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An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1β, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1β, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Arbutin, a naturally soluble glycosylated phenol has antioxidant, antimicrobial, antitumor and anti-inflammatory properties. The current exploration appraises the treatment of arthritis by use of Arbutin (25, 50 and 100 mg/kg) orally in CFA-induced rat arthritis model. Body weight changes, paw size, and joint diameter were recorded till the 28th day in the arthritic-induced rats. Hematological, biochemical, oxidative and inflammatory biomarkers were measured through the blood samples of anesthetized rats. Arbutin markedly decreased paw volume, PGE-2, anti-CCP and 5-LOX levels, however, maintained metabolic and hematological balance and prevented weight loss. Radiology and histology changes improved significantly in the ankle joints of rats. Moreover, Arbutin increased gene pointers such as IL-10 and IL-4 while significantly reducing the levels of CRP and WBCs, whereas Hb, platelets and RBCs count markedly raised in post-treatments. Antioxidant levels of SOD, CAT and GSH were improved and MDA level was reduced in treated groups. Rt-PCR investigation showed a significant reduction of the interleukin-1β, TNF-α, interleukin-6, cyclooxygenase-2, NF-κB and IL-17 and increased expression of gene pointers like IL-4, and IL-10 in treated groups. Assessment of molecular docking revealed a strong binding interaction of Arbutin against 5-LOX, IL-17, TNF-alpha and interleukin-6, cyclooxygenase-2, nuclear factor-κB, IL-4 and iNOS providing a strong association between experimental and theoretical results. As a result, Arbutin has significantly reduced CFA-induced arthritis by modulation of anti-inflammatory cytokines, i.e., IL-10 and IL-4, the pro-inflammatory cytokines panel such as NF-κB, TNF-alpha, IL-1β, IL-6, PGE-2, 5-LOX and COX-2 and oxidative biomarkers., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1β and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1β. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Vascular catheter-related infections and thrombosis are common and may lead to serious complications after catheterization. Reducing the incidence of such infections has become a significant challenge., Objectives: This study aims to develop a super hydrophobic nanocomposite drug-loaded vascular catheter that can effectively resist bacterial infections and blood coagulation., Methods: In this study, a SiO 2 nanocoated PTFE (Polytetrafluoroethylene) catheter (PTFE-SiO 2 ) was prepared and further optimized to prepare a SiO 2 nanocoated PTFE catheter loaded with imipenem/cilastatin sodium (PTFE-IC@dMSNs). The catheters were characterized for performance, cell compatibility, anticoagulant performance, in vitro and in vivo antibacterial effect and biological safety., Results: PTFE-IC@dMSNs catheter has efficient drug loading performance and drug release rate and has good cell compatibility and anticoagulant effect in vitro. Compared with the PTFE-SiO 2 catheter, the inhibition ring of the PTFE-IC@dMSNs catheter against Escherichia coli increased from 3.98 mm 2 to 4.56 mm 2 , and the antibacterial rate increased from about 50.8 % to 56.9 %, with a significant difference (p < 0.05). The antibacterial zone against Staphylococcus aureus increased from 8.63 mm 2 to 11.74 mm 2 , and the antibacterial rate increased from approximately 83.5 % to 89.3 %, showing a significant difference (p < 0.05). PTFE-IC@dMSNs catheter also has good biocompatibility in vivo. Furthermore, the PTFE-IC@dMSNs catheter can reduce the adhesion of blood cells and have excellent anticoagulant properties, and even maintain these properties even with the addition of imipenem/cilastatin sodium., Conclusion: Compared with PTFE, PTFE-SiO 2 and PTFE-IC@dMSNs catheters have good characterization performance, cell compatibility, and anticoagulant properties. PTFE SiO 2 and PTFE-IC@dMSNs catheters have good antibacterial performance and tissue safety against E. coli and S. aureus. Relatively, PTFE-SiO 2 and PTFE-IC@dMSNs catheter has better antibacterial properties and histocompatibility and has potential application prospects in anti-bacterial catheter development and anticoagulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases., Methodology: First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed., Results: The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rβ1. Exon 7 of the IL-12Rβ1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function., Conclusion: Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rβ-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rβ1, TYK2, or JAK2 in IFN-γ production, warranting further investigation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The toxic effects of heavy metals are drastic, including accumulation. Fish species are important bio-indicators of heavy metal pollution in aquatic bodies. The current study aimed to assess the seasonal variation of heavy metals in the vital organs of mostly consumed fishes in River Jhelum, Pakistan. Samples of fish, including Wallago attu (Malhi), Rita rita (Khagga), and Mystus seenghala (Singhari), were collected from four different sites, i.e., Khushab, Muhammad Wala (M. Wala), 8.R.D and Rasool barrage during summer and winter seasons. Heavy metals such as iron (Fe), lead (Pb), chromium (Cr), cobalt (Co) and Cadmium (Cd) were estimated through acid digestion and spectrometric analysis. Results showed a significantly higher (P < 0.05) amount of these metals in the liver, followed by the kidneys of fish species. There were seasonal variations in the absorption of these metals as well. Cr (11.71) and Fe (58.66) were detected in higher amounts in Khagga which showed the greatest affinity for certain metals in some cases. In contrast, Singhari showed the greatest affinity to other metals in other cases. Comparative analysis revealed that there was a highly significant (P < 0.05) difference for the accumulation of almost all metals in both seasons and summer had the highest concentration of Cd, Pb, Co, Cr and Fe as compared to winter in all four sampling stations in the case of kidney and liver of all the three fishes. Elevated levels of heavy metals were detected in the summer due to increased temperature. Heavy metals found in the River Jhelum may demonstrate that metals can significantly affect the fish species., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The mucus layers of fish serve as the main interface between the organism and the environment. They play an important biological and ecological role. The current study focuses on Nile tilapia epidermal mucus reared under different commercial feeds (coded A and B) and environments (biofloc technology and earthen pond systems). Crude protein levels in feed A and B were 30% and 28%, respectively. Water parameters in all culturing systems were suitable for tilapia throughout the study period. The antimicrobial potency of tilapia (n = 5 from each) epidermal mucus was tested in vitro against human and fish pathogenic strains viz. Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Francisella noatunensis, and Aeromonas hydrophila. To determine the antimicrobial activity, zones of inhibition (ZOI) were measured in millimetres and compared with two antibiotics (chloramphenicol and ciprofloxacin). SDS-PAGE analysis was performed on skin mucus samples of tilapia to determine protein quantity and size (molecular weight). Results of tilapia skin mucus (crude and aqueous) revealed a strong antibacterial effect against all the selected pathogenic strains. However, variation has been observed in the mucus potency and ZOI values between the biofloc and pond tilapia mucus. The crude mucus of tilapia fed on feed A and cultured in the pond exhibited strong antibacterial effects and high ZOI values compared to the mucus of biofloc tilapia, aqueous mucus extracts and positive control chloramphenicol (antibiotic). The SDS-PAGE results showed that the high molecular weight proteins were found in the collected epidermal mucus of BFT-B (240 kDa) and EP-B (230 kDa). Several peptides in fish skin mucus may play a crucial role in the protection of fish against disease-causing pathogens. Thus, it can be utilized in the human and veterinary sectors as an 'antimicrobial' for treating various bacterial infections., (© 2023 John Wiley & Sons Ltd.)

