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Phytotherapy has rendered a new insight towards the treatment of various cancers, including oral cancer with fewer side effects, over the traditional chemotherapeutic drugs to overcome chemoresistance. Shikonin (Shk) is a natural biologically active alkaloid found in the Lithospermum erythrorhizon plant's root. It has potent cytotoxic activities against various cancers. Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC 50 ) at 0.5 µM for SCC9 and 1.25 µM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer., (© 2024 Wiley Periodicals LLC.)

Chemotherapeutics are most often used to treat cancer, but side effects, drug resistance, and toxicity often compromise their effectiveness. In contrast, phytocompound plumbagin possesses a distinct pleiotropic nature, targeting multiple signaling pathways, such as ROS generation, cell death, cellular proliferation, metastasis, and drug resistance, and is shown to enhance the efficacy of chemotherapeutic drugs. Plumbagin has been shown to act synergistically with various chemotherapeutic drugs and enhance their efficacy in drug-resistant cancers. The pleiotropic nature is believed to be due to plumbagin's unique structure, which contains a naphthoquinone ring and a hydroxyl group responsible for plumbagin's various biological responses. Despite limitations such as restricted bioavailability and delivery, recent developments aim to address these challenges and harness the potential of plumbagin as an anticancer therapeutics. This review delves into the structural aspect of the plumbagin molecule contributing to its pleiotropic nature, explores the diverse mechanism that it targets, and discusses emerging strategies to overcome its limitations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Exosomes play a pivotal part in cancer progression and metastasis by transferring various biomolecules. Recent research highlights their involvement in tumor microenvironment remodeling, mediating metastasis, tumor heterogeneity and drug resistance. The unique cargo carried by exosomes garners the interest of researchers owing to its potential as a stage-specific biomarker for early cancer detection and its role in monitoring personalized treatment. However, unanswered questions hinder a comprehensive understanding of exosomes and their cargo in this context. This review discusses recent advancements and proposes novel ideas for exploring exosomes in cancer progression, aiming to deepen our understanding and improve treatment approaches., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phytocompounds have shown hopeful results in cancer therapy. Piperlongumine (PIP), a naturally derived bioactive alkaloid found in our dietary spice, exhibits promising pharmacological relevance including anticancer activity. This study reconnoitred the anti-lung cancer effect of PIP and the allied mechanisms, in vitro and ex vivo. The cytotoxic, anti-proliferative, and apoptotic effects of PIP on lung cancer cells (LCC) were checked via cell viability, colony formation, cell migration, invasion, comet assay, and various staining techniques. Further, multicellular spheroids assay explored the anti-lung cancer potential of PIP, ex vivo. Preliminary results explored that PIP exerts selective cytotoxic and anti-proliferative effects on LCC by DNA damage and cell cycle arrest. PIP remarkably escalated the cellular and mitochondrial reactive oxygen species (ROS) generation and promoted dissipation of mitochondrial membrane potential (MMP), which triggers activation of caspase-dependent apoptotic pathway in LCC. Mechanistically, PIP showed F-actin deformation mediated significant anti-migratory and anti-invasive activity against LCC. Herein, we also found that F-actin dis-organization modulates the expression of epithelial to mesenchymal transition (EMT) markers and inhibits the expression of stemness marker proteins, like SOX9, CD-133, and CD-44. Moreover, PIP effectively reduced the size of spheroids with strong apoptotic and cytotoxic effects, ex vivo. This has been the first study to discover the high expression of SOX9 supporting the survival of LCC, whereas its inhibition induces higher sensitivity to PIP treatment. This study concludes a newer therapeutic agent (PIP) with promising anticancer activity against LCC by escalating ROS and attenuating MMP, stemness, and EMT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Visible-light-driven photocatalytic oxidation by photogenerated holes has immense potential for environmental remediation applications. While the electron-mediated photoreduction reactions are often at the spotlight, active holes possess a remarkable oxidation capacity that can degrade recalcitrant organic pollutants, resulting in nontoxic byproducts. However, the random charge transfer and rapid recombination of electron-hole pairs hinder the accumulation of long-lived holes at the reaction center. Herein, a novel method employing defect-engineered indium (In) single-atom photocatalysts with nitrogen vacancy (Nv) defects, dispersed in carbon nitride foam (In-Nv-CNF), is reported to overcome these challenges and make further advances in photocatalysis. This Nv defect-engineered strategy produces a remarkable extension in the lifetime and an increase in the concentration of photogenerated holes in In-Nv-CNF. Consequently, the optimized In-Nv-CNF demonstrates a remarkable 50-fold increase in photo-oxidative degradation rate compared to pristine CN, effectively breaking down two widely used antibiotics (tetracycline and ciprofloxacin) under visible light. The contaminated water treated by In-Nv-CNF is completely nontoxic based on the growth of Escherichia coli. Structural-performance correlations between defect engineering and long-lived hole accumulation in In-Nv-CNF are established and validated through experimental and theoretical agreement. This work has the potential to elevate the efficiency of overall photocatalytic reactions from a hole-centric standpoint., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Lithium-ion batteries (LIBs) are widely used as power storage systems in electronic devices and electric vehicles (EVs). Recycling of spent LIBs is of utmost importance from various perspectives including recovery of valuable metals (mostly Co and Li) and mitigation of environmental pollution. Recycling methods such as direct recycling, pyrometallurgy, hydrometallurgy, bio-hydrometallurgy (bioleaching) and electrometallurgy are generally used to resynthesise LIBs. These methods have their own benefits and drawbacks. This manuscript provides a critical review of recent advances in the recycling of spent LIBs, including the development of recycling processes, identification of the products obtained from recycling, and the effects of recycling methods on environmental burdens. Insights into chemical reactions, thermodynamics, kinetics, and the influence of operating parameters of each recycling technology are provided. The sustainability of recycling technologies ( e.g. , life cycle assessment and life cycle cost analysis) is critically evaluated. Finally, the existing challenges and future prospects are presented for further development of sustainable, highly efficient, and environmentally benign recycling of spent LIBs to contribute to the circular economy.

