Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease progressing to end-stage renal disease. There is a pressing need for the identification of early ADPKD biomarkers to enable timely intervention and the development of effective therapeutic approaches. Here, we profiled human urinary extracellular vesicles small RNAs by small RNA sequencing in patients with ADPKD and compared their differential expression considering healthy control individuals to identify dysregulated small RNAs and analyze downstream interaction to gain insight about molecular pathophysiology. METHODS: This is a cross-sectional study where urine samples were collected from a total of 23 PKD1-ADPKD patients and 28 healthy individuals. Urinary extracellular vesicles were purified, and small RNA was isolated and sequenced. Differentially expressed Small RNA were identified and functional enrichment analysis of the critical miRNAs was performed to identify driver genes and affected pathways. RESULTS: miR-320b, miR-320c, miR-146a-5p, miR-199b-3p, miR-671-5p, miR-1246, miR-8485, miR-3656, has_piR_020497, has_piR_020496 and has_piR_016271 were significantly upregulated in ADPKD patient urine extracellular vesicles and miRNA-29c was significantly downregulated. Five 'driver' target genes (FBRS, EDC3, FMNL3, CTNNBIP1 and KMT2A) were identified. CONCLUSIONS: The findings of the present study make significant contributions to the understanding of ADPKD pathogenesis and to the identification of novel biomarkers and potential drug targets aimed at slowing disease progression in ADPKD.

Prediction of the 3D conformation of a small peptide vaccine targeting Aß42 oligomers.

The original etiology of Alzheimer's disease (AD) is the deposition of amyloid-beta (Aß) proteins, which starts from the aggregation of the Aß oligomers. The optimal therapeutic strategy targeting Aß oligomer aggregation is the development of AD vaccines. Despite the fact that positive progress has been made for experimental attempts at AD vaccines, the physicochemical and even structural properties of these AD vaccines remain unclear. In this study, through immunoinformatic and molecular dynamics (MD) simulations, we first designed and simulated an alternative of vaccine TAPAS and found that the structure of the alternative can reproduce the 3D conformation of TAPAS determined experimentally. Meanwhile, immunoinformatic methods were used to analyze the physicochemical properties of TAPAS, including immunogenicity, antigenicity, thermal stability, and solubility, which confirm well the efficacy and safety of the vaccine, and validate the scheme reliability of immunoinformatic and MD simulations in designing and simulating the TAPAS vaccine. Using the same scheme, we predicted the 3D conformation of the optimized ACI-24 peptide vaccine, an Aß peptide with the first 15 residues of Aß42 (Aß1-15). The vaccine was verified once to be effective against both full-length Aß1-42 and truncated Aß4-42 aggregates, but an experimental 3D structure was absent. We have also explored the immune mechanism of the vaccine at the molecular level and found that the optimized ACI-24 and its analogues can block the growth of either full-length Aß1-42 or truncated Aß4-42 pentamer by contacting the hydrophobic residues within the N-terminus and ß1 region on the contact surface of either pentamer. Additionally, residues (D1, D7, S8, H13, and Q15) were identified as the key residues of the vaccine to contact either of the two Aß oligomers. This work provides a feasible implementation scheme of immunoinformatic and MD simulations for the development of AD small peptide vaccines, validating the power of the scheme as a parallel tool to the experimental approaches and injecting molecular-level information into the understanding and design of anti-AD vaccines.

Identification and characterization of the conformation and size of amyloid-ß (42) oligomers targeting the receptor LilrB2.

