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Akhtar Rasul,1,* Muhammad Imran Khan,2,* Mujeeb Ur Rehman,1,* Ghulam Abbas,1,* Nosheen Aslam,3,* Shabbir Ahmad,4,* Khizar Abbas,5,* Pervaiz Akhtar Shah,6,* Muhammad Iqbal,7,* Ali Mohammad Ahmed Al Subari,6,* Talal Shaheer,8,* Shahid Shah9,* 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan; 2Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan; 3Department of Biochemistry, Government College University, Faisalabad, Pakistan; 4Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau, People’s Republic of China; 5Department of Pharmacognosy, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan; 6University College of Pharmacy, University of the Punjab, Lahore, Pakistan; 7Faculty of Pharmacy, Gomal University, Dera Ismail Khan, Pakistan; 8Department of Pharmacognosy, Xian Jiaotong University, Xian, People’s Republic of China; 9Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan*All authors contributed equally to this workCorrespondence: Akhtar Rasul Email akhtar.rasul@gcuf.edu.pkBackground: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies.Materials and Methods: Five niosomal formulations (F7 to F11) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F10, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits.Results: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F10 exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion).Conclusion: The formulation F10 demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F10 formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.Keywords: in vitro study, cyclosporine A, niosomes, nonionic surfactants

Newcastle disease (ND) is one of the highly contagious disease responsible for devastating outbreaks and considerable economic losses to poultry industry in China. However, no information is available about NDV in Tibet region; the aim of this study was to determine the genetic characterization and evolutionary analysis of NDV in Tibetan chickens. Four NDVs were isolated from an outbreak in Tibetan chickens. The pathogenicity of the isolates was determined by mean death time (MDT), intracerebral pathogenicity index (ICPI) and amino acid sequencing (112 to 117) of F protein. While the genetic characterization of F gene was determined by sequencing the isolated NDVs and phylogenetic relationship was established with the help of reference strains. Pathogenicity experiments revealed that XZ-F10 and XZ-F20 strains were lentogenic pathotype, while the remaining XZ-F2-1 and XZ-F4-6 strains were velogenic pathotype. The deduced amino acid sequences of the cleavage site of the F protein confirmed our results. Phylogenic analysis of these strains indicated that both XZ-F2-1 and XZ-F4-6 belong to genotype VII. However, XZ-F10 and XZ-F20 strains were assigned to genotypes II. The present study highlights the need for continuous surveillance of NDV in Tibetan chickens; moreover, this study will provide a reference for the local government to make the strategies and control emerging NDV in Tibet.

Teruhiko Makino,1 Yoshiaki Takegami,1 Mati Ur Rehman,1 Yoko Yoshihisa,1 Waka Ishida,2 Takashi Toyomoto,3 Tadamichi Shimizu11Department of Dermatology, University of Toyama, Toyama, Japan; 2Department of Dermatology, Niigata Central Hospital, Joetsu, Japan; 3Department of Dermatology, Saiseikai Takaoka Hospital, Takaoka, JapanBackground: The long-term follow-up of chronic urticaria (CU) is important to ensure the adequate treatment of patients. Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines.Methods: This study was designed to assess the optimal dose of olopatadine to suppress symptoms of chronic urticarial itch in well-controlled patients. After CU patients were treated with 10 mg olopatadine, patients having a visual analogue scale (VAS) itch score of less than 20 were randomly allocated into one of three groups: 10 mg/day (n = 35), 5 mg/day (n = 30), or no medication (n = 32).Results: The suppressive effects of both the 5 mg and 10 mg olopatadine treatments on the VAS itch score were more significant and longer lasting over a period of 4 weeks than the no-medication treatment. Both the 5-mg group and the 10-mg group showed improved urticarial symptoms and maintained their VAS itch score within normal limits compared to the no-medication group. The differences between the 5-mg and 10-mg groups were not significant.Conclusion: These results demonstrate that treatment with olopatadine at a dose of 5 mg once daily is effective and safe for the management and prevention of CU symptoms for itch in well-controlled patients.Keywords: chronic urticaria, olopatadine, dose, antihistamine, itch, histamine