Background: In recent decades, phytotherapy has remained as a key therapeutic option for the treatment of various cancers. Evodiamine, an excellent phytocompound from Evodia fructus, exerts anticancer activity in several cancers by modulating drug resistance. However, the role of evodiamine in cisplatin-resistant NSCLC cells is not clear till now. Therefore, we have used evodiamine as a chemosensitizer to overcome cisplatin resistance in NSCLC., Methods: Here, we looked into SOX9 expression and how it affects the cisplatin sensitivity of cisplatin-resistant NSCLC cells. MTT and clonogenic assays were performed to check the cell proliferation. AO/EtBr and DAPI staining, ROS measurement assay, transfection, Western blot analysis, RT-PCR, Scratch & invasion, and comet assay were done to check the role of evodiamine in cisplatin-resistant NSCLC cells., Results: SOX9 levels were observed to be higher in cisplatin-resistant A549 (A549CR) and NCI-H522 (NCI-H522CR) compared to parental A549 and NCI-H522. It was found that SOX9 promotes cisplatin resistance by regulating β-catenin. Depletion of SOX9 restores cisplatin sensitivity by decreasing cell proliferation and cell migration and inducing apoptosis in A549CR and NCI-H522CR. After evodiamine treatment, it was revealed that evodiamine increases cisplatin-induced cytotoxicity in A549CR and NCI-H522CR cells through increasing intracellular ROS generation. The combination of both drugs also significantly inhibited cell migration by inhibiting epithelial to mesenchymal transition (EMT). Mechanistic investigation revealed that evodiamine resensitizes cisplatin-resistant cells toward cisplatin by decreasing the expression of SOX9 and β-catenin., Conclusion: The combination of evodiamine and cisplatin may be a novel strategy for combating cisplatin resistance in NSCLC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Rv1176c of Mycobacterium tuberculosis H37Rv belongs to the PadR-s1 subfamily of the PadR family of protein. Rv1176c forms a stable dimer in solution. Its stability is characterized by a thermal melting transition temperature (Tm) of 39.4 °C. The crystal structure of Rv1176c was determined at a resolution of 2.94 Å, with two monomers in the asymmetric unit. Each monomer has a characteristic N-terminal winged-helix-turn-helix DNA-binding domain. Rv1176c C-terminal is a coiled-coil dimerization domain formed of α-helices α5 to α7. In the Rv1176c dimer, there is domain-swapping of the C-terminal domain in comparison to other PadR homologs. In the dimer, there is a long inter-subunit tunnel in which different ligands can bind. Rv1176c was found to bind to the promoter region of its own gene with high specificity. M. smegmatis MC 2 155 genome lacks homolog of Rv1176c. Therefore, it was used as a surrogate to characterize the functional role of Rv1176c. Expression of Rv1176c in M. smegmatis MC 2 155 cells imparted enhanced tolerance towards oxidative stress. Rv1176c expressing M. smegmatis MC 2 155 cells exhibited enhanced intracellular survival in J774A.1 murine macrophage cells. Overall, our studies demonstrate Rv1176c to be a PadR-s1 subfamily transcription factor that can moderate the effect of oxidative stress., 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. Published by Elsevier B.V.)

Lung cancer remains a significant global health concern with limited treatment options and poor prognosis, particularly in advanced stages. Small extracellular vesicles such as exosomes, secreted by cancer cells, play a pivotal role in mediating drug resistance in lung cancer. Exosomes have been found to facilitate intercellular communication by transferring various biomolecules between cancer cells and their microenvironment. Additionally, exosomes can transport signaling molecules promoting cancer cell survival and proliferation conferring resistance to chemotherapy. Moreover, exosomes can modulate the tumor microenvironment by inducing phenotypic changes hindering drug response. Understanding the role of exosomes in mediating drug resistance in lung cancer is crucial for developing novel therapeutic strategies and biomarkers to overcome treatment limitations. In this review, we summarize the current knowledge on conventional and emerging drug resistance mechanisms and the involvement of exosomes as well as exosome-mediated factors mediating drug resistance in lung cancer., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

The direct impacts of climate change involve a multitude of phenomena, including rising sea levels, intensified severe weather events such as droughts and flooding, increased temperatures leading to wildfires, and unpredictable fluctuations in rainfall. This comprehensive review intends to examine firstly the probable consequences of climate change on extreme weather events such as drought, flood and wildfire. This review subsequently examines the release and transformation of contaminants in terrestrial, aquatic, and atmospheric environments in response to extreme weather events driven by climate change. While drought and flood influence the dynamics of inorganic and organic contaminants in terrestrial and aquatic environments, thereby influencing their mobility and transport, wildfire results in the release and spread of organic contaminants in the atmosphere. There is a nascent awareness of climate change's influence of climate change-induced extreme weather events on the dynamics of environmental contaminants in the scientific community and decision-making processes. The remediation industry, in particular, lags behind in adopting adaptive measures for managing contaminated environments affected by climate change-induced extreme weather events. However, recognizing the need for assessment measures represents a pivotal first step towards fostering more adaptive practices in the management of contaminated environments. We highlight the urgency of collaboration between environmental chemists and climate change experts, emphasizing the importance of jointly assessing the fate of contaminants and rigorous action to augment risk assessment and remediation strategies to safeguard the health of our environment., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Exosomes have been the hidden treasure of the cell in terms of cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by the parent cells hold promising aspects in cancer diagnosis and therapy. NEx has low immunogenicity, high biocompatibility, low toxicity and high stability which enables them to be an ideal prognostic biomarker in cancer diagnosis. However, due to heterogeneity, NEx lacks specificity and accuracy to be used as therapeutic drug delivery vehicle in cancer therapy. Transforming these NEx with their innate structure and multiple receptors to engineered exosomes (EEx) can provide better opportunities in the field of cancer theranostics. The surface of the NEx exhibits numeric receptors which can be modified to pave the direction of its therapeutic drug delivery in cancer therapy. Through surface membrane, EEx can be modified with increased drug loading potentiality and higher target specificity to act as a therapeutic nanocarrier for drug delivery. This review provides insights into promising aspects of NEx as a prognostic biomarker and drug delivery tool along with its need for the transformation to EEx in cancer theranostics. We have also highlighted different methods associated with NEx transformations, their nano-bio interaction with recipient cells and major challenges of EEx for clinical application in cancer theranostics., (© 2024 Wiley-VCH GmbH.)

Enolase, a ubiquitous enzyme, catalyzes the reversible conversion of 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP) in the glycolytic pathway of organisms of all three domains of life. The underlying mechanism of the 2PG to PEP conversion has been studied in great detail in previous work, however that of the reverse reaction remains to be explored. Here we present structural snapshots of Mycobacterium tuberculosis (Mtb) enolase in apo, PEP-bound and two 2PG-bound forms as it catalyzes the conversion of PEP to 2PG. The two 2PG-bound complex structures differed in the conformation of the bound product (2PG) viz the widely reported canonical conformation and a novel binding pose, which we refer to here as the alternate conformation. Notably, we observed two major differences compared with the forward reaction: the presence of Mg B is non-obligatory for the reaction and 2PG assumes an alternate conformation that is likely to facilitate its dissociation from the active site. Molecular dynamics studies and binding free energy calculations further substantiate that the alternate conformation of 2PG causes distortions in both metal ion coordination and hydrogen-bonding interactions, resulting in an increased flexibility of the active-site loops and aiding product release. Taken together, this study presents a probable mechanism involved in PEP to 2PG catalysis that is likely to be mediated by the conformational change of 2PG at the active site., (open access.)