Insects feed on plants and cause the growth of plants to be restricted. Moreover, the application of traditional pesticides causes harmful effects on non-target organisms and poses serious threats to the environment. The use of conventional pesticides has negative impacts on creatures that are not the intended targets. It also presents significant risks to the surrounding ecosystem. Insects that are exposed to these chemicals eventually develop resistance to them. This review could benefit researcher for future development of nanopesticides research. This is because a holistic approach has been taken to describe the multidimensional properties of nanopesticides, health and environmental concerns and its possible harmful effects on non-target organisms and physiochemical entities. The assessment of effects of the nanopesticides is also being discussed through the drosophotoxicology. The future outlooks have been suggested to take a critical analysis before commercialization or formulation of the nanopesticides., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The characteristics of phytocompounds and essential oils have undergone extensive research in the medical and pharmaceutical sectors due to their extensive usage. In spite of the fact that these molecules are widely used, terpenes, terpenoids, and their derivatives have not yet been well characterized. This study intends to evaluate the prospective activity of incensole acetate (IA), a compound identified and isolated from Catharanthus roseus essential oil by GC/MS analysis and column chromatography, and to analyze the anticancer effect of an IA biosynthesized nanoemulsion against breast cancer. The in silico activity of IA against breast cancer targets was observed by molecular docking, ADMET assessment and molecular dynamics simulations. The IA-mediated nanoformulation exhibited cytotoxicity against breast cancer cell lines at an effective concentration when analyzed by MTT and crystal violet assay. The increased interleukin serum indicators were significantly improved as a result of nanoemulsion treatment in a DMBA-induced rat model. In addition, the anticancer properties of IA biosynthesized nanoemulsion are supported due to their potential effects on biochemical parameters, oxidative stress markers, proinflammatory cytokines, and upon tumor growth profiling in cancer-induced rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Introduction: The Punjab Cancer Registry's catchment area includes the districts of Faisalabad and Nankana Sahib. It is an observational and descriptive study that covers the 3 years from 2017 to 2019, evaluating the distribution of cancer in these two districts., Material and Methods: Data on incident cancer cases diagnosed between 2017 and 2019 among residents of Faisalabad and Nankana Sahib in Pakistan, reported by the participating centres of the Registry, were reviewed retrospectively. Figures and proportions for adults, children and adolescents were computed., Results: During 2017 and 2019, 5678 cases were reported from Faisalabad and 390 from Nankana Sahib, with over 50% seen in females. In both districts combined, among adult females, cancers of the breast, reproductive system, and hepatobiliary system were commonly diagnosed, while cancer of the lip/oral cavity/pharynx, hepatobiliary system and non-Hodgkin lymphoma were the leading diagnoses among adult males. In children and young adults (0-19 years), acute lymphoblastic leukaemia, Hodgkin lymphoma and non-Hodgkin lymphoma were the most common diagnoses., Conclusion: The cancer distribution reported from Faisalabad and Nankana Sahib is of utmost importance. However, the underreporting of cancer cases cannot be ruled out. More input from the collaborators is needed to ensure the completeness of cancer surveillance in the region., Competing Interests: The registry is a member of the International Association of Cancer Registries, France, and is registered under Pakistan’s Societies Registration Act. The registry is supported by the Shaukat Khanum Memorial Trust., (Copyright: © 2023 Badar F, et al.)

The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines ( 4a - 4i ) in good yields (65-94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), 1 H-NMR, 13 C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3-4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess Agrobacterium tumefaciens -induced tumors to evaluate the anti-tumor activities of compounds ( 4a - 4i ), using Vinblastine as a standard drug. The compound 4g showed the lowest IC 50 value (1.12 ± 0.2), which is even better than standard Vinblastine (IC 50 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds 4g and 4h showed the best affinities toward protein, with a binding energy value of -6.8 kcal/mol.

