Cholic Acid-Grafted Thiolated Chitosan-Enveloped Nanoliposomes for Enhanced Oral Bioavailability of Azathioprine: In Vitro and In Vivo Evaluation.

The purpose of the present study was to develop a cholic acid-grafted thiolated chitosan (CA-CS-TGA) polymeric biomaterial for attaining improved permeation via attaching thiol groups and cholic acid moieties. For this purpose, a CA-CS-TGA graft was prepared, and modification was confirmed via FTIR analysis. The prepared CA-CS-TGA graft was used to coat the azathioprine-loaded nanoliposomes (ENLs), with subsequent characterization in terms of zeta size, zeta potential, and SEM analysis. Pharmaceutical evaluation was carried out in terms of drug release studies, and ex vivo permeation and in vivo oral bioavailability were studied. The particle size and zeta potential of CA-CS-TGA coated nanoliposomal formulation CA-CS-TGA-NLs were found to be 245 ± 15.6 and +22.4 ± 0.58, respectively, compared to that of nonenveloped nanoliposomal formulation 165.7 ± 12.3 and -21.8 ± 0.14, respectively, indicating successful coating. CA-CS-TGA-NLs indicated 64% of drug release in 24 h at pH 7.4. Ex vivo permeation enhancement and relative oral bioavailability studies indicated a 2.84-fold enhanced permeation and 6-fold enhanced oral bioavailability of CA-CS-TGA-NLs compared to Azathioprine suspension. Based on the results, it can be concluded that grafting the CA-CS-TGA polymer onto nanoliposomes seems to be a promising strategy to enhance the oral bioavailability of Azathioprine.

Seizures as the only presentation of Pulmonary Embolism in the absence of Respiratory Symptoms.

Pulmonary embolism is a life-threatening emergency. Seizure as the clinical presentation of pulmonary embolism is extremely rare. In this case report a 47-year-old female had an episode of seizure after undergoing total abdominal hysterectomy with bilateral salpingo-oophorectomy due to myometrial uterine fibroids. The patient had no past history of seizure or cardiovascular disease. Based on raised D-Dimers and echocardiography a provisional diagnosis of pulmonary embolism was made, which was confirmed on CT angiogram that showed bilateral saddle pulmonary embolism. Clinicians need to be aware that Pulmonary embolism is a possibility as the differential diagnosis for unexplained, new-onset of seizure activity.

Ca n neutral clusters: a two-step G 0 W 0 and DFT benchmark.

Electronic and structural properties of calcium clusters with a varying size range of 2-20 atoms are studied using a two-step scheme within the GW and density functional theory (DFT) with generalized gradient approximation (GGA). The GGA overestimates the binding energies, optimized geometries, electron affinities, and ionization potentials reported in the benchmark. The ground-state structure geometry and binding energy were obtained from the DFT for the ground-state structure of each cluster. The binding energy of the neutral clusters of the calcium series follows an increasing trend, except for a few stable even and odd clusters. The electronic properties of the calcium cluster were studied with an all-electron FHI-aims code. In the G 0 W 0 calculation, the magic cluster Ca10 has relatively high ionization potential and low electron affinity. The obtained ionization potentials from the G 0 W 0 @PBE calculation showed that the larger cluster has less variation, whereas the electron affinities of the series have an increasing trend. The ionization potentials from the G 0 W 0 benchmark for the calcium cluster series have not yet been described in the literature.

Immunological assay using a solid-state pore with a low limit of detection.

Emerging infectious diseases, cancer, and other diseases are quickly tested mainly via immune reactions based on specific molecular recognition between antigens and antibodies. By changing the diameter of solid-state pores, biomolecules of various sizes can be rapidly detected at the single-molecule level. The combination of immunoreactions and solid-state pores paves the way for an efficient testing method with high specificity and sensitivity. The challenge in developing this method is achieving quantitative analysis using solid-state pores. Here, we demonstrate a method with a low limit of detection for testing tumor markers using a combination of immunoreactions and solid-state pore technology. Quantitative analysis of the mixing ratio of two and three beads with different diameters was achieved with an error rate of up to 4.7%. The hybrid solid-state pore and immunoreaction methods with prostate-specific antigen (PSA) and anti-PSA antibody-modified beads achieved a detection limit of 24.9 fM PSA in 30 min. The hybrid solid-state pore and immunoreaction enabled the rapid development of easy-to-use tests with lower limit of detection and greater throughput than commercially available immunoassay for point-of-care testing.

A remarkable study to unveil the relationship between fluorescence life time decay(ns) and nonlinear optical parameters of series of porphyrin and polyoxometalates hybrids.

