Machine learning-based classification of structured light modes under turbulence and eavesdropping effects.

This paper considers the classification of multiplexed structured light modes, aiming to bolster communication reliability and data transfer rates, particularly in challenging scenarios marked by turbulence and potential eavesdropping. An experimental free-space optic (FSO) system is established to transmit 16 modes [8-ary Laguerre Gaussian (LG) and 8-ary superposition LG (Mux-LG) mode patterns] over a 3-m FSO channel, accounting for interception threats and turbulence effects. To the best of authors' knowledge, this paper is the first to consider both factors concurrently. We propose four machine/deep learning algorithms-artificial neural network, support vector machine, 1D convolutional neural network, and 2D convolutional neural network-for classification purposes. By fusing the outputs of these methods, we achieve promising classification results exceeding 92%, 81%, and 69% in cases of weak, moderate, and strong turbulence, respectively. Structured light modes exhibit significant potential for a variety of real-world applications where reliable and high-capacity data transmission is crucial.

Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

Autoimmune diabetes mellitus after COVID-19 vaccination in adult population: a systematic review of case reports.

BACKGROUND: Autoimmune/type 1 diabetes mellitus (T1DM) is a recently described rare occurrence following the administration of adjuvants such as coronavirus disease 2019 (COVID-19) vaccines. This systematic review aimed to review all available literature on the potential association between COVID-19 vaccines and T1DM. METHODS: The Directory of Open Access Journals, MEDLINE, Google Scholar, and Scopus were systematically searched for all published studies from inception to July 2022. Articles reporting T1DM development within 8 weeks of administration of COVID-19 vaccine were included. Two reviewers independently performed the risk of bias assessment following the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports. RESULTS: Eight eligible studies were retrieved, comprising 12 patients diagnosed with T1DM after being vaccinated with a COVID-19 vaccine. Six patients (50%) reported T1DM after receiving the second dose. Five patients (41.7%) presented with diabetic ketoacidosis, of which four presented within the first eight days after vaccination. Five patients (41.7%) had genetic susceptibility, with RNA binding motif protein 45 (RBM45/DRB1) and major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) mutations being prominent. INTERPRETATION: In this review, we have shown a small number of new-onset diabetes cases coincidently occurring soon after the COVID-19 vaccine, especially in those with genetic susceptibility. Despite being older, these patients had a similar phenotype to T1DM. While there might be a causal relationship between COVID-19 vaccines and T1DM development, this should not influence decisions regarding vaccination since the overall benefit outweighs the risk. Further larger prospective trials are needed to assess causal relationship and to clarify the potential roles of COVID-19 vaccine-derived antigens in autoimmune disease development. PROTOCOL REGISTRATION: PROSPERO-CRD42022342093.

Epidemiological associations of asthma status and tobacco use, substance use, and substance misuse among adults in the United States, 2015-2019.

Objective: Adults with asthma have a higher prevalence of substance use. However, knowledge is scarce regarding the associations between adults with asthma and tobacco use, substance use, and substance misuse. This study aimed to use national samples of United States adults to assess the comprehensive use and misuse of substances in adults with asthma.Method: This cross-sectional study comprised data drawn from the 2015 to 2019 National Survey on Drug Use and Health. Weighted logistic regressions were used to measure the associations of asthma status (lifetime and current) with last month's tobacco use; substance use (alcohol, marijuana, cocaine, crack, heroin, hallucinogens, inhalants); and substance misuse (pain relievers, tranquilizers, stimulants, sedatives). All regression models were controlled for sociodemographic characteristics, comorbidity, last-month serious psychological distress, and co-substance use and misuse. Results: Adults with lifetime asthma (Nweighted = 115,600,887) were less likely to use cigarettes, cigars, smokeless tobacco, inhalants, and polyuse of any substance. In contrast, adults with current asthma (Nweighted = 765,096,31) were more likely to use pipe tobacco, cocaine, non-prescribed tranquilizers, and less likely to use polytobacco products. Adults with lifetime asthma were associated with fewer last-month tobacco and inhalant use than those without lifetime asthma. However, adults with current asthma were associated with greater last month's pipe tobacco, cocaine, and non-prescribed tranquilizers. Conclusion: Thus, further longitudinal studies are recommended among adults with asthma to effectively design tailored treatment and prevention interventions.