Coal miners are continuously exposed to coal mine dust and airborne particulate that act as a potential risk to their health. The present study evaluates the DNA damage in coal miners using the Buccal Micronucleus Cytome (BMCyt) assay. The samples of the blood and buccal epithelial cells of 40 coal miners and 20 control subjects were taken from coal mines of Pail and Padhrar, Pakistan, to establish buccal anomaly frequencies of metal levels in the blood. Besides this, work history and duration hours were also analyzed. Results revealed that micronucleus frequencies positively correlated with the metal concentrations in the miner's blood. The change in the extent of nuclear damage per unit change in the year was 0.170 for micronuclei; however, with addition in each year of working experience, nuclear buds and broken egged nuclei increased by 0.316 and 0.194 units, where each year increases karyolysis by 0.349 units and karyorrhexis by 0.308 units, respectively. An increase in work hours and working years was positively correlated with cytogenetic damage. Nuclear damage in coal miners due to occupational exposure is obvious and increases with increasing work experience. Hence, the Buccal Micronucleus Cytome assay has proved to be an effective cytogenetic biomonitoring tool for assessing genetic and nuclear damage in coal miners., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fish feed quality is the main determinant of fish flesh quality, so it is important for successful aquaculture. The current study determines the concentration of heavy metals in fish feeds (A and B), water, and their bioaccumulation in gills, liver, and muscle of C. carpio cultured in different environments (biofloc technology and earthen pond systems). In addition, the correlation between heavy metals in fish feeds with bioaccumulated metals in fish tissues was also determined. Results revealed that most heavy metal concentration was significantly greater (P < 0.05) in feed B than in feed A but in permissible range, while all the heavy metal concentration was notably higher in earthen ponds than in biofloc technology. Result from the bioaccumulation factor and concentration of the metals showed that heavy metals were highly accumulated in the fish liver followed by gills. The metal concentration in fish feeds and fish edible parts (muscle) was lower than the WHO standard level; however, the amount of Pb was higher in the fish muscle, liver, and gills, which is harmful for human consumption and also for fish health. Though the correlation test revealed that all of the metals from the feeds were positively correlated to the metals in fish tissues, but most of the estimated correlation was significant and linearly correlated. It can be concluded that producers must measure feed quality correctly to avoid heavy metal contamination because it may assimilate and accumulate in the food chain., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The pharmacological effectiveness of indoles, benzoxazepines and benzodiazepines initiated our synthesis of indole fused benoxazepine/benzodiazepine heterocycles, along with enhanced biological usefulness of the fused rings. Activated indoles 5 , 6 and 7 were synthesized using modified Bischler indole synthesis rearrangement. Indole 5 was substituted with the trichloroacetyl group at the C 7 position, yielding 8, exclusively due to the increased nucleophilic character of C 7 . When trichloroacylated indole 8 was treated with basified ethanol or excess amminia, indole acid 9 and amide 10 were yielded, respectively. Indole amide 10 was expected to give indole fused benoxazepine/benzodiazepine 11a / 11b on treatment with alpha halo ester followed by a coupling agent, but when the reaction was tried, an unexpectedly rearranged novel product, 1,3-bezodiazine 12, was obtained. The synthetic compounds were screened for anticholinesterase and antibacterial potential; results showed all products to be very important candidates for both activities, and their potential can be explored further. In addition, 1,3-bezodiazine 12 was explored by DFT studies, Hirshfeld surface charge analysis and structural insight to obrain a good picture of the structure and reactivity of the products for the design of derivatised drugs from the novel compound.

For successful aquaculture, the primary need is the quality of fish feed, which determines fish flesh quality. The current study was conducted to evaluate the number and concentration of heavy metals in commonly used fish feeds and fish gills, liver, and muscle of biofloc technology and earthen pond systems. Besides this, the correlation between heavy metals in fish feeds with detected metals in the gills, liver, and muscle of fish was also determined. Results revealed that heavy metals concentration, including Cu and Cd, in feed B was significantly greater than in feed A, but the Zn level in feed A was significantly higher than in feed B. Furthermore, the concentration of heavy metals in fish of both aquaculture systems was significantly higher in the liver than in the gills and muscle. The metal concentration in fish feeds and fish edible parts (muscle) was lower than the WHO standard level; however, the amount of Pb was higher in the fish muscle, which is harmful for human consumption. Though the correlation test revealed that all of the metals from the feeds were positively correlated to the metals detected in the fish, but most of the estimated correlation was insignificant. From the current study, it can be concluded that the fish feed producers need to measure feed quality adequately to avoid hazardous contamination by heavy metals in the feed. The ultimate consumer, fish and humans, may, otherwise, be predisposed to assimilate and accumulate these heavy metals., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important ( R )-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester ( 5 ) to understand its properties for further chemical transformations. The methyl anthranilate ( 2 ) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine ( 4 ) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with ( 2 ) furnished isoindole ( 5 ). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of ( 5 ) in which N-H⋯O bonding stabilizes the molecular configuration of ( 5 ), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole ( 5 ) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product ( 5 ). In vitro and in silico analysis of ( 5 ) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus ., Competing Interests: The authors declare no conflict of interest.