Background: vital capacity and its relationship with posture has previously been studied. Variances in posture has an effect on the inspiratory and expiratory pressures. Spirometry is the preferred choice for measurement of vital capacities. Chronic deviations in posture could have long lasting effects on vital capacity. Physical therapists are prone to suffering long term musculoskeletal disorders, thus affirming the need to have screening protocols in place to prevent onset of such disorders. Methods: two hundred undergraduate physical therapy students were included in the study. Rounded shoulder posture was assessed using vernier calipers (in supine, distance between tip of shoulder and table was measured). Forced vital capacity and forced expiratory volumes were assed using spirometry. Conclusions: significant differences were obtained in readings of forced vital capacity and forced expiratory volume between those with rounded shoulders and those without (p-value= 0.000 and 0.003 respectively).Postural changes effect vital capacities. Undergraduate students should be educated regarding proper postures, in order to prevent long term effects. [ABSTRACT FROM AUTHOR]

2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-β Glycyrrhetinic acid (18β-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18β-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18β-GA at two different doses (45 and 75 mg kg−1 b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18β-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18β-GA. Our findings suggest that pretreatment with 18β-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation. [ABSTRACT FROM PUBLISHER]

Chemoprevention opens new window in the prevention of all types of cancers including colon cancer. Aloin, an anthracycline in plant pigment, can be utilized as a protective agent in cancer induction. In the present study, we have evaluated the chemopreventive efficacy of aloin against 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions in the colon of Wistar rats. DMH-induced aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have been used as biomarkers of colon cancer. Efficacy of aloin against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, ACF, MDF, histopathological changes, and expression levels of molecular markers of inflammation and tumor promotion. Aloin pretreatment ameliorates the damaging effects induced by DMH through a protective mechanism that involved reduction in increased oxidative stress enzymes (p < 0.001), ACF, MDF, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6, proliferating cell nuclear antigen protein expression, and tumor necrosis factor-α (p < 0.001) release. From the results, it could be concluded that aloin clearly protects against chemically induced colon toxicity and acts reasonably by inducing antioxidant level, anti-inflammatory and antiproliferative markers. [ABSTRACT FROM AUTHOR]

We report a unique case of a 37-year-old patient, a known case of scleroderma, complaining of bilateral acute visual disturbance, which was diagnosed later on as Purtscher’s retinopathy. After systemic assessment, she was diagnosed with bilateral kidney disease, consequently requiring further management accordingly.

Herein, bacterial-assisted synthesis of AgCoO 2 is carried out. In the first step, E. coli was separated from soil samples via the "serial dilution method." Ten milliliters of bacterial supernatant was mixed with cobalt chloride and silver nitrate hatched at 38°C for 24 h to get AgCoO 2 nanoparticles (NPs). XRD results confirm the synthesis of AgCoO 2 NPs while EDX results confirm the absence of any other elements than Ag, Co, and O. An average NP size of 12-26 nm was determined by TEM examination, and the surface of the particles was seen rough, irregularly shaped borders. The antibacterial activity of the constructed NPs was checked against S. aureus, E. coli, Bacillus subtilus, and Pseudomanas areguinosa using agar well diffusion method. The maximum zone of inhibition was 27 mm at 40 mg/mL against Bacillus subtilus. The performance of the synthesized NPs as photocatalysts was also assessed, and several operational parameters that control the photodegradation of the harmful dyes were tried to tune as well, and 85% degrading efficiency was obtained at 60 o C for 240 min for 30 mg of catalyst dose These NPs were also used to produce hydrogen by methanolysis., (© 2024 Wiley Periodicals LLC.)

Epigenetic modifications, particularly RNA methylation and histone alterations, play a crucial role in heredity, development, and disease. Among these, RNA 5-methylcytosine (m5C) is the most prevalent RNA modification in mammalian cells, essential for processes such as ribosome synthesis, translational fidelity, mRNA nuclear export, turnover, and translation. The increasing volume of nucleotide sequences has led to the development of machine learning-based predictors for m5C site prediction. However, these predictors often face challenges related to training data limitations and overfitting due to insufficient external validation. This study introduces m5C-Seq, an ensemble learning approach for RNA modification profiling, designed to address these issues. m5C-Seq employs a meta-classifier that integrates 15 probabilities generated from a novel, large dataset using systematic encoding methods to make final predictions. Demonstrating superior performance compared to existing predictors, m5C-Seq represents a significant advancement in accurate RNA modification profiling. The code and the newly established datasets are made available through GitHub at https://github.com/Z-Abbas/m5C-Seq., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