Relationship between excited state dynamics and nonlinear optical (NLO) parameters is very unique. Herein, three different polyoxometalates (POMs) namely WD-POM (Wells-Dawson POM) based porphyrin hybrids WDPOM3PyP, Trans-2WDPOM2PyP, and 3WDPOMPyP (having one, two, and three WD-POM respectively), and their porphyrin precursors with (Trishydroxyl amino methane) namely Tris3PyP, Trans-2Tris2PyP, and 3TrisPyP respectively have been used for the study. Fluorescence decay and Z-scan studies by using nanosecond (ns) time span conveys the corresponding lifespan for each excited state, along with the NLO analysis respectively. The calculated lifetime data were found in the range of 3WDPOMPyP (τ1 = 5.65 ns), Trans-2WDPOM2PyP (τ1 = 2.21 ns), and WDPOM3PyP (τ1 = 1.96 ns). Third order NLO measurements represented that WDPOM3PyP showed better NLO response (χ3 = 2.26 × 10-10esu and ß = 1.54 × 10-5 esu) as compared to Trans-2WDPOM2PyP (χ3 = 1.73 × 10-10 esu and ß = 1.53 × 10-5 esu), and 3WDPOMPyP (χ3 = 1.55 × 10-10 esu and ß = 0.65 × 10-5 esu) obtained at wavelength of 532 nm. Electrochemical studies have shown that the minor energy differences between the singlet and triplet excited states are responsible for intercrossing system (ISC) that helps in the transfer of electrons from porphyrin moiety to WD-POM. By absorbing a photon, the excited species were produced causing an initial charge transfer. This charge transfer state undergoes an electron transfer decaying to the lowest triplet state, and singlet state causing an increase in NLO. The obtained results indicated potential uses in photonic and all-optical switching devices.

Enzyme-mediated green synthesis of glycosaminoglycans and catalytic process intensification.

Glycosaminoglycans (GAGs) are a family of structurally complex heteropolysaccharides that play pivotal roles in biological functions, including the regulation of cell proliferation, enzyme inhibition, and activation of growth factor receptors. Therefore, the synthesis of GAGs is a hot research topic in drug development. The enzymatic synthesis of GAGs has received widespread attention due to their eco-friendly nature, high regioselectivity, and stereoselectivity. The enhancement of the enzymatic synthesis process is the key to its industrial applications. In this review, we overviewed the construction of more efficient in vitro biomimetic synthesis systems of glycosaminoglycans and presented the different strategies to improve enzyme catalysis, including the combination of chemical and enzymatic methods, solid-phase synthesis, and protein engineering to solve the problems of enzyme stability, separation and purification of the product, preparation of structurally defined sugar chains, etc., and discussed the challenges and opportunities in large-scale green synthesis of GAGs.

Assessment of peripheral dose as a function of distance and depth from cobalt-60 beam in water phantom using TLD-100.

BACKGROUND: Innovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100). METHODS: The PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm. RESULTS: The results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor. CONCLUSION: It is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.

Testicular Mixed Germ Cell Tumor (TMGCT) Management: Addressing Infection and Tumor Marker Dynamics.

We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular carcinoma. Elevated serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) levels were observed. Biopsy confirmed a mixed germ cell tumor (MGCT). Concurrently, the patient was diagnosed with an infection and treated with antibiotics. Remarkably, following antibiotic therapy, fever resolved, and tumor marker levels significantly decreased. Subsequent orchidectomy confirmed the diagnosis of MGCT. This case underscores the importance of recognizing and treating concurrent infections, which may influence both clinical presentation and tumor marker levels in testicular germ cell tumors.

Extraction of cellulose from halophytic plants for the synthesis of a novel biocomposite.

Cellulose nanofibers, a sustainable and promising material with widespread applications, exhibit appreciable strength and excellent mechanical and physicochemical properties. The preparation of cellulosic nanofibers from food or agricultural residue is not sustainable. Therefore, this study was designed to use three halophytic plants (Cressa cretica, Phragmites karka, and Suaeda fruticosa) to extract cellulose for the subsequent conversion to cellulosic nanofibers composites. The other extracted biomass components including lignin, hemicellulose, and pectin were also utilized to obtain industrially valuable enzymes. The maximum pectinase (31.56 IU mL-1), xylanase (35.21 IU mL-1), and laccase (15.89 IU mL-1) were produced after the fermentation of extracted pectin, hemicellulose, and lignin from S. fruticosa, P. karka, and C. cretica, respectively. Cellulose was methylated (with a degree of substitution of 2.4) and subsequently converted into a composite using polyvinyl alcohol. Scanning electron microscopy and Fourier-transform infrared spectroscopy confirmed the successful synthesis of the composites. The composites made up of cellulose from C. cretica and S. fruticosa had a high tensile strength (21.5 and 15.2 MPa) and low biodegradability (47.58% and 44.56%, respectively) after dumping for 3 months in soil, as compared with the composite from P. karka (98.79% biodegradability and 4.9 MPa tensile strength). Moreover, all the composites exhibited antibacterial activity against gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and gram-positive bacteria (Staphylococcus aureus). Hence, this study emphasizes the possibility for various industrial applications of biomass from halophytic plants.

