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Toxic metal(loid)s, e.g., mercury, arsenic, lead, and cadmium are known for several environmental disturbances creating toxicity to humans if accumulated in high quantities. Although not discussed critically, the organo-forms of these inorganic metal(loid)s are considered a greater risk to humans than their elemental forms possibly due to physico-chemical modulation triggering redox alterations or by the involvement of biological metabolism. This extensive review describes the chemical and physical causes of organometals and organometal(loid)s distribution in the environment with ecotoxicity assessment and potential remediation strategies. Organo forms of various metal(loid)s, such as mercury (Hg), arsenic (As), lead (Pb), tin (Sn), antimony (Sb), selenium (Se), and cadmium (Cd) have been discussed in the context of their ecotoxicity. In addition, we elaborated on the transformation, speciation and transformation pathways of these toxic metal(loid)s in soil-water-plant-microbial systems. The present review has pointed out the status of toxic organometal(loid)s, which is required to make the scientific community aware of this pressing condition of organometal(loid)s distribution in the environment. The gradual disposal and piling of organometal(loid)s in the environment demand a thorough revision of the past-present status with possible remediation strategies prescribed as reflected in this review., 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 B.V. All rights reserved.)

The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90's interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine., (© 2024. The Author(s).)

Protein-protein interactions (PPIs) play a crucial role in cellular function and disease manifestation, with dysfunctions in PPI networks providing a direct link between stressors and phenotype. The dysfunctional Protein-Protein Interactome (dfPPI) platform, formerly known as epichaperomics, is a newly developed chemoproteomic method aimed at detecting dynamic changes at the systems level in PPI networks under stressor-induced cellular perturbations within disease states. This review provides an overview of dfPPIs, emphasizing the novel methodology, data analytics, and applications in disease research. dfPPI has applications in cancer research, where it identifies dysfunctions integral to maintaining malignant phenotypes and discovers strategies to enhance the efficacy of current therapies. In neurodegenerative disorders, dfPPI uncovers critical dysfunctions in cellular processes and stressor-specific vulnerabilities. Challenges, including data complexity and the potential for integration with other omics datasets are discussed. The dfPPI platform is a potent tool for dissecting disease systems biology by directly informing on dysfunctions in PPI networks and holds promise for advancing disease identification and therapeutics., Competing Interests: Declaration of competing interest Memorial Sloan Kettering Cancer Center holds the intellectual rights to the epichaperome portfolio. G.C. is an inventor of related intellectual property. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bisphenol A is a fluorophoric platform that is used to develop chemosensors for various species. Herein, we report a bisphenol A based Schiff-base molecule, 4,4'-(propane-2,2-diyl)bis(2-(( E )-((2-hydroxy-5-methylphenyl)imino)methyl)phenol) (Me-H 4 L), as a selective chemosensor for Al 3+ . Among the several metal ions, it shows a significant increment in its fluorescence intensity (50 fold) at 535 nm in the presence of Al 3+ ions. The enhanced fluorescence was attributed to the CHEFF mechanism and inhibition of CN isomerization. The limit of detection value of Me-H 4 L for Al 3+ was determined to be 9.65 μM. Its quantum yield and lifetime increased considerably in the presence of the cation. Some theoretical calculations were performed to explain the interaction between Al 3+ and the probe. Furthermore, Me-H 4 L was applied in cell imaging studies using animal cells and plant roots.

We developed a generally applicable method, CRISPR/Cas9-targeted long-read sequencing (CTLR-Seq), to resolve, haplotype-specifically, the large and complex regions in the human genome that had been previously impenetrable to sequencing analysis, such as large segmental duplications (SegDups) and their associated genome rearrangements. CTLR-Seq combines in vitro Cas9-mediated cutting of the genome and pulse-field gel electrophoresis to isolate intact large (i.e., up to 2,000 kb) genomic regions that encompass previously unresolvable genomic sequences. These targets are then sequenced (amplification-free) at high on-target coverage using long-read sequencing, allowing for their complete sequence assembly. We applied CTLR-Seq to the SegDup-mediated rearrangements that constitute the boundaries of, and give rise to, the 22q11.2 Deletion Syndrome (22q11DS), the most common human microdeletion disorder. We then performed de novo assembly to resolve, at base-pair resolution, the full sequence rearrangements and exact chromosomal breakpoints of 22q11.2DS (including all common subtypes). Across multiple patients, we found a high degree of variability for both the rearranged SegDup sequences and the exact chromosomal breakpoint locations, which coincide with various transposons within the 22q11.2 SegDups, suggesting that 22q11DS can be driven by transposon-mediated genome recombination. Guided by CTLR-Seq results from two 22q11DS patients, we performed three-dimensional chromosomal folding analysis for the 22q11.2 SegDups from patient-derived neurons and astrocytes and found chromosome interactions anchored within the SegDups to be both cell type-specific and patient-specific. Lastly, we demonstrated that CTLR-Seq enables cell-type specific analysis of DNA methylation patterns within the deletion haplotype of 22q11DS., Competing Interests: Competing interests statement:The authors declare no competing interest.

