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The convergence of polymer and pharmaceutical sciences has advanced drug delivery systems significantly. Carbohydrate polymers, especially carboxymethylated ones, offer versatile benefits for pharmaceuticals. Interpenetrating polymer networks (IPNs) combine synthetic and natural polymers to enhance drug delivery. The study aims to develop IPN beads using sodium carboxymethyl cellulose (SCMC) and carboxymethyl konjac glucomannan (CMKGM) for controlled release of ibuprofen (IB) after oral administration. Objectives include formulation optimization, characterization of physicochemical properties, evaluation of pH-dependent swelling and drug release behaviors to advance biocompatible and efficient oral drug delivery systems. The beads were analyzed using SEM, FTIR, DSC, and XRD techniques. Different ratio of polymers (CMKGM:SCMS) and crosslinker concentrations (2&4 %w/v) were used, significantly impacting bead size, swelling, drug encapsulation, and release characteristics. DSC results indicated higher thermal stability in IPN beads compared to native polymers. XRD revealed IB dispersion within the polymer matrix. IPN beads size ranged from 580 ± 0.56 to 324 ± 0.27 µm, with a nearly spherical shape. IPN beads exhibited continuous release in alkaline conditions (pH 7.4) and minimal release in acidic media (pH 1.2). These findings suggest that the formulated IPN beads can modulate drug release in both acidic and alkaline environments, potentially mitigating the gastric adverse effects often associated with oral administration of IB.
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Lumbar canal stenosis (LCS) is a common spinal disease affecting the elderly. Primarily it is asymptomatic until there is neurogenic claudication. Minimally invasive surgical (MIS) techniques are used to treat patients with lumbar spinal stenosis (LSS), while tubular system with alternative multilevel decompression is specifically used for those with minimal back pain and no mechanical instability on dynamic imaging. The aim of the study is to evaluate surgical outcome of Slalom procedure and complications in Middle East population. One hundred and five patients with lumbar stenosis (61 males and 44 females) underwent the procedure between 2015-2021 who were regularly followed-up using preoperative and postoperative COMI score (the core outcome measure index) at six months after index surgery. Progressive improvement in COMI score from average seven pre-op score to an average of three after six months of index surgery. The postoperative complications were dural tear (6.67%), Postoperative infection (3.81%), mechanical instability (1.9%), postoperative neuritis (8.57%) and death (1.9%).
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Descompressão Cirúrgica , Vértebras Lombares , Complicações Pós-Operatórias , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Feminino , Masculino , Descompressão Cirúrgica/métodos , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversosRESUMO
The process of drying agricultural products for food preservation is a difficult task that requires a significant amount of energy. The increasing cost and depletion of fossil fuels have led to the development of a food dryer that utilizes renewable energy sources. This research paper proposes the design and performance evaluation of an indirectly forced convection desiccant integrated solar dryer (IFCDISD) at the Solar Energy Research Lab at USPCAS-E, NUST Pakistan. Tomatoes were chosen as the test product due to their importance and widespread consumption. The drying process involves slicing the tomatoes and placing them on the IFCDISD rack, where a desiccant called calcium chloride (CaCl2) is integrated into the dryer. The experiments were conducted during both sunshine (SS) hours and Off-sunshine (OSS) hours. The IFCDISD operates using sunlight during SS hours and utilizes the absorbed heat of CaCl2 in OSS hours via a forced DC brushless fan powered by battery charged thro solar panel. The tomatoes were weighed before and after each drying mode, and the moisture removal was calculated. The results show that the dryer efficiency was 50.14 % on day 1, 66 % on day 2, and an overall efficiency of 58.07 %. The moisture content removal was 42.858 % on day 1, 22.9979 % on day 2, and an overall moisture content removal of 58.07 %. Moreover, the payback period is 5.1396 and the carbon mitigation was recorded as 2.0335, and the earned carbon credit was recorded as 11559.6.
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It is mentioned that understanding linear and non-linear thermo-elasticity systems is important for understanding temperature, elasticity, stresses, and thermal conductivity. One of the most crucial aspects of the current research is the solution to these systems. The fractional form of several thermo-elastic systems is explored, and elegant solutions are provided. The solutions of fractional and integer thermo-elastic systems are further discussed using tables and diagrams. The closed contact between the LRPSM and exact solutions is displayed in the graphs. Plotting fractional problem solutions demonstrates their convergence towards integer-order problem solutions for suitable modeling. The tables confirm that greater precision is rapidly attained as the terms of the derived series solution increase. The faster convergence and stability of the suggested method support its modification for other fractional non-linear complex systems in nature.