Changes in the patterns of respiratory support and incidence of bronchopulmonary dysplasia; a single center experience.

BACKGROUND: With the advances in neonatal intensive care, the survival rate of extremely preterm infants is increasing. However, bronchopulmonary dysplasia (BPD) remains a major cause of morbidity among infants in this group. This study examined the changes in respiratory support modalities, specifically heated humidified high-flow nasal cannula (HHHFNC), and their association with BPD incidence among preterm infants born at < 29 weeks of gestation. METHOD: This population-based retrospective cohort study included infants born at < 29 weeks of gestation between 2016 and 2020. Data regarding the use and duration of respiratory support modalities were obtained, including mechanical ventilation, continuous positive airway pressure, HHHFNC, and low-flow oxygen therapy. Additionally, the incidence of BPD was determined in the included infants. Trend analysis for each respiratory support modality and BPD incidence rate was performed to define the temporal changes associated with changes in BPD rates. In addition, a logistic regression model was developed to identify the association between BPD and severity grade using HHHFNC. RESULTS: Three Hundred and sixteen infants were included in this study. The use and duration of HHHFNC therapy increased during the study period. Throughout the study period, the overall incidence of BPD was 49%, with no significant trends. The BPD rate was significantly higher in the infants who received HHHFNC than in those who did not (52% vs. 39%, P = 0.03). Analysis of BPD severity grades showed that both grade 1 BPD (34% vs. 21%, P = 0.03) and grade 2 BPD (12% vs. 1%, P < 0.01) were significantly more common among infants who received HHHFNC than among those who did not. In contrast, the incidence of grade 3 BPD was lower in infants who received HHFNC (6% vs. 17%, P < 0.01). The duration in days of HHHFNC was found to significantly predict BPD incidence (OR 1.04 [95%CI: 1.01-1.06], P < 0.01) after adjusting for confounding variables. CONCLUSION: The use of HHHFNC in extremely preterm infants born at < 29 weeks of gestation is increasing. There was a significant association between the duration of HHHFNC therapy and the development of BPD in extremely preterm infants born at < 29 weeks of gestation.

Correction: Ashraf et al. Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches. Molecules 2022, 27, 4652.

The updated affiliation information can be seen in the affiliation part of this correction [...].

The associations between cigarette smoking behavior and the use of heated tobacco products among Arab cigarette smokers: Findings from Saudi Arabia, Egypt, Kuwait, and Yemen.

As the availability of tobacco forms has evolved, emerging products known as heated tobacco products (HTPs) are increasingly being consumed worldwide and are claimed to be less harmful than tobacco cigarette smoking. To date, it is unknown whether Arab cigarette smokers are using or susceptible to HTPs. Therefore, this study aimed to assess the association between cigarette smoking behavior and the use of and susceptibility to HTPs in the Eastern Mediterranean region. Arab cigarette smokers (n = 628) from Saudi Arabia, Egypt, Kuwait, and Yemen were recruited using a convenience sampling technique. A cross-sectional survey comprised questions related to sociodemographic characteristics, cigarette smoking behavior characteristics (quitting attempts and desire to quit cigarette smoking, nicotine dependence, and consideration of switching to nicotine products with reduced health risks), and awareness of, use of, and susceptibility to use of HTPs. Descriptive and logistic regression models were used for analysis. The participants indicated a high frequency of past quitting attempts and a desire to quit smoking cigarettes. They were also considering switching to a nicotine product with reduced health risks. However, their awareness of HTPs was relatively low (24.2%), and the proportion of participants who had ever used HTPs or were currently using them was quite low as well (10.7% and 5.0%, respectively). A history of quit attempts was associated with more likely lifetime use of HTPs (adjusted odds ratio [AOR] = 2.63, 95% confidence interval [CI] [1.21-5.71]). Nicotine-dependent cigarette smokers were more likely to be susceptible to HTP use (AOR = 1.12, 95% CI [1.01-1.24]). Moreover, those who would consider switching to a product that provided nicotine and could reduce health risks by 99% were more likely to be susceptible to using HTPs (AOR = 2.17, 95% CI [1.05-4.51]). Awareness of HTPs is relatively low among Arab cigarette smokers. Attempts to quit cigarette smoking, nicotine dependence, and the consideration of switching to a product that delivers nicotine with reduced health risks were significantly associated with using HTPs. The findings of this study provide potential for evidence-based treatment for smokers and will help prevent the use of tobacco industry tactics in marketing HTPs.