2D semiconductors show promise as a competitive candidate for developing future integrated circuits due to their immunity to short-channel effects and high carrier mobility at atomic layer thicknesses. The inherent defects and Fermi level pinning effect lead to n-type transport characteristics in most 2D semiconductors, while unstable and unsustainable p-type doping by various strategies hinders their application in many areas, such as complementary metal-oxide-semiconductor (CMOS) devices. In this study, an intralayer/interlayer codoping strategy is introduced that stabilizes p-type doping in 2D semiconductors. By incorporating oppositely charged ions (F and Li) with the intralayer/interlayer of 2D semiconductors, remarkable p-type doping in WSe 2 and MoTe 2 with air stability up to 9 months is achieved. Notably, the hole mobility presents a 100-fold enhancement (0.7 to 92 cm 2 V -1 s -1 ) with the codoping procedure. Structural and elemental characterizations, combined with theoretical calculations validate the codoping mechanism. Moreover, a CMOS inverter and more complex logic functions such as NOR and XNOR, as well as large-area device arrays are demonstrated to showcase its applications and scalability. These findings suggest that stable and straightforward intralayer/interlayer codoping strategy with charge-space synergy holds the key to unlocking the potential of 2D semiconductors in complex and scalable device applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This study focused on developing a thermosensitive gel with nanostructured lipid carriers (NLCs) loaded with paroxetine (PAR) to enhance the treatment and management of depression via nasal administration. Micro emulsion technique was utilized for the PAR-NLCs preparation. The acetyl alcohol and oleic acid were used in the ratio of 76:24. In the NLCs Tween 40, Span40 and Myrj 52 were used as a surfactant. The NLCs were then added into Poloxamer mixture to get thermosensitive NLCs based gel. Characterization, in vitro and in vivo studies were performed to check the efficiency of formulation in drug delivery. The entrapment efficiency of optimized PAR-NLCs was about 90%. The particle size, zeta potential and PDI were 155 ± 1.4 nm, -25.9 ± 0.5 mV, and 0.12 ± 0.01 respectively. The optimized gel showed a gelling temperature of 31.50 ± 0.50°C and a gelling time of 1 ± 0.12 s with a pH of 6, suitable for nasal administration. The in vitro release assay of PAR-NLC-gel showed a cumulative release of about 59% in the first 6 h after comparison with PAR-NLCs which showed almost 100%release. In vivo studies included forced swim test and tail suspension tests showed significant potential for treating depression when compared to PAR-NLCs. PAR-NLCs and NLCs based gel enhanced the tissue architecture and suppressed the expression of TNF-α in brain cortex from histological and immunohistochemical analysis. PAR- NLCs gel-based delivery system can prove to be an effective delivery system for brain targeting through nose for the better management of depression., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1β., Methods: Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals., Results: The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1β in the cortex and hippocampus of mice brains., Conclusions: Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bovine mastitis is a complex infectious disease that develops in the mammary gland, predominantly caused by a bacterial infection of mammary tissue. Genetic variability of mastitis is well established and depends upon different quantitative trait loci (QTL) related to mastitis resistance or susceptibility. The susceptibility is often attributed to single-nucleotide polymorphisms (SNPs) in the variable cow breed genomes. Several global investigative attempts have resulted in studies mapping mastitis to the variations in the relevant genes. Reports have been attributed to dramatic genetic expression changes in Toll-Like Receptor 4 (TLR4) genes in mastitis-positive cows. However, the mechanism behind this variable genetic expression of TLR4 genes has been studied poorly. The present study aims to investigate SCM through various screening tests like somatic cell count (SCC), electric conductivity (EC), pH, and California mastitis test (CMT) in milk samples. This study also aims to investigate possible mechanisms behind this variable expression of TLR4 by comparative SNP evaluation and transcriptional factor profile mining. So that the important genetic mutations and effects thereof can be exploited in selecting specific breeds with higher mastitis resistance and milk yield. Seventy Holstein Frisian (HF) crossbred dairy cows were selected in the present study. The animals were screened based on various diagnostic tests (SCC, pH, EC, and CMT). Blood samples (5 mL) were collected for extraction of DNA followed by amplification of PPR1 and PPR2 of the promoter region and 5'UTR of the bovine TLR4 gene using specific primers. Sanger's enzymatic DNA sequencing technique sequenced the amplified PCR products. Further, the identification of SNPs was done through various bioinformatic tools used in this study. The findings of the present study revealed that CMT, EC, pH, and SCC could be used for the early detection of subclinical mastitis. In the present study, a significant increase in the EC, pH, and SCC in milk samples of animals affected with SCM was found