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In this study, an accurate analytical solution is presented for fuzzy FPDEs. It is done by using a novel method called the Laplace-residual power series (LRPSM) to build a series solution to the given problems. The fundamental instruments of the employed method are the Laplace transform, fractional Laurent, and fractional power series. Using the idea of a limit at infinity, we provide a series solution to a fuzzy FPDE with quick convergence and simple coefficient finding. We analyze three cases to obtain approximate and exact solutions to show the effectiveness and reliability of the Laplace- residual power series approach. To demonstrate the accuracy of the suggested procedure, we compare the findings to the real data.
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Deep proteomic profiling of rare cell populations has been constrained by sample input requirements. Here, we present DROPPS (droplet-based one-pot preparation for proteomic samples), an accessible low-input platform that generates high-fidelity proteomic profiles of 100-2,500 cells. By applying DROPPS within the mammary epithelium, we elucidated the connection between mitochondrial activity and clonogenicity, identifying CD36 as a marker of progenitor capacity in the basal cell compartment. We anticipate that DROPPS will accelerate biology-driven proteomic research for a multitude of rare cell populations.
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Biomarcadores , Antígenos CD36 , Glândulas Mamárias Animais , Proteômica , Células-Tronco , Proteômica/métodos , Antígenos CD36/metabolismo , Animais , Feminino , Células-Tronco/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Epitélio/metabolismo , Camundongos , Humanos , Mitocôndrias/metabolismoRESUMO
Aluminum (Al) toxicity poses a significant challenge to agricultural productivity, particularly in acidic soils. The banana crop, predominantly cultivated in tropical and subtropical climates, often grapples with low pH and Al toxicity. This study seeks to explore the differential responses of two banana genotypes with varying Al tolerance (Baodao and Baxi) to Al exposure (100 and 500 µM) for 24 h. Microscopic analysis uncovered distinctive structural modifications in root cells, with Baodao displaying more severe alterations in response to Al stress. There was higher superoxide (O2-.) and hydrogen peroxide (H2O2) production and lipid peroxidation in Baodao indicating enhanced oxidative stress and membrane damage. Al accumulation in root tips was higher in Baxi than Baodao, while the roots of Baodao had a higher accumulation of callose. Nutrient content analysis revealed alterations in ion levels, highlighting the impact of Al exposure on nutrient uptake and homeostasis. In summary, Al differentially affects callose deposition, which, in turn, leads to Al uptake and nutrient homeostasis alteration in two contrasting banana genotypes. This intricate interplay is a key factor in understanding plant responses to aluminum toxicity and can inform strategies for crop improvement and soil management in aluminum-stressed environments.
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Alumínio , Genótipo , Glucanos , Homeostase , Musa , Estresse Oxidativo , Alumínio/toxicidade , Musa/efeitos dos fármacos , Solo/química , Raízes de Plantas/efeitos dos fármacos , Nutrientes , Poluentes do Solo/toxicidadeRESUMO
Biofluids contain molecules in circulation and from nearby organs that can be indicative of disease states. Characterizing the proteome of biofluids with DIA-MS is an emerging area of interest for biomarker discovery; yet, there is limited consensus on DIA-MS data analysis approaches for analyzing large numbers of biofluids. To evaluate various DIA-MS workflows, we collected urine from a clinically heterogeneous cohort of prostate cancer patients and acquired data in DDA and DIA scan modes. We then searched the DIA data against urine spectral libraries generated using common library generation approaches or a library-free method. We show that DIA-MS doubles the sample throughput compared to standard DDA-MS with minimal losses to peptide detection. We further demonstrate that using a sample-specific spectral library generated from individual urines maximizes peptide detection compared to a library-free approach, a pan-human library, or libraries generated from pooled, fractionated urines. Adding urine subproteomes, such as the urinary extracellular vesicular proteome, to the urine spectral library further improves the detection of prostate proteins in unfractionated urine. Altogether, we present an optimized DIA-MS workflow and provide several high-quality, comprehensive prostate cancer urine spectral libraries that can streamline future biomarker discovery studies of prostate cancer using DIA-MS.
