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The use of cinnamaldehyde and Vitamin C can improve immunity and intestinal health. A two-way factorial design was employed to investigate the main and interactive effects of cinnamaldehyde and vitamin C on the growth, carcass, and intestinal health of broiler chickens. A total of 288 one-day-old female Arbor Acres broiler chicks were randomly distributed among four treatment groups, consisting of six replicate cages with 12 birds each. Four treatments were basal diet or control (CON), supplemental cinnamaldehyde (CA) 300 g/ton (g/t), vitamin C (VC) 300 g/t, and cinnamaldehyde 300 g/t, and vitamin C 300 g/t (CA + VC), respectively. The results showed that supplemental CA did not affect the growth performance or slaughter performance of broilers at 21 days (d), 42 days (d), and 1-42 days (d); however, it could improve intestinal barrier function at 42 d of age and reduce the mRNA expression of inflammatory factors in the intestine at 21 d and 42 d of age. Supplemental VC showed a trend towards increasing body weight gain (BWG) at 21 d ( p = 0.094), increased breast muscle rate (at 21-d 5.33%, p < 0.05 and at 42-d 7.09%, p = 0.097), and decreased the abdominal fat (23.43%, p < 0.05) and drip loss (20.68%, p < 0.05) at 42-d. Moreover, VC improves intestinal morphology and intestinal barrier function and maintains a balanced immune response. The blend of CA and VC significantly upregulated the mRNA expression of myeloid differentiation factor 88 ( MyD-88 ) in the intestine at 21 d of age, the mRNA expression of catalase ( CAT ), Occludin , Claudin-1 , Mucin-2 , nuclear factor-kappa B ( NF-κB ) and toll-like receptor 4 ( TLR-4 ) in the intestine at 42 d of age ( p < 0.01), and downregulated the mRNA expression of interleukin 10 ( IL-10 ), interleukin 6 ( IL-6 ), tumor necrosis factor-alpha ( TNF-α ) in the intestine at 21-d and 42-d of age, and interleukin-1 beta ( IL-1β ) mRNA in intestine at 42 d of age ( p < 0.01). This study suggested that the combination of CA and VC had the potential to regulate intestinal health and result in better carcass character of broilers.

Peste des petits ruminants (PPR) is an extremely transmissible viral disease caused by the PPR virus that impacts domestic small ruminants, namely sheep and goats. This study aimed to employ a methodical approach to evaluate the regional occurrence of PPR in small ruminants in Pakistan and the contributing factors that influence its prevalence. A thorough search was performed in various databases to identify published research articles between January 2004 and August 2023 on PPR in small ruminants in Pakistan. Articles were chosen based on specific inclusion and exclusion criteria. A total of 25 articles were selected from 1275 studies gathered from different databases. The overall pooled prevalence in Pakistan was calculated to be 51% (95% CI: 42-60), with heterogeneity I 2 = 100%, τ 2 = 0.0495, and p = 0. The data were summarized based on the division into five regions: Punjab, Baluchistan, KPK, Sindh, and GB and AJK. Among these, the pooled prevalence of PPR in Sindh was 61% (95% CI: 46-75), I 2 = 100%, τ 2 = 0.0485, and p = 0, while in KPK, it was 44% (95% CI: 26-63), I 2 = 99%, τ 2 = 0.0506, and p < 0.01. However, the prevalence of PPR in Baluchistan and Punjab was almost the same. Raising awareness, proper surveillance, and application of appropriate quarantine measures interprovincially and across borders must be maintained to contain the disease.

Duckweed ( Lemnaceae ) rises as a crucial model system due to its unique characteristics and wide-ranging utility. The significance of physiological research and phytoremediation highlights the intricate potential of duckweed in the current era of plant biology. Special attention to duckweed has been brought due to its distinctive features of nutrient uptake, ion transport dynamics, detoxification, intricate signaling, and stress tolerance. In addition, duckweed can alleviate environmental pollutants and enhance sustainability by participating in bioremediation processes and wastewater treatment. Furthermore, insights into the genomic complexity of Lemnaceae species and the flourishing field of transgenic development highlight the opportunities for genetic manipulation and biotechnological innovations. Novel methods for the germplasm conservation of duckweed can be adopted to preserve genetic diversity for future research endeavors and breeding programs. This review centers around prospects in duckweed research promoting interdisciplinary collaborations and technological advancements to drive its full potential as a model organism.

This paper addresses the problem of feature encoding for gait analysis using multimodal time series sensory data. In recent years, the dramatic increase in the use of numerous sensors, e.g., inertial measurement unit (IMU), in our daily wearable devices has gained the interest of the research community to collect kinematic and kinetic data to analyze the gait. The most crucial step for gait analysis is to find the set of appropriate features from continuous time series data to accurately represent human locomotion. This paper presents a systematic assessment of numerous feature extraction techniques. In particular, three different feature encoding techniques are presented to encode multimodal time series sensory data. In the first technique, we utilized eighteen different handcrafted features which are extracted directly from the raw sensory data. The second technique follows the Bag-of-Visual-Words model; the raw sensory data are encoded using a pre-computed codebook and a locality-constrained linear encoding (LLC)-based feature encoding technique. We evaluated two different machine learning algorithms to assess the effectiveness of the proposed features in the encoding of raw sensory data. In the third feature encoding technique, we proposed two end-to-end deep learning models to automatically extract the features from raw sensory data. A thorough experimental evaluation is conducted on four large sensory datasets and their outcomes are compared. A comparison of the recognition results with current state-of-the-art methods demonstrates the computational efficiency and high efficacy of the proposed feature encoding method. The robustness of the proposed feature encoding technique is also evaluated to recognize human daily activities. Additionally, this paper also presents a new dataset consisting of the gait patterns of 42 individuals, gathered using IMU sensors.

