Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis.

Streptococcus pneumoniae (pneumococcus) is a multidrug-resistant pathogen associated with pneumonia, otitis media, meningitis and other severe complications that are currently a global threat to human health. The World Health Organization listed Pneumococcus as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat Pneumococcus. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, S. pneumoniae phage genomes were screened to create a database of endolysins for molecular modelling and diversity analysis of these lytic proteins. A total of 89 lytic proteins were curated from 81 phage genomes and categorized into eight groups corresponding to their different enzymatically active (EAD) domains and cell wall binding (CBDs) domains. We then constructed three-dimensional structures that provided insights into these endolysins. Group I, II, III, V, and VI endolysins showed conserved catalytic and ion-binding residues similar to existing endolysins available in the Protein Data Bank. While performing structural and sequence analysis with template lysin, an additional cell wall binding repeat was observed in Group II lysin, which was not previously known. Molecular docking performed with choline confirmed the existence of this additional repeat. Group III endolysins showed 99.16 % similarity to LysME-EF1, a lysin derived from Enterococcus faecalis. Furthermore, the comparative computational analysis revealed the existence of CBDs in Group III lysin. This study provides the first insight into the molecular and diversity analysis of S. pneumoniae phage endolysins that could be valuable for developing novel lysin-based therapeutics.

Hypoxia-induced TIMAP Upregulation in Endothelial Cells and TIMAP-dependent Tumour Angiogenesis.

TIMAP, the endothelial cell-predominant protein phosphatase 1ß regulatory subunit also known as PPP1R16B, promotes in vitro endothelial cell proliferation and angiogenic sprouting. TIMAP was first identified as a target of TGF-ß1 mediated repression, but the molecular pathways regulating its expression in endothelial cells are not well-defined. This study examined the role of BMP9, hypoxia and angiogenic growth factors in the regulation of TIMAP expression and determined whether TIMAP plays a role in tumor angiogenesis and growth in vivo. BMP9, which potently activated the SMAD1/5/8 pathway in endothelial cells, significantly reduced TIMAP mRNA and protein expression. Conversely, hypoxia and the prolyl hydroxylase inhibitor Roxadustat raised TIMAP mRNA and protein levels by inhibiting the BMP9 pathway. Angiogenic growth factors, most prominent among them VEGFA and IGF-I, raised endothelial TIMAP levels partly by attenuating BMP9 pathway activation, but also through BMP pathway-independent mechanisms. Cultured breast cancer E0771 cells released mediators that raised TIMAP expression in endothelial cells, effects that were inhibited by the VEGF inhibitor Sunitinib in conjunction with the IGF-1 inhibitor Picropodophyllin. In the mouse E0771 breast cancer model in vivo, tumor growth and tumor angiogenesis were markedly attenuated in TIMAP deficient, compared to wild-type littermates. These findings indicate that TIMAP plays a critical pro-angiogenic function during tumor angiogenesis in vivo, likely through hypoxia-driven inhibition of the BMP9 pathway and through elaboration of angiogenic growth factors by tumor cells.

A review of metallic nanoparticles: present issues and prospects focused on the preparation methods, characterization techniques, and their theranostic applications.

Metallic nanoparticles (MNPs) have garnered significant attention due to their ability to improve the therapeutic index of medications by reducing multidrug resistance and effectively delivering therapeutic agents through active targeting. In addition to drug delivery, MNPs have several medical applications, including in vitro and in vivo diagnostics, and they improve the biocompatibility of materials and nutraceuticals. MNPs have several advantages in drug delivery systems and genetic manipulation, such as improved stability and half-life in circulation, passive or active targeting into the desired target selective tissue, and gene manipulation by delivering genetic materials. The main goal of this review is to provide current information on the present issues and prospects of MNPs in drug and gene delivery systems. The current study focused on MNP preparation methods and their characterization by different techniques, their applications to targeted delivery, non-viral vectors in genetic manipulation, and challenges in clinical trial translation.

B-type plexins regulate mitosis via RanGTPase.