Most of the human cancers are dependent on telomerase to extend the telomeres. But ∼10% of all cancers use a telomerase-independent, homologous recombination mediated pathway called alternative lengthening of telomeres (ALT). Due to the poor prognosis, ALT status is not being considered yet in the diagnosis of cancer. No such specific treatment is available to date for ALT positive cancers. ALT positive cancers are dependent on replication stress to deploy DNA repair pathways to the telomeres to execute homologous recombination mediated telomere extension. SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like 1) is associated with the ALT telomeres to resolve replication stress thus providing telomere stability. Thus, the dependency on replication stress regulatory factors like SMARCAL1 made it a suitable therapeutic target for the treatment of ALT positive cancers. In this study, we found a significant downregulation of SMARCAL1 expression by stabilizing the G-quadruplex (G4) motif found in the promoter of SMARCAL1 by potent G4 stabilizers, like TMPyP4 and BRACO-19. SMARCAL1 downregulation led toward the increased localization of PML (promyelocytic leukemia) bodies in ALT telomeres and triggered the formation of APBs (ALT-associated promyelocytic leukemia bodies) in ALT positive cell lines, increasing telomere replication stress and DNA damage at a genomic level. Induction of replication stress and hyper-recombinogenic phenotype in ALT positive cells mediated by G4 stabilizing molecules already highlighted their possible application as a new therapeutic window to target ALT positive tumors. In accordance with this, our study will also provide a valuable insight toward the development of G4-based ALT therapeutics targeting SMARCAL1.

Neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology.

Floral biochemistry and stress physiology is an underexplored aspect of mangroves, which should be investigated as part of preservation and restoration efforts. A thriving true mangrove tree (Bruguiera gymnorrhiza (L.) Lamk.) and a threatened mangrove-associate species (Heritiera fomes Buch. Ham.) were studied in the Sundarban region of India for seasonal variations in floral odours, non-volatile phytochemicals, antioxidant enzyme activities, and surface water chemistry in surrounding habitat. Both species were found to exhibit significant differences in floral volatilomes, protein contents, antioxidant enzyme activities, total flavonoids, and total phenolic contents between spring and autumn blooms. The bird-pollinated flowers of B. gymnorrhiza also showed considerable seasonal differences in floral anthocyanin and proline contents, indicating vulnerability of the post-anthesis open flowers to environmental factors. Contrarily to previous findings, B. gymnorrhiza floral bouquet appeared to be enriched in various classes of volatiles - dominated by sulphurous compounds in bud stage and terpenoids in open stage. Floral anthocyanins, contributing to the striking colouration of the calyx, were found to comprise cyanidin and delphinidin derivatives. Other glycosides of cyanidin and delphinidin were detected in H. fomes flowers, contributing to visual guides to potential food rewards for pollinating insects. Floral tissue in H. fomes was found to be protected by densely overlapping layers of stellate trichomes containing sesquiterpenoids as phytoprotectants. Comparison of the two floral species suggested that H. fomes flowering is optimized to oligohaline (but not freshwater) vernal conditions; whereas B. gymnorrhiza blooms are adapted for biologically enriched (including abundant herbivores and microbial growth), mesohaline forest habitats., (© 2024. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Arsenic (As) contamination of rice grain poses a serious threat to human health. Therefore, it is crucial to reduce the bioavailability of As in the soil and its accumulation in rice grains to ensure the safety of food and human health. In this study, mango (Mangifera indica) leaf-derived biochars (MBC) were synthesized and modified with iron (Fe) to produce FeMBC. In this study, 0.5 and 1% (w/w) doses of MBC and FeMBC were used. The results showed that 1% FeMBC enhanced the percentage of filled grains/panicle and biomass yield by 17 and 27%, respectively, compared to the control. The application of 0.5 and 1% FeMBC significantly (p < 0.05) reduced bioavailable soil As concentration by 33 and 48%, respectively, in comparison to the control. The even higher As flux in the control group as compared to the biochar-treated groups indicates the lower As availability to biochar-treated rice plant. The concentration of As in rice grains was reduced by 6 and 31% in 1% MBC and 1% FeMBC, respectively, compared to the control. The reduction in As concentration in rice grain under 1% FeMBC was more pronounced due to reduced bioavailability of As and enhanced formation of Fe-plaque. This may restrict the entry of As through the rice plant. The concentrations of micronutrients (such as Fe, Zn, Se, and Mn) in brown rice were also improved after the application of both MBC and FeMBC in comparison to the control. This study indicates that the consumption of parboiled rice reduces the health risk associated with As compared to cooked sunned rice. It emphasizes that 1% MBC and 1% FeMBC have great potential to decrease the uptake of As in rice grains., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs)., 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 B.V. All rights reserved.)