Experimental observations revealed that the amyloid-ß 42 oligomer (AßO) can directly bind to the LilrB2 D1D2(LDD) receptor with nanomolar-affinity, leading to changes in synaptic plasticity and cognitive deficits. However, the dependence of neurotoxicity on the morphology, size, and aggregation stage (SP1, SP2) of AßO, as well as the specific molecular mechanism of AßO-LDD interaction, remain uncertain. To address these uncertainties, we investigated the interaction between the LDD neuroreceptor and AßO with different Aß42 species (nontoxic species, toxic species, and protofibril) and sizes. Our results showed that the LDD selectively binds AßO species rather than the Aß42 monomer, accommodating various Aß42 dimers and trimers as well as SP2 AßO, in a specific pose in the pocket of the LDD receptor (region I). Additionally, protofibrils with exposed ß1/ß2 regions can also bind to region I of the LDD receptor, as observed experimentally (Cao, et al., Nat. Chem., 2018, 10, 1213; and Aim et al., Nat. Commun., 2021, 12, 3451). More extensively, we identified two additional regions of the LDD receptor, regions II and III, suitable for binding to larger AßO species at the SP1 with different molecular weights and conformations, accounting for the stronger binding strength obtained experimentally. We suggest that the two regions are more competitive than region I in causing toxicity by AßO binding. The detailed and systematic characterization for the complexes generated between the LDD receptor and various AßO species, including the protofibril, offers deep insight into the dependence of neurotoxicity on the AßO size and conformation at the molecular level, and provides novel and specific targets for drug design of Alzheimer's disease.

Origin of stronger binding of ionic pair (IP) inhibitor to Aß42 than the equimolar neutral counterparts: synergy mechanism of IP in disrupting Aß42 protofibril and inhibiting Aß42 aggregation under two pH conditions.

Fibrous aggregates of beta-amyloid (Aß) is a hallmark of Alzheimer's disease (AD). Several major strategies of drugs or inhibitors, including neutral molecules, positive or negative ions, and dual-inhibitor, are used to inhibit the misfolding or aggregation of Aß42, among which a kind of dual-inhibitor composed of a pair of positive and negative ions is emerging as the most powerful candidate. This knowledge lacks the origin of the strong inhibitory effect and synergy mechanisms blocking the development and application of such inhibitors. To this end, we employed 1 : 1 ionic pairs (IP) of oppositely charged benzothiazole molecules (+)BAM1-EG6 (Pos) and (-)BAM1-EG6 (Neg) as well as equimolar neutral BAM1-EG6 (Neu) counterpart at two pH conditions (5.5 and 7.0) to bind Aß42 targets, Aß42 monomer (AßM), soluble pentamer (AßP), and pentameric protofibril (AßF) models, respectively, corresponding to the products of three toxic Aß42 development pathways, lag, exponential and fibrillation phases. Simulated results illustrated the details of the inhibitory mechanisms of IP and Neu for the AßY (Y = M, P, or F) in the three different phases, characterizing the roles of Pos and Neg of IP as well as their charged, hydrophobic groups and linker playing in the synergistic interaction, and elucidated a previously unknown molecular mechanism governing the IP-Aß42 interaction. Most importantly, we first revealed the origin of the stronger binding of IP inhibitors to Aß42 than that of the equimolar neutral counterparts, observing a perplexing phenomenon that the physiological condition (pH = 7.0) than the acidic one (pH = 5.5) is more favorable to the enhancement of IP binding, and finally disclosed that solvation is responsible to the enhancement because at pH 7.0, AßP and AßF act as anionic membranes, where solvation plays a critical role in the chemoelectromechanics. The result not only provides a new dimension in dual-inhibitor/drug design and development but also a new perspective for uncovering charged protein disaggregation under IP-like inhibitors.

New 2,4-dihydro-1H-1,2,4-triazole-3-selones and 3,3'-di(4H-1,2,4-triazolyl)diselenides. Synthesis, biological evaluation, and in silico studies as antibacterial and fungicidal agents.

