Machine Learning and Deep Learning in Synthetic Biology: Key Architectures, Applications, and Challenges.

Machine learning (ML), particularly deep learning (DL), has made rapid and substantial progress in synthetic biology in recent years. Biotechnological applications of biosystems, including pathways, enzymes, and whole cells, are being probed frequently with time. The intricacy and interconnectedness of biosystems make it challenging to design them with the desired properties. ML and DL have a synergy with synthetic biology. Synthetic biology can be employed to produce large data sets for training models (for instance, by utilizing DNA synthesis), and ML/DL models can be employed to inform design (for example, by generating new parts or advising unrivaled experiments to perform). This potential has recently been brought to light by research at the intersection of engineering biology and ML/DL through achievements like the design of novel biological components, best experimental design, automated analysis of microscopy data, protein structure prediction, and biomolecular implementations of ANNs (Artificial Neural Networks). I have divided this review into three sections. In the first section, I describe predictive potential and basics of ML along with myriad applications in synthetic biology, especially in engineering cells, activity of proteins, and metabolic pathways. In the second section, I describe fundamental DL architectures and their applications in synthetic biology. Finally, I describe different challenges causing hurdles in the progress of ML/DL and synthetic biology along with their solutions.

Organelle-targeting ratiometric fluorescent probes: design principles, detection mechanisms, bio-applications, and challenges.

Biological species, including reactive oxygen species (ROS), reactive sulfur species (RSS), reactive nitrogen species (RNS), F-, Pd2+, Cu2+, Hg2+, and others, are crucial for the healthy functioning of cells in living organisms. However, their aberrant concentration can result in various serious diseases. Therefore, it is essential to monitor biological species in cellular organelles such as the cell membrane, mitochondria, lysosome, endoplasmic reticulum, Golgi apparatus, and nucleus. Among various fluorescent probes for species detection within the organelles, ratiometric fluorescent probes have drawn special attention as a potential way to get beyond the drawbacks of intensity-based probes. This method depends on measuring the intensity change of two emission bands (caused by an analyte), which produces an efficient internal referencing that increases the detection's sensitivity. This review article discusses the literature publications (from 2015 to 2022) on organelle-targeting ratiometric fluorescent probes, the general strategies, the detecting mechanisms, the broad scope, and the challenges currently faced by fluorescent probes.

Advancing Women in Chemistry: A Step Toward Gender Parity.

As chemistry progressed over the years, modern society witnessed the significant contribution of women chemists. However, the persisting gender imbalance in the scientific community, attributed to improper societal norms and several other reasons, is a matter of concern. The manuscript highlights some great women chemists, such as Nobel Prize awardees, who have created history through their outstanding research work and are role models for other women. Since women continue to encounter recurring obstacles to moving forward in their area, the "leaky pipeline" of women in chemical science remains problematic. Numerous factors, including having to shoulder the labor of childcare and household work and a lack of awareness of regulations and possibilities, contribute to prejudices and the gender gap in higher-level administrative and decision-making roles. To close the gender gap and empower women chemists, we highlight some initiatives (awards, fellowships, schemes, and grants) that have been put forth by governments, organizations, foundations, companies, industries, and publishing societies. As per statistics, only 4% of female scientists have been awarded the Nobel Prize in chemistry until now. Only 35%, 22%, 14%, 26%, and 5% of women are serving as editors-in-chief, while 38%, 40%, 18%, 22%, and 21% are working as associate editors of the American Chemical Society (ACS), Royal Society of Chemistry (RSC), Wiley, Elsevier, and Springer journals, respectively. A further issue is that women receive far fewer honors in chemistry. To promote a more encouraging atmosphere for women scientists at all career phases, we listed some recommendations that research grant funders, academic institutions, publishers, and scientific organizations can follow. For gender parity, the paper sought to address the current situation of women in the chemical sciences. Women's contributions to chemistry will promote innovation and progress in the field.

Recent Advances and Mechanistic Insights into Antibacterial Activity, Antibiofilm Activity, and Cytotoxicity of Silver Nanoparticles.

The substantial increase in multidrug-resistant (MDR) pathogenic bacteria is a major threat to global health. Recently, the Centers for Disease Control and Prevention reported possibilities of greater deaths due to bacterial infections than cancer. Nanomaterials, especially small-sized (size ≤10 nm) silver nanoparticles (AgNPs), can be employed to combat these deadly bacterial diseases. However, high reactivity, instability, susceptibility to fast oxidation, and cytotoxicity remain crucial shortcomings for their uptake and clinical application. In this review, we discuss various AgNPs-based approaches to eradicate bacterial infections and provide comprehensive mechanistic insights and recent advances in antibacterial activity, antibiofilm activity, and cytotoxicity (both in vitro and in vivo) of AgNPs. The mechanistic of antimicrobial activity involves four steps: (i) adhesion of AgNPs to cell wall/membrane and its disruption; (ii) intracellular penetration and damage; (iii) oxidative stress; and (iv) modulation of signal transduction pathways. Numerous factors affecting the bactericidal activity of AgNPs such as shape, size, crystallinity, pH, and surface coating/charge have also been described in detail. The review also sheds light on antimicrobial photodynamic therapy and the role of AgNPs versus Ag+ ions release in bactericidal activities. In addition, different methods of synthesis of AgNPs have been discussed in brief.