The performance of organic solar cells (OSCs) has been improving steadily over the last few years, owing to the optimization of device fabrication, fine-tuning of morphology, and thin-film processing. Thiophene core containing fused ring-type non-fullerene acceptors (NFAs) achieved significant proficiency for highly efficient OSCs. Quantum chemical computations are utilized herein with the motive of suggesting new NIR sensitive, highly efficient low-band gap materials for OSCs. A series of extended conjugated A-π-D-π-A architectured novel fused-ring NFAs (FUIC-1-FUIC-6) containing thieno[2,3- b ]thiophene-based donor core are proposed by substituting the end-capped units of synthesized molecule F10IC. Different properties including frontier molecular orbital analysis, density of states analysis, transition density matrix analysis, excitation energy, reorganizational energies of both holes (λ h ) and electrons (λ e ), and open-circuit voltage ( V oc ) were performed employing the density functional theory approach. Charge transfer analysis of the best-designed molecule with the donor complex was analyzed to comprehend the efficiency of novel constructed molecules (FUIC-1-FUIC-6) and compared with the reference. End-caped acceptor alteration induces the reduction of the energy gap between HOMO-LUMO (1.88 eV), tunes the energy levels, longer absorption in the visible and near-infrared regions, larger V oc , smaller reorganizational energies, and binding energy values in designed structures (FUIC-1-FUIC-6) in comparison to reference (FUIC). The designed molecules show the best agreement with the PTBT-T donor polymer blend and cause the highest charge from the HOMO to the LUMO orbital. Our findings predicted that thieno[2,3- b ] thiophene-based newly designed molecules would be efficient NFAs with outstanding photovoltaic characteristics and can be used in future applications of OSCs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A Schiff base ligand HL, ( E )-2-((adamantan-1-ylimino)methyl)-6-allylphenol, was synthesized by condensation of amantadine with 3-allyl-2-hydroxybenzaldehyde, followed by the synthesis of its Zn(ii), Co(ii), Cr(iii), and VO(iv) complexes under reflux conditions. The synthesized compounds were comprehensively elucidated by using different spectroscopic and analytical techniques: UV-Vis, 1 H and 13 C-NMR, FT-IR, ESI-MS, thermal, and single-crystal XRD analysis. The chemical composition of the synthesized compounds was also verified by molar conductance and elemental analysis. An octahedral geometry for Cr(iii) and Co(ii) complexes, tetrahedral for Zn(ii) complex, and square pyramidal geometry have been proposed for VO(iv) complexes. The antidiabetic activities of the synthesized compounds were also evaluated by performing in vitro α-amylase and α-glucosidase inhibition studies. The Co(ii) complex exhibited the highest α-glucosidase inhibitory activity, whereas oxovanadium(iv) and zinc(ii) complexes were also found to be effective against α-amylase. In alkaline phosphatase (ALP) inhibition studies, the HL was found to be inactive, while the complexes showed remarkable enzyme inhibition in the following order: VO > Zn > Co, in a concentration-dependent manner., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The present study involved the targeted synthesis and characterization of novel indole amines with anti-acetylcholinesterase profiling. A series of proposed indole amines was virtually screened against human acetylcholinesterase. A few indole amines (23, 24, and 25) showing strong enzyme binding in the in silico studies were synthesized in the laboratory and characterized using spectroscopic (IR, UV, NMR, single crystal XRD) and spectrometric (EIMS, HR-EIMS) methods. The indole amine 23 was crystallized from EtOH and analyzed with single crystal XRD. These ligands interacted with the PAS site in the enzyme, and their binding may disrupt the activity. The in vitro acetylcholinesterase inhibition studies revealed that the IC 50 values for indole amines 25 and 24 (4.28 and 4.66 μM, respectively) were comparable to that of galantamine (4.15 μM) and may be studied further as cost-effective acetylcholinesterase inhibitors., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

The dose frequency of drugs belonging to class II is usually high and associated with harmful effects on the body. The study aimed to enhance the solubility of the poorly water-soluble drug amoxicillin (AM) by the solid dispersion (SD) technique. Six different SDs of AM, F1-F6, were prepared by the spray drying technique using two other carriers, HP-β-CD (F1-F3) and HPMC (F4-F6), in 1:1, 1:2, and 1:3 drug-to-polymer ratios. These SDs were analyzed to determine their practical yield, drug content, and aqueous solubility using analytical techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and powder X-ray diffraction. The effect of polymer concentration on SDs was determined using aqueous solubility, in vitro dissolution, and in vivo studies. The results showed no drug-polymer interactions in SDs. Solubility studies showed that SDs based on the drug-to-polymer ratio of 1:2 (F2 and F5) were highly soluble in water compared to those with ratios of 1:1 and 1:3. In vitro dissolution studies also showed that SDs with a ratio of 1:2 released the highest drug concentration from both polymeric systems. The SDs based on HPMC confirmed the more sustained release of the drug as compared to that of HP-β-CD. All the SDs were observed as stable and amorphous, with a smooth spherical surface. In vivo studies reveal the enhancement of pharmacokinetics parameters as compared to standard AM. Hence, it is confirmed that spray drying is an excellent technique to enhance the solubility of AM in an aqueous medium. This may contribute to the enhancement of the pharmacokinetic behaviors of SDs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: This study evaluates the efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy in treating multiple myeloma (MM)., Method: This retrospective study involves seventy-two patients, newly diagnosed with multiple myeloma, divided into two groups; one with plasmapheresis without plasma transfusion tandem with the chemotherapy group (Trial group), while the second was chemotherapy group (Control group). The levels of Plasma Globulin, β2-microglobulin, Creatinine, Vascular endothelial growth factor (VEGF), and IL-6 were monitored after plasmapheresis, at initial diagnosis, and after four chemotherapy courses. Overall response rate of groups after four courses of chemotherapy was analyzed, and the adverse events were recorded., Results and Discussion: The baseline data showed that sixty-seven percent of patients were at the ISS III stage and showed more severe renal insufficiency in the Trial group. The Plasma Globulin, β2-microglobulin, VEGF and IL-6 levels were significantly different between the two groups during the initial diagnosis. After three times plasmapheresis, Plasma Globulin, β2-microglobulin, VEGF, and IL-6 were significantly reduced in the plasmapheresis group. The Creatinine levels were also lowered, but the differences were not statistically significant. After four courses of chemotherapy, the levels of VEGF and IL-6 in the two groups were significantly reduced than the initial diagnosis; the differences were statistically considerable. No adverse events were found in the trial group as compared to the control group., Conclusion: Plasmapheresis reduces Globulin, β2-microglobulin, serum VEGF and IL-6 levels in MM, improves renal functions, and releases some patients from dialysis dependence.

Myocardial infarction is irreversible cardiac tissue necrosis due to the blockage of one of the arteries. It leads to an insufficient supply of oxygen and nutrients, creating muscular damage in the affected regions. In the present study, aqueous methanolic extract of Thymus linearis was prepared to evaluate its activity against ischemic stress due to free radical production. GC-MS analysis was performed to evaluate the phytochemicals present in the plant extract. A chemical database of 30 compounds was virtually screened against NF-κB, COX2, and MCL, where γ-cadinene, β-bisabolene, and β-caryophyllene were found to be the best interacting ligands. To systematically assess cardioprotective activity against ischemia, isoproterenol and doxorubicin were used to induce cardiotoxicity in rats. The prepared extract of T. linearis (100 mg/kg) was given daily to animals for 21 days before injecting isoproterenol (85 mg/kg of animal weight) subcutaneously in two doses on the 20th and 21st days. In the case of doxorubicin, cardiotoxicity was induced in rats by a single injection (15 mg/kg) on the seventh day, and the extract was given to animals for 10 consecutive days. Animals' blood samples were used to monitor cardiac, liver, and other marker enzymes, including LDH, CPK, and AST. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were also assayed in blood plasma to determine the degree of oxidative stress. H&E staining was performed to evaluate cardioprotection by plant extract, showing significant preventive effects in reducing cardiac injury induced by isoproterenol and doxorubicin., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy.

