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Background: Botulinum neurotoxin type A (BoNT-A) is well-established for treatment of glabellar lines (GLs), and mostly formulated as powders requiring reconstitution for injection. The approved liquid formulation, ready-to-use (RTU) abobotulinumtoxinA was developed to ease injection procedures and prevent reconstitution errors. This multicenter, open-label, Phase IV study evaluated GL treatment experience using RTU abobotulinumtoxinA versus powder BoNT-A (onabotulinumtoxinA)., Methods: Females with experience of BoNT-A facial treatment were randomized 2:1 to GL treatment with 50 U RTU abobotulinumtoxinA (N = 99) or 20 U powder BoNT-A (N = 51) and followed-up for 6 months or 1 month, respectively. Assessments included: time to prepare each product for injection (primary endpoint); investigators' experience with product preparation/reconstitution; investigators' and subjects' treatment experience; safety; and for the RTU product: aesthetic improvement of GLs; subject satisfaction., Results: Compared with powder BoNT-A, RTU abobotulinumtoxinA required statistically significantly less preparation time (mean 0:33 vs. 1:34 min: s; p < 0.0001). Investigators preferred RTU abobotulinumtoxinA over powder BoNT-A (81% of treatment sessions) and found it allowed more time to communicate with subjects (97%). All investigators (100%) also found it easy-to-use, easy-to-learn, and that it fulfilled their expectations. Subjects found the RTU abobotulinumtoxinA treatment comfortable (91%), and through 6 months posttreatment, most reported satisfaction with their appearance (≥88%), looking natural (≥95%) and refreshed (≥80%). At Month 1, 99% of RTU-treated subjects had investigator-assessed improved aesthetic appearance in GLs, maintained in 76% at Month 6. No serious adverse events occurred., Conclusion: RTU abobotulinumtoxinA for GL treatment is well-tolerated, efficacious, shows high levels of subject satisfaction throughout 6 months, saves time, and is preferred by clinicians over powder BoNT-A., Gov Registry: NCT05277337., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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.

Accelerating perovskite solid solution discovery and sustainable synthesis is crucial for addressing challenges in wireless communication and biosensors. However, the vast array of chemical compositions and their dependence on factors such as crystal structure, and sintering temperature require time-consuming manual processes. To overcome these constraints, we introduce an automated materials discovery approach encompassing machine learning (ML) assisted material screening, robotic synthesis, and high-throughput characterization. Our proposed platform for rapid sintering and dielectric analysis streamlines the characterization of perovskites and the discovery of disordered materials. The setup has been successfully validated, demonstrating processing materials within minutes, in stark contrast to conventional procedures that can take hours or days. Following setup validation with established samples, we showcase synthesizing single-phase solid solutions within the barium family, such as (Ba x Sr 1-x )CeO 3 , identified through ML-guided chemistry., (© 2024. The Author(s).)

Approximately 2.2% of Libyans have chronic hepatitis B (CHB) and are at the highest risk of developing end-stage disease complications. Several resource-limited countries, including Libya, may be far from achieving the WHO goal of hepatitis B elimination by 2030 as a result of several testing and linkage to care (LTC) barriers. In Libya, data about the current HBV infection situation is scarce. Therefore, our study aimed to evaluate the trends of HBV in eastern Libya, Tobruk region, and try to identify the region-specific gaps and barriers that could potentially delay the WHO goal of HBV elimination. An eighteen-year retrospective review of records of the main district medical center in the region was done to estimate the trends of HBV infection and qualitative interviews with the clinical staff of the CHB registry in the region were conducted to investigate the current status of HBV management. Out of 392,952 records, 371 (0.09%) HBV-positive were recorded and declining trends of the infection were noticed over the study period. Until late 2019, there was no linkage to care or follow-up for people with HBV infection. However, a CHB registry was established in late 2019 to manage HBV infections in the region, yet there are several barriers such as the lack of diagnostic infrastructure for liver function assessment and antiviral treatment. Despite the significant decline observed in the occurrence of HBV infection and introduction of important HBV management steps such as establishment of the CHB registry, there are still several barriers that could delay the elimination of the infection., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

p53 is a tumor suppressor gene activated in response to cellular stressors that inhibits cell cycle progression and induces pro-apoptotic signaling. The protein level of p53 is well balanced by the action of several E3 ligases and deubiquitinating enzymes (DUBs). Several DUBs have been reported to negatively regulate and promote p53 degradation in tumors. In this study, we identified USP19 as a negative regulator of p53 protein level. We demonstrate a direct interaction between USP19 and p53 by pull down assay. The overexpression of USP19 promoted ubiquitination of p53 and reduced its protein half-life. We also demonstrate that CRISPR/Cas9-mediated knockout of USP19 in cervical cancer cells elevates p53 protein levels, resulting in reduced colony formation, cell migration, and cell invasion. Overall, our results indicate that USP19 negatively regulates p53 protein levels in cervical cancer progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Nonlinear optics (NLO) is an interesting field that discloses the interaction between intense light and matter, leading to a deeper understanding of NLO phenomena. Organic chromophores are considered as promising materials for NLO due to their exceptional structural versatility, ease of processing, and rapid response to NLO effects. Functional materials based on thiophene have been indispensable in advancing organic optoelectronics. Specifically, dithiophene-based compounds display weaker aromaticity, reduced steric hindrance, and additional sulfur-sulfur interactions. Hence, by utilizing dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene (DTBDT) as the core structure, designing of a set of organic compounds with D1-π-D2-π-A-type framework, namely ZR1D1-ZR1D8, was carried out in this study. The analysis of frontier molecular orbitals (FMOs) revealed that compound ZR1D2 has the lowest band gap of 1.922 eV among all the investigated chromophores. The correlation of global reactivity parameters (GRPs) with the band gap values indicates that ZR1D2 displays a hardness of 0.961 eV and a softness of 0.520 eV -1 . Among the studied compounds, ZR1D2 demonstrated a broad absorption spectrum that extended across the visible region. The maximum absorption wavelengths were observed at 766.470 nm for ZR1D2 and 749.783 nm for ZR1D5. These DTBDT-based dyes exhibit a remarkable NLO response with exceptionally high first hyperpolarizability (β tot ) values. Among them, compound ZR1D2 stands out with the highest average linear polarizability (⟨α⟩ = 3.0 × 10 -22 esu), first hyperpolarizability (β tot  = 4.1 × 10 -27 esu), and second hyperpolarizability (γ tot  = 7.5 × 10 -32 esu) values. In summary, this investigation offers valuable insights into the potential use of DTBDT-based organic chromophores, particularly ZR1D2, for advanced applications in NLO. These findings suggest promising opportunities for researchers to synthesize these molecules and utilize these compounds in hi-tech NLO-based applications., Methodology: The density functional theory computations were performed at the M06/6-311G(d,p) functional to explore their structural effects on electronic and NLO findings. Various analyses like highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps, absorption maxima, density of states, open circuit voltage, binding energies of electrons and holes, and transition density matrix are employed to investigate photovoltaic efficiencies of the derivatives. Different software packages like Avogadro, Multiwfn, Origin, GaussSum, PyMOlyze, and Chemcraft were used to deduce conclusions from the output files., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts., (© 2024 Wiley Periodicals LLC.)