Alternanthera yellow vein virus (AlYVV), a monopartite begomovirus , has been identified infecting a diverse range of crops and native plants in Pakistan, India, and China. However, distinctive yellow vein symptoms, characteristic of begomovirus infection, were observed on the Ageratum conyzoides weed in Oman, prompting a thorough genomic characterization in this study. The results unveiled a complete genome sequence of 2745 base pairs and an associated betasatellite spanning 1345 base pairs. In addition, Sequence Demarcation Tool analyses indicated the highest nucleotide identity of 92.8% with a previously reported AlYVV-[IN&#95;abalpur&#95;A&#95;17:LC316182] strain, whereas the betasatellite exhibited a 99.8% nucleotide identity with isolates of tomato leaf curl betasatellite. Thus, our findings propose a novel AlYVV Oman virus (AlYVV-OM) variant, emphasizing the need for additional epidemiological surveillance to understand its prevalence and significance in Oman and the broader region. To effectively manage the spread of AlYVV-OM and minimize its potential harm to (agro)ecosystems, future research should focus on elucidating the genetic diversity of AlYVV-OM and its interactions with other begomoviruses.

The market for nanoparticles has grown significantly over the past few decades due to a number of unique qualities, including antibacterial capabilities. It is still unclear how nanoparticle toxicity works. In order to ascertain the toxicity of synthetic cobalt iron oxide (CoFe 2 O 4 ) nanoparticles (CIONPs) in rabbits, this study was carried out. Sixteen rabbits in total were purchased from the neighborhood market and divided into two groups (A and B), each of which contained eight rabbits. The CIONPs were synthesized by the co-precipitation method. Crystallinity and phase identification were confirmed by X-ray diffraction (XRD). The average size of the nanoparticles (13.2 nm) was calculated by Scherrer formula (Dhkl = 0.9 λ/β cos θ) and confirmed by TEM images. The saturation magnetization, 50.1 emug -1 , was measured by vibrating sample magnetometer (VSM). CIONPs were investigated as contrast agents (CA) for magnetic resonance images (MRI). The relaxivity (r = 1/T) of the MRI was also investigated at a field strength of 0.35 T (Tesla), and the ratio r 2 /r 1 for the CIONPs contrast agent was 6.63. The CIONPs were administrated intravenously into the rabbits through the ear vein. Blood was collected at days 5 and 10 post-exposure for hematological and serum biochemistry analyses. The intensities of the signal experienced by CA with CIONPs were 1427 for the liver and 1702 for the spleen. The treated group showed significantly lower hematological parameters, but significantly higher total white blood cell counts and neutrophils. The results of the serum biochemistry analyses showed significantly higher and lower quantities of different serum biochemical parameters in the treated rabbits at day 10 of the trial. At the microscopic level, different histological ailments were observed in the visceral organs of treated rabbits, including the liver, kidneys, spleen, heart, and brain. In conclusion, the results revealed that cobalt iron oxide (CoFe 2 O 4 ) nanoparticles induced toxicity via alterations in multiple tissues of rabbits.

Background: Breast cancer (BC) is one of the most common female cancers. Clinical and histopathological information is collectively used for diagnosis, but is often not precise. We applied machine learning (ML) methods to identify the valuable gene signature model based on differentially expressed genes (DEGs) for BC diagnosis and prognosis., Methods: A cohort of 701 samples from 11 GEO BC microarray datasets was used for the identification of significant DEGs. Seven ML methods, including RFECV-LR, RFECV-SVM, LR-L1, SVC-L1, RF, and Extra-Trees were applied for gene reduction and the construction of a diagnostic model for cancer classification. Kaplan-Meier survival analysis was performed for prognostic signature construction. The potential biomarkers were confirmed via qRT-PCR and validated by another set of ML methods including GBDT, XGBoost, AdaBoost, KNN, and MLP., Results: We identified 355 DEGs and predicted BC-associated pathways, including kinetochore metaphase signaling, PTEN, senescence, and phagosome-formation pathways. A hub of 28 DEGs and a novel diagnostic nine-gene signature ( COL10A, S100P, ADAMTS5 , WISP1 , COMP , CXCL10 , LYVE1 , COL11A1 , and INHBA ) were identified using stringent filter conditions. Similarly, a novel prognostic model consisting of eight-gene signatures ( CCNE2 , NUSAP1 , TPX2 , S100P , ITM2A , LIFR , TNXA , and ZBTB16 ) was also identified using disease-free survival and overall survival analysis. Gene signatures were validated by another set of ML methods. Finally, qRT-PCR results confirmed the expression of the identified gene signatures in BC., Conclusion: The ML approach helped construct novel diagnostic and prognostic models based on the expression profiling of BC. The identified nine-gene signature and eight-gene signatures showed excellent potential in BC diagnosis and prognosis, respectively.

This study describes an applied and enhanced real-time vehicle-counting system that is an integral part of intelligent transportation systems. The primary objective of this study was to develop an accurate and reliable real-time system for vehicle counting to mitigate traffic congestion in a designated area. The proposed system can identify and track objects inside the region of interest and count detected vehicles. To enhance the accuracy of the system, we used the You Only Look Once version 5 (YOLOv5) model for vehicle identification owing to its high performance and short computing time. Vehicle tracking and the number of vehicles acquired used the DeepSort algorithm with the Kalman filter and Mahalanobis distance as the main components of the algorithm and the proposed simulated loop technique, respectively. Empirical results were obtained using video images taken from a closed-circuit television (CCTV) camera on Tashkent roads and show that the counting system can produce 98.1% accuracy in 0.2408 s.

Biological networks are often large and complex, making it difficult to accurately identify the most important nodes. Node prioritization algorithms are used to identify the most influential nodes in a biological network by considering their relationships with other nodes. These algorithms can help us understand the functioning of the network and the role of individual nodes. We developed CentralityCosDist, an algorithm that ranks nodes based on a combination of centrality measures and seed nodes. We applied this and four other algorithms to protein-protein interactions and co-expression patterns in Arabidopsis thaliana using pathogen effector targets as seed nodes. The accuracy of the algorithms was evaluated through functional enrichment analysis of the top 10 nodes identified by each algorithm. Most enriched terms were similar across algorithms, except for DIAMOnD. CentralityCosDist identified more plant-pathogen interactions and related functions and pathways compared to the other algorithms.

Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of high-priority transcription factors (TFs), dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis . We identified distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficient nodes. Dynamic transcriptional regulatory modeling of integrated TF targets and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs, as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that could potentially be used in future genetic crop engineering programs.