Consensus statement on measures to promote equitable authorship in the publication of research from international partnerships.

Despite the acknowledged injustice and widespread existence of parachute research studies conducted in low- or middle-income countries by researchers from institutions in high-income countries, there is currently no pragmatic guidance for how academic journals should evaluate manuscript submissions and challenge this practice. We assembled a multidisciplinary group of editors and researchers with expertise in international health research to develop this consensus statement. We reviewed relevant existing literature and held three workshops to present research data and holistically discuss the concept of equitable authorship and the role of academic journals in the context of international health research partnerships. We subsequently developed statements to guide prospective authors and journal editors as to how they should address this issue. We recommend that for manuscripts that report research conducted in low- or middle-income countries by collaborations including partners from one or more high-income countries, authors should submit accompanying structured reflexivity statements. We provide specific questions that these statements should address and suggest that journals should transparently publish reflexivity statements with accepted manuscripts. We also provide guidance to journal editors about how they should assess the structured statements when making decisions on whether to accept or reject submitted manuscripts. We urge journals across disciplines to adopt these recommendations to accelerate the changes needed to halt the practice of parachute research.

Isolation of Thioinosine and Butenolides from a Terrestrial Actinomycetes sp. GSCW-51 and Their in Silico Studies for Potential against SARS-CoV-2.

In our continuous screening for bioactive microbial natural products, the culture extracts of a terrestrial Actinomycetes sp. GSCW-51 yielded two new metabolites, i. e., 5-hydroxymethyl-3-(1-hydroxy-6-methyl-7-oxooctyl)dihydrofuran-2(3H)-one (1), 5-hydroxymethyl-3-(1,7-dihydroxy-6-methyloctyl)dihydrofuran-2(3H)-one (2), and two known compounds; 5'-methylthioinosine (3), and 5'-methylthioinosine sulfoxide (4), which are isolated first time from any natural source, along with four known compounds (5-8). The structures of the new compounds were deduced by HR-ESI-MS, 1D and 2D NMR data, and in comparison with related compounds from the literature. Additionally, owing to the current COVID-19 pandemic situation, we also computationally explored the therapeutic potential of our isolated compounds against SARS-CoV-2. Compound 4 showed the best binding energies of -6.2 and -6.6 kcal/mol for Mpro and spike proteins, respectively. The intermolecular interactions were also studied using 2-D and 3-D imagery, which also supported the binding energies as well as put several insights under the spotlight. Furthermore, Lipinski's rule of 5 was used to predict the drug likeness of compounds 1-4, which indicated all compounds obey Lipinski's rule of 5. The study of bioavailability radars of the compounds 1-4 also confirmed their drug likeness properties where all the five crucial drug likeness parameters are in color area, which is safe to be used as drugs. Our isolation and computational findings highly encourage the scientific community to do further in vitro and in vivo studies of compounds 1-4.

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M-1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Insighting isatin derivatives as potential antiviral agents against NSP3 of COVID-19.

The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than -7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ -8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson-Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02298-7.

Exploring the inhibitory potential of novel bioactive compounds from mangrove actinomycetes against nsp10 the major activator of SARS-CoV-2 replication.

The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti-inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine, xiamycin c, xiamycin d, xiamycin e, xiamycin methyl ester, and xiamycin A (obeyed RO5 rule) are selected based on higher binding energy, low inhibition constant values, and better-docked positions. The effective hydrogen and hydrophobic (alkyl, π -sigma, π - π T shaped and π -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2. Quantum chemistry methods such as frontier molecular orbitals and molecular electrostatic potential are used to explain the thermal stability and chemical reactivity of ligands. The toxicity profile shows that selected ligands are safe by absorption, distribution, metabolism, excretion, and toxicity profiling and also effective for inhibition of nsp10 protein of SARS-CoV-2. The molecular dynamic simulation investigation of apo and halo forms of nsp10 done by RMSD of C α atoms of nsp10, all amino acid residues RMSF, count total number of hydrogen bonds and radius of gyration (R g). MD simulations reveal the complexes are stable and increase the structural compactness of nsp10 in the binding pocket. The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-021-01997-x.