The present study depicts the true failed scenario of the arsenic (As) removal units (ARU) in West Bengal by evaluating their treated water quality. Annual As removal efficiency of the 12 studied ARUs range between 35.2% and 82.6%. A comprehensive physico-chemical parameters and trace elements analysis find almost 25% and 16.7% of treated drinking water samples with poor water quality index (WQI) and high heavy metal evaluation index (HEI), respectively. The pond-based water treatment plant maintains the production of continuous As-safe water with a range between 60.2% and 66.7% due to its high Fe/As ratio. It's a discontent concluding the treated drinking water of the groundwater based-ARUs were observed with sufficient As mediated cancer risk (3 ×10 -3 ). The non-cancer risk (HQ) of As is safe for the surface water treatment plant (0.38), whereas it is threatening for the groundwater based-ARUs (7.44). However, the drinking water samples are safe in view of HQ from the other trace elements like Hg, Al, Cd, Cr, Pb, F - and NO 3 - . Small scale ARU could be a feasible mitigation strategy in reducing the As menace in the long run if the plants are maintained correctly. Nevertheless, surface treated water is the most sustainable solution as withdrawal of groundwater for drinking purpose is not a viable practice., 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.)

Millions of people worldwide are affected by arsenic (As) contamination, particularly in South and Southeast Asian countries, where large-scale dependence on the usage of As-contaminated groundwater in drinking and irrigation is a familiar practice. Rice (Oryza sativa) cultivation is commonly done in South and Southeast Asian countries as a preferable crop which takes up more As than any other cereals. The present article has performed a scientific meta-data analysis and extensive bibliometric analysis to demonstrate the research trend in global rice As contamination scenario in the timeframe of 1980-2023. This study identified that China contributes most with the maximum number of publications followed by India, USA, UK and Bangladesh. The two words 'arsenic' and 'rice' have been identified as the most dominant keywords used by the authors, found through co-occurrence cluster analysis with author keyword association study. The comprehensive perceptive attained about the factors affecting As load in plant tissue and the nature of the micro-environment augment the contamination of rice cultivars in the region. This extensive review analyses soil parameters through meta-data regression assessment that influence and control As dynamics in soil with its further loading into rice grains and presents that As content and OM are inversely related and slightly correlated to the pH increment of the soil. Additionally, irrigation and water management practices have been found as a potential modulator of soil As concentration and bioavailability, presented through a linear fit with 95% confidence interval method., 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.)

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations characterized by distinct interactomes-namely, protein assemblies-under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly, and disease.

P38γ (MAPK12) is predominantly expressed in triple negative breast cancer cells (TNBC) and induces stem cell (CSC) expansion resulting in decreased survival of the patients due to metastasis. Abundance of G-rich sequences at MAPK12 promoter implied the functional probability to reverse tumorigenesis, though the formation of G-Quadruplex (G4) structures at MAPK12 promoter is elusive. Here, we identified two evolutionary consensus adjacent G4 motifs upstream of the MAPK12 promoter, forming parallel G4 structures. They exist in an equilibria between G4 and duplex, regulated by the binding turnover of Sp1 and Nucleolin that bind to these G4 motifs and regulate MAPK12 transcriptional homeostasis. To underscore the gene-regulatory functions of G4 motifs, we employed CRISPR-Cas9 system to eliminate G4s from TNBC cells and synthesized a naphthalene diimide (NDI) derivative (TGS24) which shows high-affinity binding to MAPK12-G4 and inhibits MAPK12 transcription. Deletion of G4 motifs and NDI compound interfere with the recruitment of the transcription factors, inhibiting MAPK12 expression in cancer cells. The molecular basis of NDI-induced G4 transcriptional regulation was analysed by RNA-seq analyses, which revealed that MAPK12-G4 inhibits oncogenic RAS transformation and trans-activation of NANOG. MAPK12-G4 also reduces CD44 High /CD24 Low population in TNBC cells and downregulates internal stem cell markers, arresting the stemness properties of cancer cells., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

