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Introduction Rising prevalence rates of type 2 diabetes mellitus (T2DM), particularly in younger populations, have made early-onset T2DM (diagnosed before age 40) an increasingly significant health concern. Early-onset T2DM is often associated with more rapid progression and increased complications, including cardiovascular disease (CVD). However, its specific impact on cardiovascular outcomes remains inadequately understood, particularly compared to T2DM in older populations. This study aimed to assess how glycemic management affects the course of CVD in individuals with early-onset T2DM. Methodology During the six months between December 2, 2023, and August 5, 2024, a longitudinal cohort study was carried out at Ayub Teaching Hospital in Abbottabad. In total, 470 adults with early-onset T2DM were included in the study cohort after applying exclusion criteria. Participants were classified into two groups based on glycated hemoglobin (HbA1c) values: those with HbA1c ≤ 7% and those with HbA1c > 7%. Using SPSS version 27 (IBM Corp., Armonk, NY, US), data were analyzed as follows: Baseline characteristics were compiled using descriptive statistics, with mean and standard deviation for continuous variables and frequencies for categorical variables. Time to cardiovascular events relative to glycemic control levels was assessed using Kaplan-Meier survival analysis. To examine the relationship between HbA1c levels and the risk of CVD development, Cox proportional hazards models were employed, adjusting for potential confounders such as age, sex, diabetes duration, BMI, and lipid profile. Differences in continuous variables were analyzed using two-sample t-tests, with p-values < 0.05 considered statistically significant. Results This study assessed the impact of glycemic management on CVD progression in individuals with early-onset T2DM. A total of 470 participants were included, with those having HbA1c > 7% showing a significantly higher risk for cardiovascular events (hazard ratio: 1.88, 95% CI: 1.25-2.85, p < 0.01). Participants with higher HbA1c levels also exhibited worse lipid profiles, including elevated LDL cholesterol (130.4 mg/dL vs. 115.2 mg/dL, p < 0.01) and triglycerides (178.6 mg/dL vs. 150.7 mg/dL, p < 0.01), along with increased blood pressure. These findings highlight the critical role of glycemic control in CVD risk, particularly in younger populations with early-onset T2DM. Conclusion Maintaining HbA1c levels below 7% is crucial for reducing cardiovascular risk in individuals with early-onset T2DM. This study highlights the importance of comprehensive management strategies that focus on glycemic control, lipid regulation, and blood pressure management. These strategies should be implemented through evidence-based interventions, such as lifestyle modifications (e.g., dietary changes, physical activity), pharmacological treatments (e.g., metformin, statins, antihypertensive medications), and regular monitoring to improve cardiovascular outcomes. While the findings are based on a cohort from Ayub Teaching Hospital, they are likely relevant to similar populations with early-onset T2DM, though generalizability to other regions or healthcare settings should be considered with caution., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Review Board (IRB), Ayub Teaching Hospital, Abbottabad issued approval ATH/EC- 10/17(2). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gilani et al.)

Elevated serine peptidase inhibitor, Kazal type 1 (SPINK1) levels in ∼10%-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis and identified tyrosine kinase KIT as highly enriched. Furthermore, high to moderate levels of KIT expression were detected in ∼85% of SPINK1-positive PCa specimens. We show KIT signaling orchestrates SPINK1-mediated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling led to restoration of AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide distinct treatment modalities for advanced-stage SPINK1-positive patients., Competing Interests: N.P. is a consultant to Astrazeneca., (© 2024 The Authors.)

Microbial fuel cells (MFCs) seem to have emerged in recent years to degrade the organic pollutants from wastewater. The current research also focused on phenol biodegradation using MFCs. According to the US Environmental Protection Agency (EPA), phenol is a priority pollutant to remediate due to its potential adverse effects on human health. At the same time, the present study focused on the weakness of MFCs, which is the low generation of electrons due to the organic substrate. The present study used rotten rice as an organic substrate to empower the MFC's functional capacity to degrade the phenol while simultaneously generating bioenergy. In 19 days of operation, the phenol degradation efficiency was 70% at a current density of 17.10 mA/m 2 and a voltage of 199 mV. The electrochemical analysis showed that the internal resistance was 312.58 Ω and the maximum specific capacitance value was 0.00020 F/g on day 30, which demonstrated mature biofilm production and its stability throughout the operation. The biofilm study and bacterial identification process revealed that the presence of conductive pili species ( Bacillus genus) are the most dominant on the anode electrode. However, the present study also explained well the oxidation mechanism of rotten rice with phenol degradation. The most critical challenges for future recommendations are also enclosed in a separate section for the research community with concluding remarks.