Biodegradable microplastics (BMPs) are considered to be environmentally friendly compared to non-biodegradable plastics (NMPs). However, BMPs are likely to become toxic during their transport because of the adsorption of pollutants (e.g., heavy metals) onto them. This study investigated the uptake of six heavy metals (Cd 2+ , Cu 2+ , Cr 3+ , Ni 2+ , Pb 2+ , and Zn 2+ ) by a common BMPs (polylactic acid (PLA)) and compared their adsorption characteristics to those of three types of NMPs (polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC)) for the first time. The order of heavy metal adsorption capacity among the four MPs was PE > PLA > PVC > PP. The findings suggest that BMPs contained more toxic heavy metals than some NMPs. Among the six heavy metals, Cr 3+ showed considerably stronger adsorption than other heavy metals in both BMPS and NMPs. The adsorption of heavy metals on MPs can be well explained using the Langmuir isotherm model, while the adsorption kinetic curves showed the best fit to the pseudo-second-order kinetic equation. Desorption experiments revealed that BMPs released a higher percentage of heavy metals (54.6-62.6%) in the acidic environment in a shorter time (~ 6 h) compared to NMPs. Overall, this study provides insights into interactions of BMPs and NMPs with heavy metals and their removal mechanisms in aquatic environment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Oral cancer is the sixteenth most prevalent cancer in the world and the third-most in India. Despite of several treatment modalities, the cure rate of oral cancer is still low due to drug resistance mechanisms, which are caused by many reasons. It is necessary to improve the existing treatment strategies and discover neoteric therapy to kill cancer cells, which will give oral cancer's cure rate more success. So this review aims to delineate the molecular mechanisms behind cisplatin resistance, specifically the role of the tumor microenvironment, extracellular vesicles, and altered signaling pathways and its overcoming strategies in oral cancer., Design: This review was designed by searching words like cancer, oral cancer, cisplatin-resistance, tumor microenvironment, aberrant signalings, and extracellular vesicles, overcoming strategies for cisplatin resistance in databases like PubMed, Google Scholar, web science, and Scopus. Data available in this review is from 2017 to 2021., Results: After searching too much data, we found these 98 data appropriate for our review. From these data, we found that tumor microenvironment, extracellular vesicles, and altered signaling pathways like PI3K/AKT, EGFR, NOTCH, Ras, PTEN, Nf-κβ, and Wnt signaling have a crucial role in resistance development towards cisplatin in oral cancer., Conclusions: Lastly, this review explores the alternative strategies to overcome cisplatin resistance likely, the combination therapy and targeted therapy by combining more than one chemotherapeutic drug or inhibitors of signaling pathways and also by using nanoparticle loaded drugs that will reduce the drug efflux, which gives new treatment strategies., 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 Elsevier Ltd. All rights reserved.)

Hydrothermal process is an emerging technology that contributes to sustainable production of biomass-derived chemicals, fuels, and materials. This technology uses hot compressed water to convert various biomass feedstocks including recalcitrant organic compounds in biowastes into desired solid, liquid, and gaseous products. In recent years, considerable progress has been made in the hydrothermal conversion of lignocellulosic as well as nonlignocellulosic biomass to value-added products and bioenergy to fulfill the principles of circular economy. However, it is important to assess hydrothermal processes in terms of their capabilities and limitations from different sustainability aspects so that further advances can be made toward improvement of their technical maturity and commercialization potential. The key aims of this comprehensive review are to (a) explain the inherent properties of biomass feedstocks and physio-chemical characteristics of their bioproducts, (b) elucidate related transformation pathways, (c) clarify the role of hydrothermal process for biomass conversion, (d) evaluate the capability of hydrothermal treatment coupled with other technologies for producing novel chemicals, fuels and materials, (e) explore different sustainability assessments of hydrothermal processes for potential large-scale applications, and (f) offer our perspectives to facilitate the transition from a primarily petro-based to an alternative biobased society in the context of changing climate.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Receptor binding domain (RBD) of SARS-CoV-2 is a prime vaccine target against which neutralizing antibody responses are directed. Purified RBD as a vaccine candidate warrants administration of multiple doses along with adjuvants and use of delivery systems to improve its immunogenicity. The present investigation examines the immunogenicity of RBD delivered by biodegradable polymer particles from single dose administration. Mice upon single point immunization of RBD entrapped microparticles generated improved antibody response. The polymer microparticles showed better temperature stability and could be stored at 37 degrees for one month without any considerable loss of immunogenicity. Further, immunization with microparticles could elicit memory antibody response upon challenge after four months of single dose administration. Thus, using microparticles entrapping RBD as a vaccine candidate confer improved immunogenicity, temperature stability and recall response. These thermostable microparticles seem to be a potentially cost-effective approach which can help in dose reduction, provide a wider access of vaccines and accelerate the end of global pandemic., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Spent lithium-ion batteries (LIBs) are increasingly generated due to their widespread use for various energy-related applications. Spent LIBs contain several valuable metals including cobalt (Co) and lithium (Li) whose supply cannot be sustained in the long-term in view of their increased demand. To avoid environmental pollution and recover valuable metals, recycling of spent LIBs is widely explored using different methods. Bioleaching (biohydrometallurgy), an environmentally benign process, is receiving increased attention in recent years since it utilizes suitable microorganisms for selective leaching of Co and Li from spent LIBs and is cost-effective. A comprehensive and critical analysis of recent studies on the performance of various microbial agents for the extraction of Co and Li from the solid matrix of spent LIBs would help for development of novel and practical strategies for effective extraction of precious metals from spent LIBs. Specifically, this review focuses on the current advancements in the application of microbial agents namely bacteria (e.g., Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans ) and fungi (e.g., Aspergillus niger ) for the recovery of Co and Li from spent LIBs. Both bacterial and fungal leaching are effective for metal dissolution from spent LIBs. Among the two valuable metals, the dissolution rate of Li is higher than Co. The key metabolites which drive the bacterial leaching include sulfuric acid, while citric acid, gluconic acid and oxalic acid are the dominant metabolites in fungal leaching. The bioleaching performance depends on both biotic (microbial agents) and abiotic factors (pH, pulp density, dissolved oxygen level and temperature). The major biochemical mechanisms which contribute to metal dissolution include acidolysis, redoxolysis and complexolysis. In most cases, the shrinking core model is suitable to describe the bioleaching kinetics. Biological-based methods (e.g., bioprecipitation) can be applied for metal recovery from the bioleaching solution. There are several potential operational challenges and knowledge gaps which should be addressed in future studies to scale-up the bioleaching process. Overall, this review is of importance from the perspective of development of highly efficient and sustainable bioleaching processes for optimum resource recovery of Co and Li from spent LIBs, and conservation of natural resources to achieve circular economy., 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 Biswal and Balasubramanian.)