World's highest arsenic (As) contamination is well-documented for the groundwater system of southwestern region (mainly Jashore district) of Bangladesh, where the majority of inhabitants are underprivileged. To mitigate As poisoning in southwestern Bangladesh, numerous steps have been taken so far by the government and non-governmental organizations (NGOs). Among them, digging deep tube wells and As removal by naturally deposited Fe(OH) 3 species are being widely practiced in the contaminated areas. However, these actions have been left unmonitored for decades, making people unaware of this naturally occurring deadly poison in their drinking water. Hence, water samples (n = 63, both treated and untreated) and soil samples (n = 4) were collected from different spots in Jashore district to assess the safety level of drinking water and to understand the probable reasons for high As(III) contamination. About 93.7% of samples were found to contain As(III) above 10 μg/L; among them, 38% contained above 50 μg/L. The study shows that current As(III) removal strategies in the study area are ineffective. In this connection, a simple low-cost As(III) removal adsorbent is proposed that can be prepared with very cheap and locally available materials like iron sludge and charcoal. The adsorbent was characterized in terms of SEM, EDX, and XPS. The optimal dosage of the adsorbent was investigated for real-life application concerning several vital water quality parameters. The Fe-C adsorbent exhibited a maximum As(III) removal efficiency of 92% in real groundwater samples. The study will allow policymakers for informed decision-making regarding water body management as well as enable the local people to avail As-safe water in a way that aligns with their economic factors., 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.)

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Selenium is a trace element required for the active function of numerous enzymes and various physiological processes. In recent years, selenium nanoparticles draw the attention of scientists and researchers because of its multifaceted uses. The process involved in chemically synthesized SeNPs has been found to be hazardous in nature, which has paved the way for safe and ecofriendly SeNPs to be developed in order to achieve sustainability. In comparison to chemical synthesis, SeNPs can be synthesized more safely and with greater flexibility utilizing bacteria, fungi, and plants. This review focused on the synthesis of SeNPs utilizing bacteria, fungi, and plants; the mechanisms involved in SeNP synthesis; and the effect of various abiotic factors on SeNP synthesis and morphological characteristics. This article discusses the synergies of SeNP synthesis via biological routes, which can help future researchers to synthesize SeNPs with more precision and employ them in desired fields., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fluoride (F - ) enrichment in groundwater of the lower Gangetic plain in West Bengal, India is a major concern. Fluoride contamination and its toxicity were reported earlier in this region; however, limited evidence was available on the precise site of contamination, hydro-geochemical attributions of F - mobilization and probabilistic health risk caused by fluoridated groundwater. The present study addresses the research gap by exploring the spatial distribution and physico-chemical parameters of fluoridated groundwater along with the depth-wise sedimental distribution of F - . Approximately, 10 % of the groundwater samples (n = 824) exhibited high F -  ≥ 1.5 mg/l from 5, out of 19 gram-panchayats and Baruipur municipality area and the maximum F - was observed in Dhapdhapi-II gram-panchayat with 43.7 % of samples showed ≥1.5 mg/l (n = 167). The distribution patterns of cations and anions in fluoridated groundwater were Na +  > Ca 2+  > Mg 2+  > Fe > K + and Cl -  > HCO 3 -  > SO 4 2-  > CO 3 2-  > NO 3 -  > F - . Different statistical models like Piper and Gibbs diagram, Chloro Alkaline plot, Saturation index were applied to better understand the hydro-geochemical characteristics for F - leaching in groundwater. Fluoridated groundwater is of Na-Cl type which implies strong saline character. The intermediate zone between evaporation and rock dominance area controls F - mobilization along with ion-exchange process occurring between groundwater and host silicate mineral. Furthermore, saturation index proves geogenic activities related to groundwater F - mobilization. All cations present in sediment samples are closely interlinked with F - in the depth range of 0-18.3 m. Mineralogical analyses revealed that muscovite is the most responsible mineral for F - mobilization. The probabilistic health risk assessment disclosed severe health hazard in the order of infants > adults > children > teenagers through F - tainted groundwater. At P95 percentile dose, all the studied age groups showed THQ >1 from Dhapdhapi-II gram-panchayat. Supply of F - safe drinking water is required through reliable water supply strategies in the studied area., 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.)

Mushroom cultivation has been identified as a cost-effective technique for converting lignocellulosic wastes. This study utilized a combination of two distinct agro-wastes as a substrate for better Pleurotus ostreatus cultivation. Oyster mushroom has been cultivated on substrates made up of rice straw and sugarcane bagasse with different ratios. This technique gives a significant difference between mycelium running, fruit body formation, yield, biological efficiency, and better-quality taste of Pleurotus ostreatus mushroom. A minimum of 19 days were required for 1st harvesting from bag number T4 where substrate ratio was used at 3:2. The maximum yield was found as T4 (886 g/kg) in bag number on the dry substrate from the first flushing. According to proximate analyses, protein contents were increased in treatment bags compared with the control. Anyhow, the enrichment of L-glutamine content in the fruit body was found at 11.8 mg/g from 1st flushing in T4 bag, among the other bags and the flavour was changed due to the substrate level composition. According to the study, 3:2 is an ideal substrate ratio for the development of oyster mushrooms cultivation. According to this ratio, it helps the farmer for minimum time to grow the mushroom fruit body and reduce the lignocellulosic waste materials from the environmental pollution along with increasing the flavour in the fruitbody compared with commonly produced mushroom substrate (T6). Therefore, more research should be conducted to assess the consequences of combining different substrates and decreasing the lignocellulosic biomass by converting a protein-rich edible product through the oyster mushroom., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks., (© 2023. The Author(s).)