Aberrant mitosis can result in aneuploidy and cancer. The small GTPase, Ran, is a key regulator of mitosis. B-type Plexins regulate Ran activity by acting as RanGTPase activating proteins (GAPs) and have been implicated in cancer progression. However, whether B-type plexins have a role in mitosis has not so far been investigated. We show here that PlexinB1 functions in the control of mitosis. Depletion of PlexinB1 affects mitotic spindle assembly, significantly delaying anaphase. This leads to mitotic catastrophe in some cells, and prolonged application of the spindle assembly checkpoint. PlexinB1 depletion also promoted acentrosomal microtubule nucleation and defects in spindle pole refocussing and increased the number of cells with multipolar or aberrant mitotic spindles. An increase in lagging chromosomes or chromosomal bridges at anaphase was also found upon PlexinB1 depletion. PlexinB1 localises to the mitotic spindle in dividing cells. The mitotic defects observed upon PlexinB1 depletion were rescued by an RCC1 inhibitor, indicating that PlexinB1 signals, via Ran, to affect mitosis. These errors in mitosis generated multinucleate cells, and nuclei of altered morphology and abnormal karyotype. Furthermore, Semaphorin4D-treatment increased the percentage of cells with micronuclei, precursors of chromothripsis. Implications: Defects in B-type plexins may contribute to the well-established role of plexins in cancer progression by inducing chromosomal instability.

Numerical analysis and device modelling of a lead-free Sr3PI3/Sr3SbI3 double absorber solar cell for enhanced efficiency.

Halide perovskites are the most promising options for extremely efficient solar absorbers in the field of photovoltaic (PV) technology because of their remarkable optical qualities, increased efficiency, lightweight design, and affordability. This work examines the analysis of a dual-absorber solar device that uses Sr3SbI3 as the bottom absorber layer and Sr3PI3 as the top absorber layer of an inorganic perovskite through the SCAPS-1D platform. The device architecture includes ZnSe as the electron transport layer (ETL), while the active layer consists of Sr3PI3 and Sr3SbI3 with precise bandgap values. The bandgap value of Sr3SbI3 is 1.307 eV and Sr3PI3 is 1.258 eV. By employing double-graded materials of Sr3PI3/Sr3SbI3, the study achieves an optimized efficiency of up to 34.13% with a V OC of 1.09 V, FF of 87.29%, and J SC of 35.61 mA cm-2. The simulation explores the influence of absorber layer thickness, doping level, and defect density on electrical properties like efficiency, short-circuit current, open-circuit voltage, and fill factor. It also examines variations in temperature and assesses series and shunt resistances in addition to electrical factors. The simulation's output offers valuable insights and suggestions for designing and developing double-absorber solar cells.

Valorization of Agriculture Residues into Value-Added Products: A Comprehensive Review of Recent Studies.

Global agricultural by-products usually go to waste, especially in developing countries where agricultural products are usually exported as raw products. Such waste streams, once converted to "value-added" products could be an additional source of revenue while simultaneously having positive impacts on the socio-economic well-being of local people. We highlight the utilization of thermochemical techniques to activate and convert agricultural waste streams such as rice and straw husk, coconut fiber, coffee wastes, and okara power wastes commonly found in the world into porous activated carbons and biofuels. Such activated carbons are suitable for various applications in environmental remediation, climate mitigation, energy storage, and conversions such as batteries and supercapacitors, in improving crop productivity and producing useful biofuels.

All-protonic fuel cell designs and developments fuelled by ammonia.

Ammonia is a gas that produces zero carbon emissions when used in energy storage systems. Hence, there is increasing interest for the application of ammonia as fuel in various energy storage devices, specifically solid oxide fuel cells (SOFCs), as it has the potential to be efficient and environmentally friendly. In addition, compared to other fuel cells, SOFCs fed with ammonia offer various benefits such as such as sustainability and safety. This review compares and contrasts the opportunities and challenges of ammonia fuel cell technologies and helps to analyze their working principles. The main goal of this review is to investigate the viability of an "all-protonic" fuel cell using ammonia fuel while also highlighting the key challenges and limitations of implementing such technology.

Current strategies to address data scarcity in artificial intelligence-based drug discovery: A comprehensive review.