Streptomyces are factories of antimicrobial secondary metabolites. We isolated a Streptomyces species associated with the Pelargonium graveolens rhizosphere. Its total metabolic extract exhibited potent antibacterial and antifungal properties against all the tested pathogenic microbes. Whole genome sequencing and genome analyses were performed to take a look at its main characteristics and to reconstruct the metabolic pathways that can be associated with biotechnologically useful traits. AntiSMASH was used to identify the secondary metabolite gene clusters. In addition, we searched for known genes associated with plant growth-promoting characteristics. Finally, a comparative and pan-genome analysis with three closely related genomes was conducted. It was identified as Streptomyces vinaceusdrappus strain AC-40. Genome mining indicated the presence of several secondary metabolite gene clusters. Some of them are identical or homologs to gene clusters of known metabolites with antimicrobial, antioxidant, and other bioactivities. It also showed the presence of several genes related to plant growth promotion traits. The comparative genome analysis indicated that at least five of these gene clusters are highly conserved through rochei group genomes. The genotypic and phenotypic characteristics of S. vinaceusdrappus strain AC-40 indicate that it is a promising source of beneficial secondary metabolites with pharmaceutical and biotechnological applications.

Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of genetic, environmental, and immunologic variables in people with type 1 diabetes. These factors cause pancreatic beta cell death and insulin insufficiency. Insulin resistance and irregular insulin production cause hyperglycemia in type 2 diabetes patients. Hyperglycemia activates a number of complicated interconnected metabolic processes. Hyperglycemia is a major contributor to the onset and progression of diabetes' secondary complications such as neuropathy, nephropathy, retinopathy, cataracts, periodontitis, and bone and joint issues. Studies on the health benefits of ginger and its constituent's impact on hyperglycemia and related disorders have been conducted and gingerol proved to be a potential pharmaceutically active constituent of ginger ( Zingiber officinale ) that has been shown to lower blood sugar levels, because it possesses antioxidant properties and it functions as an antioxidant in the complicated biochemical process that causes hyperglycemia to be activated. Gingerol not only helps in treating hyperglycemia but also shows effectivity against diseases related to it, such as cardiopathy, kidney failure, vision impairments, bone and joint problems, and teeth and gum infections. Moreover, fresh ginger has various gingerol analogues, with 6-gingerol being the most abundant. However, it is necessary to investigate the efficacy of its other analogues against hyperglycemia and associated disorders at various concentrations in order to determine the appropriate dose for treating these conditions.

The challenges in making animal models of complex human epilepsy phenotypes with varied aetiology highlights the need to develop alternative disease models that can address the limitations of animal models by effectively recapitulating human pathophysiology. The advances in stem cell technology provide an opportunity to use human iPSCs to make disease-in-a-dish models. The focus of this review is to report the current information and progress in the generation of epileptic patient-specific iPSCs lines, isogenic control cell lines, and neuronal models. These in vitro models can be used to study the underlying pathological mechanisms of epilepsies, anti-seizure medication resistance, and can also be used for drug testing and drug screening with their isogenic control cell lines.

Tenofovir alafenamide (TAF) is an antiretroviral (ARV) drug that is used for the management and prevention of human immunodeficiency virus (HIV). The clinical availability of ARV delivery systems that provide long-lasting protection against HIV transmission is lacking. There is a dire need to formulate nanocarrier systems that can help in revolutionizing the way to fight against HIV/AIDS. Here, we aimed to synthesize a polymer using chitosan and polyethylene glycol (PEG) by the PEGylation of chitosan at the hydroxyl group. After successful modification and confirmation by FTIR, XRD, and SEM, TAF-loaded PEGylated chitosan nanoparticles were prepared and analyzed for their particle size, zeta potential, morphology, crystallinity, chemical interactions, entrapment efficacy, drug loading, in vitro drug release, and release kinetic modeling. The fabricated nanoparticles were found to be in a nanosized range (219.6 nm), with ~90% entrapment efficacy, ~14% drug loading, and a spherical uniform distribution. The FTIR analysis confirmed the successful synthesis of PEGylated chitosan and nanoparticles. The in vitro analysis showed ~60% of the drug was released from the PEGylated polymeric reservoir system within 48 h at pH 7.4. The drug release kinetics were depicted by the Korsmeyer-Peppas release model with thermodynamically nonspontaneous drug release. Conclusively, PEGylated chitosan has the potential to deliver TAF from a nanocarrier system, and in the future, cytotoxicity and in vivo studies can be performed to further authenticate the synthesized polymer.

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes ( 5-HTT, NR3C1, OXTR, and FKBP5 ) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients-short form (QSC-R10). A survival database, the Kaplan-Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT ( p = 0.02) and OXTR ( p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II ( p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world's most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines' excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins' neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer's, Parkinson's, multiple sclerosis, and cognitive deficit.

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats.

In the present study KrF Excimer laser has been employed to irradiate the Cadmium (Cd) targets for various number of laser pulses of 500, 1000, 1500 and 2000, at constant fluence of 3.6 J cm -2 . Scanning Electron Microscopy (SEM) analysis was utilized to reveal the formation of laser induced nano/micro structures on the irradiated target (Cd) surfaces. SEM results show the generation of cavities, cracks, micro/nano wires/rods, wrinkles along with re-deposited particles during irradiation in air, whereas subsurface boiling, pores, cavities and Laser Induced Periodic Surface Structures (LIPSS) on the inner walls of cavities are revealed at the central ablated area after irradiation in propanol. The ablated volume and depth of ablated region on irradiated Cd targets are evaluated for various number of pulses and is higher in air as compared to propanol ambient. Fast Fourier Transform Infrared spectroscopy (FTIR), Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Diffraction (XRD) analyses show the presence of oxides and hydro-oxides of Cd after irradiation in propanol, whereas the existence of oxides is observed after irradiation in air ambient. Nano-hardness tester was used to investigate mechanical modifications of ablated Cd. It reveals an increase in hardness after irradiation which is more pronounced in propanol as compared to air.

The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer.