Transcription factors (TFs) represent the most commonly deregulated DNA-binding class of proteins associated with multiple human cancers. They can act as transcriptional activators or repressors that rewire the cistrome, resulting in cellular reprogramming during cancer progression. Deregulation of TFs is associated with the onset and maintenance of various cancer types including prostate cancer. An emerging subset of TFs has been implicated in the regulation of multiple cancer hallmarks during tumorigenesis. Here, we discuss the role of key TFs which modulate transcriptional cicuitries involved in the development and progression of prostate cancer. We further highlight the role of TFs associated with key cancer hallmarks, including, chromatin remodeling, genome instability, DNA repair, invasion, and metastasis. We also discuss the pluripotent function of TFs in conferring lineage plasticity, that aids in disease progression to neuroendocrine prostate cancer. At the end, we summarize the current understanding and approaches employed for the therapeutic targeting of TFs and their cofactors in the clinical setups to prevent disease progression., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Antimicrobial resistance has posed a serious health concern worldwide, which is mainly due to the excessive use of antibiotics. In this study, gold nanoparticles synthesized from the plant Tinospora cordifolia were used against multidrug-resistant Pseudomonas aeruginosa . The active components involved in the reduction and stabilization of gold nanoparticles were revealed by gas chromatography-mass spectrophotometry(GC-MS) of the stem extract of Tinospora cordifolia. Gold nanoparticles (TG-AuNPs) were effective against P. aeruginosa at different concentrations (50,100, and 150 µg/mL). TG-AuNPs effectively reduced the pyocyanin level by 63.1% in PAO1 and by 68.7% in clinical isolates at 150 µg/mL; similarly, swarming and swimming motilities decreased by 53.1% and 53.8% for PAO1 and 66.6% and 52.8% in clinical isolates, respectively. Biofilm production was also reduced, and at a maximum concentration of 150 µg/mL of TG-AuNPs a 59.09% reduction inPAO1 and 64.7% reduction in clinical isolates were observed. Lower concentrations of TG-AuNPs (100 and 50 µg/mL) also reduced the pyocyanin, biofilm, swarming, and swimming. Phenotypically, the downregulation of exopolysaccharide secretion from P. aeruginosa due to TG-AuNPs was observed on Congo red agar plates.

The green synthesis method of was used for the synthesis of silver nanoparticles using Camellia sinensis (green tea). The Camellia sinensis silver nanoparticles (CS-AgNPs) were characterized using different techniques, including UV-Vis (ultra violet-visible), SEM (scanning electron microscopy), TEM (transmission electron microscopy), and XRD (X-ray diffraction). The average size of the CS-AgNPs was 52 nm, according to TEM. The CS-AgNPs showed excellent antibacterial and antifungal activity. The MIC (minimum inhibitory concentration) against bacterial isolates varied from 31.25 to 62.5 µg/mL, whereas for fungal isolates, the MIC varied from 125 to 250 µg/mL. The presence of a zone in the well diffusion assay showed the antimicrobial nature of CS-AgNPs. Further, CLSM (confocal laser scanning microscopy) showed that CS-AgNPs possess antibiofilm activity. The interaction of CS-AgNPs with the Candidal cells was analyzed using TEM, and it was revealed that CS-AgNPs entered the cell and disrupted the cell machinery.