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Neoplasias da Próstata , Proteoma , Proteômica , Humanos , Masculino , Neoplasias da Próstata/urina , Neoplasias da Próstata/diagnóstico , Proteoma/análise , Proteômica/métodos , Próstata/metabolismo , Próstata/patologia , Biblioteca de Peptídeos , Biomarcadores Tumorais/urina , Espectrometria de Massas em Tandem/métodos , Fluxo de TrabalhoRESUMO
Application of machine learning in plant breeding is a recent concept, that has to be optimized for precise utilization in the breeding program of high yielding crop plants. Identification and efficient utilization of heterotic grouping pattern aided with machine learning approaches is of utmost importance in hybrid cultivar breeding as it can save time and resources required to breed a new plant hybrid/variety. In the present study, 109 genotypes of sunflower were investigated at morphological, biochemical (SDS-PAGE) and molecular levels (through micro-satellites (SSR) markers) for heterotic grouping. All the three datasets were combined, scaled, and subjected to unsupervised machine learning algorithms, i.e., Hierarchical clustering, K-means clustering and hybrid clustering algorithm (hierarchical + K-means) for assessment of efficiency and resolution power of these algorithms in practical plant breeding for heterotic grouping identification. Following the application of machine learning unsupervised clustering approach, two major groups were identified in the studied sunflower germplasm, and further classification revealed six smaller classes in each major group through hierarchical and hybrid clustering approach. Due to high resolution, obtained in hierarchical clustering, classification achieved through this algorithm was further used for selection of potential parents. One genotype from each smaller group was selected based on the maximum seed yield potential and hybridized in a line × tester mating design producing 36 F1 cross combinations. These F1s along with their parents were studied in open field conditions for validating the efficacy of identified heterotic groups in sunflowers genetic material under study. Data for 11 agronomic and qualitative traits were recorded. These 36 F1 combinations were tested for their combining ability (General/Specific), heterosis, genotypic and phenotypic correlation and path analysis. Results suggested that F1 hybrids performed better for all the traits under investigation than their respective parents. Findings of the study validated the use of machine learning approaches in practical plant breeding; however, more accurate and robust clustering algorithms need to be developed to handle the data noisiness of open field experiments.
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Asteraceae , Helianthus , Vigor Híbrido , Hibridização Genética , Helianthus/genética , Genótipo , Melhoramento Vegetal , Aprendizado de MáquinaRESUMO
Chordomas are clinically aggressive tumors with a high rate of disease progression despite maximal therapy. Given the limited therapeutic options available, there remains an urgent need for the development of novel therapies to improve clinical outcomes. Cell surface proteins are attractive therapeutic targets yet are challenging to profile with common methods. Four chordoma cell lines were analyzed by quantitative proteomics using a differential ultracentrifugation organellar fractionation approach. A subtractive proteomics strategy was applied to select proteins that are plasma membrane enriched. Systematic data integration prioritized PLA2R1 (secretory phospholipase A2 receptor-PLA2R1) as a chordoma-enriched surface protein. The expression profile of PLA2R1 was validated across chordoma cell lines, patient surgical tissue samples, and normal tissue lysates via immunoblotting. PLA2R1 expression was further validated by immunohistochemical analysis in a richly annotated cohort of 25-patient tissues. Immunohistochemistry analysis revealed that elevated expression of PLA2R1 is correlated with poor prognosis. Using siRNA- and CRISPR/Cas9-mediated knockdown of PLA2R1, we demonstrated significant inhibition of 2D, 3D and in vivo chordoma growth. PLA2R1 depletion resulted in cell cycle defects and metabolic rewiring via the MAPK signaling pathway, suggesting that PLA2R1 plays an essential role in chordoma biology. We have characterized the proteome of four chordoma cell lines and uncovered PLA2R1 as a novel cell-surface protein required for chordoma cell survival and association with patient outcome.
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Cordoma , Humanos , Cordoma/genética , Cordoma/metabolismo , Proteômica , Membrana Celular/metabolismo , Proteínas de Membrana , Organelas/metabolismo , Organelas/patologia , Receptores da Fosfolipase A2/metabolismoRESUMO
Micronuclei (MN) are induced by various genotoxic stressors and amass nuclear- and cytoplasmic-resident proteins, priming the cell for MN-driven signaling cascades. Here, we measured the proteome of micronuclear, cytoplasmic, and nuclear fractions from human cells exposed to a panel of six genotoxins, comprehensively profiling their MN protein landscape. We find that MN assemble a proteome distinct from both surrounding cytoplasm and parental nuclei, depleted of spliceosome and DNA damage repair components while enriched for a subset of the replisome. We show that the depletion of splicing machinery within transcriptionally active MN contributes to intra-MN DNA damage, a known precursor to chromothripsis. The presence of transcription machinery in MN is stress-dependent, causing a contextual induction of MN DNA damage through spliceosome deficiency. This dataset represents a unique resource detailing the global proteome of MN, guiding mechanistic studies of MN generation and MN-associated outcomes of genotoxic stress.