Detection of a brain tumor in the early stages is critical for clinical practice and survival rate. Brain tumors arise in multiple shapes, sizes, and features with various treatment options. Tumor detection manually is challenging, time-consuming, and prone to error. Magnetic resonance imaging (MRI) scans are mostly used for tumor detection due to their non-invasive properties and also avoid painful biopsy. MRI scanning of one patient's brain generates many 3D images from multiple directions, making the manual detection of tumors very difficult, error-prone, and time-consuming. Therefore, there is a considerable need for autonomous diagnostics tools to detect brain tumors accurately. In this research, we have presented a novel TumorResnet deep learning (DL) model for brain detection, i.e., binary classification. The TumorResNet model employs 20 convolution layers with a leaky ReLU (LReLU) activation function for feature map activation to compute the most distinctive deep features. Finally, three fully connected classification layers are used to classify brain tumors MRI into normal and tumorous. The performance of the proposed TumorResNet architecture is evaluated on a standard Kaggle brain tumor MRI dataset for brain tumor detection (BTD), which contains brain tumor and normal MR images. The proposed model achieved a good accuracy of 99.33% for BTD. These experimental results, including the cross-dataset setting, validate the superiority of the TumorResNet model over the contemporary frameworks. This study offers an automated BTD method that aids in the early diagnosis of brain cancers. This procedure has a substantial impact on improving treatment options and patient survival.

The presence of antimicrobial-resistance genes (ARGs) in mobile genetic elements (MGEs) facilitates the rapid development and dissemination of multidrug-resistant bacteria, which represents a serious problem for human health. This is a One Health study which aims to investigate the co-occurrence of antimicrobial resistance determinants among clinical and environmental isolates of K. pneumoniae and E. coli . Various bioinformatics tools were used to elucidate the bacterial strains' ID, resistome, virulome, MGEs, and phylogeny for 42 isolates obtained from hospitalized patients ( n = 20) and environmental sites (including fresh vegetables, fruits, and drinking water) ( n = 22). The multilocus sequence typing (MLST) showed that K. pneumoniae belonged to ten sequence types (STs) while the E. coli belonged to seventeen STs. Multidrug-resistant isolates harbored β-lactam, aminoglycoside resistance determinants, and MGE were detected circulating in the environment (drinking water, fresh vegetables, and fruits) and in patients hospitalized with postoperative infections, neonatal sepsis, and urinary tract infection. Four K. pneumoniae environmental isolates (7E, 16EE, 1KE, and 19KE) were multidrug-resistant and were positive for different beta-lactam and aminoglycoside resistance determinants. bla CTX-M-15 in brackets of ISEc 9 and Tn 3 transposases was detected in isolates circulating in the pediatrics unit of Soba hospital and the environment. This study documented the presence of bacterial isolates harboring a similar pattern of antimicrobial resistance determinants circulating in hospitals and environments. A rapid response is needed from stakeholders to initiate a program for infection prevention and control measures to detect such clones disseminated in the communities and hospitals.

Plants grow together with microbes that have both negative and positive impacts on the host, while prokaryotes are in turn also hosts for viruses, co-evolving together in a complex interrelationship. Most research focuses on the interaction of either bacterial pathogens interacting with the plant host, or the impact on viruses on their pathogenic bacterial hosts. Few studies have investigated the co-evolution of bacterial pathogens with their host plants as well as with their bacterial viruses. In this work, we aimed to identify the genes that were associated with both phage sensitivity and host pathogenicity of the bacterium Xanthomonas oryzae pv. oryzae (Xoo), which is the most important bacterial rice pathogen. Using the Tn5 transposon mutation technology, we created a library of Xoo strain C2 comprising 4524 mutants, which were subsequently tested for phage infectability. The phage infection tests showed that less than 1% of the mutants ( n = 36) were resistant to phage infection, which was attributed to the Tn5 insertion in 19 genes. Interestingly, three out of 19 genes that conveyed resistance to the phage resulted in reduced pathogenicity to rice seedlings compared to the wild type. We identified three genes involved in both phage infection and bacterial virulence, which were studied by knockout mutants and complementation experiments. All of the three knockout mutants were resistant to infection by phage X2, while the complemented strains restored the susceptibility to the bacterial virus. Surprisingly, the genes are also essential for pathogenicity, which we confirmed by single knockout mutants corresponding to the Tn5 mutants. All three genes are involved in lipopolysaccharide synthesis, thus changing the cell envelope surface molecule composition. Our work shows a possible balance in terms of the connection between bacterial virulence and phage resistance, supporting the deployment of phages for the biocontrol of plant pathogens.

Background: Rosinidin is a flavonoid anthocyanin pigmentation found in shrub flowers such as Catharanthus roseus and Primula rosea . The molecular docking studies predicted that rosinidin has adequate structural competency, making it a viable medicinal candidate for the treatment of a wide range of disorders. The current study intends to assess rosinidin nephroprotective efficacy against nephrotoxicity induced by cisplatin in rats., Materials and Methods: Oral acute toxicity tests of rosinidin were conducted to assess potential toxicity in animals, and it was shown to be safe. The nephroprotective effect of rosinidin 10, and 20 mg/kg were tested in rats for 25 days with concurrent administration of cisplatin. Several biochemical parameters were measured to support enzymatic and non-enzymatic oxidative stress such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH). Likewise, changes in several non-protein-nitrogenous components and blood chemistry parameters were made to support the theory linked with the pathogenesis of chemical-induced nephrotoxicity., Results: Cisplatin caused significant changes in biochemical, enzymatic, and blood chemistry, which rosinidin efficiently controlled., Conclusions: The present investigation linked rosinidin with nephroprotective efficacy in experimental models.

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.

Severe infections such as viral, bacterial, or fungal sepsis can cause an inflammatory response in the host, leading to organ failure and septic shock-phosphodiesterase-4 (PDE-4) inhibiting related agents from suppressing cyclic adenosine monophosphate (cAMP) degradation. Regulatory organisations have approved some substances in this category to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with chronic bronchitis and a history of COPD exacerbations. Roflumilast has been shown to alleviate inflammatory responses, thus regulating airway inflammation. Additionally, roflumilast therapy dramatically enhanced B-cell lymphoma 2 (Bcl-2) expression, an anti-apoptotic marker lowered in septic animals. Previous research has indicated that roflumilast may help reverse sepsis-induced liver and lung harm, but whether it is also effective in reversing sepsis-induced renal impairment remains unknown. Therefore, this review determines whether roflumilast protects against renal dysfunction, inflammatory response, and apoptosis in sepsis-induced kidney damage. Additionally, we discussed the molecular mechanism through which roflumilast exerts its protective effect to uncover a possible treatment agent for sepsis-induced renal impairment.