The reaction of aromatic ring-substituted isoselenocyanates with 2-thiopheacetic and 4-pyridinecarboxylic acid hydrazides yielded selenosemicarbazides which were further converted into previously unknown 1,2,4-triazole-3-selones and 3,3'-di(4H-1, 2,4-triazolyl)diselenides. The structures of the obtained compounds were studied by NMR spectroscopy, IR spectroscopy, and high-resolution mass spectroscopy (HR-MS). The bactericidal and fungicidal activity of some obtained compounds was evaluated in molecular modeling studies such as docking and simulation studies. The compound 3ba was reported as the most promising compound to show robust binding energy with different antibacterial and antifungal compounds. The compounds were observed in strong hydrophilic and hydrophobic interactions and remained in stable binding conformation with the receptor enzymes. Furthermore, the interatomic interaction energies were dominated by Van der Waals and electrostatic energies indicating the formation of stable complexes.

Engineering processive cellulase of Clostridium thermocellum to divulge the role of the carbohydrate-binding module.

The processive cellulase (CelO) is an important modular enzyme of Clostridium thermocellum. To study the effect of the carbohydrate-binding module (CBM3b) on the catalytic domain of CelO (GH5), four engineered derivatives of CelO were designed by truncation and terminal fusion of CBM3b. These are CBM at the N-terminus, native form (CelO-BC, 62 kDa); catalytic domain only (CelO-C, 42 kDa); CBM at the C-terminus (CelO-CB, 54 kDa) and CBM attached at both termini (CelO-BCB, 73 kDa). All constructs were cloned into pET22b (+) and expressed in Escherichia coli BL21 (DE3) star. The expression levels of CelO-C, CelO-CB, CelO-BC, and CelO-BCB were 35%, 35%, 30%, and 20%, respectively. The enzyme activities of CelO-C, CelO-CB, CelO-BC, and CelO-BCB against 1% regenerated amorphous cellulose (RAC) were 860, 758, 985, and 1208 units per µmole of the enzyme, respectively. The enzymes were partially purified from the lysate of E. coli cells by heat treatment followed by anion exchange FPLC purification. Against RAC, CelO-C, CelO-CB, CelO-BC, and CelO-BCB showed KM values of 32, 33, 45, and 43 mg⋅mL-1 and Vmax values of 3571, 3846, 3571, and 4545 U⋅min-1 , respectively. CBM3b at the N-terminus of GH5 linked through a P/T-rich linker was found to enhance the catalytic activity and thermostability of the enzyme.

Potential of magnetic quinoa biosorbent composite and HNO3 treated biosorbent for effective sequestration of chromium (VI) from contaminated water.

The present study aims to prepare novel quinoa biosorbent (QB), acid activated QB (QB/Acid) and its nanocomposite with magnetic nanoparticles (QB/MNPs) for batch scale Cr removal from contaminated water. The Cr adsorption was systematically studied at different pH (2-9), adsorbent dosage (1-3 g/L), initial concentration (25-200 mg/L), contact time (180 min) and competing ions in water. Maximum Cr adsorption was observed onto QB/MNPs (57.4 mg/L), followed by QB/Acid (46.35 mg/g) and QB (39.9 mg/g). The Cr removal by QB/MNPs was higher than QB/Acid and QB. Results revealed that the highest Cr removal was obtained at optimum pH 4, 25 mg/L, and 2 g/L dosage. The FTIR spectra displayed various functional groups on adsorbents surface serving as a potential scaffold to remove Cr from contaminated water. The equilibrium and kinetic Cr adsorption data best fitted with Freundlich and pseudo-second order models, respectively (R2 ≥ 0.96). The QB/MNPs showed excellent reusability in five adsorption/desorption cycles (4.7% decline) with minor leaching of Fe (below threshold level). The coexisting ions in groundwater showed an inhibitory effect on Cr sequestration (5%) from water. The comparison of Cr adsorption by QB/MNPs and QB/Acid showed better potential for Cr sequestration than various previously explored adsorbents in the literature.