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Cromotripsia , Proteoma , Humanos , Proteoma/genética , Proteoma/metabolismo , Proteômica , Núcleo Celular/genética , Núcleo Celular/metabolismo , Dano ao DNA/genéticaRESUMO
Rapid urban expansion and a booming population are placing immense pressure on our agricultural systems, leading to detrimental impacts on soil fertility and overall health. Due to the extensive use of agrochemicals in agriculture, the necessity to meet the expanding demand for food has also resulted in unsustainable farming practices. Around the world, biochar, a multipurpose carbonaceous material, is being used to concurrently solve issues with enhancing soil fertility, plant growth, and development under both normal and stressful circumstances. It improves water retention, fosters nutrient absorption, and promotes microbial activity, creating a fertile environment that supports sustainable and resilient agriculture. Additionally, biochar acts as a carbon sink, contributing to long-term carbon sequestration and mitigating climate change impacts. The major benefit of biochar is that it helps the adsorption process with its highly porous structures and different functional groups. Understanding the elements involved in biochar formation that determine its characteristics and adsorptive capacity is necessary to assure the viability of biochar in terms of plant productivity and soil health, particularly biological activity in soil. This paper focuses on the development, composition, and effects of biochar on soil fertility and health, and crop productivity.
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The utilization of nanobiochar in agricultural practices has garnered substantial interest owing to its promising potential. Its nano-size particles possess an enhanced ability to infiltrate plant cells, potentially instigating biochemical and physiological responses that augment stress tolerance. In our study, we aimed to assess the impact and extent of exogenously applied nanobiochar on the growth dynamics and antioxidative responses in Spinacia oleracea L. (spinach) plants subjected to salt stress (50 mM NaCl) and drought stress (maintained at 60% field capacity) compared with respective controls (0 mM NaCl and 100% field capacity). Following a 15-day exposure to stress conditions, nanobiochar solution (at concentrations of 0, 1, 3, and 5% w/v) was sprayed on spinach plants at weekly intervals (at 14, 21, and 28 days after sowing). The foliar application of nanobiochar markedly improved biomass, net assimilation rate, leaf area, and various other growth parameters under drought and salinity stress conditions. Notably, the application of 3% nanobiochar caused the most significant enhancement in growth traits, photosynthetic pigments, and nutrient content, indicating its efficiency in directly supplying nutrients to the foliage. Furthermore, under drought stress conditions, the application of 3% nanobiochar elicited a notable 62% increase in catalase activity, a two-fold rise in peroxidase activity, and a 128% increase in superoxide dismutase activity compared to the control (without nanobiochar). Additionally, nanobiochar application enhanced membrane stability, evidenced by reduced lipid peroxidation and electrolyte leakage. The foliar application of 3% nanobiochar was found as a promising strategy to significantly enhance spinach growth parameters, nutrient assimilation, and antioxidative defense mechanisms, particularly under conditions of drought and salinity stress.
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Carvão Vegetal , Secas , Spinacia oleracea , Salinidade , Cloreto de Sódio , AntioxidantesRESUMO
High-grade serous ovarian carcinoma (HGSC) is the most prevalent subtype of epithelial ovarian cancer. The combination of a high rate of recurrence and novel therapies in HGSC necessitates an accurate assessment of the disease. Currently, HGSC response to treatment and recurrence are monitored via immunoassay of serum levels of the glycoprotein CA125. CA125 levels predictably rise at HGSC recurrence; however, it is likely that the disease is progressing even before it is detectable through CA125. This may explain why treating solely based on CA125 increase has not been associated with improved outcomes. Thus, additional biomarkers that monitor HGSC progression and cancer recurrence are needed. For this purpose, we developed a scheduled parallel reaction monitoring mass spectrometry (PRM-MS) assay for the quantification of four previously identified HGSC-derived glycopeptides (from proteins FGL2, LGALS3BP, LTBP1, and TIMP1). We applied the assay to quantify their longitudinal expression profiles in 212 serum samples taken from 34 HGSC patients during disease progression. Analyses revealed that LTBP1 best-mirrored tumor load, dropping as a result of cancer treatment in 31 out of 34 patients and rising at HGSC recurrence in 28 patients. Additionally, LTBP1 rose earlier during remission than CA125 in 11 out of 25 platinum-sensitive patients with an average lead time of 116.4 days, making LTBP1 a promising candidate for monitoring of HGSC recurrence.