The sol-gel technique was used to fabricate ZnO Nano-swirlings (ZNsw) at a predetermined agitation rate (of >> 1900 rpm), with around 21.94 gm of zinc acetate dihydrate and 0.2 g cetyltrimethylammoniumbromide (CTAB) and a cationic surfactant (drop-wise). The impact of the predetermined agitation condition on the molecular size and morphology of ZNsw is examined, and the outcomes are dissected by useful characterization tools and techniques viz. XRD, SEM embedded with EDS, TEM, FT-IR and UV-visible. The SEM and TEM results suggest that the product formed into a big cluster of adequate ZNsw, containing a significant quantity of folded long thread-lengths. Each group indicated a fair amount of the volume of these lengths. The photocatalytic process of ZNsw was carried out as a result of the irradiation time due to the deterioration of Azo Dye AR183, resulting in approximately 79 percent dye discoloration following an 80-min UV light irradiation in the presence of ZNsw. Additionally, the synthesized ZNsw was tested for antagonistic activity, and the growth hindrance of two plant pathogenic fungal strains found. Per cent inhibition in growth of Rhizoctonia solani and Alternaria alternata were observed in response to ZNsw., (© 2022. The Author(s).)

In this work, a polypyrrole-polyethyleneimine (PPy-PEI) nano-adsorbent was successfully synthesized for the removal of methylene blue (MB) from an aqueous solution. Synthetic dyes are among the most prevalent environmental contaminants. A new conducting polymer-based adsorbent called (PPy-PEI) was successfully produced using ammonium persulfate as an oxidant. The PEI hyper-branched polymer with terminal amino groups was added to the PPy adsorbent to provide more effective chelating sites for dyes. An efficient dye removal from an aqueous solution was demonstrated using a batch equilibrium technique that included a polyethyleneimine nano-adsorbent (PPy-PEI). The best adsorption parameters were measured at a 0.35 g dosage of adsorbent at a pH of 6.2 and a contact period of 40 min at room temperature. The produced PPy-PEI nano-adsorbent has an average particle size of 25-60 nm and a BET surface area of 17 m 2 /g. The results revealed that PPy-PEI nano-composite was synthesized, and adsorption was accomplished in the minimum amount of time. The maximum monolayer power, qmax, for MB was calculated using the isothermal adsorption data, which matched the Langmuir isotherm model, and the kinetic adsorption data, which more closely fitted the Langmuir pseudo-second-order kinetic model. The Langmuir model was used to calculate the maximum monolayer capacity, or qmax, for MB, which was found to be 183.3 mg g -1 . The as-prepared PPy-PEI nano-adsorbent totally removes the cationic dyes from the aqueous solution., Competing Interests: The authors declare no conflict of interest.