Quinoa is a cereal crop and after harvesting quinoa straws are either burnt or thrown away which can cause several environmental problems. It would be beneficial to utilize quinoa straws and its modified forms as adsorbents for the water remediation. Therefore, current study aims to estimate the adsorption capacity of quinoa biomass as biosorbent (QB) and its modifications (QB/Acid and QB/MNPs) to treat Cr (VI) contaminated water. The influence of various parameters governing the Cr removal from water has been evaluated. The reusability of QB/MNPs has also been evaluated for its economical use without losing effectiveness for Cr removal from water. The comparison of Cr adsorption by QB/MNPs and QB/Acid showed better adsorption potential for Cr sequestration than various previously explored adsorbents in the literature.

Inhibiting miR-195-5p Induces Proliferation of Human Corneal Endothelial Cells.

Transparency of the human cornea is responsible for clear vision, which is maintained by a monolayer of non-proliferative human corneal endothelial cells (HCEnCs). Dysfunction of these cells can result in irreversible corneal blindness. It is important to identify key factors that limit the proliferation of HCEnCs and thus attempt to reverse them. Extracellular vesicles contain cargo which includes microRNAs (miRNAs) that can modulate a cellular function. In non small cell lung cancer, expression of miR-195-5p has been shown to inhibit proliferation; therefore, we aimed to investigate the inhibitory effect of miR-195-5p in inducing the proliferation of HCEnCs. Human corneal endothelial cell line (HCEC-12) and primary HCEnCs were cultured with miR-195-5p scramble, mimic or inhibitor. Corneal tissues from human cadaveric and FECD donors, and from pigs, mice and rabbits, were used for RT-PCR. miR-195-5p showed an abundance value of 11,363.31 a.u. When normalized against HCEnCs from cadaveric donors, FECD tissues showed a significant upregulation of miR-195-5p (p < 0.05) but was significantly downregulated in pig (p < 0.001), mouse (p < 0.01) and rabbit (p < 0.001) CEnCs, which have known proliferative capacity. Proliferation, cell doubling, and wound healing rates were significantly higher when miR-195-5p was inhibited. Inhibiting miR-195-5p showed a significant improvement in viability (HEC staining), decreased cell apoptosis (TdT-dNTP staining) and expression of ZO-1, NA+/K+-ATPase and Ki-67 markers. Expression of miR-195-5p is found in HCEnCs and FECD cells, which restricts the proliferation of these cells. However, inhibiting miR-195-5p can induce the proliferation of HCEnCs, which opens exciting directions for future research in prolonging FECD pathogenesis by increasing the proliferative capacity of HCEnCs using anti-miR therapy in vivo.

BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies.

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These bromobenzofuran-oxadiazole structural hybrids BF1-9 were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3ß, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs BF-2, BF-5, and BF-6 displayed the best anti-cancer potential and with the least cell viabilities (12.72 ± 2.23%, 10.41 ± 0.66%, and 13.08 ± 1.08%), respectively, against HepG2 liver cancer cell line, and they also showed excellent molecular docking scores against EGFR, PI3K, mTOR, and Tubulin polymerization enzymes, which are major cancer targets. Bromobenzofuran-oxadiazoles BF-2, BF-5, and BF-6 displayed excellent binding affinities with the active sites of EGFR, PI3K, mTOR, and Tubulin polymerization enzymes in the molecular docking studies as well as in MMGBSA and MM-PBSA studies. The stable bindings of these structural hybrids BF-2, BF-5, and BF-6 with the enzyme targets EGFR and PI3K were further confirmed by molecular dynamic simulations. These investigations revealed that 2,5-dimethoxy-based bromobenzofuran-oxadiazole BF-5 (10.41 ± 0.66% cell viability) exhibited excellent cytotoxic therapeutic efficacy. Moreover, computational studies also suggested that the EGFR, PI3K, mTOR, and Tubulin polymerization enzymes were the probable targets of this BF-5 scaffold. In silico approaches, such as molecular docking, molecular dynamics simulations, and DFT studies, displayed excellent association with the experimental biological data of bromobenzofuran-oxadiazoles BF1-9. Thus, in silico and in vitro results anticipate that the synthesized bromobenzofuran-oxadiazole hybrid BF-5 possesses prominent anti-liver cancer inhibitory effects and can be used as lead for further investigation for anti-HepG2 liver cancer therapy.