Sequential one-pot synthesis of N-sulfonyl spiroaziridine oxindoles from spiroepoxy oxindoles.

The N-sulfonyl spiroaziridine oxindole is a recently developed versatile precursor in the synthesis of a wide range of 3,3-disubstituted spirooxindoles. It is usually prepared in three steps from isatin and needs costly and hardly available sulfinimides and hazardous peracid. A sequential and one-pot direct strategy for the synthesis of terminal N-sulfonyl spiroaziridine oxindoles has been developed under ambient conditions with excellent yields (up to 95%) from easily accessible spiroepoxy oxindoles by regioselective amination with aqueous ammonia and a subsequent ring enclosure reaction of the resulting 1,2-amino alcohol using easily available sulfonyl chloride and a base. Other salient features of the protocol include inexpensive substrate requirement and the ease of isolation of the desired product by performing single column chromatographic purification after two consecutive steps.

Benzene, Toluene, and Monosubstituted Derivatives: Diabatic Nature of the Oscillator Strengths of S1 ← S0 Transitions.

For benzene, toluene, aniline, fluorobenzene, and phenol, even sophisticated treatments of electron correlation, such as MRCI and XMS-CASPT2 calculations, show oscillator strengths typically lower than experiment. Inclusion of a simple pseudo-diabatization approach to perturb the S1 state with approximate vibronic coupling to the S2 state for each molecule results in more accurate oscillator strengths. Their absolute values agree better with experiment for all molecules except aniline. When the coupling between the S1 and S2 states is strong at the S0 geometry, the simple diabatization scheme performs less well with respect to the oscillator strengths relative to the adiabatic values. However, we expect the scheme to be useful in many cases where the coupling is weak to moderate (where the maximum component of the coupling has a magnitude less than 1.5 au). Such calculations give an insight into the effects of vibronic coupling of excited states on UV/vis spectra.

Levels of residues and dietary risk assessment of the fungicides myclobutanil, penconazole, tebuconazole, and triadimenol in squash.

Triazole fungicides may potentially harm human health. The 'quick, easy, cheap, effective, rugged, and safe' approach has become popular for extraction and cleanup during pesticide residue analysis. We aimed to (a) validate a method for the simultaneous determination of myclobutanil, penconazole, tebuconazole, and triadimenol in squash using LC-MS/MS and (b) determine the pre-harvest intervals (PHIs) and assess the related risk of consuming squash cultivated under open-field conditions in Saudi Arabia. Using acetonitrile as the extraction solvent and fourfold dilution in deionized water led to weak signal suppression (<-6.1%). The limits of quantitation ranged from 10 to 40 µg/kg. Mean recovery and relative standard deviation ranged from 81.7 to 96.3% and from 3.6 to 11.4%. The half-lives ranged from 2.22 to 3.83 days, and the dissipation followed first-order kinetics. The terminal residues of myclobutanil, penconazole, tebuconazole, and triadimenol were <0.771, <0.307, <0.459, and <0.954 mg/kg, respectively, 7 days after two or three applications of recommended dosages. The PHIs of 7.1-11.4, 8.7-13.1, 3.8-5.3, and 11.3-14.3 days are suggested after the application of the recommended dose and double the recommended dose. A consumer risk assessment based on estimated dietary intake indicated that the consumption of squash treated with the recommended doses does not pose a significant health risk.

Synthesis and Assessment of Two Malonyl Dihydrazide Derivatives as Corrosion Inhibitors for Carbon Steel in Acidic Media: Experimental and Theoretical Studies.

Despite the extensive use of carbon steel in all industrial sectors, particularly in the petroleum industry, its low corrosion resistance is an ongoing problem for these industries. In the current work, two malonyl dihydrazide derivatives, namely 2,2'-malonylbis (N-phenylhydrazine-1-carbothiamide (MBC) and N'1, N'3-bis(-2-hydroxybenzylidene) malonohydrazide (HBM), were examined as inhibitors for the carbon steel corrosion in 1.0 M HCl. Both MBC and HBM were characterised using thin-layer chromatography, elemental analysis, infrared spectroscopy, and nuclear magnetic resonance techniques. The corrosion tests were performed using mass loss measurements, polarisation curves, and electrochemical impedance spectroscopy. It is obtained from the mass loss studies that the optimal concentration for both inhibitors is 2.0 × 10-5 mol/L, and the inhibition efficiencies reached up to 90.7% and 84.5% for MBC and HBM, respectively. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarisation (PDP) indicate an increased impedance in the presence of both MBC and HBM and mixed-type inhibitors, respectively. Both inhibitors can mitigate corrosion in the range of 298-328 K. Values of free energy changes obtained from the Langmuir model suggest that the inhibitors suppress the corrosion process principally by chemisorption. The computational investigations were conducted to identify the factors connected with the anti-corrosive properties of the examined inhibitors.