Objective: To study the clinical diagnostic value of neutrophil CD64 index, PCT, and CRP in patients with acute pancreatitis with abdominal infection. Methods: A number of patients with acute pancreatitis (n = 234) participated in the study. According to the infection and health conditions, they were further divided into the non-infection group (n = 122), infection group (n = 78), and sepsis group (n = 34), and 40 healthy subjects were selected in the control group (n = 40). Expression levels of infection indexes, such as CD64 index, PCT, and CRP, were detected and compared. ROC curves were drawn to compare the efficacy of each index in the diagnosis of acute pancreatitis with abdominal infection and sepsis. The study was retrospectively registered under the China Clinical Trial Registry as a trial number ChiCTR2100054308. Results: All indexes were significantly higher in three clinical groups than the healthy control group (p < 0.05). The CD64 index, CD64 positive rate, and PCT in the infected group were significantly higher than those in the uninfected group (ALL p < 0.05). The PCT of patients infected with Gram-negative bacteria was significantly higher than that of Gram-positive bacteria-infected patients (p < 0.05). CD64 index had the best diagnostic efficiency for acute pancreatitis infection, with 82.14% sensitivity, 88.51% specificity, and 0.707 Youden indexes. The CD64 Youden index (0.780) for sepsis diagnosis was the highest, while the AUC of PCT was the highest (0.897). Conclusion: CD64 index combined with PCT has good sensitivity and specificity in diagnosing acute pancreatitis infection and sepsis.

Background and Objective : Helicobacter pylori is a human-stomach-dwelling organism that causes many gastric illnesses, including gastritis, ulcer, and gastric cancer. The purpose of the study was to perform differential proteomic analysis on H. pylori isolates from gastritis, ulcer, and gastric cancer patients. Materials and Methods : H. pylori was isolated from antrum and fundus biopsies obtained from patients who visited the Department of Gastroenterology. Using nano-LC-QTOF MS/MS analysis, differentially regulated proteins were identified through proteome profiling of pooled samples of H. pylori isolated from gastritis, ulcer, and gastric cancer patients. Antigenic scores and cellular localization of proteins were determined using additional prediction tools. Results : A total of 14 significantly regulated proteins were identified in H. pylori isolated from patients with either gastritis, ulcer, or gastric cancer. Comparative analysis of groups revealed that in the case of cancer vs. gastritis, six proteins were overexpressed, out of which two proteins, including hydrogenase maturation factor (hypA) and nucleoside diphosphate kinase (ndk) involved in bacterial colonization, were only upregulated in isolates from cancer patients. Similarly, in cancer vs. ulcer, a total of nine proteins were expressed. Sec-independent protein translocase protein (tatB), involved in protein translocation, and pseudaminic acid synthase I (pseI), involved in the synthesis of functional flagella, were upregulated in cancer, while hypA and ndk were downregulated. In ulcer vs. gastritis, eight proteins were expressed. In this group, tatB was overexpressed. A reduction in thioredoxin peroxidase (bacterioferritin co-migratory protein (bcp)) was observed in ulcer vs. gastritis and cancer vs. ulcer. Conclusion : Our study suggested three discrete protein signatures, hypA, tatB, and bcp, with differential expression in gastritis, ulcer, and cancer. Protein expression profiles of H. pylori isolated from patients with these gastric diseases will help to understand the virulence and pathogenesis of H. pylori .

Porphyrin-based non-fullerene acceptors (NFAs) have shown pronounced potential for assembling low-bandgap materials with near-infrared (NIR) characteristics. Herein, panchromatic-type porphyrin-based molecules (POR1-POR5) are proposed by modulating end-capped acceptors of a highly efficient porphyrin-based NFA PORTFIC(POR) for organic solar cells (OSCs). Quantum chemical structure-property relationship has been studied to discover photovoltaic and optoelectronic characteristics of POR1-POR5. Results show that optoelectronic properties of the POR1-POR5 are better in all aspects when compared with the reference POR. All proposed NFAs particularly POR5 proved to be the preferable porphyrin-based NIR sensitive NFA for OSCs applications owing to lower energy gap (1.56 eV), transition energy (1.11 eV), binding energy (E b =0.986 eV), electron mobility (λ e =0.007013E h ), hole mobility (λ h =0.004686 E h ), high λ max =1116.27 nm and open-circuit voltage (V oc =1.96 V) values in contrast to the reference POR and other proposed NFAs. This quantum chemical insight provides sufficient evidence about excellent potential of the proposed porphyrin-based NIR sensitive NFA derivatives for their use in OSCs., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