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review.

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007-2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau-Demjanov rearrangement, Aza-Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.

The Corey-Seebach Reagent in the 21st Century: A Review.

The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.

Quorum Quenchers from Reynoutria japonica in the Battle against Methicillin-Resistant Staphylococcus aureus (MRSA).

Over the past decade, methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of biofilm formation and a major contributor to antimicrobial resistance. The genes that govern biofilm formation are regulated by a signaling mechanism called the quorum-sensing system. There is a need for new molecules to treat the infections caused by dangerous pathogens like MRSA. The current study focused on an alternative approach using juglone derivatives from Reynoutria japonica as quorum quenchers. Ten bioactive compounds from this plant, i.e., 2-methoxy-6-acetyl-7-methyljuglone, emodin, emodin 8-o-b glucoside, polydatin, resveratrol, physcion, citreorosein, quercetin, hyperoside, and coumarin were taken as ligands and docked with accessory gene regulator proteins A, B, and C and the signal transduction protein TRAP. The best ligand was selected based on docking score, ADMET properties, and the Lipinski rule. Considering all these parameters, resveratrol displayed all required drug-like properties with a docking score of -8.9 against accessory gene regulator protein C. To further assess the effectiveness of resveratrol, it was compared with the commercially available antibiotic drug penicillin. A comparison of all drug-like characteristics showed that resveratrol was superior to penicillin in many aspects. Penicillin showed a binding affinity of -6.7 while resveratrol had a score of -8.9 during docking. This was followed by molecular dynamic simulations wherein inhibitors in complexes with target proteins showed stability inside the active site during the 100 ns simulations. Structural changes due to ligand movement inside the cavity were measured in the protein targets, but they remained static due to hydrogen bonds. The results showed acceptable pharmacokinetic properties for resveratrol as compared to penicillin. Thus, we concluded that resveratrol has protective effects against Staphylococcus aureus infections and that it suppresses the quorum-sensing ability of this bacterium by targeting its infectious proteins.

Recent Trends in the Petasis Reaction: A Review of Novel Catalytic Synthetic Approaches with Applications of the Petasis Reaction.

The Petasis reaction, also called the Petasis Borono-Mannich reaction, is a multicomponent reaction that couples a carbonyl derivative, an amine and boronic acids to yield substituted amines. The reaction proceeds efficiently in the presence or absence of a specific catalyst and solvent. By employing this reaction, a diverse range of chiral derivatives can easily be obtained, including α-amino acids. A broad substrate scope, high yields, distinct functional group tolerance and the availability of diverse catalytic systems constitute key features of this reaction. In this review article, attention has been drawn toward the recently reported methodologies for executing the Petasis reaction to produce structurally simple to complex aryl/allyl amino scaffolds.

Comparison of As removal efficiency and health risks from aqueous solution using as-synthesized Fe0 and Cu0: modelling, kinetics and reusability.