Silver (Ag), a naturally occurring, rare and precious metal, is found in major minerals such as cerargyrite (AgCl), pyrargyrite (Ag 3 SbS 3 ), proustite (Ag 3 AsS 3 ), and stephanite (Ag 5 SbS 4 ). From these minerals, Ag is released into soil and water through the weathering of rocks and mining activities. Silver also enters the environment by manufacturing and using Ag compounds in electroplating and photography, catalysts, medical devices, and batteries. With >400 t of Ag NPs produced yearly, Ag NPs have become a rapidly growing source of anthropogenic Ag input in the environment. In soils and natural waters, most Ag is sorbed to soil particles and sediments and precipitated as oxides, carbonates, sulphides, chlorides and hydroxides. Silver and its compounds are toxic, and humans and other animals are exposed to Ag through inhalation of air and the consumption of Ag-contaminated food and drinking water. Remediation of Ag-contaminated soil and water sources can be achieved through immobilization and mobilization processes. Immobilization of Ag in soil and groundwater reduces the bioavailability and mobility of Ag, while mobilization of Ag in the soil can facilitate its removal. This review provides an overview of the current understanding of the sources, geochemistry, health hazards, remediation practices and regulatory mandates of Ag contamination in complex environmental settings, including soil and aquatic ecosystems. Knowledge gaps and future research priorities in the sustainable management of Ag contamination in these settings are also discussed., 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 Elsevier B.V. All rights reserved.)

Recently, increasing attention is given on the resource and energy recovery (e.g. short-chain fatty acids (SCFAs) and phosphorus (P)) from waste active sludge (WAS) under the "Dual carbon goals". This study compared four thiosulfate-assisted Fe 2+ /persulfate (TAFP) pretreatments of WAS, i.e. in-situ TAFP pretreatment (R1), ex-situ TAFP pretreatment (R2), in-situ TAFP pretreatment + pH adjustment (R3) and ex-situ TAFP pretreatment + pH adjustment (R4), followed by anaerobic fermentation over 20 days for SCFA production and P recovery. The results showed that the maximal SCFA yields in R1-4 were 730.2 ± 7.0, 1017.4 ± 13.9, 860.1 ± 40.8, and 1072.0 ± 33.2 mg COD/L, respectively, significantly higher than Control (365.2 ± 17.8 mg COD/L). The findings indicated that TAFP pretreatments (particularly ex-situ TAFP pretreatment) enhanced WAS disintegration and provided more soluble organics and subsequently promoted SCFA production. The P fractionation results showed the non-apatite inorganic P increased from 11.6 ± 0.2 mg P/g TSS in Control to 11.8 ± 0.5 (R1), 12.4 ± 0.3 (R2), 13.2 ± 0.7 (R3) and 12.7 ± 0.7 mg P/g TSS (R4), suggesting TAFP pretreatments improved P bioavailability due to formation of Fe-P mineral (Fe(H 2 PO 4 ) 2 ·2H 2 O), which could be recycled through magnetic separators. These findings were further strengthened by the analysis of microbial community and related marker genes that fermentative bacteria containing SCFA biosynthesis genes (e.g. pyk, pdhA, accA and accB) and iron-reducing bacteria containing iron-related proteins (e.g. feoA and feoB) were enriched in R1-4 (dominant in ex-situ pretreatment systems, R2 and R4). Economic evaluation further verified ex-situ TAFP pretreatment was cost-effective and a better strategy over other operations to treat WAS for SCFA production and P recovery., 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 Elsevier B.V. All rights reserved.)

Given the paucity of antiviral treatments for monkeypox disease, caused by the Monkeypox virus (MPXV), there is a pressing need for the development/identification of new drugs to treat the infection. MPXV possesses a linear dsDNA genome that is replicated by a DNA replication complex of which DNA polymerase (DPol) forms an important component. Owing to the importance of DPol in the viral life cycle, identifying/designing small molecules abolishing its function could yield new antivirals. In this study, we first used the AlphaFold artificial intelligence program to model the 3D structure of the MPXV DPol; like the fold of DPol from other organisms, the MPXV DPol structure has the characteristic exonuclease, thumb, palm, and fingers sub-domains arrangement. Subsequently, we have identified several inhibitors through virtual screening of ZINC and antiviral libraries. Molecules with phenyl scaffold along with alanine-based and tetrazole-based molecules showed the best docking score of -8 to -10 kcal/mol. These molecules bind in the palm and fingers sub-domains interface region, which partially overlaps with the DNA binding path. The delineation of DPol/inhibitor interactions showed that majorly active site residues ASP549, ASP753, TYR550, ASN551, SER552, and ASN665 interact with the inhibitors. These compounds exhibit good Absorption, Distribution, Metabolism and Excretion properties., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Evodiamine is a major alkaloid component found in the fruit of Evodia rutaecarpa. It shows the anti-proliferative potential against a wide range of cancers by suppressing cell growth, invasion, and metastasis and inducing apoptosis both in vitro and in vivo. Evodiamine shows its anticancer potential by modulating aberrant signaling pathways. Additionally, the review focuses on several therapeutic implications of evodiamine, such as epigenetic modification, cancer stem cells, and epithelial to mesenchymal transition. Moreover, combinatory drug therapeutics along with evodiamine enhances the anticancer efficacy of chemotherapeutic drugs in various cancers by overcoming the chemo resistance and radio resistance shown by cancer cells. It has been widely used in preclinical trials in animal models, exhibiting very negligible side effects against normal cells and effective against cancer cells. The pharmacokinetic and pharmacodynamics-based collaborations of evodiamine are also included. Due to its poor bioavailability, synthetic analogs of evodiamine and its nano capsule have been formulated to enhance its bioavailability and reduce toxicity. In addition, this review summarizes the ongoing research on the mechanisms behind the antitumor potential of evodiamine, which proposes an exciting future for such interests in cancer biology., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Electrochemical pretreatment (EPT) is an efficient technology to improve volatile fatty acids (VFAs) production during anaerobic fermentation of waste activated sludge (WAS). This study investigated the co-effects of different current intensities, electrolyte NaCl dosage and pretreatment time for promoting VFAs production. The results showed that it was considerably enhanced by 51.6 % when EPT was performed at 1.0 A, 1.0 g/L and 60 min, and response surface methodology strategy adjusted the optimal EPT conditions to 1.0 A, 1.2 g/L and 66 min. The potential mechanisms were proposed that EPT at optimal conditions greatly enhanced solubilization and hydrolysis of WAS and selectively inactivated methanogens, causing the enrichment of acidogenic bacteria (i.e., Lactobacillus, Saccharimonadales, Tetrasphaera and Prevotella) due to generated reactive chlorine species. Finally, the economic analysis indicated the promising application potential with the profit of EPT at optimal conditions increasing by 36.0 %., 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 © 2022 Elsevier Ltd. All rights reserved.)