In the current work, organic cyclopenta-thiophene (CPT) based derivatives (FICR and FICD1-FICD5) were designed by the modulation of end-capped acceptor group of the reference molecule i.e., FICR, to explore their nonlinear optical (NLO) response. The effect of terminal acceptor and donor groups in the tailored compounds was explored by using DFT based quantum calculations. The UV-Vis analysis, frontier molecular orbitals (FMOs), transition density matrix (TDM), natural bond orbitals (NBOs), density of states (DOS), nonlinear optical (NLO) analyses were performed at M06/6-311G(d,p) functional. The LUMO-HOMO band gaps of FICD1-FICD5 were found to be smaller (1.75-1.92 eV) comparative to FICR (1.98 eV). Moreover, the global reactivity parameters (GRPs) were correlated with the results of other analyses. FICD2 and FICD5 with lowest band gap 1.73 and 1.75 eV showed less hardness (0.86 and 0.87 eV, respectively), high softness (0.58 and 0.57 eV -1 ), and larger absorption spectrum (815 and 813 nm) in gaseous phase and (889 and 880 nm) in solvent phase among all entitled compounds. All the designed chromophores (FICD1-FICD5) demonstrated a significant NLO response as compared to FICR. Particularly, FICD2 and FICD5 exhibited the highest average linear polarizability (<α>) [2.86 × 10 -22 and 2.88 × 10 -22 esu], first hyperpolarizability (β tot ) (8.43 × 10 -27 and 8.35 × 10 -27 esu) and second hyperpolarizability (γ tot ) (13.20 × 10 -32 and 13.0 × 10 -32 esu) values as compared to the other derivatives. In nutshell, structural modeling of CPT based chromophores with extended acceptors, can be significantly utilized to achieve potential NLO materials., (© 2024. The Author(s).)

The present study describes the synthesis, characterization, and evaluation of tetrahydropiperine (THP), piperic acid (PA), and tetrahydropiperic acid (THPA) as anti-inflammatory agents. THPA demonstrated potent anti-inflammatory activity among all the compounds. The anti-inflammatory potential was investigated in both in-vitro and in-vivo experimental models. Our findings demonstrated that THPA effectively suppressed the production of pro-inflammatory mediators, including nitric oxide and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in both in vitro and in vivo. Additionally, THPA attenuated the expression of i-NOS and COX-2 in RAW 264.7 macrophages. The oral administration of THPA significantly reduced carrageenan induced paw edema thickness and alleviated liver, lung, and kidney injury induced by LPS. THPA also reduced the infiltration of inflammatory cells, prevented the occurrence of significant lesions, and mitigated tissue damage. Moreover, THPA significantly improved the survival rate of mice challenged with LPS. Our western blot studies also found that LPS induced NF-κB activation was downregulated by treatment with THPA in an in vivo system. These results collectively illustrated the potential of THPA as a therapeutic agent for treating inflammatory diseases., 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 © 2024 Elsevier Ltd. All rights reserved.)

Herein, a series of heterocyclic organic compounds (PYFD1-PYFD7) are designed with different acceptor moieties at the terminal position of a reference compound (PYFR) for nonlinear optical (NLO) active materials. The optoelectronic characteristics of the designed chromophores were investigated using density functional theory (DFT) calculations with the M06/6-311G(d,p) functional. Frontier molecular orbital (FMO) analysis revealed a significant decrease in the energy of the band gaps (2.340-2.602 eV) for the derivatives as compared to the PYFR reference compound (3.12 eV). An efficient transfer of charge from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) was seen, which was further corroborated by the density of states (DOS) and transition density matrix (TDM) heat maps. The results of the global reactivity parameters (GRPs) indicated that all derivatives exhibited greater softness ( σ = 0.384-0.427 eV) and lower hardness ( η = 0.394-1.302 eV) as compared to PYFR, indicating a higher level of polarizability in the derivatives. Moreover, all of the derivatives showed significant findings in terms of nonlinear optical (NLO) results as compared to the reference chromophore. PYFD2 showed the most effective NLO response ( α = 1.861 × 10 -22 and β tot = 2.376 × 10 -28 esu), including a lowered band gap of 2.340 eV, the maximum softness value of 0.4273 eV, and the lowest hardness value of 1.170 eV as compared to other chromophores. The incorporation of different acceptors and thiophene as a π-spacer in this structural alteration significantly contributed to achieving remarkable NLO responses. Therefore, our findings may motivate experimentalists to synthesize these designed NLO active materials for the current advanced technological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Water contamination due to organic pollutants is a challenging issue around the globe, and several attempts have been made to deal with this issue. Out of which, the semiconductor-based photocatalytic process had gained much attention and proved to be an efficient, easy, and economical process for the removal of organic dyes from aqueous solutions. For this purpose, the iron oxide-zirconium dioxide nanocomposite (Fe 2 O 3 -ZrO 2 NC) was prepared via a simple mechanochemical process using a mortar and pestle, followed by a calcination process at 300, 600, and 900 °C. Different physicochemical analyses were carried out in order to investigate the successful synthesis of Fe 2 O 3 -ZrO 2 NC and the effect of temperature on the crystallinity, surface area, pore size, phase composition, sample morphology, and particle/crystallite size. The Fe 2 O 3 -ZrO 2 NCs were subjected to a photocatalytic test under solar light irradiation against fluorescein dye in an aqueous medium, and the photocatalytic performance was examined under the influence of calcination temperatures, pH, catalyst dose, and initial concentration. The stability of the Fe 2 O 3 -ZrO 2 NCs was also checked by recycling them for five reuse cycles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report an efficient sample preparation method (freezing) for onsite fat and meat analysis via a specially designed thermoelectric cooling and temperature-controlling system. This investigation also focused on the effect of phase change on the sensitivity and reproducibility of LIBS emission signals and plasma parameters. The plasma emissions of animal fats (lard) were recorded when the sample was frozen (-2 °C), fluid (15 °C), and in a liquid state (37 °C) with a thermoelectric cooling system. At each temperature, the plasma emissions were acquired at laser pulse energy from 50 to 300 mJ and detector gate delay (DGD) from 0.5 to 5 μs. With increasing sample temperature, the DGD, where the optical emission intensity reached a maximum, decreased. At a laser pulse energy of 200 mJ and a sample temperature of -2 °C, the emission signals increased fourfold, the signal-to-noise ratio (SNR) improved tenfold, and the self-absorption in the emission lines decreased significantly. The repeatability of the emission signals and plasma parameters of frozen and liquid fat samples was determined using the relative standard deviation (RSD) of Se I (473.08 nm) and K I (766.48 nm) emission lines. The RSDs of the emission signals improved from 40 to 18 % and 37 to 16 %, whereas the shot-to-shot RSDs of the electron temperature and electron number density get improved from 11 to 6 % and 12 to 6.8 %, respectively., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SAMI UL HAQ reports administrative support, equipment, drugs, or supplies, and statistical analysis were provided by National Institute of Lasers and Optronics College, Pakistan Institute of Engineering and Applied Sciences, Nilore, Islamabad, 45,650, Pakistan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Introduction: During the COVID-19 pandemic, evidence emerged that immunosuppressed children were less affected by COVID-19 infections compared with immunosuppressed adults. The aim of our study was to investigate how COVID-19 infections affected paediatric kidney transplant recipients (pKTR) in the UK., Methods: Questionnaires regarding COVID-19 infection data and care of pKTR during the COVID-19 pandemic were sent to all 13 UK paediatric nephrology centres examining asymptomatic and symptomatic pKTR with positive COVID-19 PCR testing from 1 April 2020 to 1 December 2021., Results: 63 pKTR who were 3.1 (range 0.1-15) years post-transplantation had COVID-19 infection with positive SARS-CoV-2 PCR RNA. Classical COVID-19 symptoms were present in half of the patients; with atypical presentations including diarrhoea (13%) and lethargy (13%) also noted, while a third of patients were asymptomatic. Eighteen patients (28%) were hospitalised including five asymptomatic patients admitted for other reasons. No patients needed ventilation or intensive care admission, and one patient received supplemental oxygen. There was evidence of acute kidney injury (AKI) in 71% of patients, but no patients needed kidney replacement therapy with haemofiltration or dialysis., Conclusion: We report 10.4% of the UK paediatric renal transplantation population had documented COVID-19 infections with positive SARS-CoV-2 PCR RNA with 28% of those affected requiring hospitalisation. The increased incidence of AKI, particularly after the first wave of the COVID-19 pandemic, was possibly due to increased testing. There was low morbidity and mortality compared with the adult population., Competing Interests: Competing interests: SDM had unpaid roles during COVID-19 pandemic with national COVID-19 working groups of the UK Kidney Association, UK Renal Registry, The British Association for Paediatric Nephrology, National Health Service Blood and Transplant and National Institute for Health and Care Research., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This study employed various experimental techniques to produce graphene oxide (GO) under different conditions, such as the inclusion or exclusion of NaNO 3 , and reduced graphene oxide (RGO) with or without the catalyst CaCl 2 . The procedure of decreasing RGO was carried out using the reducing agent NaBH 4 . Moreover, the prepared mixtures were utilized in the degradation process of methylene blue (MB) dye using photo-catalysis, with exposure to both ultraviolet (UV) light and sunlight. When exposed to UV and sunlight irradiation, WN-GO showed rapid and ecologically friendly breakdown of MB dye in comparison to N-GO. WN-GO exhibited exceptional adsorption capabilities, surpassing other tested materials like N-GO, WN-C-RGO and C-RGO. Although WN-C-RGO has demonstrated satisfactory performance in terms of photo-catalytic degradation, as the concentration-time graph of the MB dye revealed significant degradation, with a reduction of up to 90% and 62.5% under UV light and sunlight exposure, respectively. These results offer insightful information on the potential of graphene-based materials to address other environmental issues, particularly in the areas of water treatment., Competing Interests: The authors hereby declare that we 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.)