The present work focused on the utilization of three local wastes, i.e., rambutan (Nephelium lappaceum), langsat (Lansium parasiticum), and mango (Mangifera indica) wastes, as organic substrates in a benthic microbial fuel cell (BMFC) to reduce the cadmium and lead concentrations from synthetic water. Out of the three wastes, the mango waste promoted a maximum current density (87.71 mA/m 2 ) along with 78% and 80% removal efficiencies for Cd 2+ and Pb 2+ , respectively. The bacterial identification proved that Klebsiella pneumoniae, Enterobacter, and Citrobacter were responsible for metal removal and energy generation. In the present work, the BMFC mechanism, current challenges, and future recommendations are also enclosed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Photocatalytic degradation can be increased by improving photo-generated electrons and broadening the region of light absorption through conductive polymers. In that view, we have synthesized Polyaniline (PANI) with CdS, CdS-ZnS, and CdS-TiO 2 nanocomposites using the chemical precipitation method, characterized and verified for the photo-degradation of Acid blue-29 dye. This paper provides a methodical conception about in what way conductive polymers "PANI" enhances the performance rate of composite photocatalysts (CdS, CdS-ZnS and CdS-TiO 2 ). The nanocomposites charge transfer, molar ratio, surface morphology, particle size, diffraction pattern, thermal stability, optical and recombination of photo-generated charge carrier properties were determined. The production of nanocomposites and their efficient photocatalytic capabilities were observed. The mechanism of photocatalysis involved with PC, CZP and CTP nanocomposites are well presented by suitable diagrams representing the exchange of electrons and protons among themselves with supported equations. We discovered that increasing the number of nanocomposites in the membranes boosted both photocatalytic activity and degradation rate. CdS-Zinc-PANI (CZP) and CdS-TiO 2 -PANI(CTP) nanocomposites show entrapment at the surface defects of Zinc and TiO 2 nanoparticles due to the demolition of unfavorable electron kinetics, and by reducing the charge recombination, greater photocatalytic activity than CdS-PANI (CP) with the same nanoparticle loading was achieved. With repeated use, the photocatalysts' efficiency dropped very little, hinting that they may be used to remove organic pollutants from water. The photocatalytic activity of CZP and CTP photocatalytic membranes was greater when compared to CdS-PANI, which may be due to the good compatibility between CdS and Zinc and TiO 2 , as well efficient charge carrier separation. PANI can also increase the split-up of photo-excited charge carriers and extend the absorption zone when combined with these nanoparticles. As a result, the development of outrageous performance photocatalysts and their potential uses in ecological purification and solar power conversion has been facilitated. The novelty of this article is to present the degradation of AB-29 Dye using nanocomposites with polymers and study the enhanced degradation rate. Few studies have been carried out on polymer nanocomposites and their application in the degradation of AB-29 dyes and remediation of water purposes. Nanoparticle CdS is a very effective photocatalyst, commonly used for water purification along with nanoparticle ZnS and TiO 2 ; but cadmium ion-leaching makes it ineffective for practical and commercial use. In the present work, we have reduced the leaching of hazardous cadmium ions by trapping them in a polyaniline matrix, hence making it suitable for commercial use. We have embedded ZnS and TiO 2 along with CdS in a polyaniline matrix and compared their photocatalytic activity, stability, and reusability, proving our nano-composites suitable for commercial purposes with enhanced activities and stabilities, which is a novelty. All synthesized nanocomposites are active within the near-ultraviolet to deep infrared (i.e., 340-850 nm). This gives us full efficiency of the photocatalysts in the sunlight and further proves the commercial utility of our nanocomposites.

Although regarded as environmentally stable, bioelectrochemical fuel cells or, microbial fuel cells (MFCs) continue to face challenges with sustaining electron transport. In response, we examined the performance of two graphene composite-based anode electrodes-graphene oxide (GO) and GO-polymer-metal oxide (GO-PANI-Ag)-prepared from biomass and used in MFCs. Over 7 days of operation, GO energy efficiency peaked at 1.022 mW/m 2 and GO-PANI-Ag at 2.09 mW/m 2 . We also tested how well the MFCs could remove heavy metal ions from synthetic wastewater, a secondary application of MFCs that offers considerable benefits. Overall, GO-PANI-Ag had a higher removal rate than GO, with 78.10% removal of Pb(II) and 80.25% removal of Cd(II). Material characterizations, electrochemical testing, and microbial testing conducted to validate the anodes performance confirmed that using new materials as electrodes in MFCs can be an attractive approach to improve the electron transportation. When used with a natural organic substrate (e.g., sugar cane juice), they also present fewer challenges. We also optimized different parameters to confirm the efficiency of the MFCs under various operating conditions. Considering those results, we discuss some lingering challenges and potential possibilities for MFCs.

Neurodegenerative diseases are a group of debilitating maladies involving protein aggregation. To this day, all advances in neurodegenerative disease therapeutics have helped symptomatically but have not prevented the root cause of the disease, i.e., the aggregation of involved proteins. Antibiotics are becoming increasingly obsolete due to the rising multidrug resistance strains of bacteria. Thus, antibiotics, if put to different use as therapeutics against other diseases, could pave a new direction to the world of antibiotics. Hence, we studied the antibiotic levofloxacin for its potential anti-amyloidogenic behavior using human lysozyme, a protein involved in non-systemic amyloidosis, as a model system. At the sub-stoichiometric level, levofloxacin was able to inhibit amyloid formation in human lysozyme as observed by various spectroscopic and microscopic methods, with IC 50 values as low as 8.8 ± 0.1 μM. Levofloxacin also displayed a retarding effect on seeding phenomena by elongating the lag-phase (from 0 to 88 h) at lower concentration, and arresting lysozyme fibrillation at the lag stage in sub-stoichiometric concentrations. Structural and computational analyses provided mechanistic insight showing that levofloxacin stabilizes the lysozyme in the native state by binding to the aggregation-prone residues, and thereby inhibiting amyloid fibrillation. Levofloxacin also showed the property of disrupting amyloid fibrils into a smaller polymeric form of proteins which were less cytotoxic as confirmed by hemolytic assay. Therefore, we throw new light on levofloxacin as an amyloid inhibitor and disruptor which could pave way to utilization of levofloxacin as a potential therapeutic against non-systemic amyloidosis and neurodegenerative diseases., (Copyright © 2021. Published by Elsevier Inc.)