Gel beads are formed when alginate acid reacts with divalent cations, particularly Ca 2+ . As a result of this feature, it is one of the best materials for making gel beads. Furthermore, it swells only slightly at acidic pH, resulting in stable alginate acid beads, but swells and dissolves rapidly at higher pH values, leading to pH-responsive release. Our current study aimed to embed folate-modified chitosan 5FU nanoparticles (FA-CS-5FU-NPs) into calcium alginate beads for colon-targeted delivery. Calcium alginate beads were developed successfully. Based on the method of drying, two types of beads were obtained: freeze-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bf) and oven-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bo). The size of (FA-CS-5FU-NP-Bf) was significantly larger than (FA-CS-5FU-NP-Bo). Swelling index (SI), erosion index (EI), and water-uptake index (WUI) of (FA-CS-5FU-NP-Bf) beads were significantly higher than FA-CS-5FU-NP-Bo beads at simulated intestinal pH. An insignificant difference was observed in the release rate of 5FU between (FA-CS-5FU-NP-Bf) and FA-CS-5FU-NP-Bo. The release rate of FA-CS-5FU-NPs was significantly higher than FA-CS-5FU-NP-Bf and FA-CS-5FU-NP-Bo. Pharmacokinetic parameters of 5FU solution, FA-CS-5FU-NPs, and FA-CS-5FU-NP-Bo were analyzed. Solution of pure 5FU showed significantly higher C max and lower AUC, T 1/2 , and Vd than both FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo, suggesting that FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo have sustained-release behavior. Biodistribution studies also show that maximum drug amounts were found in the colon from nanoparticles-embedded beads. FA-CS-5FU-NPs-Bo avoid releasing drugs in the stomach and small intestine and make them available in the colon region in higher concentrations to target the colon region specifically.

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug-excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed C max ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, T max was 8 h to 10 h, and t 1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis.

Poor solubility is the major challenge involved in the formulation development of new chemical entities (NCEs), as more than 40% of NCEs are practically insoluble in water. Solid dispersion (SD) is a promising technology for improving dissolution and, thereby, the bioavailability of poorly soluble drugs. This study investigates the influence of a pH-sensitive acrylate polymer, EPO, on the physicochemical properties of rosuvastatin calcium, an antihyperlipidemic drug. In silico docking was conducted with numerous polymers to predict drug polymer miscibility. The screened-out polymer was used to fabricate the binary SD of RoC in variable ratios using the co-grinding and solvent evaporation methods. The prepared formulations were assessed for physiochemical parameters such as saturation solubility, drug content and in vitro drug release. The optimized formulations were further ruled out using solid-state characterization (FTIR, DSC, XRD and SEM) and in vitro cytotoxicity. The results revealed that all SDs profoundly increased solubility as well as drug release. However, the formulation RSE-2, with a remarkable 71.88-fold increase in solubility, presented 92% of drug release in the initial 5 min. The molecular interaction studied using FTIR, XRD, DSC and SEM analysis evidenced the improvement of in vitro dissolution. The enhancement in solubility of RoC may be important for the modulation of the dyslipidemia response. Therefore, pharmacodynamic activity was conducted for optimized formulations. Our findings suggested an ameliorative effect of RSE-2 in dyslipidemia and its associated complications. Moreover, RSE-2 exhibited nonexistence of cytotoxicity against human liver cell lines. Convincingly, this study demonstrates that SD of RoC can be successfully fabricated by EPO, and have all the characteristics that are favourable for superior dissolution and better therapeutic response to the drug.

The COVID-19 pandemic has impacted economic activity in numerous sectors due to multiple forms of disruption, including border closures, a stay-at-home policy, and social isolation; the electricity consumption trends in this region will undoubtedly improve. This article examines the impact of COVID-19 on electricity generation and consumption in China during the first two quarters (Q1-Q2) of 2020 and 2021. Furthermore, several governments' perspectives on COVID-19's implications for renewable energy development, notably offshore wind power and solar photovoltaics (PV), were examined. Results of this article show that COVID-19 impacts the power industry. According to the analysis, during the first two quarters of 2020, the amount of electricity generated and consumed by China decreased by 1.4 and 1.3 percent, respectively, the capacity of the power plants increased by 5.3 GW and coal consumption dropped by 3.6 g/kWh. Investments in the power generation sector increased by 51.5 billion yuan and investment in the power grid grew by 0.7 billion. Additionally, new generation capacity decreased by 378 GW during the first two quarters of 2020. During the first two quarters of 2021, electricity consumption and production grew by 13.7 and 16.2 percent, respectively. Power plants' capacity increased by 9.5 GW, while coal consumption for power supply fell by 0.8 g/kWh. The investment in power generation projects increased by 8.9 billion, while investment in power grid projects increased by 4.7 billion. Compared to last year's same period, 14.92 GW of new capacity was installed. Due to lockdown measures, such as studying at home or working at home, domestic power use in the first two quarters of 2020-2021 increased by 6.6 and 4.5 percent, respectively. To minimize COVID-19's impact on renewable energy development and assist in building offshore wind power plants, economic and financial measures have been put in place to reduce the epidemic's effect on solar PV systems.

Apigenin (AGN) is a potent phytochemical with strong antioxidant and anticancer potential. But its therapeutic efficacy is limited due to its high lipophilic characteristics. Therefore, the present investigation aimed to develop AGN-loaded polymer-lipid hybrid nanoparticles (AGN-PLHNPs). Herein, we successfully developed AGN-PLHNPs and optimized them by a 33-Box-Behnken de-sign. The poly (lactic-co-glycolic acid) (PLGA; coded as F1), phospholipon 90 G (PL-90G; coded as F2), and poloxamer 188 (P-188; coded as F3) were considered as the independent factors while particle size (PS; coded as R1), entrapment efficiency (%EE; R2), and cumulative drug release (%CDR; R3) were selected as dependent responses. The average PS, %EE, and %CDR of the AGN-PLHNPs were observed in the range of 101.93 nm to 175.26 nm, 58.35% to 81.14%, and 71.21% to 93.31%, respectively. The optimized AGN-PLHNPs revealed better homogeneity (poly-dispersity index < 0.2) and colloidal stability with high zeta potential (>25 mV). It also exhibited fast release in the initial 4 h after that sustained release up to 48 h of study. Moreover, the results of both DPPH as well as ABTS assays revealed significant improvement in the antioxidant activity. Furthermore, the optimized AGN-PLHNPs exhibited enhanced cytotoxicity efficacy against MCF-7 as well as MDA-MB-231 breast cancer cell lines.