Andrographolide (AD) is a potent natural product with a wide range of pharmacological activities. However, it has low oral bioavailability due to poor solubility and dissolution rate. Solid dispersion (SD) is a promising technique to improve the solubility and dissolution rate of such molecules. In this study, SD formulation of AD was prepared using Kollidon-SR (KSR) and Poloxamer-407 (P-407) as carriers. SD was prepared using the solvent evaporation method and evaluated for the modulation of solubility of AD. The developed SD formulation was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Further, dissolution rate, yield, drug content, stability, flowability, and pharmacokinetic profile of SD were evaluated. The compatibility of SD with the Caco-2 cells and its impact on the P-glycoprotein (P-gp) mediated efflux was also investigated. Furthermore, carrageenan-induced paw edema, and adjuvant-induced arthritic model were used to evaluate the efficacy of SD. The results showed that SD 3 (AD + KSR + P-407, 1:6:8) exhibited the highest solubility and dissolution rate, and significantly improved pharmacokinetic profile compared to native AD. SD 3 was found to be stable during storage and displayed excellent yield, drug content, and flowability. This formulation was found to be compatible with the Caco-2 cells and retarded the efflux of P-gp substrate. SD 3 also demonstrated substantially better efficacy than native AD in terms of paw edema inhibition (carrageenan-induced paw edema, Wistar rats), and overall improvement of disease condition (in terms of paw edema, arthritic score, AST, ALT, cytokines, radiological changes, and histopathology) in arthritic Wistar rats. In conclusion, SD 3 exhibited improved solubility, dissolution rate, pharmacokinetic profile, and pharmacological activity than native AD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prem N. Gupta reports a relationship (that includes employment) with Council of Scientific and Industrial Research (CSIR)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the current study, three novel 1,4-phenylenediamine-based chromophores (3a-3c) were synthesized and characterized and then their nonlinear optical (NLO) characteristics were explored theoretically. The characterization was done by spectroscopic analysis, i.e. FT-IR, UV-Visible, and NMR spectroscopy, and elemental analysis. Notably, these chromophores exhibited UV-Visible absorption within the range of 378.635-384.757 nm in acetonitrile solvent. Additionally, the FMO findings for 3a-3c revealed the narrowest band gap (4.129 eV) for 3c. The GRPs for these chromophores were derived from HOMO-LUMO energy values, which showed correspondence with FMO results by depicting a minimum hardness (2.065 eV) for 3c. Among these compounds, 3c displayed the highest nonlinear behavior with maximum μ tot , β tot and γ tot values of 4.79 D, 8.00 × 10 -30 and 8.13 × 10 -34 a.u., respectively. Our findings disclosed that the synthesized 1,4-phenylenediamine chromophores may be considered promising candidates for nonlinear optical materials, showing potential applications in the realm of optoelectronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. Future work on developing pan-cancer assays with their respective validities confirmed using well-designed, prospective clinical trials is crucial in pushing for the greater use of these tools in oncology.

Koenimbine (1), a carbazole alkaloid isolated from Murraya koenigii, belongs to the Rutaceae family. Various pharmacological effects such as anti-diabetic, melanogenesis inhibition, anti-diarrheal, anti-cancer, and anti-inflammatory properties of koenimbine have already been reported. In the current study, we investigated the anti-inflammatory role of koenimbine (1) and its novel semi-synthetic derivative 8-methoxy-3,3,5-trimethylpyrano[3,2-a] carbazole-11(3H)-yl) (3-(trifluoromethyl) phenyl) methanone (1G) in both in vitro and in vivo biological systems. Our results demonstrated that the anti-inflammatory activity of 1G significantly lowered the production of NO, pro-inflammatory cytokines (IL-6, TNF-α & IL-1β), LTB4 following LPS stimulation in RAW 264.7 macrophages. Furthermore, 1G significantly attenuated the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner and also decreased the production of reactive oxygen species (ROS) in LPS-activated RAW 264.7 cells. In addition, the oral administration of 1G reduced the inflammatory response in carrageenan-induced paw edema in BALB/C mice. Moreover, it effectively reduced NO, IL-6, IL-1β & TNF-α levels, liver markers (AST, ALT), and kidney markers (BUN, CRE, and Urea). Also, 1G reverted the infiltration of inflammatory cells and tissue damage in lungs, liver and kidney enhanced the survival rate in LPS-challenged mice. 1G blocks NF-κB p65 from translocating into the nucleus and activating inflammatory gene transcription. These results illustrated that 1G suppresses the inflammatory effects both in-vitro and in-vivo studies via downregulating the nuclear factor kappa-B (NF-κB) signaling pathway. In conclusion, our results demonstrate that semi-synthetic derivative 1G can effectively attenuate the inflammatory response via NF-κB and MAPK signaling pathways; suggesting 1G is a potential novel anti-inflammatory drug candidate in treating inflammatory disorders., 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. Published by Elsevier B.V.)

Aim: To synthesize novel more potent anti-diabetic agents. Methodology: A simple cost effective Hantzsch's synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5 H )-ones. Results: Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5 H )-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation and anti-oxidant activities it is revealed that most of the compounds possess good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of α-amylase and anti-oxidant inhibition revealed that compounds are less active against α-amylase and anti-oxidant assays. Conclusion: This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug.

Interactions between plants and herbivores are central in most ecosystems, but their strength is highly variable. The amount of variability within a system is thought to influence most aspects of plant-herbivore biology, from ecological stability to plant defense evolution. Our understanding of what influences variability, however, is limited by sparse data. We collected standardized surveys of herbivory for 503 plant species at 790 sites across 116° of latitude. With these data, we show that within-population variability in herbivory increases with latitude, decreases with plant size, and is phylogenetically structured. Differences in the magnitude of variability are thus central to how plant-herbivore biology varies across macroscale gradients. We argue that increased focus on interaction variability will advance understanding of patterns of life on Earth.

Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH 2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108-15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11-modified fibers significantly support NG108-15 neuronal cell and Schwann cell viability. NG108-15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost-effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration., (© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

A hydrothermal technique was employed to synthesize Ni/Mg/Al ternary L.D.H.s modified with montmorillonite (NMA-MMT-LDHs). Many characterization methods, including X-ray diffraction (XRD), scanning electron microscopy (S.E.M.), Fourier transform infrared (FTIR), and Brunauer, Emmett, and Teller (B.E.T.), were used to assess the physiochemical properties of the produced analytes. Congo red and methylene blue were utilized as model dyes to treat textile waste with the synthesized analytes. The batch adsorption model was utilized to conduct the adsorption experiments under varying contact time, adsorbent dosage, and solution pH conditions. A pseudo-second-order kinetics and the Langmuir adsorption model control the adsorption process. The maximum monolayer adsorption capacities of C.R. and M.B. were determined to be 344 and 200 mg/g, respectively. As the quantity of dosage increased from the 0.01-0.04 g, the percent removal efficiency (%) increased from 75 to 87 % for S2-LDH, 84-88 % for S2-MMT, 86-93 % for S3-MMT, and 95-97% for S4-MMT for C.R. dye and 82-85 % for S2-LDH, 83-89 % for S2-MMT, 83-91 % for S3-MMT, and 84-92 % for S4-MMT for M.B. dye. The removal percentage of C.R. dye for adsorbents S2-LDH, S2-MMT, S3-MMT, and S4-MMT were 75 %, 84 %, 86 %, and 95 %, respectively and 82 %, 83 %, 83 %, and 85 %, respectively for the M.B. dye removal. The presence of MMT significantly increases the affinity of Ni/Mg/Al-LDHs (NMA-LDHs), and the designed production technique can be used to produce a variety of compositionally distinct adsorbent materials., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:K. S. Al-mugren reports financial support was provided by Princess Nourah bint Abdulrahman University. K. S. Al-mugren reports a relationship with 10.13039/501100004242Princess Nourah bint Abdulrahman University that includes: employment and funding grants., (© 2023 Published by Elsevier Ltd.)

The current investigation deals with the treatment of water pollution that is caused by the leaching of nickel ions from the metallurgical industry and new-energy batteries. Therefore, an eco-friendly treatment of nickel through the use of a composite of cotton stalk biochar with nanozerovalent copper has been presented in this investigation signifying the impact of zerovalent copper in enhancing the adsorption capacity of biochar for nickel adsorption. Thermogravimetric analysis data showed the adsorbent to be significantly stable in the higher thermal range, whereas transmission electron microscopy analysis confirmed the particles to be 27 nm and also showed the cubic geometry of the particles. A much closer scanning electron microscopy analysis shows the morphology of particles to be cubic in shape. Batch adsorption indicated a positive influence of pH increase on adsorption due to the electrostatic attraction between positive nickel ions and post point of zero charge (pH PZC ) negative surface of copper biochar composite (pH > 5.5). A high adsorption rate was observed in the first 60 min, whereas adsorption increased with the increase in temperature from 303 to 318 K. Kinetic modeling confirmed the pseudo-first-order to fit best to the data. The apparent activation energy (11.96 kJ mol -1 ) is indicative of the chemical nature of the process. The adsorption data fitted well to the Langmuir adsorption model. The negative values of apparent Δ G ° and the positive values of apparent Δ H ° indicate the spontaneity and endothermicity of the process, respectively, whereas the positive values of apparent Δ S ° point toward increased randomness during the process. Postadsorption XPS suggests the adsorption of nickel on the surface of biochar composites in the form of Ni(OH) 2 and NiO(OH)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Rheumatoid arthritis (RA) is the most common inflammatory arthritis affecting 0.5-1.0% of the general population worldwide and although RA is properly considered a disease of the joints, it can cause a variety of extra-articular manifestations. This study was performed to find out any discrepancy in fracture risk estimates with and without bone mineral density (BMD) in rheumatoid arthritis (RA) patients. This observational cross-sectional study was carried out in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from July 2013 to July 2015. Total 65 consecutive patients with RA fulfilling ACR/EULAR criteria aged 40-90 year were recruited. Ten year fracture risk of these patients was evaluated by the FRAX score with and without BMD and differences were observed. FRAX score without BMD revealed that major fracture risk was low in 58(89.2%) patients, moderate in 7(10.8%) patients but re-estimation with BMD revealed that 55(84.6%) patients remained in low risk group, 8(12.3%) patients in moderate risk group and 2(3.1%) patients went to the high risk group. In case of hip fracture risk without BMD, risk was low in 58(89.2%) patients, high in 7(10.8%) patients; but with BMD, 50(76.9%) patients remained in low risk group but risk of 15(23.1%) patients became high. Almost all the high risk patients (93.3%) were ≥55 years of age. Increasing age, female sex, disease duration and use of steroid were positively correlated with increased FRAX score where as high BMI and high BMD were associated with low FRAX score. But in multivariate analysis it was found that only relation with age was at statistically significant level. Significant numbers of patients with rheumatoid arthritis have high risk of fracture especially hip fracture. The mean of FRAX score increased in both major & hip osteoporotic fracture risk after adding BMD. More than half of the patients above fifty five years or more had high risk of fracture. So, BMD should be done in patients aged more than fifty five.

The agricultural practices of breeding, farm management and cultivation have improved production, to a great extent, in order to meet the food demands of a growing population. However, the newer challenges of climate change, global warming, and nutritional quality improvement will have to be addressed under a new scenario. Plant biotechnology has emerged as a reliable tool for enhancing crop yields by protecting plants against insect pests and metabolic engineering through the addition of new genes and, to some extent, nutritional quality improvement. Plant tissue culture techniques have provided ways for the accelerated clonal multiplication of selected varieties with the enhanced production of value-added plant products to increase modern agriculture. The in vitro propagation method has appeared as a pre-eminent approach for the escalated production of healthy plants in relatively shorter durations, also circumventing seasonal effects. However, there are various kinds of factors that directly or indirectly affect the efficiency of in vitro regeneration like the concentration and combination of growth regulators, variety/genotype of the mother plant, explant type, age of seedlings and other nutritional factors, and elicitors. Nanotechnology as one of the latest and most advanced approaches in the material sciences, and can be considered to be very promising for the improvement of crop production. Nanomaterials have various kinds of properties because of their small size, such as an enhanced contact surface area, increased reactivity, stability, chemical composition, etc., which can be employed in plant sciences to alter the potential and performance of plants to improve tissue culture practices. Implementing nanomaterials with in vitro production procedures has been demonstrated to increase the shoot multiplication potential, stress adaptation and yield of plant-based products. However, nanotoxicity and biosafety issues are limitations, but there is evidence that implies the promotion and further exploration of nanoparticles in agriculture production. The incorporation of properly designed nanoparticles with tissue culture programs in a controlled manner can be assumed as a new pathway for sustainable agriculture development. The present review enlists different studies in which treatment with various nanoparticles influenced the growth and biochemical responses of seed germination, as well as the in vitro morphogenesis of many crop species. In addition, many studies suggest that nanoparticles can be useful as elicitors for elevating levels of important secondary metabolites in in vitro cultures. Recent advancements in this field also depict the suitability of nanoparticles as a promising carrier for gene transfer, which show better efficiency than traditional Agrobacterium -mediated delivery. This review comprehensively highlights different in vitro studies that will aid in identifying research gaps and provide future directions for unexplored areas of research in important crop species.

Dinoflagellates are unicellular organisms that are implicated in harmful algal blooms (HABs) caused by potent toxins that are produced through polyketide synthase (PKS) pathways. However, the exact mechanisms of toxin synthesis are unknown due to a lack of genomic segregation of fat, toxins, and other PKS-based pathways. To better understand the underlying mechanisms, the actions and expression of the PKS proteins were investigated using the toxic dinoflagellate Amphidinium carterae as a model. Cerulenin, a known ketosynthase inhibitor, was shown to reduce acetate incorporation into all fat classes with the toxins amphidinol and sulpho-amphidinol. The mass spectrometry analysis of cerulenin-reacted synthetic peptides derived from ketosynthase domains of A. carterae multimodular PKS transcripts demonstrated a strong covalent bond that could be localized using collision-induced dissociation. One multi-modular PKS sequence present in all dinoflagellates surveyed to date was found to lack an AT domain in toxin-producing species, indicating trans -acting domains, and was shown by Western blotting to be post-transcriptionally processed. These results demonstrate how toxin synthesis in dinoflagellates can be differentiated from fat synthesis despite common underlying pathway.