Herein, an electrochemical biosensor has been prepared to assess the sensitivity of an organophosphate insecticide, malathion, to acetylcholinesterase (AChE) enzyme of three insects including Apis mellifera (honeybee), Tribolium castaneum (red flour beetle), and Zootermopsis nevadensis (dampwood termite). A composite of nickel chromite (NiCr 2 O 4 ) and graphitic carbon nitride (g-C 3 N 4 ) was prepared and characterized for its morphological, chemical and electrical properties. The NiCr 2 O 4 /g-C 3 N 4 composite integrated pencil graphite electrodes were used to covalently immobilize insect AChE enzymes and amperometric response of bioelectrodes was determined through cyclic voltammetry. The prepared bioelectrodes exhibited high enzyme immobilization efficiency and electro-catalytic performance. The integrated bioelectrodes could efficiently detect malathion induced inhibition of insects' AChEs. The linear ranges for malathion were found to be 0.1-1.6 μM, 1-40 nM and 2-100 nM, and LODs were 2 nM, 0.86 nM and 2.3 nM for A. mellifera , T. castaneum , and Z. nevadensis , respectively. Additionally, the biosensing platform developed using A. mellifera AChE was found highly sensitive and effective for malathion recoveries from spiked wheat flour samples with high recovery rates. Moreover, the proposed method was adequately reproducible and selective. The results revealed that A. mellifera AChE is less sensitive to inhibition by malathion as compared to T. castaneum , and Z. nevadensis AChE. The experimental results were validated through computational docking of malathion with insect AChEs and the results were in correspondence to experimental outcomes. The proposed method can be a plausible alternate to conventional analytical methods to assess the pesticide sensitivity and toxicity of various compounds against insect enzymes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The present work reports the synthesis, characterization, and antimicrobial activities of adipic acid-capped silver nanoparticles (AgNPs@AA) and their utilization for selective detection of Hg 2+ ions in an aqueous solution. The AgNPs were synthesized by the reduction of Ag + ions with NaBH 4 followed by capping with adipic acid. Characterization of as-synthesized AgNPs@AA was carried out by different techniques, including UV-Visible spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Dynamic Light Scattering (DLS), and zeta potential (ZP). In the UV-Vis absorption spectrum, the characteristic absorption band for AgNPs was observed at 404 nm. The hydrodynamic size of as-synthesized AgNPs was found to be 30 ± 5.0 nm. ZP values (-35.5 ± 2.4 mV) showed that NPs possessed a negative charge due to carboxylate ions and were electrostatically stabilized. The AgNPs show potential antimicrobial activity against clinically isolated pathogens. These AgNPs were found to be selectively interacting with Hg 2+ in an aqueous solution at various concentrations. A calibration curve was constructed by plotting concentration as abscissa and absorbance ratio (A Control - A Hg /A Control ) as ordinate. The linear range and limit of detection (LOD) of Hg 2+ were 0.6-1.6 μM and 0.12 μM, respectively. A rapid response time of 4 min was found for the detection of Hg 2+ by the nano-probe. The effect of pH and temperature on the detection of Hg 2+ was also investigated. The nano-probe was successfully applied for the detection of Hg 2+ from tap and river water.

The study is to evaluate the impact of COVID-19 in the Pediatric Oncology Units (POUs) of Pakistan. Data from 1 April 2019 to 30 June 2019 and 1 April 2020 to 30 June 2020 for the first and second cohort, respectively, in order to compare the registration, abandonment rate, and delay in treatment. Six hundred and thirty-four were registered cases, 379 and 255 in the first and second cohort, respectively, which was significantly different <0.005. Seventy-seven were abandoned, 45 and 32 in the first and second cohort, respectively. Fifty-nine COVID-19 positive cases, 24, 4, 27, and 4 were admitted, referred, home isolated, and leave against medical advice (LAMA), respectively. Delayed treatment and reduction in new cases were observed.

Breast cancer affects more than 1 million women per year worldwide. Through this study, we developed a nanoparticle-based drug delivery system to target breast cancer cells. Aspirin has been found to inhibit thromboembolic diseases with its tumor-preventing activity. As a consequence, it relieves disease symptoms and severity. Here, mesoporous silica nanoparticles (MNPs) have been used to deliver aspirin to the tumor location. MNP-based aspirin in folic acid (F)-conjugated polydopamine (MNP-Asp-PD-PG-F) vehicles are prepared for targeted breast cancer therapy. The vehicle hinges on MNP altered with polymer polyethylene glycol (PG), polydopamine (PD), and F. The delivery vehicle was studied for in vitro drug release, cytotoxicity, and breast cancer cell proliferation. F-conjugated drug delivery vehicles let MNPs achieve an elevated targeting efficacy, ideal for cancer therapy. It was also observed that compared to free aspirin, our drug delivery system (MNP-Asp-PD-PG-F) has a higher cytotoxic and antiproliferative effect on breast cancer cells. The drug delivery system can be proposed as a targeted breast cancer therapy that could be further focused on other targeted cancer therapies. Delivering aspirin by the PD-PG-F system on the tumor sites promises a therapeutic potential for breast cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kanwal, Ma, Rehman, Khan, Elizur, Batool, Wang, Tabassum, Lu and Wang.)

Background: We aim to coat a novel polyvinyl benzyl chloride-D-glucaro-1, 4-lactonate polymer-coated bile duct stent for anti-biliary mud deposition and investigate its in vivo and in vitro impacts. Biliary mud deposition is a leading cause of plastic biliary stent obstruction after its placement. Orally administrated D-glucaro-1, 4-lactonate is a specific competitive inhibitor of β-glucuronidase that causes biliary mud deposition., Methods: In this study, the stents coated with polyvinyl benzyl chloride-D-glucaro-1,4-lactonate polymer (PVBC-DGL) were placed in an ex vivo bile duct model perfused with porcine bile and observed every week until completely blocked. Post establishing the model of bile duct stenosis in piglets, stents are observed through endoscopy, hematology, patency time, and pathological changes within 6 months., Results: The 70% PVBC-DGL stents achieved the highest percentage of the inhibitory effect when the drugs were completely released in vitro. Results were obtained from 14 pigs (5: no coating (original), 4: 0% coating, and 5: 70% coating). The overall patency time of the stents was prolonged in all groups; however, the group with 70% coated stents showed a significantly prolonged patency time as compared to no coating (original) and the 0% coating groups in pigs (23.4 ± 1.8 vs 11.2 ± 2.1 w ( p = 0.05); 23.4 ± 1.8 vs 10.5 ± 2.5 w ( p = 0.05), respectively)., Conclusion: The stents with 70% PVBC-DGL better prevent and control the deposition of bile mud and prolong the patency time of stent placement in the subject animals and may be proposed for further clinical trials in patients.

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro , in vivo , and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5 α -reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5 α -reductase II. The inhibition of 5 α -reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5 α -reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5 α -reductase II and improved cell proliferation in rabbits. The statistical analysis ( p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle's anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5 α -reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Iltaf, Noreen, Rehman, Ghumman, Batool, Mehdi, Hasan, Ijaz, Akram and Butt.)