Optimized submerged batch fermentation for metabolic switching in Streptomyces yanglinensis 3-10 providing platform for reveromycin A and B biosynthesis, engineering, and production.

The cultivation system requires that the approach providing biomass for all types of metabolic analysis is of excellent quality and reliability. This study was conducted to enhance the efficiency and yield of antifungal substance (AFS) production in Streptomyces yanglinensis 3-10 by optimizing operation conditions of aeration, agitation, carbon source, and incubation time in a fermenter. Dissolved oxygen (DO) and pH were found to play significant roles in AFS production. The optimum pH for the production of AFS in S. yanglinensis 3-10 was found to be 6.5. As the AFS synthesis is generally thought to be an aerobic process, DO plays a significant role. The synthesis of bioactive compounds can vary depending on how DO affects growth rate. This study validates that the high growth rate and antifungal activity required a minimum DO concentration of approximately 20% saturation. The DO supply in a fermenter can be raised once agitation and aeration have been adjusted. Consequently, DO can stimulate the development of bacteria and enzyme production. A large shearing effect could result from the extreme agitation, harming the cell and deactivating its products. The highest inhibition zone diameter (IZD) was obtained with 3% starch, making starch a more efficient carbon source than glucose. Temperature is another important factor affecting AFS production. The needed fermentation time would increase and AFS production would be reduced by the too-low operating temperature. Furthermore, large-scale fermenters are challenging to manage at temperatures that are far below from room temperature. According to this research, 28°C is the ideal temperature for the fermentation of S. yanglinensis 3-10. The current study deals with the optimization of submerged batch fermentation involving the modification of operation conditions to effectively enhance the efficiency and yield of AFS production in S. yanglinensis 3-10.

Assessment of textile effluent treatment by immobilized Trametes pubescens MB 89 for plant growth promotion.

Industrialization and the ever-increasing world population have diminished high-quality water resources for sustainable agriculture. It is imperative to effectively treat industrial effluent to render the treated water available for crop cultivation. This study aimed to assess the effectiveness of textile effluent treated with Trametes pubescens MB 89 in supporting maize cultivation. The fungal treatment reduced the amounts of Co, Pb and As in the textile effluent. The biological oxygen demand, total dissolved solids and total suspended solids were within the permissible limits in the treated effluent. The data indicated that the irrigation of maize with fungal-treated textile effluent improved the growth parameters of the plant including root, shoot length, leaf area and chlorophyll content. Moreover, better antioxidant activity, total phenol content and protein content in roots, stems and leaves of maize plants were obtained. Photosynthetic parameters (potential quantum yield, electron transport rate and fluorescence yield of non-photochemical losses other than heat) were also improved in the plants irrigated with treated effluent as compared to the control groups. In conclusion, the treatment of textile effluent with the immobilized T. pubescens presents a sustainable solution to minimize chemical pollution and effectively utilize water resources.

Bridging theory and practice: A comprehensive algorithm for imageless total knee arthroplasty.

Total knee arthroplasty (TKA) is a surgical procedure to treat severe knee osteoarthritis. Among several techniques available for performing TKA, imageless TKA is known for achieving precise alignment while minimizing invasiveness. This work proposes a comprehensive algorithm for imageless TKA device to calculate the varus/valgus and flexion/extension angles, as well as resection depths for cutting planes at distal femur and proximal tibia. Moreover, the algorithm calculates the hip-knee-ankle (HKA) and flexion angles of the leg. Initially, the proposed algorithm was validated in a virtual environment using a CT-scanned bone model in Solidworks. Subsequently, for the real-world validation, a SoftBone model was resected with conventional intra and extramedullary rods and cross-checked with the proposed algorithm. For the third validation, another SoftBone model was resected with the proposed algorithm and cuts were measured with a vernier caliper. During this experiment, there was an error of approximately 1 mm for both femoral and tibial resection cases when using an infrared camera with an accuracy of ±0.5 mm. However, this error could be reduced using an infrared camera with higher accuracy.