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Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Biomarcadores Tumorais , Cistadenocarcinoma Seroso/patologia , Recidiva Local de Neoplasia , Glicoproteínas , Espectrometria de Massas , Fibrinogênio , Proteínas de Ligação a TGF-beta LatenteRESUMO
Introduction: Nanoparticles play a vital role in environmental remediation on a global scale. In recent years, there has been an increasing demand to utilize nanoparticles in wastewater treatment due to their remarkable physiochemical properties. Methods: In the current study, manganese oxide nanoparticles (MnO-NPs) were synthesized from the Bacillus flexus strain and characterized by UV/Vis spectroscopy, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. Results: The objective of this study was to evaluate the potential of biosynthesized MnO-NPs to treat wastewater. Results showed the photocatalytic degradation and adsorption potential of MnO-NPs for chemical oxygen demand, sulfate, and phosphate were 79%, 64%, and 64.5%, respectively, depicting the potential of MnO-NPs to effectively reduce pollutants in wastewater. The treated wastewater was further utilized for the cultivation of wheat seedlings through a pot experiment. It was observed that the application of treated wastewater showed a significant increase in growth, physiological, and antioxidant attributes. However, the application of treated wastewater led to a significant decrease in oxidative stress by 40%. Discussion: It can be concluded that the application of MnO-NPs is a promising choice to treat wastewater as it has the potential to enhance the growth, physiological, and antioxidant activities of wheat seedlings.
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Background: Epidural hematoma is one of the most common surgical emergencies encountered in neurosurgery. This study was conducted to determine the mortality and prognostic factors in patients operated for traumatic intracranial epidural hematoma in a resource-constrained setting from a developing country. Methods: This retrospective study was conducted in the Department of Neurosurgery at Ayub Teaching Hospital Abbottabad from 1st January 2019 to 31st Dec 2021. Inclusion and exclusion criteria were created. The medical record of 116 patients admitted and operated on for traumatic extradural hematoma was retrospectively reviewed. Information was recorded using a standardized structured questionnaire. The outcome was measured in terms of the Glasgow coma outcome score. Results: Out of 116 patients, 93 were male and 23 were female.19 (16.4%) patients were in the age range 0-5 years, 42 (36.2%) were in the age range 6-15, 35(31.0%) were in the age range 16-30, 11 (9.5%) were in the age range 31-45 years, 7 (6.0%) were in the age range 46-60 years while only one patient included in this study was above 60 years. Overall mortality was 4.3%. Mortality was higher in females and in those aged less than 5 years (3.4%). 4 out of 16 patients died with GCS less than 8, while none of the patients died when GCS was above 12. Mortality was significantly higher in the presence of associated lesions (4.4% vs. 0%) and anisocoria (2.6% vs.1.7%). Patients who operated within 6 hours of trauma resulted in better outcomes with a mortality rate of 0.0% and functional recovery of 57.8 % while for those who operated after 6 hours, mortality was significantly higher (4.3%) and functional recovery was significantly low (15.5%). Conclusion: Good surgical outcomes can be achieved with early operative intervention if indicated. Female gender, low preoperative GCS score, presence of pupillary dilatation, presence of associated lesions, delayed surgical intervention and age less than 5 years are significant predictors for poor outcomes.
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Hematoma Epidural Craniano , Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Hematoma Epidural Craniano/cirurgia , Estudos Retrospectivos , Prognóstico , Escala de Coma de Glasgow , Procedimentos NeurocirúrgicosRESUMO
Collecting duct carcinoma (CDC) is an aggressive renal malignancy with limited diagnostic and therapeutic consensus. We report a case of a 69-year-old male with CDC and extensive coagulative necrosis who presented with lower extremity swelling, abdominal distention, and an enlarged left kidney causing grade IV hydronephrosis. Initial treatment with a left percutaneous nephrostomy was followed by clinical deterioration and a diagnosis of emphysematous pyelonephritis. Pathological examination of drainage material revealed extensive coagulative necrosis and was suggestive of a necrotic neoplasm. Subsequent left nephrectomy confirmed CDC with high-grade features, stromal desmoplasia, and extensive coagulative necrosis. Immunohistochemistry studies supported the diagnosis. This study highlights the diagnostic complexity of CDC and emphasizes the need for accurate reporting of atypical presentations. CDC remains a formidable clinical entity with limited treatment options and poor outcomes. Further research is essential to enhance our understanding and management of this rare and aggressive renal malignancy.