Identification of Potential Inhibitors of TGFßR1 for the treatment of Cancer through Structure-based virtual screening and Molecular dynamics simulations.

Globally, cancer is one of the leading causes of death. Resistance to conventional medications, such as chemotherapy and radiation, continues to be a significant challenge in the treatment of cancer despite the availability of numerous medicines. Therefore, the highest priority is to hunt for new therapeutic agents. Transforming growth factor-beta is a pivotal regulatory cytokine that exerts significant influence over cellular processes, particularly emphasizing its role in facilitating and modulating cell proliferation. TGFß1, identified as most promising active site of the TGF-ß signaling, is a potent drug target site that has garnered wide attention for developing new anticancer agents. The present investigation investigates the potential phytochemicals as TGFßR1 inhibitors. The SB431542 complexed TGFßR1 protein model was used to screen the natural product database to obtain a compound with high binding potential. NPC247629 has emerged as the best-scored compound among all the screened compounds, demonstrating the highest affinity towards the TGFßR1 regarding docking score -17.54 kcal/mol. The MD simulation study indicated that all proposed hits are retained inside the receptor in dynamic states. The best-screened hits, NPC247629 and NPC60735, have excellent binding affinity and hold a massive potential for TGFßR1 inhibition, paving the way for promising future investigations in cancer treatment.

Insights into properties, synthesis and emerging applications of polypyrrole-based composites, and future prospective: A review.

Recent advancements in polymer science and engineering underscore the importance of creating sophisticated soft materials characterized by well-defined structures and adaptable properties to meet the demands of emerging applications. The primary objective of polymeric composite technology is to enhance the functional utility of materials for high-end purposes. Both the inherent qualities of the materials and the intricacies of the synthesis process play pivotal roles in advancing their properties and expanding their potential applications. Polypyrrole (PPy)-based composites, owing to their distinctive properties, hold great appeal for a variety of applications. Despite the limitations of PPy in its pure form, these constraints can be effectively overcome through hybridization with other materials. This comprehensive review thoroughly explores the existing literature on PPy and PPy-based composites, providing in-depth insights into their synthesis, properties, and applications. Special attention is given to the advantages of intrinsically conducting polymers (ICPs) and PPy in comparison to other ICPs. The impact of doping anions, additives, and oxidants on the properties of PPy is also thoroughly examined. By delving into these aspects, this overview aims to inspire researchers to delve into the realm of PPy-based composites, encouraging them to explore new avenues for flexible technology applications.

Unveiling microbial degradation of triclosan: Degradation mechanism, pathways, and catalyzing clean energy.

Emerging organic contaminants present in the environment can be biodegraded in anodic biofilms of microbial fuel cells (MFCs). However, there is a notable gap existing in deducing the degradation mechanism, intermediate products, and the microbial communities involved in degradation of broad-spectrum antibiotic such as triclosan (TCS). Herein, the possible degradation of TCS is explored using TCS acclimatized biofilms in MFCs. 95% of 5 mgL-1 TCS are been biodegraded within 84 h with a chemical oxygen demand (COD) reduction of 62% in an acclimatized-MFC (A-MFC). The degradation of TCS resulted in 8 intermediate products including 2,4 -dichlorophenol which gets further mineralized within the system. Concurrently, the 16S rRNA V3-V4 sequencing revealed that there is a large shift in microbial communities after TCS acclimatization and MFC operation. Moreover, 30 dominant bacterial species (relative intensity >1%) are identified in the biofilm in which Sulfuricurvum kujiense, Halomonas phosphatis, Proteiniphilum acetatigens, and Azoarcus indigens significantly contribute to dihydroxylation, ring cleavage and dechlorination of TCS. Additionally, the MFC was able to produce 818 ± 20 mV voltage output with a maximum power density of 766.44 mWm-2. The antibacterial activity tests revealed that the biotoxicity of TCS drastically reduced in the MFC effluent, signifying the non-toxic nature of the degraded products. Hence, this work provides a proof-of-concept strategy for sustainable mitigation of TCS in wastewaters with enhanced bioelectricity generation.

Lactate acidosis and simultaneous recruitment of TGF-ß leads to alter plasticity of hypoxic cancer cells in tumor microenvironment.

Lactate acidosis is often observed in the tumor microenvironment (TME) of solid tumors. This is because glucose breaks down quickly via glycolysis, causing lactate acidity. Lactate is harmful to healthy cells, but is a major oncometabolite for solid cancer cells that do not receive sufficient oxygen. As an oncometabolite, it helps tumor cells perform different functions, which helps solid hypoxic tumor cells spread to other parts of the body. Studies have shown that the acidic TME contains VEGF, Matrix metalloproteinases (MMPs), cathepsins, and transforming growth factor-ß (TGF-ß), all of which help spread in direct and indirect ways. Although each cytokine is important in its own manner in the TME, TGF-ß has received much attention for its role in metastatic transformation. Several studies have shown that lactate acidosis can cause TGF-ß expression in solid hypoxic cancers. TGF-ß has also been reported to increase the production of fatty acids, making cells more resistant to treatment. TGF-ß has also been shown to control the expression of VEGF and MMPs, which helps solid hypoxic tumors become more aggressive by helping them spread and create new blood vessels through an unknown process. The role of TGF-ß under physiological conditions has been described previously. In this study, we examined the role of TGF-ß, which is induced by lactate acidosis, in the spread of solid hypoxic cancer cells. We also found that TGF-ß and lactate work together to boost fatty acid production, which helps angiogenesis and invasiveness.