Sustainable water processing techniques have been extensively investigated and are capable of improving water quality. Among the techniques, photocatalytic technology has shown great potential in recent years as a low cost, environmentally friendly and sustainable technology. However, the major challenge in the industrial development of photocatalyst technology is to develop an ideal photocatalyst which must have high photocatalytic activity, a large specific surface area, harvest sunlight and shows recyclability. Keeping these views, the present review highlighted the synthesis approaches of graphene/metal oxide nanocomposite, characterization techniques and their prominent applications in photocatalysis. Various parameters such as photocatalyst loading, structure of photocatalyst, temperature, pH, effect of oxidizing species and wavelength of light were addressed which could affect the rate of degradation. Moreover, the formation of intermediates during photo-oxidation of organic pollutants using these photocatalysts is also discussed. The analysis concluded with a synopsis of the importance of graphene-based materials in pollutant removal. Finally, a brief overview of the problems and future approaches in the field is also presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jamjoum, Umar, Adnan, Razali and Mohamad Ibrahim.)

Benthic microbial fuel cells (BMFCs) are considered to be one of the eco-friendly bioelectrochemical cell approaches nowadays. The utilization of waste materials in BMFCs is to generate energy and concurrently bioremediate the toxic metals from synthetic wastewater, which is an ideal approach. The use of novel electrode material and natural organic waste material as substrates can minimize the present challenges of the BMFCs. The present study is focused on cellulosic derived graphene-polyaniline (GO-PANI) composite anode fabrication in order to improve the electron transfer rate. Several electrochemical and physicochemical techniques are used to characterize the performance of anodes in BMFCs. The maximum current density during polarization behavior was found to be 87.71 mA/m 2 in the presence of the GO-PANI anode with sweet potato as an organic substrate in BMFCs, while the GO-PANI offered 15.13 mA/m 2 current density under the close circuit conditions in the presence of 1000 Ω external resistance. The modified graphene anode showed four times higher performance than the unmodified anode. Similarly, the remediation efficiency of GO-PANI was 65.51% for Cd (II) and 60.33% for Pb (II), which is also higher than the unmodified graphene anode. Furthermore, multiple parameters (pH, temperature, organic substrate) were optimized to validate the efficiency of the fabricated anode in different environmental atmospheres via BMFCs. In order to ensure the practice of BMFCs at industrial level, some present challenges and future perspectives are also considered briefly.

A study was carried out to determine the effectiveness of lignin, extracted from oil palm (Elaeis guineensis) biomass as water-in-oil (W/O) emulsifying agent. To achieve this goal, soda lignin (SL) was extracted via soda pulping process and a series of nanosized soda lignin (NSL) were prepared using homogenizer at three different speed i.e. 10,400 rpm (NSL 10), 11,400 rpm (NSL 11) and 12,400 rpm (NSL 12) for one hour. All prepared samples were characterized by FT-IR, UV-Vis spectroscopy, thermogravimetric analysis (TGA), zeta potential analyser, Transmission Electron Microscope (TEM) and Extreme High Resolution Field Emission Scanning Electron Microscope (XHR-FESEM). The result of FTIR showed that there is no prominent change occurred in spectra of all samples while a good stability was reflected by TGA curves. The percentage of creaming index and visual observations of all samples demonstrated that NSL 12 and dosage 2 g (out of 1 g, 1.5 g and 2 g) were found to be the best among all samples. Furthermore, the results of IFT indicate that NSL 12 was proven to be more stable than the commercial product. Therefore, NSL 12 is selected for toxicological studies and was found safe in both, in vitro and in vivo studies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Nanoparticles (nanoparticles) have received much attention in biological application because of their unique physicochemical properties. The metal- and metal oxide-supported nanomaterials have shown significant therapeutic effect in medical science. The mechanisms related to the interaction of nanoparticles with animal and plant cells can be used to establish its significant role and to improve their activity in health and medical applications. Various attempts have been made to discuss the antibiotic resistance and antimicrobial activity of metal-supported nanoparticles. Despite all these developments, there is still a need to investigate their performance to overcome modern challenges. In this regard, the present review examines the role of various types of metal-supported nanomaterials in different areas such as antibacterial, antifungal, anticancer, and so on. Based on the significant ongoing research and applications, it is expected that metal-supported nanomaterials play an outstanding role not only in medical but also in other important areas., (Copyright © 2020 Yaqoob, Ahmad, Parveen, Ahmad, Oves, Ismail, Qari, Umar and Mohamad Ibrahim.)