Artificial intelligence (AI) has played a vital role in computer-aided drug design (CADD). This development has been further accelerated with the increasing use of machine learning (ML), mainly deep learning (DL), and computing hardware and software advancements. As a result, initial doubts about the application of AI in drug discovery have been dispelled, leading to significant benefits in medicinal chemistry. At the same time, it is crucial to recognize that AI is still in its infancy and faces a few limitations that need to be addressed to harness its full potential in drug discovery. Some notable limitations are insufficient, unlabeled, and non-uniform data, the resemblance of some AI-generated molecules with existing molecules, unavailability of inadequate benchmarks, intellectual property rights (IPRs) related hurdles in data sharing, poor understanding of biology, focus on proxy data and ligands, lack of holistic methods to represent input (molecular structures) to prevent pre-processing of input molecules (feature engineering), etc. The major component in AI infrastructure is input data, as most of the successes of AI-driven efforts to improve drug discovery depend on the quality and quantity of data, used to train and test AI algorithms, besides a few other factors. Additionally, data-gulping DL approaches, without sufficient data, may collapse to live up to their promise. Current literature suggests a few methods, to certain extent, effectively handle low data for better output from the AI models in the context of drug discovery. These are transferring learning (TL), active learning (AL), single or one-shot learning (OSL), multi-task learning (MTL), data augmentation (DA), data synthesis (DS), etc. One different method, which enables sharing of proprietary data on a common platform (without compromising data privacy) to train ML model, is federated learning (FL). In this review, we compare and discuss these methods, their recent applications, and limitations while modeling small molecule data to get the improved output of AI methods in drug discovery. Article also sums up some other novel methods to handle inadequate data.

Lamiales epidermal dynamics: Unveiling antimicrobial resilience in a structural symphony.

This research on Lamiales epidermal anatomy not only provides in-depth understanding of their structural traits but also highlights the significance of uncovering the inherent antimicrobial resilience embedded within these plants. Such insights hold promise for advancing natural product-based approaches in medicine, potentially contributing to the development of novel antimicrobial agents inspired by Lamiales unique biological defense mechanisms. Scanning microscopic tools were utilized to conduct foliar epidermal anatomy of nine species that belong to seven genera and four families within the Lamiales order, Plantaginaceae, Scrophulariaceae, Verbenaceae, and Lamiaceae. This approach aimed to gather both qualitative and quantitative data, facilitating the assessment of taxonomic microanatomical significance. The shape of epidermal cells and their anticlinal walls; number of epidermal cells, stomata, and trichomes; type of stomata and trichomes; length and width of epidermal cells, trichomes, stomatal pore, guard cells, and subsidiary cells; and stomatal index were determined statistically. Most of the species examined were amphistomatous and showed extensive array of trichomes diversity. The exploration of Lamiales epidermal micromorphology and their antimicrobial potential were significant for their implications in multidisciplinary fields. The pharmacological research to utilize sustainable agricultural practices prompts avenues to strengths of Lamiales order for the development of novel antimicrobial solutions and ecological benefits. RESEARCH HIGHLIGHTS: Diverse trichome morphometry reveals a wide array of trichome structures across Lamiales species. Epidermal microscopic architecture variability of epidermal cell shapes and sizes signifies the interspecies variability. Secondary metabolite localization within microanatomical structures elucidates potential hotspots for antimicrobial compound production.

Scanning electron microscopic investigation on Chicory tribe (Compositae) botanical sources and their antimicrobial potential.

This study discusses the micro-level structural details of Cichorieae pollen sources elucidated by scanning electron microscopy (SEM) and explains their symmetry and morphometry. The in-depth knowledge from the electron ultrastructure of Asteraceae pollen has provided insights into enhanced pollen morphology, and the antimicrobial significance of species under study presents novel avenues for their natural defense mechanisms in the development of antimicrobial agents. In this research, both quantitative and qualitative features of pollen were examined. The pollen grains are prolate-spheroidal and oblate-spheroidal in shape, characterized by a maximum polar diameter of 55.6-61.0 µm and a maximum equatorial distance of 68.3-74.4 µm. SEM reveals various configurations such as echinate perforate-tectate, psilate, and echino-lophate perforate. The Cichorieae species have significant antimicrobial efficacy and are promising sources for the development of novel antimicrobial drugs with potential implications in pharmaceutical and healthcare industries. SEM analysis of Cichorieae pollens has provided remarkable insights into their unique structures, revealing diverse shapes and surface ornamentations, which can be used for accurate Asteraceae species identification. RESEARCH HIGHLIGHTS: SEM provides unique pollen surface structures and patterns of Chicory pollen grains. Chemical composition of Chicory botanical sources provides valuable information on their potential as antimicrobial agents. SEM imaging reveals specialized fenestrate grain structures of taxonomic importance.