A basic urea technique was successfully used to synthesize Mg/Al-Layered double hydroxides (Mg/Al LDHs), which were then calcined at 400 °C to form Mg/Al-Layered double oxides (Mg/Al LDOs). To reconstruct LDHs, Mg/Al LDOs were fabricated with different feeding ratios of Ni by the co-precipitation method. After synthesis, the Ni/Mg/Al-layered double hydroxides (NMA-LDHs) with 20% and 30% Ni (S1 and S2) were roasted at 400 °C and transformed into corresponding Ni/Mg/Al-layered double oxides (NMA-LDOs) (S1a and S2b, respectively). The physiochemical properties of synthesized samples were also evaluated by various characterization techniques, such as X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR), and Brunauer, Emmett, and Teller (BET). The adsorption behavior of methyl orange (MO) onto the synthesized samples was evaluated in batch adsorption mode under varying conditions of contact time, adsorbent quantity, and solution pH. As the dosage amount increased from 0.01-0.04 g, the removal percentage of MO dye also increased from 83% to 90% for S1, 84% to 92% for S1a, 77% to 87% for S2, and 93% to 98% for S2b, respectively. For all of the samples, the adsorption kinetics were well described by the pseudo-second-order kinetic model. The equilibrium adsorption data were well fitted to both Langmuir and Freundlich models for methyl orange (MO). Finally, three adsorption-desorption cycles show that NMA-LDHs and NMA-LDOs have greater adsorption and reusability performance for MO dye, signifying that the design and fabrication strategy can facilitate the application of the natural hydrotalcite material in water remediation.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus ( sensu stricto ). The parasite affects a wide range of livestock and wild animals. In this study, the population diversity of the Echinococcus species was investigated based on mitochondrial cytochrome b ( cyt b) and NADH dehydrogenase subunit 5 ( nad 5) genes. In addition to this, β-tubulin gene isoforms of Echinococcus granulosus were amplified to determine the resistance against benzimidazoles. For this purpose, 40 cyst samples from cattle ( n  = 20) and buffaloes ( n  = 20) were collected from the main abattoir of Sialkot. DNA extraction was performed using Qiagen Blood and Tissue Kits. Amplification was performed through PCR. Each amplicon was confirmed by GelRed™ stained agarose gel (2%). Samples were sequenced in a DNA analyzer and viewed for any misread nucleotide by using MEGA (v.11). Corrections in nucleotide sequence and multiple sequence alignment were made through the same software. NCBI-BLAST was used for sample specific sequences to identify them as belonging to a particular species. Diversity indices were estimated using DnaSP (v.6) while phylogenetic analysis was inferred using the Bayesian method using MrBayes (v.1.1). β-tubulin gene isoforms sequence analysis was performed to find out the candidate gene causing benzimidazole resistance. All 40 isolates were found positive for E. granulosus. BLAST-based searches of sequences of each isolate for each gene ( nad 5 and cyt b) confirmed their maximum similarity with the G1 genotype. Overall, high haplotype diversity (Hd nad5  = 1.00; Hd cytb  = 0.833) and low nucleotide diversity ( π nad5  = 0.00560; π = cytb  = 0.00763) was identified based on diversity indices. For both the genes, non-significant values of Tajima's D ( nad 5 = -0.81734; cyt b = -0.80861) and Fu's Fs ( nad 5 = -1.012; cyt b = 0.731) indicate recent population expansion. Bayesian phylogeny-based results of nad5 and cytb sequences confirmed their genotypic status as distinct from other Echinococcus species. This study shed light on the status of benzimidazole resistance in Echinococcus granulosus for the very first time from Pakistan. The findings of this study will significantly add in the information available on genetic diversity of Echinoccous granulosus based on cytb and nad5 genes sequences., 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 © 2023 Alvi, Alshammari, Ali, Ul Haq, Bashir, Li, Saqib, Sajid, Ghafoor, Imran, Ijaz, Fu, Saeed, Ahmad, Liu, Yan and Jia.)

There are challenges in monitoring and managing water quality due to spatial and temporal heterogeneity in contaminant sources, transport, and transformations. We demonstrate the importance of longitudinal stream synoptic (LSS) monitoring, which can track combinations of water quality parameters along flowpaths across space and time. Specifically, we analyze longitudinal patterns of chemical mixtures of carbon, nutrients, greenhouse gasses, salts, and metals concentrations along 10 flowpaths draining 1,765 km 2 of the Chesapeake Bay region. These 10 longitudinal stream flowpaths are drained by watersheds experiencing either urban degradation, forest and wetland conservation, or stream and floodplain restoration. Along the 10 longitudinal stream flowpaths, we monitored over 300 total sampling sites along a combined stream length of 337 km. Synoptic monitoring along longitudinal flowpaths revealed: (1) increasing, decreasing, piecewise, or no trends and transitions in water quality with increasing distance downstream, which provide insights into water quality processes along flowpaths; (2) longitudinal trends and transitions in water quality along flowpaths can be quantified and compared using simple linear and non-linear statistical relationships with distance downstream and/or land use/land cover attributes, (3) attenuation and transformation of chemical cocktails along flowpaths depend on: spatial scales, pollution sources, and transitions in land use and management, hydrology, and restoration. We compared our LSS patterns with others from the global literature to synthesize a typology of longitudinal water quality trends and transitions in streams and rivers based on hydrological, biological, and geochemical processes. Applications of LSS monitoring along flowpaths from our results and the literature reveal: (1) if there are shifts in pollution sources, trends, and transitions along flowpaths, (2) which pollution sources can spread further downstream to sensitive receiving waters such as drinking water supplies and coastal zones, and (3) if transitions in land use, conservation, management, or restoration can attenuate downstream transport of pollution sources. Our typology of longitudinal water quality responses along flowpaths combines many observations across suites of chemicals that can follow predictable patterns based on watershed characteristics. Our typology of longitudinal water quality responses also provides a foundation for future studies, watershed assessments, evaluating watershed management and stream restoration, and comparing watershed responses to non-point and point pollution sources along streams and rivers. LSS monitoring, which integrates both spatial and temporal dimensions and considers multiple contaminants together (a chemical cocktail approach), can be a comprehensive strategy for tracking sources, fate, and transport of pollutants along stream flowpaths and making comparisons of water quality patterns across different watersheds and regions., Competing Interests: Conflict of interest Authors GS and MG are employed by AKRF, Inc. The remaining 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.