Evaluation of a novel composite of expanded polystyrene with rGO and SEBS-g-MA.

This study displays the effect of reduced graphene oxide (rGO) nanofiller and polystyrene-b-poly(ethylene-ran-butylene)-b-polystyrene-grafted maleic anhydride (SEBS-g-MA) on the optical, thermal, and mechanical features of expanded polystyrene (EPS). First, the thin films of pristine EPS and composites were prepared using solution cast method. The prepared films were subjected to fourier-transform infrared (FTIR), SEM, UV-visible spectrophotometer, thermogravimetric analysis/differential scanning calorimetry, and universal testing machine for structural, morphological, optical, thermal, and mechanical characterizations. Optical study revealed a significant increase in refractive index and absorption of composites than EPS. Indirect band-gap energy of EPS (~4.08 eV) was reduced to ~1.61 eV for rGO composite and ~ 2.23 eV for composite composed of rGO and SEBS-g-MA. Thermal analyses presented improvement in characterization temperatures such as T10, T50, Tp, Tm, and Tg of composites, which ultimately lead to the thermal stability of prepared composites than pristine EPS. Stress-strain curves displayed higher yield strength (46.62 MPa), Young's modulus (96.29 MPa), and strain at break (0.54%) for EPS+rGO composite than pure EPS having stress at break (1.01 MPa), Young's modulus (12.44 MPa), and strain at break (0.08%). Moreover, ductility with relatively higher strain at break (0.61%) and lower Young's modulus (79.32 MPa) and yield strength (32.98 MPa) was noticed in EPS+rGO+SEBS-g-MA composite than EPS+rGO composite film. Morphological analysis revealed a change in globular morphology of EPS and inhomogeneous dispersion of rGO in EPS to homogeneously dispersed rGO in EPS matrix without globules owing to the addition of SEBS-g-MA. The increase in compatibility of EPS and rGO due to SEBS-g-MA was also observed in FTIR spectra. RESEARCH HIGHLIGHTS: Here, the solution casting approach was used to create the composite film of EPS and rGO with globules of various sizes. After adding SEBS-g-MA, the shape altered to globular free films exhibiting homogenous dispersion of rGO in EPS matrix. An optical investigation showed that composite materials had a significantly higher refractive index and absorption than EPS. The optical, thermal, and mechanical investigations suggest that the produced composites may be a great substitute for virgin EPS, allowing for a wider range of applications.

Agrochemical-free genetically modified and genome-edited crops: Towards achieving the United Nations sustainable development goals and a 'greener' green revolution.

Sustainable farming on ever-shrinking agricultural land and declining water resources for the growing human population is one of the greatest environmental and food security challenges of the 21st century. Conventional, age-old organic farming practices alone, and foods based on costly cellular agriculture, do not have the potential to be upscaled to meet the food supply challenges for feeding large populations. Additionally, agricultural practices relying on chemical inputs have a well-documented detrimental impact on human health and the environment. As the available farming methods have reached their productivity limits, new approaches to agriculture, combining friendly, age-old farming practices with modern technologies that exclude chemical interventions, are necessary to address the food production challenges. Growing genetically modified (GM) crops without chemical inputs can allow agricultural intensification with reduced adverse health and environmental impacts. Additionally, integrating high-value pleiotropic genes in their genetic improvement coupled with the use of modern agricultural technologies, like robotics and artificial intelligence (AI), will further improve productivity. Such 'organic-GM' crops will offer consumers healthy, agrochemical-free GM produce. We believe these agricultural practices will lead to the beginning of a potentially new chemical-free GM agricultural revolution in the era of Agriculture 4.0 and help meet the targets of the United Nations Sustainable Development Goals (SDGs). Furthermore, given the advancement in the genome editing (GE) toolbox, we ought to develop a new category of 'trait-reversible GM crops' to avert the fears of those who believe in ecological damage by GM crops. Thus, in this article, we advocate farming with no or minimal chemical use by combining chemical-free organic farming with the existing biofortified and multiple stress tolerant GM crops, while focusing on the development of novel 'biofertilizer-responsive GE crops' and 'trait-reversible GE crops' for the future.

The Mystery of Electrical Storm: A Case Report.