in comparison to the healthy animals. The present study also revealed 16 SNPs falling in TLR4 promoter and 5' untranslated region (5'UTR) sequences in mastitis-positive genotypes compared to reference genomes. The study also investigates the potential transcriptional factor program deployed in response to variable mastitis development resistance. In the present study, the allelic and genotype frequencies of all SNP variants in the three regions viz., PPR1, PPR2, and 5'UTR, were the same indicating the absence of heterozygous condition at the respective loci. The present study has wide applicability for researchers developing mastitis-resistant breeding programs and the data generated may aid in the selection of better genetic breeds. The transcription factor binding profiles can serve as concrete leads about the studies on bovine mastitis at the molecular level and may also aid global research groups working on transcription factor (TF)-based molecular pathology of mastitis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The World Anti-Doping Agency (WADA) has prohibited the use of clenbuterol (CLN) because it induces anabolic muscle growth while potentially causing adverse effects such as palpitations, anxiety, and muscle tremors. Thus, it is vital to assess meat quality because, athletes might have positive test for CLN even after consuming very low quantity of CLN contaminated meat. Numerous materials applied for CLN monitoring faced potential challenges like sluggish ion transport, non-uniform ion/molecule movement, and inadequate electrode surface binding. To overcome these shortcomings, herein we engineered bimetallic zeolitic imidazole framework (BM-ZIF) derived N-doped porous carbon embedded Co nanoparticles (CN-CoNPs), dispersed on conductive cellulose acetate-polyaniline (CP) electrospun nanofibers for sensitive electrochemical monitoring of CLN. Interestingly, the smartly designed CN-CoNPs wrapped CP (CN-CoNPs-CP) electrospun nanofibers offers rapid diffusion of CLN molecules to the sensing interface through amine and imine groups of CP, thus minimizing the inhomogeneous ion transportation and inadequate electrode surface binding. Additionally, to synchronize experiments, machine learning (ML) algorithms were applied to optimize, predict, and validate voltametric current responses. The ML-trained sensor demonstrated high selectivity, even amidst interfering substances, with notable sensitivity (4.7527 μA/μM/cm 2 ), a broad linear range (0.002-8 μM), and a low limit of detection (1.14 nM). Furthermore, the electrode exhibited robust stability, retaining 98.07% of its initial current over a 12-h period. This ML-powered sensing approach was successfully employed to evaluate meat quality in terms of CLN level. To the best of our knowledge, this is the first study of using ML powered system for electrochemical sensing of CLN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1 H NMR, 13 C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFR wt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFR wt activity with IC 50  = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Recent studies have illuminated the critical role of the human microbiome in maintaining health and influencing the pharmacological responses of drugs. Clinical trials, encompassing approximately 150 drugs, have unveiled interactions with the gastrointestinal microbiome, resulting in the conversion of these drugs into inactive metabolites. It is imperative to explore the field of pharmacomicrobiomics during the early stages of drug discovery, prior to clinical trials. To achieve this, the utilization of machine learning and deep learning models is highly desirable. In this study, we have proposed graph-based neural network models, namely GCN, GAT, and GINCOV models, utilizing the SMILES dataset of drug microbiome. Our primary objective was to classify the susceptibility of drugs to depletion by gut microbiota. Our results indicate that the GINCOV surpassed the other models, achieving impressive performance metrics, with an accuracy of 93% on the test dataset. This proposed Graph Neural Network (GNN) model offers a rapid and efficient method for screening drugs susceptible to gut microbiota depletion and also encourages the improvement of patient-specific dosage responses and formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ulcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that Bacillus clausii has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine B. clausii's potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)-induced UC. Bacillus clausii was administered to mice as a pre-treatment, post-treatment and adjunct treatment with sulfasalazine for 14 days. The study found that B. clausii effectively reduced the severity of colitis in mice when used preventatively. Administering B. clausii after the onset of colitis also effectively alleviated symptoms. Combining B. clausii with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. B. clausii has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro-inflammatory cytokines such as IL-1β, TNF-α and NFkB in colon tissue. Additionally, mice that received B. clausii showed a significant increase in anti-oxidant levels and improved haematological markers. In conclusion, it must be emphasized that B. clausii possesses the potential to alleviate the symptoms of UC., (© 2024 John Wiley & Sons Australia, Ltd.)