Batch scale removal of arsenic (As) from aqueous media was explored using nano-zero valent iron (Fe0) and copper (Cu0) particles. The synthesized particles were characterized using a Brunauer-Emmett-Teller (BET) surface area analyzer, a scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). The BET result showed that the surface area (31.5 m2/g) and pore volume (0.0415 cm3/g) of synthesized Fe0 were higher than the surface area (17.56 m2/g) and pore volume (0.0287 cm3/g) of Cu0. The SEM results showed that the morphology of the Fe0 and Cu0 was flowery microspheres and highly agglomerated with thin flakes. The FTIR spectra for Fe0 showed broad and intense peaks as compared to Cu0. The effects of the adsorbent dose (1-4 g/L), initial concentration of As (2 mg/L to 10 mg/L) and solution pH (2-12) were evaluated on the removal of As. Results revealed that effective removal of As was obtained at pH 4 with Fe0 (94.95%) and Cu0 (74.86%). When the dosage increased from 1 to 4 g L-1, the As removal increased from 70.59 to 93.02% with Fe0 and from 67 to 70.59% with Cu0. However, increasing the initial As concentration decreased the As removal significantly. Health risk indices, including estimated daily intake (EDI), hazard quotient (HQ), and cancer risk (CR) were employed and a significant decline (up to 99%) in risk indices was observed in As-treated water using Fe0/Cu0. Among the adsorption isotherm models, the values of R2 showed that isothermal As adsorption by Fe0 and Cu0 was well explained by the Freundlich adsorption isotherm model (R2 > 0.98) while the kinetic experimental data was well-fitted with the Pseudo second order model. The Fe0 showed excellent stability and reusability over five sorption cycles, and it was concluded that, compared to the Cu0, the Fe0 could be a promising technology for remediating As-contaminated groundwater.

Microbial adaptation and impact into the pesticide's degradation.

The imprudent use of agrochemicals to control agriculture and household pests is unsafe for the environment. Hence, to protect the environment and diversity of living organisms, the degradation of pesticides has received widespread attention. There are different physical, chemical, and biological methods used to remediate pesticides in contaminated sites. Compared to other methods, biological approaches and their associated techniques are more effective, less expensive and eco-friendly. Microbes secrete several enzymes that can attach pesticides, break down organic compounds, and then convert toxic substances into carbon and water. Thus, there is a lack of knowledge regarding the functional genes and genomic potential of microbial species for the removal of emerging pollutants. Here we address the knowledge gaps by highlighting systematic biology and their role in adaptation of microbial species from agricultural soils with a history of pesticide usage and profiling shifts in functional genes and microbial taxa abundance. Moreover, by co-metabolism, the microbial species fulfill their nutritional requirements and perform more efficiently than single microbial-free cells. But in an open environment, free cells of microbes are not much prominent in the degradation process due to environmental conditions, incompatibilities with mechanical equipment and difficulties associated with evenly distributing inoculum through the agroecosystem. This review highlights emerging techniques involving the removal of pesticides in a field-scale environment like immobilization, biobed, biocomposites, biochar, biofilms, and bioreactors. In these techniques, different microbial cells, enzymes, natural fibers, and strains are used for the effective biodegradation of xenobiotic pesticides.

Two novel phosphorus/potassium-degradation bacteria: Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 and their application in two-stage composting of corncob residue.

For effective utilization of corncob residue to realize green circular production, using composting to obtain a high-quality and low-cost biomass fertilizer has become a very important transformation avenue. In this paper, two novel phosphorus/potassium-degradation bacterial strains were isolated from tobacco straw and identified as Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 (abbreviated as SD-1/SD-3). These identified two novel bacteria SD-1/SD-3 show that the soluble phosphorus content of SD-1/SD-3 reached 360.89 mg L-1/403.56 mg L-1 in the shake flask test, and the mass concentration of soluble potassium is 136.56 mg L-1/139.89 mg L-1. In addition, the Laccase (Lac), Lignin peroxidase (LiP), and Manganese peroxidase (MnP) activities of SD-1 and SD-3 are 54.45 U L-1/394.84 U L-1/222.79 U L-1 and 46.27 U L-1/395.26 U L-1/203.98 U L-1 respectively, with the carboxy-methyl cellulase (CMCase) of 72.07 U mL-1 and 52.69 U mL-1. Meanwhile, the effects of three different combinations of cultures, i.e., no inoculation (K1), inoculation of SD-1/SD-3 on day 21 (K2) and on day 0 (G) are investigated to understand the influence on the degradation degree of corncob residue compost. The results of K2 compost treatment showed that the effective P/K content increased nearly 3.1/2.4 times, the degradation of cellulose/lignin was 49.1/68.0%, and the germination rate was 110.23%, which were higher than other experiment groups K1/G. In conclusion, knowledge of this paper will be very useful for the industrial sector for the treatment of complex corncob residue.