The suffering from arsenic toxicity is a long-standing concern in Asian countries. The role of the key factors (arsenic intake, age and sex) regulating arsenic toxicity is aimed to evaluate for a severely exposed population from Murshidabad district, West Bengal. Mean arsenic concentrations in drinking water supplied through tube well, Sajaldhara treatment plant and pipeline were observed as 208, 27 and 54 µg/l, respectively. Urinary arsenic concentration had been observed as < 3-42.1, < 3-56.2 and < 3-80 µg/l in children, teenagers and adults, respectively. Mean concentrations of hair and nail arsenic were found to be 0.84 and 2.38 mg/kg; 3.07 and 6.18 mg/kg; and 4.41 and 9.07 mg/kg, respectively, for the studied age-groups. Water arsenic was found to be associated with hair and nail (r = 0.57 and 0.60), higher than urine (r = 0.37). Arsenic deposition in biomarkers appeared to be dependent on age; however, it is independent of sex. Principal component analysis showed a direct relationship between dietary intake of arsenic and chronic biomarkers. Nail was proved as the most fitted biomarker of arsenic toxicity by Dunn's post hoc test. Monte Carlo sensitivity analysis and cluster analysis showed that the most significant factor regulating health risk is 'concentration of arsenic' than 'exposure duration', 'body weight' and 'intake rate'. The contribution of arsenic concentration towards calculated health risk was highest in teenagers (45.5-61.2%), followed by adults (47.8-49%) and children (21-27.6%). Regular and sufficient access to arsenic-safe drinking water is an immediate need for the affected population., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Rice arsenic (As) contamination and its consumption poses a significant health threat to humans. The present study focuses on the contribution of arsenic, micronutrients, and associated benefit-risk assessment through cooked rice from rural (exposed and control) and urban (apparently control) populations. The mean decreased percentages of As from uncooked to cooked rice for exposed (Gaighata), apparently control (Kolkata), and control (Pingla) areas are 73.8, 78.5, and 61.3%, respectively. The margin of exposure through cooked rice (MoE cooked rice ) < 1 signifies the existence of health risk for all the studied exposed and control age groups. The respective contributions of iAs (inorganic arsenic) in uncooked and cooked rice are nearly 96.6, 94.7, and 100% and 92.2, 90.2, and 94.2% from exposed, apparently control, and control areas. LCR analysis for the exposed, apparently control, and control populations (adult male: 2.1 × 10 -3 , 2.8 × 10 -4 , 4.7 × 10 -4 ; adult female: 1.9 × 10 -3 , 2.1 × 10 -4 , 4.4 × 10 -4 ; and children: 5.8 × 10 -4 , 4.9 × 10 -5 , 1.1 × 10 -4 ) through cooked rice is higher than the recommended value, i.e., 1 × 10 -6 , respectively, whereas HQ > 1 has been observed for all age groups from the exposed area and adult male group from the control area. Adults and children from rural area showed that ingestion rate (IR) and concentration are the respective influencing factors towards cooked rice As, whereas IR is solely responsible for all age groups from urban area. A vital suggestion is to reduce the IR of cooked rice for control population to avoid the As-induced health risks. The average intake (μg/day) of micronutrients is in the order of Zn > Se for all the studied populations and Se intake is lower for the exposed population (53.9) compared to the apparently control (140) and control (208) populations. Benefit-risk assessment supported that the Se-rich values in cooked rice are effective in avoiding the toxic effect and potential risk from the associated metal (As)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Reactive oxygen species (ROS) at low level promotes cell survival through lysosome induced autophagy induction. Glucose stress induced acidosis, hypoxia, ROS, upregulates markers related to cancer stemness and multidrug resistance. Also, lysosomal upregulation is proposed to be one of the important indicators of cell survival under ROS induced stress. Studies supported that, stimulation of Lysosome-TFEB-Ca 2+ cascade has important role in induction of chemoresistance and survival of cancerous cells., Purpose: To observe the effect of synergistic drug combination, Kaempferol and Verapamil on markers regulating chemoevasion, tumor stemness & acidosis as well as lysosome upregulation pathways, under low as well as high glucose conditions., Hypothesis: Based on our earlier observation as well as previous reports, we hypothesized, our drug combination Kaempferol with Verapamil could attenuate markers related to chemoevasion, tumor stemness & acidosis as well as lysosome-TFEB-Ca2+ pathway, all of which have indispensable association and role in chemoresistance., Methods: RNA and protein expression of candidate genes, along with ROS production and Ca2+ concentrations were measured in ex vivo models in altered glucose conditions upon treatment with KV. Also, computational approaches were utilized to hypothesize the mechanism of action of the drug combination. PCR, IHC, western blotting and molecular docking approaches were used in this study., Results: The overproduction of ROS by our candidate drugs KV, downregulated the chemoresistance and tumor acidosis markers along with ATP1B1 and resulted in lysosomal disruption with reduction of Ca 2+ release, diminishing TFEB expression under low glucose condition. An anomalous outcome was observed in high glucose conditions. We also observed KV promoted the overproduction of ROS levels thereby inducing autophagy-mediated cell death through the upregulation of LC3-II and p62 in low glucose conditions. The ex vivo studies also corroborate with in silico study that exhibited the parallel outcome., Conclusion: Our ex-vivo and in-silico studies revealed that our candidate drug combination KV, could effectively target several pathways regulating chemoresistance, that were not hitherto studied in the same experimental setup and thus may be endorsed for therapeutic purposes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Energy generation from coal poses an environmental drawback due to the abundance of some potential hazardous elements (PHEs). A few PHEs (As, Sb, Cu, Mn and Zn) are noticed in the coal collected from thermal power plants of India. Among them, As and Sb are depleted while Cu, Mn and Zn are enriched in fly and bottom ash. The short- and long-term exposure of these PHEs into the ecosystem by emission, deposition and leaching causes environmental contamination as well as pollution and health hazards. The water-leaching experiment shows that these elements have feeble mobilisation tendency and low risk. The bioavailability test reflects that bio-uptake of these PHEs into the human system may be the origin of several diseases. Proper storage and recycling of the large amount of fly and bottom ash are a serious concern of thermal power plants. Chemical characterisation of ash, including elemental mapping by scanning electron microscope, calculated enrichment ratio (ER) and relative enrichment index (REI) values, as well as lab-scale water-leaching experiments predict that combustion residues of the studied power generating unit are safe for utilisation in construction, geotechnical and even in agricultural sectors. Chemical characterisation and pre-treatment of ashes before utilisation are urgently required to prevent any possible contamination. Regular scrutiny of emission control device, proper management of ash disposal and frequent utilisation are the keys for clean energy generation. A deep chemical and physical analysis of coal from power plants prior to utilisation is the primary task for sustainable energy generation from environmental aspect., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