The recycling and treatment of wastewater using microbial fuel cells (MFCs) has been attracting significant attention as a way to control energy crises and water pollution simultaneously. Despite all efforts, MFCs are unable to produce high energy or efficiently treat pollutants due to several issues, one being the anode's material. The anode is one of the most important parts of an MFC. Recently, different types of anode materials have been developed to improve the removal rate of pollutants and the efficiency of energy production. In MFCs, carbon-based materials have been employed as the most commonly preferred anode material. An extensive range of potentials are presently available for use in the fabrication of anode materials and can considerably minimize the current challenges, such as the need for high quality materials and their costs. The fabrication of an anode using biomass waste is an ideal approach to address the present issues and increase the working efficiency of MFCs. Furthermore, the current challenges and future perspectives of anode materials are briefly discussed.

Nanotechnology is an innovative area of science that includes the design, characterization, production, and application of materials, devices and systems by controlling shape and size at the nanometer scale (1-100 nm). Nanotechnology incorporation in cosmetic formulation is considered as the hottest and emerging technology available. Cosmetic manufacturers use nanoscale size ingredients to provide better UV protection, deeper skin penetration, long-lasting effects, increased color, finish quality, and many more. Micellar nanoparticles is one of the latest field applied in cosmetic products that becoming trending and widely commercialized in local and international markets. The ability of nanoemulsion system to form small micellar nanoparticles size with high surface area allowing to effectiveness of bioactive component transport onto the skin. Oil in water nanoemulsion is playing a major role as effective formulation in cosmetics such as make-up remover, facial cleanser, anti-aging lotion, sun-screens, and other water-based cosmetic formulations. The objective of this review is to critically discuss the properties, advantageous, and mechanism of micellar nanoparticles formation in nanoemulsion system. Therefore, present article introduce and discuss the specific benefits of nanoemulsion system in forming micellar nanoparticles for cosmetic formulation which become major factors for further development of micellar-based cosmetic segments., (Copyright © 2019 Aziz, Mohd-Nasir, Ahmad, Mohd. Setapar, Peng, Chuo, Khatoon, Umar, Yaqoob and Mohamad Ibrahim.)

The authors describe a method for solvent-free mechano-chemical synthesis of a bioinspired sorbent. A 2D ultra-thin carbon sheet similar to graphene oxide was prepared using a natural waste (onion sheet). The formation of 2D carbon sheets was confirmed by Raman spectroscopy, X-ray photoelectron spectroscopy and ATR-IR. The surface morphology was characterized by field emission scanning electron microscopy and high-resolution tunneling electron microscopy. The carbon sheets were decorated with crystalline MnFe 2 O 4 nanoparticles by solid-state reaction at room temperature. The presence of magnetic particles in the final product was confirmed by vibrating sample magnetometry and electron microscopy. The synergistic effect of carbon sheets and MnFe 2 O 4 led to an enhanced sorption of arsenic species compared to bare carbon sheets or to MnFe 2 O 4 nanoparticles. A column was prepared for the simultaneous preconcentration and determination of trace levels of As(III) and As(V) from water samples. The preconcentration factors are between 900 and 833 for As(III) and As(V) species, respectively. The linearity of the calibration plot ranges from 0.4-10 ng mL -1 . The detection limits (at 3σ) for both As(III) and As(V) are 30 pg mL -1 . The Student's t values for the analysis of spiked samples are lower than the critical Student's t values at a 95% confidence level. The recoveries from spiked water samples range between 99 and 102.8%. Graphical abstract Schematic representation of the preparation of carbon sheets similar to graphene oxide from onion sheaths after pyrolysis at 800 °C. The prepared carbon sheet-MnFe 2 O 4 composite shows excellent arsenic sorption and preconcentration down to the pg mL -1 concentration.

