95% CI): 1.98 (1.30-3.01), p < 0.001). This association was stronger in non-White (vs. White) participants (OR (95% CI): 3.14 (1.82-5.43) vs. 1.01 (0.51-1.97), respectively; interaction p-value =0.01), but consistent in subgroups stratified by age and sex. CONCLUSIONS: ECG-LAA, defined as abnormal DTNPV1, is associated with an increased risk of HF, underscoring the role of atrial disease in developing HF. Racial differences in this association exist, possibly suggesting considering ECG-LAA in personalized assessments of HF risk.

Chlorothalonil exposure compromised mouse oocyte in vitro maturation through inducing oxidative stress and activating MAPK pathway.

Chlorothalonil (CTL) is widely used in agricultural production and antifoulant additive globally due to its broad spectrum and non-systemic properties, resulting in its widespread existence in foods, soil and water. Extensive evidence demonstrated that exposure to CTL induced adverse effects on organisms and in particular its reproductive toxicity has been attracted public concern. However, the influences of CTL on oocyte maturation is mysterious so far. In this study, we documented the toxic effects of CTL on oocyte in vitro maturation and the related underlying mechanisms. Exposure to CTL caused continuous activation of spindle assembly checkpoints (SAC) which in turn compromised meiotic maturation in mouse oocyte, featured by the attenuation of polar body extrusion (PBE). Detection of cytoskeletal dynamics demonstrated that CTL exposure weakened the acetylation level of α-tubulin and impaired meiotic spindle apparatus, which was responsible for the aberrant state of SAC. Meanwhile, exposure to CTL damaged the function of mitochondria, inducing the decline of ATP content and the elevation of reactive oxygen species (ROS), which thereby induced early apoptosis and DNA damage in mouse oocytes. In addition, exposure to CTL caused the alteration of the level of histone H3 methylation, indicative of the harmful effects of CTL on epigenetic modifications in oocytes. Further, the CTL-induced oxidative stress activated mitogen-activated protein kinase (MAPK) pathway and injured the maturation of oocytes. In summary, exposure to CTL damaged mouse oocyte in vitro maturation via destroying spindle assembly, inducing oxidative stress and triggering MAPK pathway activation.

Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.

Platelet rich fibrin augmented tympanoplasty versus cartilage tympanoplasty: a randomized clinical trial.

OBJECTIVES: The aim of the current study was to evaluate the efficacy of PRF-augmented fascia tympanoplasty versus cartilage tympanoplasty in repair of large TM perforations. METHODS: This randomized clinical trial included 156 patients with dry large tympanic membrane perforations. Patients were randomly allocated into 2 groups, cartilage tympanoplasty group (n = 77) and platelet rich fibrin (PRF) augmented tympanoplasty group (n = 79). Graft take rates, hearing outcomes, operative time, and postoperative complications were documented and compared. RESULTS: Graft take rate was 96.1% in the cartilage group and 93.7% PRF group with no statistically significant difference. Operative time was significantly longer in the cartilage group. No differences in the hearing outcomes and postoperative complications were reported. CONCLUSION: Application of PRF on the fascia in tympanoplasty promotes healing of the tympanic membrane. PRF is safe, cheap, readily available, and easily prepared and applied. It increases the success rates of large tympanic membrane perforations without the need for cartilage grafts.

Phytoremediation through microstructural and functional alterations in alkali weed (Cressa cretica L.) in the hyperarid saline desert.

Salt excretory halophytes are the major sources of phytoremediation of salt-affected soils. Cressa cretica is a widely distributed halophyte in hypersaline lands in the Cholistan Desert. Therefore, identification of key physio-anatomical traits related to phytoremediation in differently adapted C. cretica populations was focused on. Four naturally adapted ecotypes of non-succulent halophyte Cressa cretica L. form hyper-arid and saline desert Cholistan. The selected ecotypes were: Derawar Fort (DWF, ECe 20.8 dS m-1) from least saline site, Traway Wala Toba (TWT, ECe 33.2 dS m-1) and Bailah Wala Dahar (BWD, ECe 45.4 dS m-1) ecotypes were from moderately saline sites, and Pati Sir (PAS, ECe 52.4 dS m-1) was collected from the highly saline site. The natural population of this species was collected and carefully brought to the laboratory for different structural and functional traits. As a result of high salinity, Na+, Cl-, K+, and Ca2+ content significantly increased at root and shoot level. At root level, some distinctive modifications such as increased sclerification in vascular bundles, enlarged vascular bundles, metaxylem vessels, phloem region, and storage parenchyma (cortex) are pivotal for water storage under extreme arid and osmotic condition. At the stem level, enhanced sclerification in outer cortex and vascular bundles, stem cellular area, cortical proportion, metaxylem and phloem area, and at the leaf level, very prominent structural adaptations were thicker and smaller leaves with increased density of salt glands and trichomes at surface, few and large stomata, reduced cortical and mesophyll parenchyma, and narrow xylem vessels and phloem area represent their non-succulent nature. The ecotype collected from hypersaline environments was better adapted regarding growth traits, ion uptake and excretion, succulence, and phytoremediation traits. More importantly, structural and functional traits such as root length and biomass, accumulation of toxic ions along with K+ in root and shoot, accumulation of Ca2+ in shoot and Mg2+ in root, excretion of toxic ions were the highest in this ecotype. In conclusion, all these alterations strongly favor water conservation, which certainly contributes to ecotypes survival under salt-induced physiological drought.

Naturally adapted salt tolerant plants provide exceptional material for exploring adaptive mechanisms they use to confront high salt concentrations. Cressa cretica is a hypersaline hyperarid desert colonizer, which was previously underexplored. In the present study, we focused on the new insight on relationship among anatomical modifications, salt accumulation and excretion and phytoremediation potential of this rare species.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Cellular signaling modulated by miRNA-3652 in ovarian cancer: unveiling mechanistic pathways for future therapeutic strategies.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play pivotal roles in regulating gene expression and have been implicated in the pathogenesis of numerous cancers. miRNA-3652, though relatively less explored, has recently emerged as a potential key player in ovarian cancer's molecular landscape. This review aims to delineate the functional significance and tumor progression role of miRNA-3652 in ovarian cancer, shedding light on its potential as both a diagnostic biomarker and therapeutic target. A comprehensive literature search was carried out using established databases, the focus was on articles that reported the role of miRNA-3652 in ovarian cancer, encompassing mechanistic insights, functional studies, and its association with clinical outcomes. This updated review highlighted that miRNA-3652 is intricately involved in ovarian cancer cell proliferation, migration, and invasion, its dysregulation was linked to altered expression of critical genes involved in tumor growth and metastasis; furthermore, miRNA-3652 expression levels were found to correlate with clinical stages, prognosis, and response to therapy in ovarian cancer patients. miRNA-3652 holds significant promise as a vital molecular player in ovarian cancer's pathophysiology. Its functional role and impact on tumor progression make it a potential candidate for diagnostic and therapeutic applications in ovarian cancer. Given the pivotal role of miRNA-3652 in ovarian cancer, future studies should emphasize in-depth mechanistic explorations, utilizing advanced genomic and proteomic tools. Collaboration between basic scientists and clinicians will be vital to translating these findings into innovative diagnostic and therapeutic strategies, ultimately benefiting ovarian cancer patients. Video Abstract.