Considering the increased demand and potential of photovoltaic devices in clean, renewable electrical and hi-tech applications, non-fullerene acceptor (NFA) chromophores have gained significant attention. Herein, six novel NFA molecules IBRD1-IBRD6 have been designed by structural modification of the terminal moieties from experimentally synthesized A2-A1-D-A1-A2 architecture IBR for better integration in organic solar cells (OSCs). To exploit the electronic, photophysical and photovoltaic behavior, density functional theory/time dependent-density functional theory (DFT/TD-DFT) computations were performed at M06/6-311G(d,p) functional. The geometry, electrical and optical properties of the designed acceptor molecules were compared with reported IBR architecture. Interestingly, a reduction in bandgap (2.528-2.126 eV), with a broader absorption spectrum, was studied in IBR derivatives (2.734 eV). Additionally, frontier molecular orbital findings revealed an excellent transfer of charge from donor to terminal acceptors and the central indenoindene-core was considered responsible for the charge transfer. Among all the chromophores, IBRD3 manifested the lowest energy gap (2.126 eV) with higher λ max at 734 and 745 nm in gaseous phase and solvent (chloroform), respectively due to the strong electron-withdrawing effect of five end-capped cyano groups present on the terminal acceptor. The transition density matrix map revealed an excellent charge transfer from donor to terminal acceptors. Further, to investigate the charge transfer and open-circuit voltage (V oc ), PBDBT donor polymer was blended with acceptor chromophores, and a significant V oc (0.696-1.854 V) was observed. Intriguingly, all compounds exhibited lower reorganization and binding energy with a higher exciton dissociation in an excited state. This investigation indicates that these designed chromophores can serve as excellent electron acceptor molecules in organic solar cells (OSCs) that make them attractive candidates for the development of scalable and inexpensive optoelectronic devices., (© 2021. The Author(s).)

Compounds having nonlinear optical (NLO) characteristics have been proved to have a significant role in many academic and industrial areas; particularly, their leading role in surface interfaces, solid physics, materials, medicine, chemical dynamics, nuclear science, and biophysics is worth mentioning. In the present study, novel peptoids ( 1-4 ) were prepared in good yields via Ugi four-component reaction (Ugi-4CR). In addition to synthetic studies, computational calculations were executed to estimate the molecular electrostatic potential, natural bond orbital (NBO), frontier molecular orbital analysis, and NLO properties. The NBO analysis confirmed the stability of studied systems owing to containing intramolecular hydrogen bonding and hyperconjugative interactions. NLO analysis showed that investigated molecules hold noteworthy NLO response as compared to standard compounds that show potential for technology-related applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The SARS CoV-2 pandemic has affected millions of people around the globe. Despite many efforts to find some effective medicines against SARS CoV-2, no established therapeutics are available yet. The use of phytochemicals as antiviral agents provides hope against the proliferation of SARS-CoV-2. Several natural compounds were analyzed by virtual screening against six SARS CoV-2 protein targets using molecular docking simulations in the present study. More than a hundred plant-derived secondary metabolites have been docked, including alkaloids, flavonoids, coumarins, and steroids. SARS CoV-2 protein targets include Main protease (M Pro ), Papain-like protease (PL pro ), RNA-dependent RNA polymerase (RdRp), Spike glycoprotein (S), Helicase (Nsp13), and E-Channel protein. Phytochemicals were evaluated by molecular docking, and MD simulations were performed using the YASARA structure using a modified genetic algorithm and AMBER03 force field. Binding energies and dissociation constants allowed the identification of potentially active compounds. Ligand-protein interactions provide an insight into the mechanism and potential of identified compounds. Glycyrrhizin and its metabolite 18-β-glycyrrhetinic acid have shown a strong binding affinity for M Pro , helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PL pro and RdRp. The use of identified phytochemicals may help to speed up the drug development and provide natural protection against SARS-CoV-2.

Objective: To evaluate the Li's and Japanese scoring methods scoring for screening early gastric cancer in a healthy population., Methods: During January 2016-December 2018, profiles of the healthy people participated in a physical examination in the first people's Hospital of Shanghai were collected. A total of 342 volunteers, including 137 males and 205 females ageing 40-74, were enrolled. After recording the basic information, all volunteers were scored using the Japan scoring method and the new gastric cancer screening score (ie, Li's score). The subjects' work characteristics (ROC curve) were drawn according to the patient's endoscopic pathological examination to indicate early gastric cancer, to determine the best cut-off point for the diagnosis of early gastric cancer by Japanese scoring and Li's scoring, respectively. The sensitivity and specificity of both scoring methods were calculated as well., Results: The area under the ROC curve of Japanese and Li's score, in the diagnosis of early gastric cancer, was 0.763 and 0.837, respectively. Japanese and Li's score ≥14 were considered as the best cut-off point. The sensitivity and specificity of Li's scoring were 63.60% and 91.10%, respectively. The sensitivity and specificity of the Japanese score were 54.50% and 87.50%, respectively. The area under the ROC curve in Li's scoring is more significant than that in Japanese scoring, and there was a substantial difference in the two methods (P<0.05)., Conclusion: Both Li's scoring and Japanese scoring have shown good screening value for early gastric cancer in a healthy population, but Li's scoring is more sensitive/specific than Japanese scoring., Competing Interests: The authors declare no conflicts of interest., (© 2021 Zhang et al.)

Colorectal cancer (CRC) is one of the most common malignancies worldwide. As current therapies toward CRC, including chemotherapy and radiotherapy, pose limitations, such as multidrug resistance (MDR) as well as the intrinsic and potential cytotoxic effects, necessitating to find more effective treatment options with fewer side effects, traditional Chinese medicine (TCM) has an advantage in complementary therapies. In the present study, 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assays), trypan blue staining, colony formation, 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, cell cycle determination, and Annexin V-FITC/PI staining were used to examine the efficacy of Sanjie Yiliu Formula (SJYLF) against CRC proliferation and to investigate its underlying molecular mechanisms through protein expression of various proapoptotic factors by quantitative polymerase chain reaction (q-PCR) and Western blotting. This four-herb-TCM SJYLF can be suggested as one of the decoctions clinically effective in late-stage cancer treatment. Our results suggest that SJYLF robustly decreased the viability of only CRC cell lines (HCT-8, SW-480, HT-29, and DLD-1) and not the normal human kidney cells (HK-2). Moreover, SJYLF significantly suppressed proliferation and induced apoptosis in HCT-8 and downregulated cyclin D1, CDK4, and BCL-2, while Bax expression was upregulated at both mRNA and protein expression levels., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.