Aim of the Study: Bone morphogenic proteins (BMPs) have both inhibitory and stimulatory effects on growth of a tumor that depend on the type of cells, the dosage and the tumor microenvironment. We aimed to investigate the impact of the bone morphogenic protein-7 (BMP-7) single nucleotide polymorphism (SNP) rs230205 [A/G] on susceptibility to hepatocellular carcinoma (HCC) progression from liver cirrhosis after viral hepatitis infection in Egyptian patients., Material and Methods: The amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) method was used to genotype the rs230205 [A/G] SNP in 150 subjects (50 patients with post-hepatitis C or B cirrhosis, 50 HCC patients, and 50 controls). Expression level of BMP-7 protein was assessed using enzyme-linked immunosorbent assay (ELISA)., Results: The results revealed insignificant changes in distribution of all genotypes/alleles of the BMP-7 rs230205 [A/G] SNP between cirrhotic patients, HCC patients and controls. The AA genotype and A allele could be considered risk factors for cirrhosis (OR = 1.75, 1.50) and HCC (OR = 2.19, 1.74), respectively. The AA genotype (95% CI: 0.45-6.79) and A allele (OR = 1.50, 95% CI: 0.77-2.93) may be viewed as cirrhosis risk factors based on group segregation. Additionally, the A allele, AG and AA genotypes and their combined ORs of 2.19 (95% CI: 0.58-8.23), 1.74 (95% CI: 0.90-3.37), and 1.70 (95% CI: 0.68-4.29) could all be risk factors for HCC. No genotype or allele could be regarded as a risk factor for progression of cirrhosis to HCC, according to OR values., Conclusions: The results showed no correlation between BMP-7 rs230205 [A/G] SNP and progression of cirrhosis to HCC. To confirm our findings, additional prospective large-scale research is required., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Clinical and Experimental Hepatology.)

This roundtable brings together contributions from nine senior, mid-career and junior scholars who work on the history of science in pre-1800 Islamicate societies. The contributions reflect upon some of the challenges that have historically constrained the subfield, how they have sought to overcome them, and what they see as some of the more productive and fruitful turns the field has taken and/or should take in the future. A central trend in all contributions is how they seek to confront the combined weight of colonialism, Orientalism, and the teleological history of science that continues to haunt contemporary discussions in both academia and the general public with regards to science in pre-1800 Islamicate societies. Without diminishing the pioneering achievements of the generations of historians who have preceded us, and upon whose work we continue to rely, this combined weight has tended a) to marginalize the study of occult sciences in Islamicate societies; b) to emphasize investigations of content from an etic perspective of how we got to the present, which is primarily seen as how the scientific content is connected to the rise of modern science in Europe; and c) to concomitantly marginalize the study of science in post-1200 Islamicate societies, particularly those with little to no connection to the rise of "Western" science. The contributions build upon conversations that took place among participants in December 2019 at a workshop at New York University (NYU), Abu Dhabi Institute in New York City, funded by a grant from NYU Abu Dhabi.

Macrophage adenosine monophosphate-activated protein kinase (AMPK) limits the development of experimental colitis. AMPK activation inhibits NADPH oxidase (NOX) 2 expression, reactive oxygen species (ROS) generation, and pro-inflammatory cytokine secretion in macrophages during inflammation, while increased NOX2 expression is reported in experimental models of colitis and inflammatory bowel disease (IBD) patients. Although there are reductions in AMPK activity in IBD, it remains unclear whether targeted inhibition of NOX2 in the presence of defective AMPK can reduce the severity of colitis. Here, we investigate whether the inhibition of NOX2 ameliorates colitis in mice independent of AMPK activation. Our study identified that VAS2870 (a pan-Nox inhibitor) alleviated dextran sodium sulfate (DSS)-induced colitis in macrophage-specific AMPKβ1-deficient (AMPKβ1 LysM ) mice. Additionally, VAS2870 blocked LPS-induced TLR-4 and NOX2 expression, ROS production, nuclear translocation of NF-κB, and pro-inflammatory cytokine secretion in bone marrow-derived macrophages (BMDMs) from AMPKβ1 LysM mice, whereas sodium salicylate (SS; AMPK β1 activator) did not. Both VAS2870 and SS inhibited LPS-induced NOX2 expression, ROS production, and pro-inflammatory cytokine secretions in bone marrow-derived macrophages (BMDMs) from wildtype (AMPKβ1 fl/fl ) mice but only VAS2870 inhibited these effects of LPSs in AMPKβ1 LysM BMDMs. Furthermore, in macrophage cells (RAW 264.7), both SS and VAS2870 inhibited ROS production and the secretion of pro-inflammatory cytokines and reversed the impaired autophagy induced by LPSs. These data suggest that inhibiting NOX2 can reduce inflammation independent of AMPK in colitis.

Intestinal dysbiosis increases susceptibility to infection through the alteration of metabolic profiles, which increases morbidity. Zinc (Zn) homeostasis in mammals is tightly regulated by 24 Zn transporters. ZIP8 is unique in that it is required by myeloid cells to maintain proper host defense against bacterial pneumonia. In addition, a frequently occurring ZIP8 defective variant ( SLC39A8 rs13107325) is strongly associated with inflammation-based disorders and bacterial infection. In this study, we developed a novel model to study the effects of ZIP8-mediated intestinal dysbiosis on pulmonary host defense independent of the genetic effects. Cecal microbial communities from a myeloid-specific Zip8 knockout mouse model were transplanted into germ-free mice. Conventionalized ZIP8KO-microbiota mice were then bred to produce F1 and F2 generations of ZIP8KO-microbiota mice. F1 ZIP8KO-microbiota mice were also infected with S. pneumoniae, and pulmonary host defense was assessed. Strikingly, the instillation of pneumococcus into the lung of F1 ZIP8KO-microbiota mice resulted in a significant increase in weight loss, inflammation, and mortality when compared to F1 wild-type (WT)-microbiota recipients. Similar defects in pulmonary host defense were observed in both genders, although consistently greater in females. From these results, we conclude that myeloid Zn homeostasis is not only critical for myeloid function but also plays a significant role in the maintenance and control of gut microbiota composition. Further, these data demonstrate that the intestinal microbiota, independent of host genetics, play a critical role in governing host defense in the lung against infection. Finally, these data strongly support future microbiome-based interventional studies, given the high incidence of zinc deficiency and the rs13107325 allele in humans.