A novel circular approach to analyze the challenges associated with micro-nano plastics and their sustainable remediation techniques.

The mismanagement of consumer-discarded plastic waste (CDPW) has raised global environmental concerns about climate change. The COVID-19 outbreak has generated ∼1.6 million tons of plastic waste per day in the form of personal protective equipment (masks, gloves, face shields, and sanitizer bottles). These plastic wastes are either combustible or openly dumped in aquatic and terrestrial environments. Open dumping upsurges emerging contaminants like micro-nano plastics (MNPs) that directly enter the ecosystem and cause severe impacts on flora and fauna. Therefore, it has become an utmost priority to determine sustainable technologies that can degrade or treat MNPs from the environment. The present review assesses the sources and impacts of MNPs, various challenges, and issues associated with their remediation techniques. Accordingly, a novel sustainable circular model is recommended to increase the degradation efficiency of MNPs using biochemical and biological methods. It is also concluded that the proposed model does not only overcome environmental issues but also provides a sustainable secondary resource to meet the sustainable development goals (SDGs).

Novel and sustainable green sulfur-doped carbon nanospheres via hydrothermal process for Cd (II) ion removal.

Herein, the synthesis, characterization, and adsorption performance of a novel green sulfur-doped carbon nanosphere (S-CNs) is studied to eliminate Cd (II) ions from water effectively. S-CNs were characterized using different techniques including Raman spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), , Brunauer-Emmett-Teller (BET) specific surface area analysis and Fourier transform infrared spectrophotometry (FT-IR), were performed. The efficient adsorption of the Cd (II) ions onto S-CNs strongly depended on pH, initial concentration of Cd (II) ions, S-CNs dosage, and temperature. Four isotherm models (Langmuir, Freundlich, Temkin & Redlich Peterson) were tested for modeling. Out of four, Langmuir showed more applicability than the other three models, with a Qmax value of 242.72 mg/g. Kinetic modeling studies suggest a superior fit of the obtained experimental data with the Elovich equation (linear) and pseudo-second-order (non-linear) rather than other linear and non-linear models. Data obtained from thermodynamic modeling indicates that using S-CNs for Cd (II) ions adsorption is a spontaneous and endothermic . The current work recommends using better and recyclable S-CNs to uptake excess Cd (II) ions.

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

A comparative study based on performance and techno-economic analysis of different strategies for PV-Electrolyzer (green) hydrogen fueling incinerator system.

The integration of hydrogen in the primary energy mix requires a major technological shift in virtually every energy-related application. This study has attempted to investigate the techno-economic solar photovoltaic (PV) integrated water electrolysis and waste incineration system. Three different strategies, i.e., (i) PV + Battery(Hybrid mode with required batteries); (ii) auto-ignition (Direct coupling); and (iii) PV + Secondary-Electrolyzer(Direct coupling assisted with secondary electrolyzer), have been envisioned. The 'PV + Battery' consume 42.42 % and 15.07 % less energy than the auto-ignition and 'PV + Secondary-Electrolyzer' methods. However, the capital cost of 'PV + Battery' has been calculated to be 15.4 % and 11.8 % more than auto-ignition and 'PV + Secondary-Electrolyzer, respectively.The energy consumption relative to waste input, the 'PV + Battery' method used 80 % less energy, while auto-ignition and 'PV + Secondary-Electrolyzer' showed 70.5 % and 77.5 % less energy, respectively. Furthermore, these approaches showed a vast difference in cost-benefit for the longer run. 'PV + Battery' was forecasted to be 73.3 % and 23.3 % more expensive than auto-ignition and 'PV + Secondary-Electrolyzer' methods, respectively, for 30 years. Overall, this study can benefit from using either of these methods depending on the application, usage scale, and climatic conditions.

Advanced experimental techniques for the sensitive detection of a toxic bisphenol A using UiO-66-NDC/GO-based electrochemical sensor.

In the present study, a simple and sensitive method for detecting bisphenol A (BPA) in various environments, including groundwater, was described using a widespread electrochemical method. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects oon the nervous, reproductive, and immune systems. A novel metal-organic framework (UiO-66-NDC/GO) was synthesized, and its existence was confirmed by several characterization techniques like FTIR, UV-visible, XRD, SEM-EDX, Raman spectroscopy, and TGA. Due to the excellent electrocatalytic nature, UiO-66-NDC/GO was chosen as the sensor material and integrated on the surface of the bare carbon paste electrode (BCPE). The UiO-66-NDC/GO modified carbon paste electrode (MCPE) was engaged for the detection of BPA using techniques like cyclic Voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The applied sensor exhibited an astonishing outcome for BPA detection with high sensitivity and selectivity. The lower detection limit (LLOD) of 0.025 µM was achieved at the modified sensor with a linear concentration range of 10-70 µM. Moreover, the practical applicability of the sensor was tested on tap water, drinking water, and fresh liquid milk, giving an excellent recovery of BPA in the range of 94.8-99.3 (v.%). The proposed method could be employed for electrochemical device or a solid state device fabrication for the onsite monitoring of BPA.