c-MYC proto-oncogene harbors a putative G-quadruplex structure (Pu27) at the NHEIII 1 domain, which can shuffle between transcriptional inhibitor quadruplex and transcriptionally active duplex. In cancer cells this quadruplex destabilization is preferred and NHEIII 1 domain assume a duplex topology thereby inducing c-MYC overexpression and tumorigenesis. Hence, the c-MYC quadruplex acts as an excellent target for anti-cancer therapy. Though researcher have tried to develop G-quadruplex targeted small molecules, work with G-quadruplex targeting peptides is very limited. Here we present a peptide that can bind to c-MYC quadruplex, destabilize the tetrad core, and permit the formation of a substantially different structure from the quartet core seen in the canonical G-quadruplexes. Such conformation potentially acted as a roadblock for transcription factors thereby reducing cMYC expression. This event sensitizes the cancer cell to activate apoptotic cascade via the c-MYC-VEGF-A-BCL2 axis. This study provides a detailed insight into the peptide-quadruplex interface that encourages better pharmacophore design to target dynamic quadruplex structure. We believe that our results will contribute to the development, characterization, and optimization of G-quadruplex binding peptides for potential clinical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Epichaperomes are disease-associated pathologic scaffolds, composed of tightly bound chaperones, co-chaperones, and other factors. They mediate anomalous protein-protein interactions inside cells, which aberrantly affects the function of protein networks, and in turn, cellular phenotypes. Epichaperome study necessitates the implementation of methods that retain these protein complexes in their native cellular states for analysis. Here we describe a protocol for detection and composition analysis of epichaperomes in cell homogenates through native polyacrylamide gel electrophoresis., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Arsenic (As), a metalloid is a class I carcinogen and is a major problem in various parts of the world. Food crops are severely affected due to As poisoning and suffer from low germination, yield and disfiguration of morphological and anatomical traits. To attenuate such adverse effects and tone down As uptake by plants, the present study attempts to explore the role of K-humate (KH) in alleviation of As toxicity in rice. KH was administered in the growth media containing 800 ppb As (III) at varying doses to observe the stress alleviating capacity of the amendment. Five treatments were investigated, viz: (a) 800 ppb As (control), (b) 800 ppb As + 25 ppm KH, (c) 800 ppb As + 50 ppm KH, (d) 800 ppb As + 75 ppm KH and (e) 800 ppb As + 100 ppm KH. The results of the amendment administration were noted at 14 days after seeding (DAS). Application of KH significantly improved germination percentage, vigour indices and chlorophyll content by reducing the oxidative stress, antioxidant and antioxidant enzyme activities under As stress. In vivo detection of reactive oxygen species (ROS) using DCF-2DA fluorescent dye and scanning electron microscope (SEM) study of root further depicted that KH application effectively reduced ROS formation and improved root anatomical structure under As stress, respectively. Gradually increasing concentrations of KH was capable of decreasing the bioavailability of As to the rice plants, thus minimizing toxic effect of the metalloid., 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.)