Malic acid (MA) is an important flavor acid in fruits and acts as a mediator in a series of metabolic pathways. It is important to understand the factors affecting MA metabolism for fruit flavor improvement and to understand MA-mediated biological processes. However, the metabolic accumulation of MA is controlled by complex heredity and environmental factors, making it difficult to predict and regulate the metabolism of MA. In this study, we carried out a genome-wide association study (GWAS) on MA using eight milestone models with two-environment repeats. A series of associated SNP variations were identified from the GWAS, and 15 high-confidence annotated genes were further predicted based on linkage disequilibrium and lead SNPs. The transcriptome data of candidate genes were explored within different tomato organs as well as various fruit tissues, and suggested specific expression patterns in fruit pericarp. Based on the genetic parameters of population differentiation and SNP distribution, tomato MA content has been more influenced by domestication sweeps and less affected by improvement sweeps in the long-term history of tomato breeding. In addition, genotype × environment interaction might contribute to the difference in domestication phenotypic data under different environments. This study provides new genetic insights into how tomato changed its MA content during breeding and makes available function-based markers for breeding by marker-assisted selection., Competing Interests: The authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Currently, nanomaterials with exceptional antibacterial activity have become an emerging domain in research. The optimization of nanomaterials against infection causing agents is the next step in dealing with the present-day problem of antibiotics. In this research work, Ag 2 O, CoFe 2 O 4 , and Ag 2 O/CoFe 2 O 4 /rGO are prepared by chemical methods. Ag 2 O was prepared by co-precipitation method, while solvothermal technique was utilized for the synthesis of CoFe 2 O 4 . The ternary nanocomposite was synthesized by a simple in situ reduction using a two-step approach. The structural and morphological properties were studied by UV-Vis spectroscopy, X-ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (SEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR). From the X-ray diffraction analysis, the crystallite size is found to be 14 nm, 5 nm, and 6 nm for Ag 2 O, CoFe 2 O 4 , and Ag 2 O/CoFe 2 O 4 /rGO respectively. The synthesized nanomaterials were investigated for antibacterial activities against gram-positive strain Staphylococcus aureus (S. aureus) and gram-negative strain Escherichia coli (E. coli) using Agar well diffusion method. Ag 2 O and CoFe 2 O 4 showed zones of inhibition (ZOI) of 13 mm and 11 mm against gram positive bacteria while 12 mm against gram negative bacteria respectively, while ternary nanocomposite showed 14 mm and 13 mm of ZOI. The antibacterial activity of nanomaterials showed a gradual increment with an increase in the concentration of the materials. Ag 2 O, CoFe 2 O 4 , and Ag 2 O/CoFe 2 O 4 /rGO showed minimum inhibitory concentration (MIC) values of 4.5, 6.5, and 4.5 μg/mL for S. aureus and 6.5, 7.2, and 4.8 μg/mL for E. coli respectively. Minimum bactericidal concentrations were found to be same as the MIC values. Additionally, a time-kill curve analysis was performed and for ternary nanocomposite; the killing response was most effective as the complete killing was achieved at 3 h of incubation at 3-MIC (9.75 μg/mL). These results demonstrate that all the nanomaterials, as a kind of antibacterial material, have a great potential for a wide range of biomedical applications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nickel stannate nanocomposites could be useful for removing organic and toxic water pollutants, such as methyl orange (MO). Aim: The synthesis of a nickel oxide-tin oxide nanocomposite (NiO-SnO 2 NC) via a facile and economically viable approach using a leaf extract from Ficus elastica for the photocatalytic degradation of MO. Methods: The phase composition, crystallinity, and purity were examined by X-ray diffraction (XRD). The particles' morphology was studied using scanning electron microscopy (SEM). The elemental analysis and colored mapping were carried out via energy dispersive X-ray (EDX). The functional groups were identified by Fourier transform infrared spectroscopy (FTIR). UV-visible diffuse reflectance spectroscopy (UV-vis DRS) was used to study the optical properties such as the absorption edges and energy band gap, an important feature of semiconductors to determine photocatalytic applications. The photocatalytic activity of the NiO-SnO 2 NC was evaluated by monitoring the degradation of MO in aqueous solution under irradiation with full light spectrum. The effects of calcination temperature, pH, initial MO concentration, and catalyst dose were all assessed to understand and optimize the physicochemical and photocatalytic properties of NiO-SnO 2 NC. Results: NiO-SnO 2 NC was successfully synthesized via a biological route using F. elastica leaf extract. XRD showed rhombohedral NiO and tetragonal SnO 2 nanostructures and the amorphous nature of NiO-SnO 2 NC. Its degree of crystallinity, crystallite size, and stability increased with increased calcination temperature. SEM depicted significant morphological changes with elevating calcination temperatures, which are attributed to the phase conversion from amorphous to crystalline. The elemental analysis and colored mapping show the formation of highly pure NiO-SnO 2 NC. FTIR revealed a decrease in OH, and the ratio of oxygen vacancies at the surface of the NC can be explained by a loss of its hydrophilicity at increased temperatures. All the NC samples displayed significant absorption in the visible region, and a blue shift is seen and the energy band gap decreases when increasing the calcination temperatures due to the dehydration and formation of compacted large particles. NiO-SnO 2 NC degrades MO, and the photocatalytic performance decreased with increasing calcination temperature due to an increase in the crystallite size of the NC. The optimal conditions for the efficient NC-mediated photocatalysis of MO are 100 °C, 20 mg catalyst, 50 ppm MO, and pH 6. Conclusions: The auspicious performance of the NiO-SnO 2 NCs may open a new avenue for the development of semiconducting p-n heterojunction catalysts as promising structures for removing undesirable organic pollutants from the environment.

Optimization of supply current total harmonic distortion (THD) of multi-pulse AC-DC power converter fed induction motor drive (IMD) is always a challenging issue. Higher amount of supply current THD degrades the input power quality of IMD. The supply current THD should be controlled in such a way so that it adheres the power quality standard of IEEE-519. With the increase of the pulse number of multi-pulse AC-DC converter, supply current THD increases. In this work, an investigation has been carried out on 6-pulse, 12-pulse, 18-pulse, and 24-pulse AC-DC power converters based IMD. A thorough analysis of input current profile, THD, dynamic responses including stator current, speed, torque profile of the induction motor are highlighted in this work with the various load perturbation conditions. This work will provide a message to the industrial community about the proper selection of AC-DC power converter for IMD application considering power quality and circuit configuration issues. All the investigating works are conducted in MATLAB/Simulink platform., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Use of molecular data in human and ecological health risk assessments of industrial chemicals and agrochemicals has been anticipated by the scientific community for many years; however, these data are rarely used for risk assessment. Here, a logic framework is proposed to explore the feasibility and future development of transcriptomic methods to refine and replace the current apical endpoint-based regulatory toxicity testing paradigm. Four foundational principles are outlined and discussed that would need to be accepted by stakeholders prior to this transformative vision being realized. Well-supported by current knowledge, the first principle is that transcriptomics is a reliable tool for detecting alterations in gene expression that result from endogenous or exogenous influences on the test organism. The second principle states that alterations in gene expression are indicators of adverse or adaptive biological responses to stressors in an organism. Principle 3 is that transcriptomics can be employed to establish a benchmark dose-based point of departure (POD) from short-term, in vivo studies at a dose level below which a concerted molecular change (CMC) is not expected. Finally, Principle 4 states that the use of a transcriptomic POD (set at the CMC dose level) will support a human health-protective risk assessment. If all four principles are substantiated, this vision is expected to transform aspects of the industrial chemical and agrochemical risk assessment process that are focused on establishing safe exposure levels for mammals across numerous toxicological contexts resulting in a significant reduction in animal use while providing equal or greater protection of human health. Importantly, these principles and approaches are also generally applicable for ecological safety assessment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology.)

In this paper, we have been study a hybrid nanofluid over an exponentially oscillating vertical flat plate. Therefore the fractional derivatives definition of Caputo-Fabrizio approach is applied to transform the classical model for this hybrid nanofluid to fractional model. Together with an oscillating boundary motion, therefore the heat transfer is cause as a result of the buoyancy force produce due temperature differences between the plate and the fluid. The dimensionless classical model is generalized by transforming it to the time fractional model using Caputo-Fabrizio time fractional derivative. Exact analytical solutions are obtained by using Laplace transform method to the set of dimensionless fractional governing equations, containing the momentum and energy equations subjected to the boundary and initial conditions. Numerical computations and graphical illustrations are used to checked the results of the Caputo-Fabrizio time-fractional parameter, the second-grade parameter, the magnetic parameter and the Grashof numbers on the velocity field. An assessment for time spin-off is shown graphically of integer order versus fractional-order for these non-Newtonian hybrid nanofluid through Mathcad software. The fluid velocity increases for increasing the value of the fractional parameter, second-grade parameter and Grashof number. Also for increasing the values of the MHD parameter the fluid velocity decreases., (© 2022. The Author(s).)

The elemental composition, mineral phases, and crystalline structure of nephrite jade were investigated using calibration-free laser-induced breakdown spectroscopy (CF-LIBS), Raman spectroscopy, and X-ray diffraction (XRD). For compositional analysis, the laser-induced plasma was generated on the surface of nephrite jade. The plasma emissions were then acquired and analyzed, which revealed several elements in the sample, including Si, Mg, Ca, Li, Fe, Al, Na, K, and Ni. The plasma temperature was extracted from the Boltzmann plot before and after two-step self-absorption correction, and used in CF-LIBS calculations to get the elemental concentration. After self-absorption correction, the quantitative results obtained using CF-LIBS were found to be in close agreement with ICP-OES. The Raman spectrum of nephrite jade exhibits Si-O and M-OH stretching vibrations in the regions of 100 cm -1 to 1200 cm -1 and 3600 cm -1 to 3700 cm -1 , respectively, whereas the XRD spectrum revealed the monoclinic crystalline phase of tremolite., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

A simple process based on the dual roles of both magnesium oxide (MgO) and iron oxide (FeO) with boron (B) as precursors and catalysts has been developed for the synthesis of borate composites of magnesium and iron (Mg 2 B 2 O 5 -Fe 3 BO 6 ) at 1200°C. The as-synthesized composites can be a single material with the improved and collective properties of both iron borates (Fe 3 BO 6 ) and magnesium borates (Mg 2 B 2 O 5 ). At higher temperatures, the synthesized Mg 2 B 2 O 5 -Fe 3 BO 6 composite is found thermally more stable than the single borates of both magnesium and iron. Similarly, the synthesized composites are found to prevent the growth of both gram-positive ( Staphylococcus aureus ) and gram-negative ( Escherichia coli ) pathogenic bacteria on all the tested concentrations. Moreover, the inhibitory effect of the synthesized composite increases with an increase in concentration and is more pronounced against S. aureus as compared to E. coli ., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Pervaiz Ahmad et al.)