The COVID-19, caused by a novel coronavirus, was declared as a global pandemic by WHO more than five months ago, and we are still experiencing a state of global emergency. More than 74.30 million confirmed cases of the COVID-19 have been reported globally so far, with an average fatality rate of almost 3.0%. Seven different types of coronaviruses had been detected from humans; three of them have resulted in severe outbreaks, i.e., MERS-CoV, SARS-CoV, and SARS-CoV-2. Phylogenetic analysis of the genomes suggests that the possible occurrence of recombination between SARS-like-CoVs from pangolin and bat might have led to the origin of SARS-CoV-2 and the COVID-19 outbreak. Coronaviruses are positive-sense, single-stranded RNA viruses and harbour a genome (30 kb) consisting of two terminal untranslated regions and twelve putative functional open reading frames (ORFs), encoding for non-structural and structural proteins. There are sixteen putative non-structural proteins, including proteases, RNA-dependent RNA polymerase, helicase, other proteins involved in the transcription and replication of SARS-CoV-2, and four structural proteins, including spike protein (S), envelope (E), membrane (M), and nucleocapsid (N). SARS-CoV-2 infection, with a heavy viral load in the body, destroys the human lungs through cytokine storm, especially in elderly persons and people with immunosuppressed disorders. A number of drugs have been repurposed and employed, but still, no specific antiviral medicine has been approved by the FDA to treat this disease. This review provides a current status of the COVID-19, epidemiology, an overview of phylogeny, mode of action, diagnosis, and possible treatment methods and vaccines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Continuous inhalation of coal dust among coal workers leads to a variety of disorders. The present study aims to evaluate the potential oxidative stress associated with coal dust generated from coal mining activities among exposed workers through the antioxidant enzyme system, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In this study cohort, intensive coal mine workers were assessed for antioxidant variations. Blood samples were collected from dust-exposed workers (engaged in different activities at coal mines; n = 311) and residents of the same city (nonexposed, control group; n = 50). The workers' exposure to coal dust was categorized based on working area (administrative group, surface workers, underground workers), working hours (up to 8 h and more than 8 h), and time of service. The results showed significantly altered activities of SOD, CAT, and GSH among the whole exposed group and its categories compared to the control group. A significant difference was also observed between high- and low-exposure groups. Statistical analysis revealed a negative correlation between antioxidant activity (catalase and SOD) and coal dust levels. Besides, coal exposure was associated with the time of service, smoking status, and dietary habits. The findings of this study reveal higher oxidative stress among highly exposed coal mine workers (underground workers > surface workers > administrative group > nonexposed group), and longer working hours have more pronounced adverse effects on workers' health., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Crystalline organic compounds, 2-amino-6-methylpyrimidin-4-yl benzenesulfonate (AMPBS) and 2,6-diaminopyrimidin-4-yl benzenesulfonate (DAPBS), were prepared via O -benzenesulfonylation of 2-amino-6-methylpyrimidin-4-ol 1 and 2,6-diaminopyrimidin-4-ol 2, respectively. The structural interpretations were achieved unambiguously by single-crystal X-ray diffraction (SC-XRD) analysis. The Hirshfeld surface study showed that C-H···O, N-H···N, and especially C-H···C hydrogen bond interactions are the key contributors to the intermolecular stabilization in the crystal. Density functional theory (DFT) studies were used to obtain a better understanding of natural bond orbitals (NBOs) and nonlinear optical (NLO) analysis for AMPBS and DAPBS at the B3LYP/6-311G(d,p) level. The time-dependent density functional theory (TD-DFT)/CAM-B3LYP/6-311G(d,p) level was employed for frontier molecular orbital analysis of both compounds. DFT-based vibrations for C-H, C=N, N-H, and stretching for C-C were found to be in good agreement with the experimental data. Overall, the theoretical findings were acquired in correspondence to the SC-XRD-based parameters. Intracharge transfer occurred in AMPBS and DAPBS compounds, which was evaluated through FMO activity. Global reactivity indices had been acquired utilizing energies of HOMO-LUMO orbitals. Overall, the theoretical findings related to AMPBS and DAPBS consist of promising correspondence to experimental findings. The theoretical-based study also exhibited that both AMPBS and DAPBS compounds contain promising NLO features., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The organic compounds with a π-bond system lead to electric charge delocalization which enables them to reveal fascinating nonlinear optical properties. Mono-carbonyl curcuminoids also have an appealing skeleton from the conjugation view point. Interesting chemical structures of the 3,5-bis(arylidene)- N -benzenesulfonyl-4-piperidone derivatives motivated us to perform density functional theory (DFT)-based studies. Therefore, computations using the B3LYP/6-311G(d,p) functional of DFT were executed to explore geometric parameters, highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energies, and natural bond orbital (NBO) analyses. Moreover, three different functionals such as HF, B3LYP, and M06 with the 6-311G(d,p) basis set were used to investigate the average polarizability ⟨α⟩ and first hyperpolarizability (β tot )-based properties of all compounds. A good concurrence among calculated and experimental parameters was obtained through root mean square error calculations. The molecular stability of piperidone derivatives was examined using the Hirshfeld surface and NBO analyses. Natural population analysis was also performed to obtain insights about atomic charges. Calculated HOMO-LUMO energies showed that charge transfer interactions take place within the molecules. Moreover, global reactivity parameters including electronegativity, chemical hardness, softness, ionization potential, and electrophilicity were calculated using the HOMO and LUMO energies. The average polarizability ⟨α⟩ and first hyperpolarizability (β tot ) values of all compounds were observed to be larger in magnitude at the aforesaid functional than the standard compound., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)