Background: Daunorubicin hydrochloride (DAUN·HCl), due to low oral bioavailability poses the hindrance to be marketed as an oral formulation., Aim of the Study: To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN., Results: A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p < 0.01) inhuman colon adenocarcinoma cell line (Caco-2). For PK, CS-DAUN-PLGA-NPs as compared to DAUN-S, exhibited a 10.0 fold higher bioavailability in Wister rat's plasma due to presence of a natural biodegradable macromolecule i.e. CS coated on the PLGA-NPs. With regard to bioanalytical method, easy as well as a rapid method for DAUN-plasma quantification was developed as; 2.75 min and 528.49/321.54 m/z for DAUN along with 1.94 min and 544.36/397.41 m/z for IS i.e. Doxorubicin, for elution time and transition, respectively., Conclusion: A novel natural biodegradable approach used in the preparation of CS coated DAUN-NPs for oral administration of DAUN is reported in this study which is can be utilized as an alternate for intravenous therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A column sorbent for arsenic was obtained through immobilization of highly branched polyethylenimine (PEI) on graphene oxide (GO). The composite material enables speciation of arsenic by tuning the pH of the sample solution which governs the surface charge of the sorbent, depending on whether amino groups (-NH 2 ) are present (at high pH) or ammonium groups (-NH 3 + ; at low pH). The composite can be applied to improved speciation of arsenic (compared to unmodified GO). There is no need for oxidation or reduction of arsenic. A column procedure was applied for the sequestered extraction and speciation of As(III) and As(V) from environmental water samples before their determination by hydride generation-microwave induced plasma-atomic emission spectrometry. The method has a preconcentration factor of 440 for As(III) and of 400 for As(V). The limits of detection (at 3 S/N) are extremely low, being 1.8 ± 0.2 ngL -1 for As(III) and 1.3 ± 0.08 ngL -1 for As(V). This is much lower than the arsenic guideline value of 10 μgL -1 as given by the WHO. Graphical abstract Graphene oxide interconnected with polyethyleneimine has been employed for the speciation and determination of arsenic. Quantitation by atomic emission spectroscopy reveals a high preconcentration factor (440 and 400) and low LODs of 1.8 ± 0.2 and 1.3 ± 0.08 ngL -1 for As(III) and As(V), respectively.