Experimental and computational study of naphthalimide derivatives: Synthesis, optical, nonlinear optical and antiviral properties.

The nonlinear optical (NLO) and antiviral properties of naphthalimide Schiff base compounds (5a-c) were experimentally and computationally investigated. The synthesized compounds (5a-c) were successfully characterized via UV-Vis, FTIR, 1H NMR, fluorescence spectroscopy, and elemental analysis. The calculated average third-order NLO polarizabilities (˂γ˃) of 5a, 5b, and 5c were found to be 5, 9, and 21 times greater than the ˂γ˃ amplitude of p-NA, respectively. The computed results revealed the potential of the synthesized compounds for NLO applications. Additionally, molecular docking studies of the synthesized compounds with two crucial SARS-CoV-2 proteins were performed to examine their biochemical properties. Compound 5c exhibited a higher binding affinity with the spike protein compared to that with Mᴾᴿᴼ. The results obtained herein indicate the potential of the synthesized naphthalimide derivatives for optoelectronic and drug design applications.

Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population.

OBJECTIVE: To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population. METHODS: A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports. RESULTS: A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p=0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure. CONCLUSION: Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Apigenin as an effective anticancer natural product: Spotlight on TRAIL, WNT/ß-catenin, JAK-STAT pathways, and microRNAs.

Wealth of information gleaned from decades of high-impact research work; scientists have disentangled the complicated web of versatile regulators that underlie cancer development and progression. Use of structural biology approaches and functional genomics have helped us to gain new insights into complex nature of cancer, and it is now clear that genetic/epigenetic mutations, overexpression of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and versatility of protein binding partners have contributory roles in carcinogenesis and metastatic spread. It is becoming progressively more understandable that reprogramming of gene expression during and nontranscriptional changes during cancer development and progression are initiated and controlled by deregulated signal transduction cascades, all of which collectively create an incalculable complexity. Data obtained through preclinical and clinical trials revealed that alterations in the targeted oncogenes and other downstream, and parallel pathways played a central role in the development of resistance against different therapeutics. Phytochemicals have regained limelight, and different natural products are currently being tested for efficacy in preclinical studies. Apigenin, a plant-derived flavonoid has considerable pharmacological value and is reportedly involved in the regulation of different signaling cascades. In this review, we have attempted to summarize rapidly evolving understanding of molecular biologists and pharmacologists about the potential of apigenin in the regulation of deregulated signaling pathways in different cancers. We have emphasized on the regulation of WNT/ß-catenin and janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. We also comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant cancers. The review also gives a snapshot of microRNAs (miRNAs) that regulate wide-ranging biological processes, and it is now clear that each miRNA can control hundreds of gene targets. Apigenin was noted to upregulate miR-520b and miR-101 in different cancers to inhibit tumor growth. Moreover, apigenin-induced apoptotic rate was significantly higher when used in combination with miR-423-5p inhibitors or miR-138 mimics. Better comprehension of linear and integrated signaling pathways will be helpful in effective therapeutic targeting of deregulated signaling pathways to inhibit/prevent cancer.

One-Pot Synthesis of Enantiopure Spiro[3,4-dihydrobenzo[b][1,4]oxazine-2,3'-oxindole] via Regio- and Stereoselective Tandem Ring Opening/Cyclization of Spiroaziridine Oxindoles with Bromophenols.

A highly efficient regio- and stereoselective spiroaziridine ring opening with 2-bromophenols and a subsequent tandem cyclization reaction was developed for the one-pot synthesis of enantiopure 3,4-dihydrospiro[benzo[b][1,4]oxazine-2,3'-oxindole] with excellent enantiopurity (ee up to >99%). It is further extended to asymmetric synthesis of NH-free 3,4-dihydrospiro[benzo[b][1,4]oxazine-2,3'-xindole] retaining the optical activity.