Selective fluorescence imaging of actin protein hugely depends on the fluorescently labeled actin-binding domain (ABD). Thus, it is always a challenging task to image the actin protein ( in vivo or in vitro ) directly with an ABD-free system. To overcome the limitations of actin imaging without an ABD, we have designed a facile and cost-effective red fluorescent coumarin dye 7-hydroxy-4-methyl-8-(4-(2-oxo-2 H -chromen-3-yl)thiazol-2-ylimino)methyl-2 H -chromen-2-one ( CTC ) for actin binding. The selective binding of the dye was investigated using the gut and eye of the model organism Drosophila melanogaster and C2C12 and SCC-9 cell lines. Our result suggests two major advantages of CTC over the dyes presently used for imaging actin proteins. First, the dye can bind to actin efficiently without any secondary intermediate. Second, it is much more stable at room temperature and exhibits excellent photostability. To the best of our knowledge, this is the first fluorescent dye that can bind to the actin protein without employing any secondary intermediate/actin-binding domain. These findings could pave the way for many biologists and physicists to successfully employ the CTC dye for imaging and tracking actin proteins by fluorescence microscopy in various in vivo and in vitro systems.

Evodiamine (EVO), a natural dietary alkaloid extracted from the roots of the Evodia rutaecarpa, has shown anticancer activities. Here, we have investigated EVO's role in inhibiting cell proliferation and migration in A549 and NCI-H522 lung cancer cells. EVO decreased the cell viability in A549 and NCI-H522 cells in a dose- and time-dependent manner. It also induced apoptosis by downregulating the expression of antiapoptotic Bcl-2 and upregulating the expression of cleaved caspase-3 and PARP. In addition, the treatment of EVO elevated the level of reactive oxygen species (ROS) generation inside the cells to induce the cell death pathways. In contrast, the pretreatment of ROS scavenger, N-acetyl cysteine, reverses the effect of EVO and attenuates cell death. Moreover, excess ROS generation in response to EVO resulted in the depletion of mitochondrial membrane potential. Furthermore, it induced DNA damage and arrested the cell cycle at the G2/M phase in A549 and NCI-H522 cells. Our study also investigated that EVO significantly suppressed tumorigenicity by inhibiting colony formation and tumorsphere formation. However, the treatment of EVO downregulated the cancer stem cell markers CD44 and CD133 in non-small-cell lung cancer. The inhibitory effect of EVO on cell invasion was mediated by altering the expression of E-cadherin, ZO-1, N-cadherin, and Vimentin. Additionally, we have revealed that EVO treatment showed downregulation of SOX9, an upstream component of β-catenin. Lastly, we have demonstrated that EVO targets the SOX9-β-catenin axis by reducing SOX9 and β-catenin expression. These findings suggested that EVO could be a promising agent for treating human lung cancer., (© 2022 Wiley Periodicals LLC.)

The dysregulated expression of the transcription factor (TF) Sry-related HMG box 9 (SOX9) has been extensively correlated with various biological effects, including the initiation and progression of cancer. Differential expression of SOX9 has been positively correlated with cancer cell growth, invasion, migration, metastasis, and therapy resistance. Studies showed that expression of SOX9 affects the expression of various miRNAs and vice versa, resulting in the development of cancer drug resistance. However, modulating the expression of SOX9 reverses drug resistance by modulating the expression of miRNAs. Therefore, in this review, we summarize current research focusing on SOX9 as a cancer therapeutic target and a prognostic biomarker of cancer drug resistance., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest relating to the submission of this review., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Excess nitrogen in stormwater degrades surface water quality via eutrophication and related processes. Bioretention has been recognized as a highly effective low-impact development (LID) technology for the management of high runoff volumes and reduction of nitrogen (N) pollutants through various mechanisms. This paper provides a comprehensive and critical review of recent developments on the biological N removal processes occurring in bioretention systems. The key plant- and microbe-mediated N transformation processes include assimilation (N uptake by plants and microbes), nitrification, denitrification, and anammox (anaerobic ammonia oxidation), but denitrification is the major pathway of permanent N removal. Overall, both laboratory- and field-scale bioretention systems have demonstrated promising N removal performance (TN: >70%). The phyla Bacteroidetes and Proteobacteria are the most abundant microbial communities found to be enriched in biofilter media. Furthermore, the denitrifying communities contain several functional genes (e.g., nirK / nirS , and nosZ ), and their concentrations increase near the surface of media depth. The N removal effectiveness of bioretention systems is largely impacted by the hydraulics and environmental factors. When a bioretention system operates at: low hydraulic/N loading rate, containing a saturation zone, vegetated with native plants, having deeper and multilayer biofilter media with warm climate temperature and wet storm events periods, the N removal efficiency can be high. This review highlights shortcomings and current knowledge gaps in the area of total nitrogen removal using bioretention systems, as well as identifies future research directions on this topic.

The unintended crystallization of proteins which generally originate from the expression host instead of the target recombinant proteins is periodically reported. Despite the massive technological advances in the field, assigning a structural model to the corresponding diffraction data is not a trivial task. Here, the structure of acyl-carrier protein synthase (AcpS) from Mycobacterium smegmatis (msAcpS), which crystallized inadvertently in an experimental setup to grow crystals of a Mycobacterium tuberculosis protein using M. smegmatis as an expression system, is reported. After numerous unsuccessful attempts to solve the structure of the target protein by the molecular-replacement method no convincing solutions were obtained, indicating that the diffraction data may correspond to a crystal of an artifactual protein, which was finally identified by the Sequence-Independent Molecular replacement Based on Available Databases (SIMBAD) server. The msAcpS structure was solved at 2.27 Å resolution and structural analysis showed an overall conserved fold. msAcpS formed a trimeric structure similar to those of other reported structures of AcpS from various organisms; however, the residues involved in trimer formation are not strictly conserved. An unrelated metal ion (Ni 2+ ), which was possibly incorporated during protein purification, was observed in the proximity of His49 and His116. Structural and sequence differences were observed in the loop connecting the α3 and α4 helices that is responsible for the open and closed conformations of the enzyme. Moreover, the structural analysis of msAcpS augments the current understanding of this enzyme, which plays a crucial role in the functional activation of acyl-carrier proteins in the fatty-acid biosynthesis pathway.