We present observations from a laboratory-controlled study on the impacts of extreme wetting and drying on a wetland soil microbiome. Our approach was to experimentally challenge the soil microbiome to understand impacts on anaerobic carbon cycling processes as the system transitions from dryness to saturation and vice-versa. Specifically, we tested for impacts on stress responses related to shifts from wet to drought conditions. We used a combination of high-resolution data for small organic chemical compounds (metabolites) and biological (community structure based on 16S rRNA gene sequencing) features. Using a robust correlation-independent data approach, we further tested the predictive power of soil metabolites for the presence or absence of taxa. Here, we demonstrate that taking an untargeted, multidimensional data approach to the interpretation of metabolomics has the potential to indicate the causative pathways selecting for the observed bacterial community structure in soils.

Objective: Present study was designed to explore the efficacy of vitamin C and E (VC&VE) against fluoride mediated testicular, epididymal and spermatozoal anomalies., Materials and Methods: Thirty two adult Wistar rats were divided into four groups. Group-I was control; Group-II received sodium fluoride (NaF) at 15 mg/kg/day dose; Group-III was provided with VC (200 mg/kg/day) and VE (400 mg/kg/day) plus NaF; Group-IV received only VC&VE. Structural integrity and oxidative stress markers (superoxide dismutase, catalase, malondialdehyde and protein carbonyl) of testis and epididymis were assessed. Spermatozoal parameters (count, motility, viability and hypo-osmotic swelling) were evaluated. Testicular functional maker enzymes (acid phosphatase, alkaline phosphatase and lactate dehydrogenase) were also assessed. Integrity of testicular and spermatozoal DNA was evaluated. Testicular fluoride content was measured., Result: Fluoride induced structural changes and alterations of oxidative stress markers were observed in testis and epididymis. Spermatozoal potentials were altered and reduced activities of testicular functional marker enzymes were observed. Fluoride caused testicular and spermatozoal DNA damages. VC&VE supplementation resulted in protection from all fluoride mediated alterations and helped in attenuating testicular fluoride accumulation., Conclusion: Antioxidant properties of VC&VE ameliorated fluoride mediated reproductive damages but only supplementation did not exhibit any notable effect compared to control rats.

Rice (Oryza sativa L.) is considered as the staple food for 50% of the world's population. Humans are exposed to arsenic (As) through rice consumption, which is a global health issue that requires attention. The present review reflects the scenario of rice grown in As endemic regions of Asia that has a significant portion of inorganic As (iAs) compared to other rice grown areas around the world. Post-harvesting, pre-cooking, and cooking procedures in South and South-East Asian countries employ As-contaminated groundwater. Polishing of brown rice and parboiling, washing and cooking with As-safe water can reduce As concentration and nutrient level in cooked rice. However, in rural parts of South-east Asia, rice is usually cooked using As-contaminated groundwater and consumption of this As enriched rice and water may cause a significant health exposure in humans. Bioaccessibility and bioavailability of As can be determined using in-vitro and in-vivo techniques that can be utilized as a tool to assess As exposure in humans. Arsenic in cooked rice may be reduced by using newly developed cooking procedures such as Kateh cooking, steam percolating, and the parboiled and absorbed (PBA) method. For individuals living in rural regions, using rainwater or treated surface water for drinking and cooking is also an alternative. Although this study examined the processes involved in the post-harvesting, pre-cooking, and cooking stages, there are still significant research gaps in this area that must be addressed in near future., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chemoresistance is an imminent therapeutic challenge for breast cancer. Previous evidence suggests that breast cancer stem cells (BCSC) develop resistance through upregulation of stemness and chemo-evasion markers viz. SOX2, OCT4, NANOG, MDR1 and CD44, following anticancer chemotherapeutic treatments. Early studies suggest an inhibitory role of Kaempferol in BCSC propagation through downregulation of epithelial to mesenchymal transition. We hypothesized that the pathway involved in chemoresistance could be effectively addressed through Kaempferol (K), alone or in combination with Verapamil (V), which is an inhibitor of MDR1. We used K in combination with V, in multiple assays to determine if there was an inhibitory effect on BCSC. Both K and KV attenuated pH-dependent mammosphere formation in primary BCSC and MDA-MB-231 cells. RNA and protein (immunocytochemistry, western blot) expression of candidate markers viz. SOX2, OCT4, NANOG, MDR1 and CD44 were carried out in the presence or absence of candidate drugs in ex-vivo grown primary BCSC and MDA-MB-231 cell line. Immunoprecipitation assay, cell cycle analysis was carried out in MDA-MB-231. Our candidate drugs were not only anti-proliferative, but also downregulated candidate genes expression at RNA and protein level in both settings, with more robust efficacy in KV treatment than K; induced G2/M dependent cell cycle arrest, and interrupted physical association of CD44 with NANOG as well as MDR1 in MDA-MB-231. In primary tumor explant but not in adjacent normal tissue, our candidate drugs K and KV induced robust γH2AX expression. Thus, our candidate drugs are effective in attenuating BCSC survival., (Copyright © 2022. Published by Elsevier Inc.)