COVID-19: inflammatory responses, structure-based drug design and potential therapeutics.

The COVID-19 pandemic caused by SARS-CoV-2 is responsible for the global health emergency. Here, we explore the diverse mechanisms of SARS-CoV-induced inflammation. We presume that SARS-CoV-2 likely contributes analogous inflammatory responses. Possible therapeutic mechanisms for reducing SARS-CoV-2-mediated inflammatory responses comprise FcR inactivation. Currently, there is no specific remedy available against the SARS-CoV-2. Consequently, recognizing efficacious antiviral leads to combat the virus is crucially desired. The coronavirus (CoV) main protease (Mpro also called 3CLpro), which plays an indispensable role in viral replication and transcription, is an interesting target for drug design. This review compiles the latest advances in biological and structural research, along with development of inhibitors targeting CoV Mpros. It is anticipated that inhibitors targeting CoV Mpros could be advanced into wide-spectrum antiviral drugs in case of COVID-19 and other CoV-related diseases. The crystal structural and docking results have shown that Ebselen, N3, TDZD-8 and α-ketoamide (13b) inhibitors can bind to the substrate-binding pocket of COVID-19 Mpro. α-ketoamide-based inhibitor 13b inhibits the replication of SARS-CoV-2 in human Calu3 lung cells. Quantitative real-time RT-PCR (qRT-PCR) showed that the treatment with Ebselen, TDZD-8 and N3 reduced the amounts of SARS-CoV-2, respectively, 20.3-, 10.19- and 8.4-fold compared to the treatment in the absence of inhibitor. Moreover, repurposing of already present drugs to treat COVID-19 serves as one of the competent and economic therapeutic strategies. Several anti-malarial, anti-HIV and anti-inflammatory drugs as mentioned in Table 2 were found effective for the COVID-19 treatment. Further, hydroxychloroquine (HCQ) was found more potent than chloroquine (CQ) in inhibiting SARS-CoV-2 in vitro. Furthermore, convalescent plasma from patients who have recuperated from viral infections can be employed as a therapy without the appearance of severe adverse events. Hence, it might be valuable to examine the safety and efficacy of convalescent plasma transfusion in SARS-CoV-2-infected patients.

Applications of artificial intelligence to drug design and discovery in the big data era: a comprehensive review.

Artificial intelligence (AI) renders cutting-edge applications in diverse sectors of society. Due to substantial progress in high-performance computing, the development of superior algorithms, and the accumulation of huge biological and chemical data, computer-assisted drug design technology is playing a key role in drug discovery with its advantages of high efficiency, fast speed, and low cost. Over recent years, due to continuous progress in machine learning (ML) algorithms, AI has been extensively employed in various drug discovery stages. Very recently, drug design and discovery have entered the big data era. ML algorithms have progressively developed into a deep learning technique with potent generalization capability and more effectual big data handling, which further promotes the integration of AI technology and computer-assisted drug discovery technology, hence accelerating the design and discovery of the newest drugs. This review mainly summarizes the application progression of AI technology in the drug discovery process, and explores and compares its advantages over conventional methods. The challenges and limitations of AI in drug design and discovery have also been discussed.

Protein mixtures of environmentally friendly zein to understand protein-protein interactions through biomaterials synthesis, hemolysis, and their antimicrobial activities.

Industrially important zein protein has been employed to understand its interactions with two model proteins bovine serum albumin (BSA) and cytochrome c (Cyc,c) following the in vitro synthesis of Au NPs so as to expand its applicability for biological applications. Interactions were studied under the effect of temperature variation by UV-visible and fluorescence emission studies. Temperature induced unfolding in the protein mixtures indicated their degree of mutual interactions through simultaneous nucleation of gold nanoparticles (Au NPs) and their subsequent shape control effects. Zein + BSA mixtures showed favorable protein-protein interactions over the entire mole fraction range with maximum close to x(BSA) = 0.24, whereas zein + Cyc,c showed such interactions only in the zein rich region with significant demixing in the Cyc,c rich region of the mixtures. Both hydrophobic as well as hydrophilic domains in the unfolded states were driving such interactions in the case of zein + BSA mixtures while demixing was the result of the predominant hydrophilic nature of Cyc,c and its self-aggregation behavior in the Cyc,c rich region in contrast to the predominant hydrophobic nature of zein. Zein + BSA mixtures produced small roughly spherical Au NPs fully coated with protein, whereas the demixing zone of zein + Cyc,c mixtures generated highly anisotropic NPs with little protein coating. To explore their biological applications, protein conjugated NPs of both mixtures were subjected to hemolysis where NPs coated with the former mixture showed little hemolysis and may act as drug delivery vehicles in systemic circulation in comparison to the latter. Both kinds of NPs further demonstrated their extraordinary antimicrobial activities with different kinds of strains and proved to be highly important environmentally friendly biomaterials.