Piperine (PPN), one of the most investigated phytochemicals, is known to have excellent therapeutic efficacy against a variety of ailments including breast cancer. However, its physicochemical properties such as poor aqueous solubility restrict its clinical application. Therefore, the present investigation was designed to develop PPN encapsulated lipid polymer hybrid nanoparticles (PPN-LPHNPs) to overcome the limitation. The developed PPN-LPHNPs were optimized by the three-factor, three-level Box−Behnken design (33-BBD). The optimized PPN-LPHNPs were then evaluated for their drug release profile, cytotoxicity assay against MDA-MB-231 and MCF-7 cells, and gastrointestinal stability as well as colloidal stability. In addition, the optimized PPN-LPHNPs were evaluated for ex vivo intestinal permeation and in vivo pharmacokinetic in albino Wistar rats. As per the results, the optimized PPN-LPHNPs showed a small average particles size of <160 nm with a low (<0.3) polydispersity index, and highly positive surface charge (>+20 mV). PPN-LPHNPs revealed excellent gastrointestinal as well as colloidal stability and sustained release profiles up to 24 h. Furthermore, PPN-LPHNPs revealed excellent cytotoxicity against both MDA-MB-231 and MCF-7 cancer cells compared to the free PPN. Moreover, animal studies revealed that the PPN-LPHNPs exhibited a 6.02- and 4.55-fold higher intestinal permeation and relative oral bioavailability, respectively, in comparison to the conventional PPN suspension. Thus, our developed LPHNPs present a strong potential for improved delivery of PPN.

This study attempted to develop and evaluate controlled-release matrix-type transdermal patches with different ratios of hydrophilic polymers (sodium carboxymethylcellulose and hydroxypropyl methylcellulose) for the local delivery of methotrexate. Transdermal patches were formulated by employing a solvent casting technique using blends of sodium carboxymethylcellulose (CMC-Na) and hydroxypropylmethylcellulose (HPMC) polymers as rate-controlling agents. The F1 formulated patch served as the control formulation with a 1:1 polymer concentration. The F9 formulation served as our optimized formulation due to suitable physicochemical properties yielded through the combination of CMC-Na and HPMC (5:1). Drug excipient compatibilities (ATR-FTIR) were performed as a preformulation study. The ATR-FTIR study depicted great compatibility between the drug and the polymers. Physicochemical parameters, kinetic modeling, in vitro drug release, ex vivo drug permeation, skin drug retention, and in vivo studies were also carried out for the formulated patches. The formulated patches exhibited a clear, smooth, elastic nature with good weight uniformity, % moisture uptake, drug content, and thickness. Physicochemical characterization revealed folding endurance ranging from 62 ± 2.21 to 78 ± 1.54, tensile strength from 9.42 ± 0.52 to 12.32 ± 0.72, % swelling index from 37.16 ± 0.17 to 76.24 ± 1.37, and % drug content from 93.57 ± 5.34 to 98.19 ± 1.56. An increase in the concentration of the CMC-Na polymer (F9) resulted in increased drug release from the formulated transdermal patches. Similarly, drug permeation and retention were found to be higher in the F9 formulation compared to the other formulations (F1-F8). A drug retention analysis revealed that the F9 formulation exhibited 13.43% drug retention in the deep layers of the skin compared to other formulations (F1-F8). The stability study indicated that, during the study period of 60 days, no significant changes in the drug content and physical characteristics were found. ATR-FTIR analysis of rabbit skin samples treated with the formulated transdermal patches revealed that hydrophilic polymers mainly affect the skin proteins (ceramide and keratins). A pharmacokinetic profile revealed C max was 1.77.38 ng/mL, T max was 12 h, and t 1/2 was 17.3 ± 2.21. In vivo studies showed that the skin drug retention of F9 was higher compared to the drug solution. These findings reinforce that methotrexate-based patches can possibly be used for the management of psoriasis. This study can reasonably conclude that methotrexate transdermal matrix-type patches with CMC-Na and HPMC polymers at different concentrations effectively sustain drug release with prime permeation profiles and better bioavailability. Therefore, these formulated patches can be employed for the potential management of topical diseases, such as psoriasis.

Diabetes is one of the world's most important public health issues, impacting both public health and socioeconomic advancement; moreover, current pharmacotherapy is still insufficient. The natural flavonoid rosinidin has a long history of use in pharmaceuticals and nutritional supplements, but its role in diabetes has been unknown. The current study was intended to confirm the anti-diabetic activity of rosinidin in our laboratory setting, along with its mechanism. Streptozotocin (60 mg/kg, ip) treatment used to induce type II diabetes in rats and the test medication rosinidin was then administered orally (at doses of 10 mg/kg and 20 mg/kg) for biochemical and histopathological analysis. Treatment with rosinidin reduced negative consequences of diabetes. Rosinidin exerted a protective effect on a number of characteristics, including anti-diabetic responses (lower blood glucose, higher serum insulin and improved pancreatic function) and molecular mechanisms (favorable effects on lipid profiles, total protein, albumin, liver glycogen, proinflammatory cytokine, antioxidant and oxidative stress markers, AST, ALT and urea). Furthermore, the improved pancreatic architecture observed in tissues substantiated the favourable actions of rosinidin in STZ-induced diabetic rats.

Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants ( N. hindustana , V. negundo , and A. albiflora ) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana , V. negundo , and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana , V. negundo , and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis.

Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-β were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.

(1) Background: Pneumocystis jirovecii pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim-Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies; (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle-Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs); (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients' compliance to daily regimen plan; (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.

