The causal effect of oxidative stress on the risk of glaucoma.

Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848-0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248-0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119-4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927-0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890-0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810-0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978-0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.

Effect of the gut microbiome in glaucoma risk from the causal perspective.

OBJECTIVE: Evidence from observational studies has reported possible associations between the gut microbiome (GM) and glaucoma. However, the causal effect of GM on glaucoma risk remains to be determined. METHODS AND ANALYSIS: We conducted two-sample bidirectional Mendelian randomisation (MR) analyses to explore the causal association between GM and glaucoma. Genome-wide association study summary statistics of 196 GM taxa (n=18 340) and glaucoma (18 902 cases and 358 375 controls) were obtained from MiBioGen and FinnGen Consortium. Inverse variance weighted, MR-Egger, weighted median, weighted mode, Mendelian Randomisation Pleiotropy Residual Sum and Outlier, MR-Egger intercept and Cochran's Q statistical analyses were used to supplement MR results and sensitivity analysis. An independent cohort from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium (1715 cases and 359 479 controls) was used to validate causal effects. RESULTS: Results of the MR analysis suggested that the family Oxalobacteraceae (OR 0.900, 95% CI 0.843 to 0.961, p=0.002) and the genus Eggerthella (OR 0.881, 95% CI 0.811 to 0.957, p=0.003) had a negative effect on glaucoma, whereas the genus Bilophila (OR 1.202, 95% CI 1.074 to 1.346, p=0.001), LachnospiraceaeUCG010 (OR 1.256, 95% CI 1.109 to 1.423, p=0.0003) and Ruminiclostridium 9 (OR 1.258, 95% CI 1.083 to 1.461, p=0.003) had a positive effect on glaucoma. Among these, the positive causal effect of LachnospiraceaeUCG010 (OR 1.002, 95% CI 1.000 to 1.004, p=0.033) on glaucoma was replicated in an independent cohort. CONCLUSION: This MR analysis from large population studies demonstrated the causal effect of GM on glaucoma risk and supported the role of GM in influencing glaucoma susceptibility.

Quantum digital signature with unidimensional continuous-variable against the measurement angular error.

The continuous-variable quantum digital signature (CV-QDS) scheme relies on the components of quantum key generation protocol (KGP) to negotiate classical signature, which is more compatible with optical fibers. Nevertheless, the measurement angular error of heterodyne detection or homodyne detection will cause security issues when performing KGP in the distribution stage. For that, we propose to utilize unidimensional modulation in KGP components, which only requires to modulate single quadrature and without the process of basis choice. Numerical simulation results show that the security under collective attack, repudiation attack and forgery attack can be guaranteed. We expect that the unidimensional modulation of KGP components could further simplify the implementation of CV-QDS and circumvent the security issues caused by the measurement angular error.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in allergic airway inflammation.

As a pattern recognition receptor which activates innate immune system, toll-like receptor 2 (TLR2) has been reportedly mediates allergic airway inflammation (AAI), yet the underlying mechanism remains elusive. Here, in a murine AAI model, TLR2-/- mice showed decreased airway inflammation, pyroptosis and oxidative stress. RNA-sequencing revealed that allergen-induced hif1 signaling pathway and glycolysis were significantly downregulated when TLR2 was deficient, which were confirmed by lung protein immunoblots. Glycolysis inhibitor 2-Deoxy-d-glucose (2-DG) inhibited allergen-induced airway inflammation, pyroptosis, oxidative stress and glycolysis in wild type (WT) mice, while hif1α stabilizer ethyl 3,4-dihydroxybenzoate (EDHB) restored theses allergen-induced changes in TLR2-/- mice, indicating TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in AAI. Moreover, upon allergen challenge, lung macrophages were highly activated in WT mice but were less activated in TLR2-/- mice, 2-DG replicated while EDHB reversed such effect of TLR2 deficiency on lung macrophages. Likewise, both in vivo and ex vivo WT alveolar macrophages (AMs) exhibited higher TLR2/hif1α expression, glycolysis and polarization activation in response to ovalbumin (OVA), which were all inhibited in TLR2-/- AMs, suggesting AMs activation and metabolic switch are dependent on TLR2. Finally, depletion of resident AMs in TLR2-/- mice abolished while transfer of TLR2-/- resident AMs to WT mice replicated the protective effect of TLR2 deficiency on AAI when administered before allergen challenge. Collectively, we suggested that loss of TLR2-hif1α-mediated glycolysis in resident AMs ameliorates allergic airway inflammation that inhibits pyroptosis and oxidative stress, therefore the TLR2-hif1α-glycolysis axis in resident AMs may be a novel therapeutic target for AAI.

Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress.

Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex belonging to the mitochondrial respiratory chain and uniquely links the tricarboxylic acid (TCA) cycle with oxidative phosphorylation. Cancer-related SDH mutations promote succinate accumulation, which is regarded as an oncometabolite. Post-translational modifications of SDH complex components are known to regulate SDH activity, although the contribution of SUMOylation remains unclear. Here, we show that SDHA is SUMOylated by PIAS3 and deSUMOylated by SENP2, events dictating the assembly and activity of the SDH complex. Moreover, CBP acetylation of SENP2 negatively regulates its deSUMOylation activity. Under glutamine deprivation, CBP levels decrease, and the ensuing SENP2 activation and SDHA deSUMOylation serve to concurrently dampen the TCA cycle and electron transport chain (ETC) activity. Along with succinate accumulation, this mechanism avoids excessive reactive oxygen species (ROS) production to promote cancer cell survival. This study elucidates a major function of mitochondrial-localized SENP2 and expands our understanding of the role of SUMOylation in resolving metabolic stress.

The single-atom iron nanozyme mimicking peroxidase remodels energy metabolism and tumor immune landscape for synergistic chemodynamic therapy and photothermal therapy of triple-negative breast cancer.

Chemotherapy, as one main strategy to relieve tumor progression, has a weak effect on triple-negative breast cancer (TNBC) chest wall metastasis. The development of near-infrared (NIR) light-responsive nanomaterials for chemodynamic therapy (CDT) and photothermal therapy (PTT) is a promising platform but still challenging in biomedicine. This study reports a peroxidase mimicking nanozyme (Fe-N-C SAzyme) against TNBC by CDT and PTT. Fe-N-C SAzyme generated reactive oxygen species (ROS) by decomposing H2O2 into hydroxyl radicals (•OH) and also induced light-to-heat conversion under the exposure of 808 nm laser irradiation. With these biological characteristics, the obtained Fe-N-C SAzymes displayed enhanced cell cytotoxicity and inhibition of cancer cell proliferation both in vitro and in vivo at a low dose of nanoagent and a moderate NIR laser power density. Besides, Fe-N-C nanoagent with its excellent ROS generation brought metabolic reprogramming of elevated glycolysis in tumor cells. In vivo experiments, when combined with PTT, the enhanced antitumor effect was found by the elimination of M-MDSC in tumor microenvironment. Fe-N-C SAzymes can serve as a new synergistic CDT and PTT nanoagent to simultaneously reprogram tumor metabolism and tumor microenvironment. It will provide prospects for chemodynamic/photothermal combined cancer therapy for TNBC chest wall metastasis based on the use of a single nanosystem.

Bioinformatics analysis reveals potential biomarkers associated with the occurrence of intracranial aneurysms.

To better understand the molecular mechanisms of intracranial aneurysm (IA) pathogenesis, we used gene coexpression networks to identify hub genes and functional pathways associated with IA onset. Two Gene Expression Omnibus (GEO) datasets encompassing intracranial aneurysm tissue samples and cerebral artery control samples were included. To discover functional pathways and potential biomarkers, weighted gene coexpression network analysis was employed. Next, single-gene gene set enrichment analysis was employed to investigate the putative biological roles of the chosen genes. We also used receiver operating characteristic analysis to confirm the diagnostic results. Finally, we used a rat model to confirm the hub genes in the module of interest. The module of interest, which was designated the green module and included 115 hub genes, was the key module that was most strongly and negatively associated with IA formation. According to gene set variation analysis results, 15 immune-related pathways were significantly activated in the IA group, whereas 7 metabolic pathways were suppressed. In two GEO datasets, SLC2A12 could distinguish IAs from control samples. Twenty-nine hub genes in the green module might be biomarkers for the occurrence of cerebral aneurysms. SLC2A12 expression was significantly downregulated in both human and rat IA tissue. In the present study, we identified 115 hub genes related to the pathogenesis of IA onset and deduced their potential roles in various molecular pathways; this new information may contribute to the diagnosis and treatment of IAs. By external validation, the SLC2A12 gene may play an important role. The molecular function of SLC2A12 in the process of IA occurrence can be further studied in a rat model.