Artemisinin and its derivatives had played a biocidal role in biomedical remedies, while they were expected to enhance the activity of antibiotics against multiple drug-resistant (MDR) bacteria. The current study evaluated the interaction of artemisinin (ART), dihydroartemisinin (DHA), artesunate (AS), and artemisinic acid (AA) with β-lactam and fluoroquinolones antibiotics against Escherichia coli . Antibiotic strip test ( E -test), Kirby Bauer's disc test (KB method), and broth microdilution method were adopted for susceptibility analysis, while the checkerboard method was applied to assess synergisms. ART, DHA, AS, and AA showed significantly enhanced antibacterial effects of β-lactam antibiotics against different strains of E. coli . The study showed ciprofloxacin to be most effective by presenting the least MIC (0.017125 ± 0.0022 μg/ml), while oxacillin was least effective (MIC 256 μg/ml) against E. coli . Synergism between AA and penicillin G (75%), ampicillin (25%), and oxacillin (50%) was observed in all isolates tested. AA and AS significantly decreased the MIC of ampicillin (-0.912 ± 0.908 μg/ml) and ciprofloxacin (-0.901 ± 0.893 g/ml), respectively. Artemisinin and its derivatives increased antibiotic accumulation within E. coli in a dose-dependent manner. The time-kill assay significantly reduced the bacterial number within 24 h of incubation. The study thus concludes greater room for improvement in enhancing the efficacy of antibiotics if used with artemisinin and its derivatives., 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 Ul Haq, Wang, Guo, Aqib, Muneer, Saqib, Ahmad, Ghafoor, Iftikhar, Chen and Liang.)

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand-receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome., Competing Interests: S.S. reports grants from AstraZeneca, BMS, Janssen, Von Tobel foundation, Fill the Gap, and has served on all institutional advisory board for BMS, AstraZeneca, MSD. N.M. reports personal fees from Takeda Oncology, Pfizer, and Novartis, outside of the submitted work. M.-S.T. reports research grant from Bayer and AstraZeneca, outside the submitted work, and personal fees from AstraZeneca, Amgen, BMS, Daiichi-Sankyo and Lilly, outside the submitted work. D. de Carvalho received research funds from Pfizer and is co-founder and shareholder of Adela Inc. S.V.B. is inventor on patents related to cell-free DNA mutation and methylation analysis technologies that have been licensed to Roche and Adela, respectively, and is co-founder of, has ownership in, and serves in a leadership role at Adela. G.L. reports grants and personal fees from AstraZeneca and Takeda; grants from Boehringer Ingelheim; and personal fees from Hoffman La Roche, Merck, Bristol Myers Squibb, and Pfizer outside the submitted work. B.H.L. reports grants from Pfizer; and grants, personal fees, and non-financial support from AstraZeneca outside the submitted work., (© 2022 The Author(s).)

Objectives: A possible association between blood group systems (ABO and Rh) and coronavirus disease 2019 (COVID-19) severity has recently been investigated by various studies with conflicting results. However, due to variations in the prevalence of the ABO and Rh blood groups in different populations, their association with COVID-19 might be varied as well. Therefore, we conducted this study on Libyan participants to further investigate this association and make population-based data available to the worldwide scientific community., Methods: In this case-control study, ABO and Rh blood groups in 419 confirmed COVID-19 cases in Zawia, Libya, and 271 healthy controls were compared using descriptive statistics and χ 2 tests., Results: Blood group A was significantly more prevalent in patients with severe COVID-19 (64/125; 51.2%) than in patients with nonsevere COVID-19 (108/294, 36.7%) (P < .034), whereas the O blood group prevalence was higher in nonsevere COVID-19 cases (131/294, 44.5%) compared with severe cases (43/125, 34.4%) (P < .001)., Conclusions: The results showed a significant association between blood group A and the severity of COVID-19, whereas patients with blood group O showed a low risk of developing severe COVID-19 infection. No significant association was found between Rh and susceptibility/severity of the disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this work, graphene oxide (GO) and its reduced graphene oxide-zinc oxide nanocomposite (rGO-ZnO) was used for the removal of Cr (VI) from aqueous medium. By employing a variety of characterization techniques, morphological and structural properties of the adsorbents were determined. The adsorption study was done by varying concentration, temperature, pH, time, and amount of adsorbent. The results obtained confirmed that rGO-ZnO is a more economical and promising adsorbent for removing Cr (VI) as compared to GO. Kinetic study was also performed, which suggested that sorption of Cr (VI) follows the pseudo-first-order model. For equilibrium study, non-linear Langmuir was found a better fitted model than its linearized form. The maximum adsorption capacity calculated for GO and rGO-ZnO nanocomposite were 19.49 mg/g and 25.45 mg/g, respectively. Endothermic and spontaneous nature of adsorption was detected with positive values of ΔS (change in entropy), which reflects the structural changes happening at the liquid/solid interface.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT., Methods: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m 2 ., Results: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population., Conclusions: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood., Competing Interests: Competing interests: LP declares funding from the National Institute for Health Research (NIHR) and Kidney Research UK (KRUK). BCR declares funding from KRUK, honoraria from Alexion Pharmaceuticals and Magnolia Innovation, and consultancy payment from Chiesi. MM reports previous honoraria and travel expenses from Alexion. SM declares a role as head of the UK Renal Registry Audit and Informatics group. KT declares a role as clinical lead of the National Institute for Health and Care Excellence Medical Technologies Advisory Committee during the study period. DN declares funding/payment from the Health Foundation, UK Kidney Association, Chiang Mai University and GSK., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Governments around the globe are trying to find sustainable solutions for lessening pressure on natural resources and reducing carbon emissions. Daily household consumption of food, energy, and water has an impact on stocks of natural resources, environmental quality, and climate change. Households have significant potential for increasing conservation actions for efficient use of natural resources and greenhouse gas emissions. Households could contribute to a clean and healthy environment by adopting sustainable household practices through lower per capita consumption and carbon emissions. This study explored the role of different sustainable household consumption practices in promoting a clean environment as well as the factors affecting the adoption of these practices in Pakistan. Factor analysis and an ordered probit model were used to analyze the data from 1424 participants chosen through a multistage random sampling technique. The factor analysis identified 35 sustainable household practices for sustainable consumption. These 35 practices were grouped into the underlying factors of "Food" (14 items), "Energy" (12 items), and "Water" (9 items). The results from the econometric model showed a significant relationship between gender, education, residential area, family size, and income and the adoption of sustainable household consumption practices. Statistically, higher levels of reported sustainable consumption practices were apparent among females, households living in urban areas, more educated people, individuals of large family sizes, and more affluent households. Therefore, public policies for taking care of the environment need to put households at the center while at the same time promoting mass uptake of sustainable consumption practices related to food, energy, and water. In addition, the sector-specific policies also need to be augmented through focus on household-level consumption and production dynamics for achieving the UN's SDGs.