Electrical storm is a cardiac emergency, defined as three or more hemodynamically unstable ventricular tachyarrythmias within 24 hours or ventricular tachycardia reoccurring within five minutes. The trigger for an electrical storm can be reversible like drug toxicity and electrolyte imbalances or can be irreversible like structural heart disease. Symptomatic patients can have chest pain, palpitations or syncopal episodes. We present a case of a gentleman in his 60s who was diagnosed with electrical storm which started as an out-of-hospital cardiac arrest. Uniqueness in the case lies in the unknown aetiology after all the investigations came back as normal and management of such cases is based on pacemakers and use of antiarrythmic agents to control and prevent further attacks.

N-Alkylation through the Borrowing Hydrogen Pathway Catalyzed by the Metal-Organic Framework-Supported Iridium-Monophosphine Complex.

Further development in the area of medicinal chemistry requires facile and atom-economical C-N bond formation from readily accessible precursors using recyclable and reusable catalysts with low process toxicity. In this work, direct N-alkylation of amines with alcohols is performed with a series of Ir-phosphine-functionalized metal-organic framework (MOF) heterogeneous catalysts. The grafted monophosphine-Ir complexes were studied comprehensively to illustrate the ligand-dependent reactivity. The afforded MOF catalysts exhibited high reactivity and selectivity toward N-alkylamine product formation, especially UiO-66-PPh2-Ir, which showed 90% conversion after recycling with no catalyst residue remaining in the product after the reaction. Furthermore, analyses of the active catalyst, mechanistic studies, control experiments, and H2 adsorption tests are consistent with the conclusion that immobilization of the iridium complex on the MOF support enables the formation of the iridium-monophosphine complex and enhances its stability during the reaction. To illustrate the potential of the catalyst for application in medicinal chemistry, two pharmaceutical precursors were synthesized with up to 99% conversion and selectivity.

Rice false smut pathogen: implications for mycotoxin contamination, current status, and future perspectives.

Rice serves as a staple food across various continents worldwide. The rice plant faces significant threats from a range of fungal, bacterial, and viral pathogens. Among these, rice false smut disease (RFS) caused by Villosiclava virens is one of the devastating diseases in rice fields. This disease is widespread in major rice-growing regions such as China, Pakistan, Bangladesh, India, and others, leading to significant losses in rice plantations. Various toxins are produced during the infection of this disease in rice plants, impacting the fertilization process as well. This review paper lightens the disease cycle, plant immunity, and infection process during RFS. Mycotoxin production in RFS affects rice plants in multiple ways, although the exact phenomena are still unknown.

Investigating structural and electronic properties of neutral zinc clusters: a G0W0 and G0W0Г0(1) benchmark.

The structural and electronic properties of zinc clusters (Znn) for a size range of n = 2-15 are studied using density functional theory. The particle swarm optimization algorithm is employed to search the structure and to determine the ground-state structure of the neutral Zn clusters. The structural motifs are optimized using the density functional theory approach to ensure that the structures are fully relaxed. Results are compared with the literature to validate the accuracy of the prediction method. The binding energy per cluster is obtained and compared with the reported literature to study the stability of these structures. We further assess the electronic properties, including the ionization potential, using the all-electron FHI-aims code employing G0W0 calculations, and the G0W0Г0(1) correction for a few smaller clusters, which provides a better estimation of the ionization potential compared to other methods.

Source tracking of extensively drug resistant Salmonella Typhi in food and raw vegetables using molecular approaches.

INTRODUCTION: Extensively drug resistant (XDR) strains of the Salmonella lineages have been reported to spread from Africa to South Asia. XDR strains are resistant to fluoroquinolones, chloramphenicol, co-trimoxazole, and ampicillin, resulting in treatment failure. The objectives of this study included the investigation of transmission of S. Typhi lineages and the identification of the potentially contaminated sources of the XDR typhoid outbreak from different urban areas by using molecular techniques. METHODOLOGY: Environmental samples, including food samples, were collected from different towns and the susceptibility of each isolate to the antimicrobial agents was examined. Molecular identification of different Salmonella lineages including S. Typhi, S. Paratyphi A, H58, and XDR was carried out through multiplex PCR. RESULTS AND CONCLUSIONS: A total of 328 environmental samples including raw vegetables, water, and bakery items were collected. More than half of the tested samples (64%) found harboring Salmonella spp. The Salmonella was confirmed through PCR amplification of species-specific markers that showed the presence of S. Typhi (40%), S. Paratyphi A (8%), H58 (7%), and XDR S. Typhi (6%). Raw vegetables had the highest number of Salmonella spp., indicating consumption of raw vegetables as a possible source of salmonellosis. XDR status was also affirmed through phenotypic antimicrobial susceptibility testing.