Mycobacterium tuberculosis, the causative agent of tuberculosis, demonstrates immense plasticity with which it adapts to a highly dynamic and hostile host environment. This is facilitated by a web of signalling pathways constantly modulated by a multitude of proteins that regulate the flow of genetic information inside the pathogen. Transcription factors (TFs) belongs to one such family of proteins that modulate the signalling by regulating the abundance of proteins at the transcript level. In the current study, we have characterized the putative transcriptional regulatory protein encoded by the Rv1719 gene of Mycobacterium tuberculosis. This TF belongs to the IclR family of proteins with orthologs found in both bacterial and archaeal species. We cloned the Rv1719 gene into the pET28a expression vector and performed heterologous expression of the recombinant protein with E coli as the host. Further, optimization of the purification protocol by affinity chromatography and characterization of proteins for their functional viability has been demonstrated using various biochemical and/or biophysical approaches. Scale-up of purification yielded approximately 30 mg of ~ 28 kDa protein per litre of culture. In-silico protein domain analysis of Rv1719 protein predicted the presence of the helix-turn-helix (HTH) domain suggesting its ability to bind DNA sequence and modulate transcription; a hallmark of a transcriptional regulatory protein. Further, by performing electrophoretic mobility shift assay (EMSA) we demonstrated that the protein binds to a specific DNA fragment harboring the probable binding site of one of the predicted promoters., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated organic removal performance, characteristics of the membrane dynamics, membrane fouling and the effects of biological sulfate reduction during high-salinity (1.0%) and high-sulfate (150 mgSO 4 2- -S/L) wastewater treatment using a laboratory-scale upflow anaerobic sludge bed reactor integrated with cross-flow dynamic membrane modules. Throughout the operational period, dynamic membrane was formed rapidly (within 5-10 min) following each backwashing cycle (21-16 days), and the permeate turbidity of <5-7 NTU was achieved with relatively high specific organic conversion (70-100 gTOC/kgVSS·d) and specific sulfate reduction (50-70 gSO 4 2- -S/kgVSS·d) rates. The sulfide from sulfate reduction can be reused for downstream autotrophic denitrification. 16S rRNA gene amplicon sequencing revealed that the microbial communities enriched in the sludge were different than those accumulated on the dynamic layer. Overall, this study demonstrates that the anaerobic dynamic membrane bioreactor coupled with sulfate reduction (SrDMBR) shows promising applicability in saline wastewater treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biochar has been increasingly used as a filter medium in engineered low impact development systems (e.g., bioretention systems) for decontamination of urban stormwater and management of hydrology. This review paper critically analyzes the performance of biochar-based biofiltration systems for removal of chemical and microbial pollutants present in urban runoff. Biochar-amended biofiltration systems efficiently remove diverse pollutants such as total nitrogen (32 - 61%), total phosphorus: (45 - 94%), heavy metals (27 - 100%), organics (54 - 100%) and microbial pollutants (log 10 removal: 0.78 - 4.23) from urban runoff. The variation of biofiltration performance is due to changes in biochar characteristics, the abundance of dissolved organic matter and/or stormwater chemistry. The dominant mechanisms responsible for removal of chemical pollutants are sorption, ion exchange and/or biotransformation, whereas filtration/straining is the major mechanism for bacteria removal. The pseudo-second order and Langmuir isotherm are the best models that describe the kinetics and chemical equilibrium of pollutants, respectively. This critical review provides the fundamental scientific knowledge for designing highly efficient biochar-based bioretention systems for removal of diverse pollutants from urban stormwater. The key knowledge gaps that should be addressed in future research include long-term field-scale bioretention study, development of novel methods for filter media regeneration/reuse, and dynamics of filter media microbial communities., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), employs ten enzymes including imidazoleglycerol-phosphate dehydratase (IGPD) for de novo biosynthesis of histidine. The absence of histidine-biosynthesis in humans combined with its essentiality for Mtb makes the enzymes of this pathway major anti-TB drug targets. We explored the inhibitory potential of a small molecule β-(1,2,4-Triazole-3-yl)-DL-alanine (DLA) against Mtb IGPD. DLA exhibits an in vitro inhibitory efficacy in the lower micromolar range. Higher-resolution crystal structures of native and substrate-bound Mtb IGPD provided additional structural features of this important drug target. Crystal structure of IGPD-DLA complex at a resolution of 1.75 Å, confirmed that DLA locks down the function of the enzyme by binding in the active site pocket of the IGPD mimicking the substrate-binding mode to a high degree. In our biochemical study, DLA showed an efficient inhibition of Mtb IGPD. Furthermore, DLA also showed bactericidal activity against Mtb and Mycobacterium smegmatis and inhibited their growth in respective culture medium. Importantly, owing to the favorable ADME and physicochemical properties, it serves as an important lead molecule for further derivatizations., (© 2021 Wiley Periodicals LLC.)

Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, we predict that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds nucleoside triphosphates at its proposed active site. Additionally, using molecular docking we have predicted the binding of three widely used kinase inhibitors and five well characterized anti-microbial compounds at the NiRAN domain active site along with their drug-likeliness. For the first time ever, using basic biochemical tools, this study shows the presence of a kinase like activity exhibited by the SARS-CoV-2 RdRp. Interestingly, a well-known kinase inhibitor- Sorafenib showed a significant inhibition and dampened viral load in SARS-CoV-2 infected cells. In line with the current global COVID-19 pandemic urgency and the emergence of newer strains with significantly higher infectivity, this study provides a new anti-SARS-CoV-2 drug target and potential lead compounds for drug repurposing against SARS-CoV-2., Competing Interests: The authors have declared that no competing interests exist.

A novel method for electroformation of liposomes and phytosomes using copper electrode is described. Liposomes made at 2 V and 10 Hz AC field from L-α-egg-phosphatidylcholine (egg-PC), K. pneumoniae phosphatidylethanolamine, K. pneumoniae polar lipids and E. coli polar lipids on copper electrode were (777.9 ± 118.4), (370.2 ± 100.5), (825.3 ± 21.54), and (281.3 ± 42.3) nm in diameter, respectively. Giant vesicles were formed at 30 V and 10 Hz AC field from polar lipids of K. pneumoniae and E. coli were (106 ± 29.7) and (86 ± 24.3) µm in diameter, respectively. All liposomes were unilamellar as indicated by their unilamellar indices of 50 ± 2, had surface charge comparable to vesicles made from lipid(s) with similar composition and exhibited only 1-2 mol% of oxidized lipids. Cu concentration in the liposomal samples was <1.5 ppm for large unilamellar vesicles (LUVs) and ˂5 ppm for giant unilamellar vesicles (GUVs). The vesicles were stable for >15 d without loss of their size, charge, or unilamellarity. The method was successfully applied to prepare phytosomes from egg-PC and a phytochemical fraction of Dimorphocalyx glabellus , a medicinal plant with anti-diuretic properties. Phytosomes formed were 1000-1500 nm in diameter and exhibited altered fluorescence and absorbance properties compared to the unencapsulated phytochemical. Phytosomes with phytochemical: egg-PC ratio from 0.15 to 1.5 had encapsulation efficiency ranging 90-30%, respectively, and was stable for 1 month. Our method is easy, inexpensive and convenient that will prove to be useful for preparation of liposomes and phytosomes.