LncRNA-MALAT1 Regulates Cancer Glucose Metabolism in Prostate Cancer via MYBL2/mTOR Axis.

It is known that the long noncoding RNAs (lncRNA) MALAT1 is associated with tumorigenesis and progression in various cancers; however, its functions and mechanisms in prostate cancer (PCa) initiation and progression are still unknown. In the present study, our findings revealed that MALAT1 plays a critical part in regulating PCa proliferation and glucose metabolism. Knockdown of MALAT1 affects the protein and mRNA levels of MYBL2. In addition, MALAT1 enhances the phosphorylation level of mTOR pathway by upregulating MYBL2. Knockdown of MALAT1 or MYBL2 in PCa cell lines significantly inhibits their proliferation capacity. Silencing MALAT1/MYBL2/mTOR axis in PCa cell lines affects their glycolysis and lactate levels, and we verified these findings in mice. Furthermore, we explored the underlying tumorigenesis functions of MYBL2 in PCa and found that high expression of MYBL2 was positively associated with TNM stage, Gleason score, PSA level, and poor survival rate in PCa patients. Taken together, our research suggests that MALAT1 controls cancer glucose metabolism and progression by upregulating MYBL2-mTOR axis.

Optimized Super-Wideband MIMO Antenna with High Isolation for IoT Applications.

A compact, low profile, multiple-input-multiple-output (MIMO) diversity antenna with super-wideband (SWB) characteristics has been proposed. The proposed antenna comprises four symmetric monopole-radiating elements printed on low-cost FR4 substrate with the slotted ground plane. The single antenna of a monopole structure and a quad-port MIMO antenna, with the dimensions of 30 × 20 mm2 and 60 × 55 mm2, respectively, are ideal for IoT and high-speed data applications. The proposed MIMO antenna has a high diversity gain and low envelope correlation coefficient (ECC) within the frequency range. Simulated results demonstrate the performance of the MIMO-SWB antenna, which operates from 2.3 to 23 GHz, with a high isolation level over 20 dB in the achieved frequency band. Moreover, the proposed MIMO antenna has been investigated with mirror fashion and orthogonal structure. Both structures provide similar results except for mutual coupling performance. The orthogonal adjustment for high isolation achieves better results with the proposed model. Further, the prototype of the proposed antenna is fabricated and measured effectively. Simulated and measured results show good agreement for super-wideband applications.

Lactobacillus helveticus Prevents Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Rats by Regulating ß-Defensins.

Objective: To study the preventive effect of Lactobacillus helveticus (L. helveticus) on periodontitis induced by Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in rats. Methods: Eighteen 8-week-old female rats were randomly divided into three groups: Sham group, Trehalose group, and L. helveticus SBT2171 (LH2171) group. We measured the distance of the cementoenamel junction-alveolar bone crest (CEJ-ABC) to evaluate alveolar bone resorption. Hematoxylin-eosin staining was used to observe the histopathological changes of rat hemimaxillary tissues. We detected the expression of ß-defensins, tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1ß, and IL-6 and the number of A. actinomycetemcomitans in rat gingival tissues by quantitative reverse transcriptase polymerase chain reaction. The levels of IL-1ß, IL-6, and TNF-α in rat gingival tissues were also measured by enzyme-linked immunosorbent assay. Results: Compared with the Trehalose group, the distance of CEJ-ABC was prominently reduced and alveolar bone resorption was notably improved in the LH2171 group. And the infiltration of inflammatory cells in the hemimaxillary tissue decreased obviously, periodontal fibers were arranged neatly, connective tissue small blood vessels proliferated, and the number of A. actinomycetemcomitans reduced significantly in the LH2171 group. In addition, the mRNA expression and release of inflammatory factors in the gingival tissues in the LH2171 group were notably lower than those in the Trehalose group. On the 21st and 36th day, the expression of ß-defensins in the gingival tissue of the LH2171 group increased significantly. Conclusion: L. helveticus improves alveolar bone resorption and increases the expression of ß-defensins thereby inhibiting the number of A. actinomycetemcomitans and thus prevents periodontitis.

The long noncoding RNA glycoLINC assembles a lower glycolytic metabolon to promote glycolysis.

Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long noncoding RNA (lncRNA) that we call glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic payoff phase enzymes (PGK1, PGAM1, ENO1, and PKM2) along with lactate dehydrogenase A (LDHA). The gLINC metabolon enhances glycolytic flux, increases ATP production, and enables cell survival under serine deprivation. Furthermore, gLINC overexpression in cancer cells promotes xenograft growth in mice fed a diet deprived of serine, suggesting that cancer cells employ gLINC during metabolic reprogramming. We propose that gLINC makes a functional contribution to cancer cell adaptation and provide the first example of a lncRNA-facilitated metabolon.

Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism.

The NAD+-dependent deacetylase Sirt1 has been implicated in the prevention of many age-related diseases, including cancer, type 2 diabetes, and cardiovascular disease. Resveratrol, a plant polyphenol, exhibits antiaging, antitumor, and vascular protection effects by activating Sirt1. However, the molecular mechanism of Sirt1 activation as induced by resveratrol remains unclear. By knockdown/rescue experiments, fluorometric Sirt1 activity assay, immunoprecipitation, and pull-down assays, we identify here that the tumor suppressor LKB1 (liver kinase B1) as a direct activator of Sirt1 elicited by resveratrol. Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. Functionally, LKB1-dependent Sirt1 activation increases mitochondrial biogenesis and respiration through deacetylation and activation of the transcriptional coactivator PGC-1α. These results identify Sirt1 as a context-dependent target of LKB1 and suggest that a resveratrol-stimulated LKB1-Sirt1 pathway plays a vital role in mitochondrial metabolism, a key physiological process that contributes to numerous age-related diseases.

Performance Analysis and Optimization of a Cooperative Transmission Protocol in NOMA-Assisted Cognitive Radio Networks with Discrete Energy Harvesting.

In this paper, we propose a spectrum-sharing protocol for a cooperative cognitive radio network based on non-orthogonal multiple access technology, where the base station (BS) transmits the superimposed signal to the primary user and secondary user with/without the assistance of a relay station (RS) by adopting the decode-and-forward technique. RS performs discrete-time energy harvesting for opportunistically cooperative transmission. If the RS harvests sufficient energy, the system performs cooperative transmission; otherwise, the system performs direct transmission. Moreover, the outage probabilities and outage capacities of both primary and secondary systems are analyzed, and the corresponding closed-form expressions are derived. In addition, one optimization problem is formulated, where our objective is to maximize the energy efficiency of the secondary system while ensuring that of the primary system exceeds or equals a threshold value. A joint optimization algorithm of power allocation at BS and RS is considered to solve the optimization problem and to realize a mutual improvement in the performance of energy efficiency for both the primary and secondary systems. The simulation results demonstrate the validity of the analysis results and prove that the proposed transmission scheme has a higher energy efficiency than the direct transmission scheme and the transmission scheme with simultaneous wireless information and power transfer technology.

A Hybridization of Dragonfly Algorithm Optimization and Angle Modulation Mechanism for 0-1 Knapsack Problems.

The dragonfly algorithm (DA) is a new intelligent algorithm based on the theory of dragonfly foraging and evading predators. DA exhibits excellent performance in solving multimodal continuous functions and engineering problems. To make this algorithm work in the binary space, this paper introduces an angle modulation mechanism on DA (called AMDA) to generate bit strings, that is, to give alternative solutions to binary problems, and uses DA to optimize the coefficients of the trigonometric function. Further, to improve the algorithm stability and convergence speed, an improved AMDA, called IAMDA, is proposed by adding one more coefficient to adjust the vertical displacement of the cosine part of the original generating function. To test the performance of IAMDA and AMDA, 12 zero-one knapsack problems are considered along with 13 classic benchmark functions. Experimental results prove that IAMDA has a superior convergence speed and solution quality as compared to other algorithms.

Potent Molecular Feature-based Neutralizing Monoclonal Antibodies as Promising Therapeutics Against SARS-CoV-2 Infection.