Rational design, synthesis, antiproliferative activity against MCF-7, MDA-MB-231 cells, estrogen receptors binding affinity, and computational study of indenopyrimidine-2,5-dione analogs for the treatment of breast cancer.

Based on the structural architecture of estrogen receptors (ER) agonists/antagonists, we rationally designed and synthesized indenopyrimidine-2,5-dione analogs as a starting point of current research targeting estrogen receptors. These analogs were evaluated for their antiproliferative activities against breast cancer MCF-7 (ER+), MDA-MB-231 (ER-) and non-cancerous HEK-293 cells using MTT assay. Compounds with high antiproliferative activity against MCF-7 breast cancer cells were found devoid of cytotoxicity against HEK-293 cells. Competitive binding assay of estrogen receptors ERα and ERß showed that diethanolamine derivative of 4-trifluoromethyl phenyl derivative 30 displayed 77.5-fold strong binding affinity towards ERα (IC50 = 0.004 µM) as compared to ERß (IC50 = 0.31 µM). The calculated RBA value of compound 30 indicated that it has greater affinity with ER than estradiol. By docking studies, we demonstrated that high binding affinity with ERα is due to binding orientation and interaction of CF3 with a number of key amino acid residues present in the active site of ERα.

Molecular docking study and molecular dynamics simulation of ethyl 3,5-diphenyl-1H-pyrrole-2-carboxylate and (Z)-ethyl-2-(3-oxo-1,3-diphenylprop-1-enylamino)acetate.

The present analysis has been performed in the wet-lab and computational environments. First, the synthesis of the latest heterocyclic compounds containing the alkyl organic compound fragment of acetate and glycine acid were obtained and then their crystal structure and biological activity were studied. (Z)-ethyl-2-(3-oxo-1,3-diphenylprop-1-enylamino) acetate (1) was initially retrieved on the supported reaction of dibenzene gas with glycine alkyl organic compound-complex within the presence of Y(OTF)3 catalyst in liquid medium. At an identical time, ethyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (2) was synthesized from the interaction of amino alkane with tert-BuOK in the presence of tert-BuOH/DMFA solvent. The structure of the latest compounds has been studied by 1 H, 13 C NMR. Additionally, the crystal structure of ethyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (2) is conferred. Moreover, computational drug-likeness and pharmacokinetics indicated the compounds' good drug-like molecules and friendly pharmacokinetics, making the compound valuable candidates to be explored for additional structural modification to act as a potential inhibitor of AChE and α-glycosidase enzymes.

Synthesis, crystal structure investigation and computational approach to discover potential hydrazide derivatives as a potent inhibitor of cyclooxygenase-2 enzyme.

This study reports the synthesis of two new hydrazide derivatives, namely, (E)-N'-(4- bromobenzylidene)-2-(4-isobutylphenyl)propanehydrazide (4a) and (E)-N'-benzylidene-2-(4-isobutylphenyl)propanehydrazide (4b), respectively. The compounds were synthesized by the reaction of benzaldehyde with Ibuprofen acid hydrazide. Their structures were confirmed by X-ray crystallography. To try to do a more detailed investigation, computational studies including Hirshfeld surface analyses, energy frameworks, density functional theory (DFT) optimizations, frontier orbital analyses, molecular electrostatic potential analyses, and natural bond orbital analyses of the studied compounds are performed. Moreover, molecular docking and dynamics simulations of complexes of the compounds with the cyclooxygenase-2 (COX-2) enzyme were performed to determine the anti-inflammatory potential of the compounds. These analyses predicted the compounds to show maximum chemical interactions and be dynamically stable during simulation time. Furthermore, estimation of binding free energies confirmed the high binding affinity of the compounds for the COX-2 enzyme.