Bioretention is a popular stormwater management strategy that is often utilized in urban environments to combat water quality and hydrological impacts of stormwater. This goal is achieved by selective designing of a system, which consists of suitable vegetation at the top planted on an engineered media with drainage system and possible underdrain at the bottom. Bibliometric analysis on bioretention studies indicates that most of the original research contributions are derived from a few countries and selected research groups. Hence, most of the bioretention systems installed in diverse geographical locations are based on guidelines from climatically different countries, which often lead to operational failures. The current review critically analyzes recent research findings from the bioretention literature, provides the authors' perspectives on the current state of knowledge, highlights the key knowledge gaps in bioretention research, and points out future research directions to make further advances in the field. Specifically, the role and desired features of bioretention components, the importance of fundamental investigations in laboratory, field-based studies and modeling efforts, the real-time process control of bioretention cells, bioretention system design considerations, and life cycle assessment of full-scale bioretention systems are discussed. The importance of local conditions in guiding bioretention designs in difference climates is emphasized. At the end of the review, current technical challenges are identified and recommendations to overcome them are provided. This comprehensive review not only offers fundamental insights into bioretention technology, but also provides novel ideas to combat issues related to urban runoff and achieve sustainable stormwater management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this study, a phylogenetic tree was constructed using 1854 sequences of various Lrp/AnsC (FFRPs) and ArsR proteins from pathogenic and non-pathogenic organisms. Despite having sequence similarities, FFRPs and ArsR proteins functioning differently as a transcriptional regulator and de-repressor in the presence of exogenous amino acids and metal ions, respectively. To understand these functional differences, the structures of various FFRPs and ArsR proteins (134 sequences) were modeled. Several ArsR proteins exhibited high similarity to the FFRPs while in few proteins, unusual structural folds were observed. However, the Helix-turn-Helix (HTH) domains are common among them and the ligand-binding domains are structurally dissimilar suggest the differences in their binding preferences. Despite low sequence conservation, most of these proteins revealed negatively charged surfaces in the active site pockets. Representative structures (PH0140 and TtArsR protein) from FFRPs and ArsR protein families were considered and evaluated for their functional differences using molecular modeling studies. Our earlier study has explained the binding preference of exogenous Tryptophan and the related transcriptional regulatory mechanism of PH0140 protein. In this study, a Cu 2+ ion-induced de-repression mechanism of the TtArsR-DNA complex was characterized through docking and molecular dynamics. Further, the proteins were purified and their efficiency for sensing Tryptophan and Cu 2+ ions were analyzed using cyclic voltammetry. Overall, the study explores the structural evolution and functional difference of FFRPs and ArsR proteins that present the possibilities of PH0140 and TtArsR as potential bio-sensory molecules., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib, continues to be a primary treatment option for lung cancer patients. However, acquisition of resistance to gefitinib is a major obstacle in lung cancer treatment and its cause is poorly understood. The present study aimed to implicate the role of SOX9-β-catenin in developed resistance to gefitinib through epithelial to mesenchymal transition (EMT) in lung cancer in vitro and ex vivo., Main Methods: Expression effect of SOX9 on survivability of lung cancer patients was demonstrated through online available Kaplan-Meier Plotter data base. Then, cell viability assay, colony forming assay, cell migration and invasion assays, flow cytometry, drug efflux assay, qRT-PCR, and western blotting were conducted to confirmed the role of SOX9 in gefitinib resistance in lung cancer cells. Dual-luciferase assay established the regulatory relation between SOX9 and β-catenin. Multicellular spheroid assay further explored that down regulation of SOX9 could reverse gefitinib resistance ex vivo., Key Findings: Kaplan-Meier method correlated the higher expression of SOX9 and β-catenin with poor overall survival of lung cancer patients. Upregulation of SOX9 was associated gefitinib resistance with increased cell proliferation, migration and invasion, single-cell colony-forming ability, reduced apoptosis, and gefitinib intake in lung cancer cells. Moreover, upregulated SOX9 promoted EMT via targeting β-catenin and knockdown of SOX9 reversed the resistance and EMT phenotype. Similarly, we found that multicellular spheroid of gefitinib resistant cells showed larger surface area with more dispersion and viability of cells, while SOX9 knockdown abolished these induced properties ex vivo., Significance: SOX9 expression could provide an innovative perspective as biomarker to understand the EGFR-TKIs resistance in lung cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recently, anaerobic self-forming dynamic membrane bioreactors (AnSFDMBRs) have attracted increasing attention, and are considered as an alternative to conventional anaerobic membrane bioreactors (AnMBRs). The key advantages of AnSFDMBRs include high flux, low propensity towards fouling, and low capital and operational costs. Although there have been several reviews on AnMBRs, very few reviews on AnSFDMBR system. Previous AnSFDMBR studies have focused on lab-scale to investigate the long-term flux, methods to improve performance and the associated mechanisms. Microbial analysis showed that the phyla namely Proteobacteria, Bacteroidetes and Firmicutes are dominant in both bulk sludge and cake biofilm, but their abundance is low in biocake. This review critically examines the fundamentals of AnSFDMBRs, operational conditions, process optimization and applications. Moreover, the current knowledge gaps (e.g., dynamic membrane module optimization, membrane surface modification and functional microbes enrichment) that should be studied in future to design an efficient AnSFDMBR system for treatment of diverse wastewaters., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show most preferable treatment for non-small cell lung carcinoma (NSCLC) with EGFR activating mutations. Despite initial impressive response of first-, to third-generation EGFR-TKIs, these agents become ineffective because of rapid emergence of EGFR mutations (T790M or C797S) mediated resistance. Allosteric mutant-selective fourth-generation EGFR inhibitors appeared to be possible therapeutic option to overcome resistance. These EGFR inhibitors are less effective as a single agent but provide synergistic effect as a combinatorial drug with conventional chemo- or immunotherapeutic. Here, we aim to highlight the comprehensive overview on combined therapeutic efficacy of allosteric EGFR inhibitors for the treatment of EGFR mutant NSCLC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dysregulation of transcription factors is one of the common problems in the pathogenesis of human cancer. Among them, SOX9 is one of the critical transcription factors involved in various diseases, including cancer. The expression of SOX9 is regulated by microRNAs (miRNAs), methylation, phosphorylation, and acetylation. Interestingly, SOX9 acts as a proto-oncogene or tumor suppressor gene, relying upon kinds of cancer. Recent studies have reported the critical role of SOX9 in the regulation of the tumor microenvironment (TME). Additionally, activation of SOX9 signaling or SOX9 regulated signaling pathways play a crucial role in cancer development and progression. Accumulating evidence also suggests that SOX9 acquires stem cell features to induce epithelial-mesenchymal transition (EMT). Moreover, SOX9 has been broadly studied in the field of cancer stem cell (CSC) and EMT in the last decades. However, the link between SOX9 and cancer drug resistance has only recently been discovered. Furthermore, its differential expression could be a potential biomarker for tumor prognosis and progression. This review outlined the various biological implications of SOX9 in cancer progression and cancer drug resistance and elucidated its signaling network, which could be a potential target for designing novel anticancer drugs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type Mtb evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ -/- mouse model, the auxotroph exhibits a similar extent of virulence as that of the wild-type. The results augment the current understanding of host-Mtb interactions and highlight the essentiality of Mtb histidine biosynthesis for its pathogenesis.