In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7μm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A sensitive and selective gas chromatography with mass spectrometry method was developed for the simultaneous determination of three organophosphorus pesticides, namely, chlorpyrifos, malathion, and diazinon in three different food commodities (milk, apples, and drinking water) employing solid-phase extraction for sample pretreatment. Pesticide extraction from different sample matrices was carried out on Chromabond C18 cartridges using 3.0 mL of methanol and 3.0 mL of a mixture of dichloromethane/acetonitrile (1:1 v/v) as the eluting solvent. Analysis was carried out by gas chromatography coupled with mass spectrometry using selected-ion monitoring mode. Good linear relationships were obtained in the range of 0.1-50 μg/L for chlorpyrifos, and 0.05-50 μg/L for both malathion and diazinon pesticides. Good repeatability and recoveries were obtained in the range of 78.54-86.73% for three pesticides under the optimized experimental conditions. The limit of detection ranged from 0.02 to 0.03 μg/L, and the limit of quantification ranged from 0.05 to 0.1 μg/L for all three pesticides. Finally, the developed method was successfully applied for the determination of three targeted pesticides in milk, apples, and drinking water samples each in triplicate. No pesticide was found in apple and milk samples, but chlorpyrifos was found in one drinking water sample below the quantification level., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of darunavir, ritonavir and tenofovir in human plasma. Sample preparation involved a simple liquid-liquid extraction using 200 μL of human plasma extracted with methyl tert-butyl ether for three analytes and internal standard. The separation was accomplished on an Acquity UPLC BEH C18 (50 mm x 2.1 mm, 1.7 μm) analytical column using gradient elution of acetonitrile/methanol (80:20, v/v) and 5.0 mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4 mL/min. The linearity of the method ranged between 20.0 and 12 000 ng/mL for darunavir, 2.0 and 2280 ng/mL for ritonavir, and 14.0 and 1600 ng/mL for tenofovir using 200 μL of plasma. The method was completely validated for its selectivity, sensitivity, linearity, precision and accuracy, recovery, matrix effect, stability, and dilution integrity. The extraction recoveries were consistent and ranged between 79.91 and 90.04% for all three analytes and internal standard. The method exhibited good intra-day and inter-day precision between 1.78 and 6.27%. Finally the method was successfully applied for human pharmacokinetic study in eight healthy male volunteers after the oral administration of 600 mg darunavir along with 100 mg ritonavir and 100 mg tenofovir as boosters., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors' intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to destruction of joints. Current treatment modalities for RA either produce symptomatic relief (NSAIDs) or modify the disease process (DMARDs). Though effective, their use is also limited by their side effects. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and antiarthritic activity of Boswellia serrata gum resin extract (BSE) in collagen induced arthritis. Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. BSE was administered at doses of 100 and 200mg/kg body weight once daily for 21 days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1β, IL-6, TNF-α, IL-10, IFN-γ and PGE2), and histological studies in joints. BSE was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of BSE resulted in significantly reduced levels of inflammatory mediators (IL-1β, IL-6, TNF-α, IFN-γ and PGE2), and increased level of IL-10. The protective effects of BSE against RA were also evident from the decrease in arthritis scoring and bone histology. The abilities to inhibit proinflammatory cytokines and modulation of antioxidant status suggest that the protective effect of Boswellia serrata extract on arthritis in rats might be mediated via the modulation of immune system., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

A novel polyaniline based composite cation exchange material has been synthesized by simple chemical route and characterized on the basis of sophisticated techniques. XRD and SEM analyses reveal the amorphous morphology of the material. The partition coefficient studies of different metal ions on the material were performed in DMW and diverse concentrations of HClO4 solutions. On the basis of high Kd values some significant separations of heavy toxic metal ions were achieved from synthetic mixtures as well as tap water samples by using columns of this exchanger. For the optimum adsorption of dye on the material, the effect of various parameters along with Langmuir and Freundlich adsorption isotherm were examined. The observed result of conducting measurement indicates that the material covers semiconductor range. The photochemical degradation of industrial dyes and antimicrobial activity were also investigated which show significant results than some of the known antibiotics. On the basis of good ion exchange capacity along with photochemical degradation and microbial activity, polyanilineTi(IV)arsenophosphate can be considered as an excellent conducting material for the treatment metal ions and degradation of organic pollutants., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine., Methods: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1β, TNF-α, IL-10 and PGE2) and histological studies in joints., Results: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1β, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology., Conclusions: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Thymoquinone (TQ) is the major active compound derived from Nigella sativa. Our aim of this work was to evaluate the antioxidant and antiarthritic activity of TQ in Wistar rat by collagen induced arthritis (CIA). TQ was administered at a dose of 5mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1β, IL-6, TNF-α, IL-10, IFN-γ and PGE(2)) and histological studies in joints. TQ was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of TQ resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1β, IL-6, TNF-α, IFN-γ and PGE(2)) and increased level of IL-10. The protective effects of TQ against RA were also evident from the decrease in arthritis scoring and bone histology. In conclusion, the fact that TQ abolished a number of factors known to be involved in RA pathogenesis indicates that the administration of thymoquinone may have potential value in the treatment of inflammatory disease., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)