Engineered nanoparticles that have distinctive targeted characteristics with high potency are modernistic technological innovations. In the modern era of research, nanotechnology has assumed critical importance due to its vast applications in all fields of science. Biologically synthesized nanoparticles using plants are an alternative to conventional methods. In the present study, Citrullus colocynthis (bitter apple) was used for the synthesis of gold nanoparticles (AuNPs). UV-Vis's spectroscopy, XRD, SEM and FTIR were performed to confirm the formation of AuNPs. UV-Vis's spectra showed a characteristic peak at the range of 531.5-541.5 nm. XRD peaks at 2 θ = 38°, 44°, 64° and 77°, corresponding to 111, 200, 220 and 311 planes, confirmed the crystalline nature of AuNPs. Spherical AuNPs ranged mostly between 7 and 33 nm, and were measured using SEM. The FTIR analysis confirmed the presence of phytochemicals on the surface of AuNPs. Successful synthesis of AuNPs by seed extract of Citrullus colocynthis (bitter apple) as a capping and reducing agent represents the novelty of the present study.

Breast cancer is a diverse disease caused by mutations in multiple genes accompanying epigenetic aberrations of hazardous genes and protein pathways, which distress tumor-suppressor genes and the expression of oncogenes. Alteration in any of the several physiological mechanisms such as cell cycle checkpoints, DNA repair machinery, mitotic checkpoints, and telomere maintenance results in genomic instability. Theranostic has the potential to foretell and estimate therapy response, contributing a valuable opportunity to modify the ongoing treatments and has developed new treatment strategies in a personalized manner. "Omics" technologies play a key role while studying genomic instability in breast cancer, and broadly include various aspects of proteomics, genomics, metabolomics, and tumor grading. Certain computational techniques have been designed to facilitate the early diagnosis of cancer and predict disease-specific therapies, which can produce many effective results. Several diverse tools are used to investigate genomic instability and underlying mechanisms. The current review aimed to explore the genomic landscape, tumor heterogeneity, and possible mechanisms of genomic instability involved in initiating breast cancer. We also discuss the implications of computational biology regarding mutational and pathway analyses, identification of prognostic markers, and the development of strategies for precision medicine. We also review different technologies required for the investigation of genomic instability in breast cancer cells, including recent therapeutic and preventive advances in breast cancer.

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades. In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation and DNA damage can eventually lead towards apoptosis. The importance of calorie restriction therapy in the extension of lifespan has also been discussed. The role of pathways involved in the regulation of lifespan such as DAF-16/FOXO (forkhead box protein O1), TOR and JNK pathways has also been particularized. The study provides an updated account of genetic factors associated with the extended lifespan and their interactive contributory role with cellular pathways.

This study aims to develop chitosan-based voriconazole nanoparticles (NPs) using spray-drying technique. The effect of surfactants and polymers on the physicochemical properties, in vitro release, and permeation of NPs was investigated. The prepared NPs containing various surfactants and polymers (e.g., Tween 20 (T20), Tween 80 (T80), sodium lauryl sulfate (SLS), propylene glycol (PG), and Polyethylene glycol-4000 (PEG-4000)) were physiochemically evaluated for size, zeta potential, drug content, percent entrapment efficiency, in vitro release, and permeation across rats' skin. A Franz diffusion cell was used for evaluating the in vitro release and permeation profile. The voriconazole-loaded NPs were investigated for antifungal activity against Candida albicans ( C. albicans ). The prepared NPs were in the nano range (i.e., 160-500 nm) and positively charged. Images taken by a scanning electron microscope showed that all prepared NPs were spherical and smooth. The drug content of NPs ranged from 75% to 90%. Nanoparticle formulations exhibited a good in vitro release profile and transport voriconazole across the rat's skin in a slow control release manner. The NPs containing SLS, T80, and PG exhibited the best penetration and skin retention profile. In addition, the formulation exhibited a potential antifungal effect against C. albicans . It was concluded that the development of chitosan NPs has a great potential for the topical delivery of voriconazole against fungal infection.

(1) Background: Inappropriate use of antimicrobials and subsequently rise of antimicrobial resistance (AMR) remains a major public health priority. Over-prescribing of broad-spectrum antibiotics is one of the main contributing factors for the emergence of AMR. We sought to describe antimicrobial prescribing trends among patients in public hospitals in Makkah hospitals. (2) Method: We undertook a point prevalence survey (PPS) in six hospitals in Makkah, Saudi Arabia, from January 2019 to July 2019. The survey included all the inpatients receiving antimicrobials on the day of PPS. Data was collected using the Global point prevalence survey (PPS) tool developed by the University of Antwerp, Belgium. (3) Results: Of 710 hospitalized patients, 447 patients (61.9%) were treated with one or more antimicrobials during the study period. The average bed occupancy among six hospitals was 74.4%. The majority of patients received antimicrobials parenterally (90.3%). Of the total prescribed antimicrobials, 415 (53.7%) antimicrobials were used in medical departments, 183 (23.7%) in surgical departments, and 175 (22.6%) in ICUs. Pneumonia (17.3%), skin and soft tissue infections (10.9%), and sepsis (6.6.%) were three common clinical indications. Ceftriaxones were the most commonly used antibiotics that were prescribed in 116 (15%) of patients, followed by piperacillin, with an enzyme inhibitor in 84 (10.9%). (4) Conclusion: There was a high prevalence of antibiotic use in the hospitals of Makkah, which could be a potential risk factor for the incidence of resistant strains, particularly MRSA infection. Public health decision-makers should take these findings into consideration to update national policies for antibiotic use in order to reduce the risks of further increases of AMR.

The use of biomaterials in the synthesis of nanoparticles is one of the most up-to-date focuses in modern nanotechnologies and nanosciences. More and more research on green methods of producing metal oxide nanoparticles (NP) is taking place, with the goal to overcome the possible dangers of toxic chemicals for a safe and innocuous environment. In this study, we synthesized copper nanoparticles (CuNPs) using Fortunella margarita leaves' extract, which reflects its novelty in the field of nanosciences. The visual observation of a color change from dark green to bluish green clearly shows the instant and spontaneous formation of CuNPs when the phytochemicals of F. margarita come in contact with Cu +2 ions. The synthesis of CuNPs was carried out at different conditions, including pH, temperature, concentration ratio and time, and were characterized with UV-Vis absorption spectra, scanning electron microscope (SEM) and X-ray diffraction (XRD). The UV-Vis analysis reveals the surface plasmon resonance property (SPR) of CuNPs, showing a characteristic absorption peak at 679 nm, while SEM reveals the spherical but agglomerated shape of CuNPs of the size within the range of 51.26-56.66 nm.