The sludge flotation and washout are frequently observed in anaerobic sulfidogenic reactor. This challenge raised the interests of re-thinking/re-designing of a compact and low-flotation bioreactor. The present study investigated to understand the temporal dynamics of microbial community and granular sludge properties in a pneumatic-mixing reactor treating sulfate-laden wastewater. The findings revealed that the reactor performance and sludge properties were dynamically changed and correlated over long-term run. In the bioreactor, a rarer type of sulfate reducing bacteria (genus Clostridium XVIII) was remarkably enriched (~30% abundance). The Clostridium XVIII-mediated COD removal (92.7 ± 3.9%) was further confirmed via mass balance which demonstrated the growth rate of total active biomass and sulfate-reducing active biomass were 19.95 and 6.0 mg-COD/L influent respectively. The PICRUSt data suggested that i) high abundance of carbohydrate metabolism and S-reductase enzymes enriched, and ii) energy metabolism enzymes decreased which implies that the new SRB communities are more energy-efficient than conventional ones., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have led to a substantial improvement in the prognosis of lung cancer patients by explicitly targeting the activating mutations within the EGFR. Initially, patients harboring tumors with EGFR mutations show progression-free survival and improvement in the response rates toward all-generation EGFR-TKIs; however, these agents fail to deliver the intended results in the long-term due to drug resistance. Therefore, it is necessary to recognize specific cardinal mechanisms that regulate the resistance phenomenon. Understanding the intricate mechanisms underlying EGFR-TKIs resistance in lung cancer could provide cognizance for more advanced targeted therapeutics. The present review features insights into current updates on the discrete mechanisms, including secondary or tertiary mutations, parallel and downstream signaling pathways, acquiring an epithelial-to-mesenchymal transition (EMT) signature, microRNAs (miRNAs), and epigenetic alterations, which lead to intrinsic and acquired resistance against EGFR-TKIs in lung cancer. In addition, this paper also reviews current possible strategies to overcome this issue using combination treatment of recently developed MET inhibitors, allosteric inhibitors or immunotherapies, transformation of EMT, targeting miRNAs, and epigenetic alterations in intrinsic and acquired EGFR-TKIs resistant lung cancer. In conclusion, multiple factors are responsible for intrinsic and acquired resistance to EGFR-TKIs and understanding of the detailed molecular mechanisms, and recent advancements in pharmacological studies are needed to develop new strategies to overcome intrinsic and acquired EGFR-TKIs resistance in lung cancer., (© 2020 Wiley Periodicals LLC.)

Eukaryotic Rab5s are highly conserved small GTPase-family proteins that are involved in the regulation of early endocytosis. Leishmania donovani Rab5a regulates the sorting of early endosomes that are involved in the uptake of essential nutrients through fluid-phase endocytosis. Here, the 1.80 Å resolution crystal structure of the N-terminal GTPase domain of L. donovani Rab5a in complex with GDP is presented. The crystal structure determination was enabled by the design of specific single-site mutations and two deletions that were made to stabilize the protein for previous NMR studies. The structure of LdRab5a shows the canonical GTPase fold, with a six-stranded central mixed β-sheet surrounded by five α-helices. The positions of the Switch I and Switch II loops confirm an open conformation, as expected in the absence of the γ-phosphate. However, in comparison to other GTP-bound and GDP-bound homologous proteins, the Switch I region traces a unique disposition in LdRab5a. One magnesium ion is bound to the protein at the GTP-binding site. Molecular-dynamics simulations indicate that the GDP-bound structure exhibits higher stability than the apo structure. The GDP-bound LdRab5a structure presented here will aid in efforts to unravel its interactions with its regulators, including the guanine nucleotide-exchange factor, and will lay the foundation for a structure-based search for specific inhibitors.

The current COVID-19 outbreak warrants the design and development of novel anti-COVID therapeutics. Using a combination of bioinformatics and computational tools, we modelled the 3D structure of the RdRp (RNA-dependent RNA polymerase) of SARS-CoV2 (severe acute respiratory syndrome coronavirus-2) and predicted its probable GTP binding pocket in the active site. GTP is crucial for the formation of the initiation complex during RNA replication. This site was computationally targeted using a number of small molecule inhibitors of the hepatitis C RNA polymerase reported previously. Further optimizations suggested a lead molecule that may prove fruitful in the development of potent inhibitors against the RdRp of SARS-CoV2., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Prognosis of pancreatic cancer patients remains extremely poor thus, the need for the development of new therapeutic options is crucial. Plumbagin, a naphthoquinone derivative from Plumbago indica has been found to possess various pharmacological properties including anticancer activity. The present study was designed to investigate the inhibitory potential of plumbagin and associated mechanisms in pancreatic cancer cells. Fluorescence and flow cytometric analysis exhibited an increased percentage of apoptotic cells in both monolayer culture and 3D tumor spheroids. Upon plumbagin treatment, reactive oxygen species content of the cancer cells escalated and prompted alleviation of the mitochondrial membrane potential, which triggers caspase-dependent apoptosis. Interestingly, N-acetylcysteine inhibited the plumbagin induced apoptosis. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased. Moreover, plumbagin treatment led to upregulation of cleaved caspase-3 and caspase-9. These results support the views that plumbagin induced stress signals by damaging mitochondria and induce ROS mediated apoptosis via intrinsic apoptotic signaling in pancreatic cancer cells. To summarize, our study suggests that plumbagin may be utilized as a future anti-cancer therapy agent against pancreatic cancer, which is a major threat owing to its stubborn intransigence towards current treatment regimens., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Plumbagin (PL) is a natural naphthoquinone compound, isolated from Plumbago zeylanica that has cytotoxic and antimigratory potential in many cancer. However, the cytotoxic mechanism of plumbagin in drug resistant lung cancer is poorly understood. To reveal the mechanism, we studied the anticancer effect of plumbagin in both gefitinib-sensitive and resistant A549 lung cancer cells. The anticancer potential of PL was demonstrated by MTT assay and the result suggested that PL showed cytotoxicity in both gefitinib-sensitive (A549) and gefitinib-resistant (A549GR) lung cancer cells. IC 50 values of PL in A549 and A549GR were 3.2 μM and 4.5 μM, respectively. Morphological changes were also observed after treatment with PL. Furthermore, PL decreased cell survival by inhibiting colony formation ability, and inhibited cell migration at very low concentrations. From Annexin V-FITC/PI, AO/EtBr, and DAPI staining, we found that increasing concentration of PL leads to increase in apoptosis of lung cancer cells. Furthermore, western blotting results suggested that Bax and Caspase 3 levels were upregulated after PL treatment. In addition, treatment of PL caused DNA damage in a dose-dependent manner. PL arrested the cell cycle at S-G 2/ M phase, and enhanced reactive oxygen species (ROS) generation. Excess ROS generated by PL disrupted mitochondrial membrane resulted in depletion of mitochondrial membrane potential (MMP). These results conclude that PL decreases lung cancer cell viability by arresting cells at S-G 2/ M phase, and induces apoptosis by activation of mitochondrial-mediated apoptotic pathway through excess ROS generation. Overall findings suggest that plumbagin shows cytotoxic and therapeutic potential against both A549 and A549GR cell lines.