Neurological disorders such as neurodegenerative diseases and nervous system tumours affect more than one billion people throughout the globe. The physiological sensitivity of the nervous tissue limits the application of invasive therapies and leads to poor treatment and prognosis. One promising solution that has generated attention is Photodynamic therapy (PDT), which can potentially revolutionise the treatment landscape for neurological disorders. PDT attracted substantial recognition for anticancer efficacy and drug conjugation for targeted drug delivery. This review thoroughly explained the basic principles of PDT, scientific interventions and advances in PDT, and their complicated mechanism in treating brain-related pathologies. Furthermore, the merits and demerits of PDT in the context of neurological disorders offer a well-rounded perspective on its feasibility and challenges. In conclusion, this review encapsulates the significant potential of PDT in transforming the treatment landscape for neurological disorders, emphasising its role as a non-invasive, targeted therapeutic approach with multifaceted applications.

Background Acute biliary pancreatitis (ABP), a major inflammatory illness, is primarily caused by gallstone blockage of the common bile duct. The pathophysiology of ABP has been linked to serum triglyceride (TG) levels, suggesting a potential role for TG in predicting disease severity. Objective The research objective was to investigate the association between serum TG levels and the severity of ABP. Methodology This retrospective cohort study sought to determine the relationship between blood TG levels and the severity of ABP. It was conducted at Lady Reading Hospital in Peshawar, Pakistan, from September 2023 to March 2024. A total of 530 ABP patients were divided into two groups based on their TG levels: normal (<150 mg/dl) and elevated (≥150 mg/dl). Clinical data were gathered, including demographics, comorbidities, laboratory results, severity ratings (APACHE II and Ranson's criteria), and clinical outcomes. Descriptive statistics, Chi-square tests, and multivariate logistic regression were used in the statistical analysis. Results Patients with elevated TG levels (n=130) demonstrated higher median Ranson's criteria (3.24 vs. 2.53, p<0.001) and APACHE II scores (10.53 vs. 8.73, p<0.001) compared to those with normal TG levels (n=400). Elevated TG levels were associated with increased severity of ABP, with ORs of 2.41 (95% CI: 1.23-4.74) for mild vs. severe ABP. Clinical outcomes such as ICU admission (21.54% vs. 3.25%, p<0.001), mortality (6.15% vs. 0.50%, p<0.001), and pancreatic necrosis (10.77% vs. 1.25%, p<0.001) were significantly worse in the elevated TG group. Conclusion Elevated serum TG levels (≥150 mg/dl) are independently associated with increased severity of ABP, as indicated by higher severity scores and poorer clinical outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Lady Reading Hospital, Peshawar, Pakistan issued approval LRH/MTI-IRB15738. 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, Haq et al.)

Terahertz (THz) spectral region from 0.1 to 3 THz is envisaged to hold immense potential in the next generation of wireless technologies. Recently, research has focused on this terahertz gap, because of its unprecedented channel capacities. At the physical layer, the design complexities and fabrication of THz devices, especially antennas are the prime bottlenecks to realize its full potential. This article introduces a cost-effective, easy-to-fabricate, and reproducible sub-THz antenna design based on a single-layer planar printed circuit board technology. The antenna incorporates carefully designed quasi-cross slots and applied machine learning-assisted global optimization techniques to achieve the desired performance metrics. The antenna performance is elucidated through numerical simulations and verified through a rigorous in-house THz experimental framework around 100-110 GHz. The proposed antenna offers a peak gain of 13.90 dBi with less than 1 dB variation within the entire band of 100-110 GHz. The antenna holds the potential to achieve terabits per second data rates and futuristic high-resolution short-range THz imaging applications., (© 2024. The Author(s).)

Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed C max 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with T max of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by-products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age-related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, β-amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age-associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases., (© 2024 John Wiley & Sons Ltd.)