Arsenic (As) in rice is posing a serious threat worldwide and consumption of As contaminated rice by human is causing health risks. A pot experiment with different levels of sulfate dosage (0, 20, 40, 60 and 80 mg/kg) was set up in this study to explore the influence of sulfate fertilizer on rice plant growth, yield, and As accumulation in rice grain. Apart from As bioaccumulation in rice grains, the As fraction of cooked rice was quantified, and the health risks associated with cooked rice consumption were also investigated. The sulfate application significantly (p ≤ 0.05) enhanced the chlorophyll, tiller number, grains per panicle, grain and biomass yield under As stressed condition. The sulfate application also reduced the oxidative stress and antioxidant activity in rice plants. Sulfate fertigation improved the accumulation of total sulfur (S) and reduced the uptake and translocation of As in rice plants. Arsenic concentration in rice grain was reduced by 50.1% in S80 treatment (80 mg of sulfate/kg of soil) as compared to S0 set. The reduction percentage of As in cooked parboiled and sunned rice with correspond to raw rice ranged from 55.9 to 74% and 40.3-60.7%, respectively. However, the sulfate application and cooking of parboiled rice reduced the potential non-cancer and cancer risk as compared to sunned rice. The S80 treatment and cooking of parboiled rice reduce the As exposure for both children and adults by 51% as compared to cooked sunned rice under S80 treatment and this trend was similar for all treatments. Therefore, sulfate application in soil can be recommended to produce safer rice grains and subsequent cooking of parboiled rice grain with low-As contaminated water need to be done to avoid any potential health risk in As endemic areas., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

c-MYC is deregulated in triple negative breast cancer (TNBC) pointing to be a promising biomarker for breast cancer treatment. Precise level of MYC expression is important in the control of cellular growth and proliferation. Designing of c-MYC -targeted antidotes to restore its basal level of cellular expression holds an optimistic approach towards anti-cancer treatment. MYC transcription is dominantly controlled by Nuclear Hypersensitive Element III-1 (NHE III1 ) upstream of the promoter region possessing G-Quadruplex silencer element ( Pu-27 ). We have investigated the selective binding-interaction profile of a natural phytophenolic compound Curcumin with native MYC G-quadruplex by conducting an array of biophysical experiments and in silico based Molecular Docking and Molecular Dynamic (MDs) simulation studies. Curcumin possesses immense anti-cancerous properties. We have observed significantly increased stability of MYC -G Quadruplex and thermodynamic spontaneity of Curcumin- MYC GQ binding with negative ΔG value. Transcription of MYC is tightly regulated by a complex mechanism involving promoters, enhancers and multiple transcription factors. We have used Curcumin as a model drug to understand the innate mechanism of controlling deregulated MYC back to its basal expression level. We have checked MYC -expression at transcriptional and translational level and proceeded for Chromatin Immuno-Precipitation assay (ChIP) to study the occupancy level of SP1, Heterogeneous nuclear ribonucleoprotein K (hnRNPK), Nucleoside Diphosphate Kinase 2 (NM23-H2) and Nucleolin at NHE III1 upon Curcumin treatment of MDA-MB-231 cells. We have concluded that Curcumin binding tends to drive the equilibrium towards stable G-quadruplex formation repressing MYC back to its threshold-level. On retrospection of the synergistic effect of upregulated c-MYC and BCL-2 in cancer, we have also reported a new pathway [ MYC-E2F-1-BCL-2- axis] through which Curcumin trigger apoptosis in cancer cells.Communicated by Ramaswamy H. Sarma.