The present study was designed to prepare Kaempferol loaded nanoparticles (KFP-Np) and evaluate hepatoprotective and antioxidant effects in hepatocellular carcinoma models. KFP was encapsulated with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Kollicoat MAE 30 DP polymers to prepare nanoparticles (Nps) by quasi-emulsion solvent diffusion technique (QESD). The prepared Nps were evaluated for different pharmaceutical characterization to select the optimum composition for the in vivo assessment. An animal model of cadmium chloride (CdCl 2 )-induced hepatocellular carcinoma in Male Sprague Dawley rats was used in vivo to test the antioxidant and hepatoprotective capacity of free and encapsulated KFP. The prepared Npsshowed nanometric size, low PDI, high drug load as well as encapsulation with a better drug release profile. There was a significant decrease in the increased serum levels of alanine transaminase (ALT), total bilirubin (TBiL), and aspartate transaminase (AST), and the lipid peroxidation's (MDA) level was attenuated, and levels of markers of the cell antioxidant defence system were restored including Glutathione S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) via oral pre-treatment with KFP-Np (50 mg/kg b.w. (body weight), 6 weeks). KFP-Np significantly declines an mRNA expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) as well as decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression. It also upregulated the mRNA expression and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). While comparing the protective effects of KFP encapsulated in Kollicoat MAE 30 DP and HPMC-AS, Nps was found to be betterthan free KFP. Insummary, result indicate that encapsulation of KFP in NPs provides a potential platform for oxidative stress induce liver injury.

In East Asians, the incidence of type 2 DM (T2DM) has increased as a result of major alterations in life. Cardiovascular problems are more likely in those with T2DM. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are novel insulin-independent antihyperglycemic drugs that limit renal glucose reabsorption and thereby improve glycemic control. They are used alone or in combination with insulin and other antihyperglycemic medications to treat diabetes, and they are also helpful in protecting against the progression of complications. This review has evaluated the available evidence not only on the efficacy of SGLT2 inhibitors in T2DM, but also on their favourable cardiovascular events in East Asians. DM is an independent risk factor for cardiovascular diseases. As a result, in addition to glycemic control in diabetes management, the therapeutic goal in East Asian diabetic patients should be to improve adverse cardiovascular outcomes. Besides establishing antidiabetic effects, several studies have reported cardioprotective benefits of SGLT2 inhibitors via numerous pathways. SGLT2 inhibitors show promising antidiabetic drugs with potential cardiovascular advantages, given that a high number of diabetic patients in East Asia have co-existing cardiovascular disorders. Despite significant positive results in favour of SGLT2, more research is needed to determine how SGLT2 inhibitors exert these impressive cardiovascular effects.

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.

In the present study, luteolin (LT)-loaded nanosized vesicles (LT-NVs) were prepared by a solvent evaporation-hydration method using phospholipid and edge activator. The formulation was optimized using three factors at a three-level Box-Behnken design. The formulated LT-NVs were prepared using the three independent variables phospholipid (A), edge activator (B) and sonication time (C). The effect of used variables was assessed on the vesicle size ( Y 1 ) and encapsulation efficiency ( Y 2 ). The selection of optimum composition (LT-NVopt) was based on the point prediction method of the software. The prepared LT-NVopt showed the particle size of 189.92 ± 3.25 nm with an encapsulation efficiency of 92.43 ± 4.12% with PDI and zeta potential value of 0.32 and -21 mV, respectively. The formulation LT-NVopt was further converted into Carbopol 934 gel (1% w / v ) to enhance skin retention. LT-NVoptG was further characterized for viscosity, spreadability, drug content, drug release, drug permeation and antioxidant, antimicrobial and cytotoxicity assessment. The evaluation result revealed optimum pH, viscosity, spreadability and good drug content. There was enhanced LT release (60.81 ± 2.87%), as well as LT permeation (128.21 ± 3.56 µg/cm 2 /h), which was found in comparison to the pure LT. The antioxidant and antimicrobial study results revealed significantly ( p ˂ 0.05) better antioxidant potential and antimicrobial activity against the tested organisms. Finally, the samples were evaluated for cytotoxicity assessment using skin cancer cell line and results revealed a significant difference in the viability % at the tested concentration. LT-NVoptG showed a significantly lower IC 50 value than the pure LT. From the study, it can be concluded that the prepared LT-NVoptG was found to be an alternative to the synthetic drug as well as conventional delivery systems.

Transdermal drug delivery systems (TDDSs) have become innovative, fascinating drug delivery methods intended for skin application to achieve systemic effects. TDDSs overcome the drawbacks associated with oral and parenteral routes of drug administration. The current investigation aimed to design, evaluate and optimize methotrexate (MTX)-loaded transdermal-type patches having ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) at different concentrations for the local management of psoriasis. In vitro release and ex vivo permeation studies were carried out for the formulated patches. Various formulations (F1-F9) were developed using different concentrations of HPMC and EC. The F1 formulation having a 1:1 polymer concentration ratio served as the control formulation. ATR-FTIR analysis was performed to study drug-polymer interactions, and it was found that the drug and polymers were compatible with each other. The formulated patches were further investigated for their physicochemical parameters, in vitro release and ex vivo diffusion characteristics. Different parameters, such as surface pH, physical appearance, thickness, weight uniformity, percent moisture absorption, percent moisture loss, folding endurance, skin irritation, stability and drug content uniformity, were studied. From the hydrophilic mixture, it was observed that viscosity has a direct influence on drug release. Among all formulated patches, the F5 formulation exhibited 82.71% drug release in a sustained-release fashion and followed an anomalous non-Fickian diffusion. The permeation data of the F5 formulation exhibited about a 36.55% cumulative amount of percent drug permeated. The skin showed high retention for the F5 formulation (15.1%). The stability study indicated that all prepared formulations had very good stability for a period of 180 days. Therefore, it was concluded from the present study that methotrexate-loaded transdermal patches with EC and HPMC as polymers at different concentrations suit TDDSs ideally and improve patient compliance for the local management of psoriasis.