Own price elasticities of the demand for sugar-sweetened beverages in Bangladesh.

BACKGROUND: Consumption of sugar-sweetened beverages (SSB) is a major global public health problem. Increasing the price of SSBs through taxation is an effective tool to reduce SSB consumption. Price-elasticity estimates are useful in measuring the effect of taxation on consumption. We estimated the own price elasticities of demand for SSBs in Bangladesh, which will inform how SSB taxes could affect behaviour. METHODS: We used Household Income and Expenditure Survey (HIES) 2016 data, which is a nationally representative dataset at the household level across the country and is conducted using stratified random sampling method. Deaton's method was used to estimate the price elasticities for SSBs in Bangladesh. RESULTS: We found that the own price elasticity for SSBs varied between - 0.53% to -1.17% by types of SSBs in Bangladesh. The price elasticity for soft drinks was - 1.17, indicating that if the price of soft drinks increases by 10% via taxes, the quantity consumed of these beverages would reduce by 11.7%. CONCLUSION: This is the first study that estimates the own price elasticities of demand for SSBs in Bangladesh. Our results suggest to raise SSB prices through increased taxation in order to reduce SSB consumption and ensure public health gains in Bangladesh.

Prevalence, antibiotic resistance pattern for bacteriuria from patients with urinary tract infections.

Background and Aims: Antibiotic resistance presents a significant global public health challenge, particularly for urinary tract infections (UTIs), and is notably severe in developing countries. Surveillance of the antimicrobial susceptibility patterns of UTI-causing bacteria is crucial for effective treatment selection. This study aimed to analyze these patterns in bacteria isolated from the urine samples of patients at Mughda Medical College Hospital, Dhaka, Bangladesh. Methods: A retrospective study (January 2019 to December 2020) at Mugdha Medical College and Hospital, Dhaka, examined clinical and laboratory data from patients with positive urine cultures (≥105 CFU/mL). The study classified patients into four age groups: children (1-<18 years), young adults (18-<33 years), middle-aged adults (33-50 years), and old adults (>50 years). The standard Kirby-Bauer method was used to assess antibiotic sensitivity to 28 common antibiotics. Results: Among 243 positive urine cultures in both community- and hospital-acquired UTIs, Escherichia coli was the most common uropathogen (65.84%), followed by Klebsiella spp. (12.34%), Enterococcus spp. (8.23%), and other types of bacteria. Conclusion: Old adults are particularly vulnerable to UTIs, with E. coli being the predominant causative agent in the study region. The observed antimicrobial resistance patterns underscore the necessity of judicious antibiotic selection to effectively treat UTIs across different age groups.

Assessment of the botanical origin of Saudi Arabian honey samples to identify pollen with chromatographic tools and packing and storage.

The increasing demand for honey purification and authentication necessitates the global utilization of advanced processing tools. Common honey processing techniques, such as chromatography, are commonly used to assess the quality and quantity of valuable honey. In this study, 15 honey samples were authenticated using HPLC and GC-MS chromatographic methods to analyze their pollen spectrum. Various monofloral honey samples were collected, including Acacia, Hypoestes, Lavandula, Tamarix, Trifolium, and Ziziphus species, based on accurate identification by apiarists in 2023 from the Kingdom of Saudi Arabia. Honey analysis revealed the extraction of pollen from 20 different honeybee floral species. Pollen identified from honey samples using advanced chromatographic tools revealed dominant vegetation resources: Ziziphus species (23%), Acacia species (25%), Tamarix species (34%), Lavandula species (26%), Hypoestes species (34%), and Trifolium species (31%). This study uses HPLC to extract phenolic compounds, revealing dominant protocatechuic acid (4.71 mg g-1), and GC-MS to analyze organic compounds in honey pollen. Specifically, 2-dodecanone was detected with a retention time of 7.34 min. The utilization of chromatographic tools in assessing honey samples for pollen identification provides a reliable and efficient method for determining their botanical origins, thereby contributing to the quality control and authentication of honey products.

Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

Did the COVID-19 pandemic affect levels of burnout, anxiety and depression among doctors and nurses in Bangladesh? A cross-sectional survey study.

INTRODUCTION: COVID-19 has caused severe disruption to clinical services in Bangladesh but the extent of this, and the impact on healthcare professionals is unclear. We aimed to assess the perceived levels of anxiety, depression and burnout among doctors and nurses during COVID-19 pandemic. METHODS: We undertook an online survey using RedCap, directed at doctors and nurses across four institutions in Bangladesh (The Sheikh Russel Gastro Liver Institute & Hospital (SRNGIH), Dhaka Medical College Hospital (DMCH), Mugda Medical College Hospital (MMCH) and M Abdur Rahim Medical College (MARMC) Hospital). We collected information on demographics, awareness of well-being services, COVID-19-related workload, as well as anxiety, depression and burnout using two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Maslach Burnout Inventory (MBI). RESULTS: Of the 3000 participants approached, we received responses from 2705 (90.2%). There was a statistically significant difference in anxiety, depression and burnout scores across institutions (p<0.01). Anxiety, depression and burnout scores were statistically worse in COVID-19 active staff compared with those not working on COVID-19 activities (p<0.01 for HADS anxiety and depression and MBI emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA)). Over half of the participants exhibited some level of anxiety (SRNGIH: 52.2%; DMCH: 53.9%; MMCH: 61.3%; MARMC: 68%) with a high proportion experiencing depression (SRNGIH: 39.5%; DMCH: 38.7%; MMCH: 53.7%; MARMC: 41.1%). Although mean burnout scores were within the normal range for each institution, a high proportion of staff (almost 20% in some instances) were shown to be classified as experiencing burnout by their EE, DP and PA scores. CONCLUSION: We identified a high prevalence of perceived anxiety, depression and burnout among doctors and nurses during the COVID-19 pandemic. This was worse in staff engaged in COVID-19-related activities. These findings could help healthcare organisations to plan for future similar events.

A dataset of microstructure features of electro-hydrodynamic assisted 5-fluorouracil-grafted alginate microbeads and physicochemical properties for effective colon targeted carriers drug delivery.

5-Fluorouracil (5-FU) has been the primary drug used in chemotherapy for colorectal carcinoma, and localizing the drug would be effective in avoiding its side effects and improving therapeutic outcomes. One approach to achieve this is by encapsulating the drug in microbeads. Alginate microbeads, in particular, exhibit promising pH-sensitive properties, making them an attractive option for colon targeting. Thus, the main aim of this study is to formulate and characterize 5-FU-encapsulated alginate microbeads as a pH-sensitive drug delivery system for controlled release in the gastrointestinal tract. In this study, the alginate microbeads encapsulating 5-FU was manufactured using electrospray methods. This method offers the advantages of promoting the formulation of uniformly small-sized microbeads with improved performance in terms of swelling and diffusion rates. The size and shape of the 5-FU microbeads are 394.23 ± 3.077 µm and have a spherical factor of 0.026 ± 0.022, respectively, which are considered acceptable and indicative of a spherical shape. The microbeads' encapsulation efficiency was found to be 69.65 ± 0.18%, which is considered high in comparison to other literature. The attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR) data confirmed the complexation of sodium alginate with calcium ions, along with the encapsulation of 5-FU in the microbeads matrix. The 5-FU microbeads displayed pH-dependent swelling, exhibiting less swelling in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). Additionally, the release of 5-FU from the microbeads is pH-dependent, with the cumulative percentage drug release being higher in simulated intestinal fluid than in SGF. The data indicate that the 5-FU microbeads can be utilized for the delivery of 5-FU in colon-targeted therapy, potentially leading to improved tumor treatment.

Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System.

Alginate is a natural biopolymer widely studied for pharmaceutical applications due to its biocompatibility, low toxicity, and mild gelation abilities. This review summarizes recent advances in alginate-based encapsulation systems for targeted drug delivery. Alginate formulations like microparticles, nanoparticles, microgels, and composites fabricated by methods including ionic gelation, emulsification, spray drying, and freeze drying enable tailored drug loading, enhanced stability, and sustained release kinetics. Alginate microspheres prepared by spray drying or ionic gelation provide gastric protection and colon-targeted release of orally delivered drugs. Alginate nanoparticles exhibit enhanced cellular uptake and tumor-targeting capabilities through the enhanced permeation and retention effect. Crosslinked alginate microgels allow high drug loading and controlled release profiles. Composite alginate gels with cellulose, chitosan, or inorganic nanomaterials display improved mechanical properties, mucoadhesion, and tunable release kinetics. Alginate-based wound dressings containing antimicrobial nanoparticles promote healing of burns and chronic wounds through sustained topical delivery. Although alginate is well-established as a pharmaceutical excipient, more extensive in vivo testing is needed to assess clinical safety and efficacy of emerging formulations prior to human trials. Future opportunities include engineered systems combining stimuli-responsiveness, active targeting, and diagnostic capabilities. In summary, this review discusses recent advances in alginate encapsulation techniques for oral, transdermal, and intravenous delivery, with an emphasis on approaches enabling targeted and sustained drug release for enhanced therapeutic outcomes.

The Fabrication of Polymer-Based Curcumin-Loaded Formulation as a Drug Delivery System: An Updated Review from 2017 to the Present.

Turmeric contains curcumin, a naturally occurring compound with noted anti-inflammatory and antioxidant properties that may help fight cancer. Curcumin is readily available, nontoxic, and inexpensive. At high doses, it has minimal side effects, suggesting it is safe for human use. However, curcumin has extremely poor bioavailability and biodistribution, which further hamper its clinical applications. It is commonly administered through oral and transdermal routes in different forms, where the particle size is one of the most common barriers that decreases its absorption through biological membranes on the targeted sites and limits its clinical effectiveness. There are many studies ongoing to overcome this problem. All of this motivated us to conduct this review that discusses the fabrication of polymer-based curcumin-loaded formulation as an advanced drug delivery system and addresses different approaches to overcoming the existing barriers and improving its bioavailability and biodistribution to enhance the therapeutic effects against cancer and other diseases.

Generative artificial intelligence in drug discovery: basic framework, recent advances, challenges, and opportunities.

There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through de novo drug design or inverse quantitative structure-activity relationship. Both methods aim to get a drug molecule with the best pharmacokinetic and pharmacodynamic profiles. However, bringing a new drug to market is an expensive and time-consuming endeavor, with the average cost being estimated at around $2.5 billion. One of the biggest challenges is screening the vast number of potential drug candidates to find one that is both safe and effective. The development of artificial intelligence in recent years has been phenomenal, ushering in a revolution in many fields. The field of pharmaceutical sciences has also significantly benefited from multiple applications of artificial intelligence, especially drug discovery projects. Artificial intelligence models are finding use in molecular property prediction, molecule generation, virtual screening, synthesis planning, repurposing, among others. Lately, generative artificial intelligence has gained popularity across domains for its ability to generate entirely new data, such as images, sentences, audios, videos, novel chemical molecules, etc. Generative artificial intelligence has also delivered promising results in drug discovery and development. This review article delves into the fundamentals and framework of various generative artificial intelligence models in the context of drug discovery via de novo drug design approach. Various basic and advanced models have been discussed, along with their recent applications. The review also explores recent examples and advances in the generative artificial intelligence approach, as well as the challenges and ongoing efforts to fully harness the potential of generative artificial intelligence in generating novel drug molecules in a faster and more affordable manner. Some clinical-level assets generated form generative artificial intelligence have also been discussed in this review to show the ever-increasing application of artificial intelligence in drug discovery through commercial partnerships.

Metasurface-based varifocal Alvarez lens at microwave frequencies.

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.