The 2019-2020 winter was marked by the emergence of a new coronavirus (SARS-CoV-2) related disease (COVID-19), which started in Wuhan, China. Its high human-to-human transmission ability led to a worldwide spread within few weeks and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this deadly pandemic has led searchers and pharmaceutical companies to develop vaccines. However, not all vaccines manufactured are safe. Besides, an alternative and effective treatment option for such an infectious disease would include pure anti-viral neutralizing monoclonal antibodies (NmAbs), which can block the virus at specific molecular targets from entering cells by inhibiting virus-cell structural complex formation, with more safety and efficiency than the CP. Indeed, there is a lot of molecular evidence about the protector effect and the use of molecular feature-based NmAbs as promising therapeutics to contain COVID-19. Thus, from the scientific publication database screening, we here retrieved antibody-related papers and summarized the repertory of characterized NmAbs against SARS-CoV-2, their molecular neutralization mechanisms, and their immunotherapeutic pros and cons. About 500 anti-SARS-CoV-2 NmAbs, characterized through competitive binding assays and neutralization efficacy, were reported at the writing time (January 2021). All NmAbs bind respectively to SARS-CoV-2 S and exhibit high molecular neutralizing effects against wild-type and/or pseudotyped virus. Overall, we defined six NmAb groups blocking SARS-CoV-2 through different molecular neutralization mechanisms, from which five potential neutralization sites on SARS-CoV-2 S protein are described. Therefore, more efforts are needed to develop NmAbs-based cocktails to mitigate COVID-19.

DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation.

Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened metabolic activity within tumor tissues can result in glutamine deficiency, necessitating metabolic reprogramming responses. Here, dual mechanisms involving the stress-responsive transcription factor DDIT3 (DNA damage induced transcript 3) that establishes an interrelationship between glycolysis and mitochondrial respiration are revealed. DDIT3 is induced during glutamine deprivation to promote glycolysis and adenosine triphosphate production via suppression of the negative glycolytic regulator TIGAR. In concert, a proportion of the DDIT3 pool translocates to the mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4. This in turn dampens the sustained levels of reactive oxygen species that follow glutamine withdrawal. Together these mechanisms constitute an adaptive survival mechanism permitting tumor cells to survive metabolic stress induced by glutamine starvation.

BAF Complex in Embryonic Stem Cells and Early Embryonic Development.

Embryonic stem cells (ESCs) can self-renew indefinitely and maintain their pluripotency status. The pluripotency gene regulatory network is critical in controlling these properties and particularly chromatin remodeling complexes. In this review, we summarize the research progresses of the functional and mechanistic studies of BAF complex in mouse ESCs and early embryonic development. A discussion of the mechanistic bases underlying the distinct phenotypes upon the deletion of different BAF subunits in ESCs and embryos will be highlighted.

An Approach to Cryptography Based on Continuous-Variable Quantum Neural Network.

An efficient cryptography scheme is proposed based on continuous-variable quantum neural network (CV-QNN), in which a specified CV-QNN model is introduced for designing the quantum cryptography algorithm. It indicates an approach to design a quantum neural cryptosystem which contains the processes of key generation, encryption and decryption. Security analysis demonstrates that our scheme is security. Several simulation experiments are performed on the Strawberry Fields platform for processing the classical data "Quantum Cryptography" with CV-QNN to describe the feasibility of our method. Three sets of representative experiments are presented and the second experimental results confirm that our scheme can correctly and effectively encrypt and decrypt data with the optimal learning rate 8e - 2 regardless of classical or quantum data, and better performance can be achieved with the method of learning rate adaption (where increase factor R1 = 2, decrease factor R2 = 0.8). Indeed, the scheme with learning rate adaption can shorten the encryption and decryption time according to the simulation results presented in Figure 12. It can be considered as a valid quantum cryptography scheme and has a potential application on quantum devices.

Potency, Safety, and Pharmacokinetic Profiles of Potential Inhibitors Targeting SARS-CoV-2 Main Protease.

Effective, safe, and pharmacokinetically suitable drugs are urgently needed to curb the ongoing COVID-19 pandemic. The main protease or 3C-like protease (Mpro or 3CLpro) of SARS-CoV-2 is considered an important target to formulate potent drugs corresponding to its crucial role in virus replication and maturation in addition to its relatively conserved active site. Promising baseline data on the potency and safety of drugs targeting SARS-CoV-2 Mpro are currently available. However, preclinical and clinical data on the pharmacokinetic profiles of these drugs are very limited. This review discusses the potency, safety, and pharmacokinetic profiles of potential inhibitors of SARS-CoV-2 Mpro and forward directions on the development of future studies focusing on COVID-19 therapeutics.