Graphene oxide-based novel MOF nanohybrid for synergic removal of Pb (II) ions from aqueous solutions: Simulation and adsorption studies.

Heavy metals represent a considerable threat, and the current study deals with synthesizing a novel MOF nanocomposite by intercalating graphene oxide (GO) and linker UiO-66-NDC. It was shown that UiO-66-NDC/GO had enhanced the removal efficiency of Pb (II) ions at pH 6. The adsorption kinetics data followed the PSO (Type 2) representing chemisorption. Adsorption data were also fitted with three different isotherms, namely Temkin, Freundlich, & Langmuir, and the Temkin model exhibited the best correlation (R2 0.99), representing the chemisorption nature of the adsorption process. The maximum adsorption capacity (qmax) of Pb (II) ions using Langmuir was found to be 254.45 mg/g (298 K). The Pb (II) adsorption process was confirmed to be exothermic and spontaneous as the thermodynamic parameters H° and G° were determined to have negative values. MOF nanocomposite also represents significant reusability for up to four regeneration cycles using 0.01 M HCl; for the next four, it works quite efficiently after regeneration. Meanwhile, the simulation findings confirm the superior dynamic stability (∼08 times) of the MOF nanocomposite as compared to the GO system. The removal of Pb (II) from simulated wastewater samples using a super nano-adsorbent using a MOF nanocomposite is described here for the first time.

2D MXene Nanomaterials as Electrocatalysts for Hydrogen Evolution Reaction (HER): A Review.

MXenes, a novel family of 2D transition metal carbide, nitride and carbonitride materials, have been gaining tremendous interest in recent days as potential electrocatalysts for various electrochemical reactions, including hydrogen evolution reaction (HER). MXenes are characterized by their etchable metal layers, excellent structural stability, versatility for heteroatoms doping, excellent electronic conductivity, unique surface functional groups and admirable surface area, suitable for the role of electrocatalyst/support in electrochemical reactions, such as HER. In this review article, we summarized recent developments in MXene-based electrocatalysts synthesis and HER performance in terms of the theoretical and experimental point of view. We systematically evaluated the superiority of the MXene-based catalysts over traditional Pt/C catalysts in terms of HER kinetics, Tafel slope, overpotential and stability, both in acidic and alkaline electrolytic environments. We also pointed out the motives behind the electro catalytic enhancements, the effect of synthesis conditions, heteroatom doping, the effect of surface terminations on the electrocatalytic active sites of various MXenes families. At the end, various possible approaches were recommended for a deeper understanding of the active sites and catalytic improvement of MXenes catalysts for HER.

Microplastics: Occurrences, treatment methods, regulations and foreseen environmental impacts.

Microplastics are a silent threat that represent a high degree of danger to the environment in its different ecosystems and of course will also have an important impact on the health of living organisms. It is evident the need to have effective treatments for their treatment, however this is not a simple task, this as a result of the behavior of microplastics in wastewater treatment plants due to their different types and nature, their long molecular chain, reactivity against water, size, shape and the functional groups they carry. Wastewater treatment plants are at the circumference of the release of these wastes into the environment. They often act as a source of many contaminations, which makes this problem more complex. Challenges such as detection in the current scenario using the latest analytical techniques impede the correct understanding of the problem. Due to microplastics, treatment plants have operational and process stability problems. This review paper will present the in-depth situation of occurrence of microplastics, their detection, conventional and advanced treatment methods as well as implementation of legislations worldwide in a comprehensive manner. It has been observed that no innovative or new technologies have emerged to treat microplastics. Therefore, in this article, technologies targeting wastewater treatment plants are critically analyzed. This will help to understand their fate, but also to develop state-of-the-art technologies or combinations of them for the selective treatment of microplastics. The pros and cons of the treatment methods adopted and the knowledge gaps in legislation regarding their implementation are also comprehensively analyzed. This critical work will offer the development of new strategies to restrict microplastics.

Biomimicry of ruminant digestion strategies for accelerating lignocellulose bioconversion in anaerobic digestion.

Biomimicking ruminant digestion strategies (RDSs) into anaerobic digestion (AD) enables efficient bioconversion of lignocellulosic biomass. Understanding RDSs is essential to translate their features into designing and developing bioprocesses and bioreactors. Here, we discuss insights into recently developed bioinspired bioprocesses, bioreactors, and future AD systems based on RDSs.

Chlorophyll sensitized (BiO)2CO3/ CdWO4/rGO nano-hybrid assembly for solar assisted photo-degradation of chlorzoxazone.

In the present laboratory scale experiment, we report the fabrication of chlorophyll sensitized (BiO)2CO3/CdWO4/rGO (BCR) photo-catalyst. The green approach has been adopted for boosting the optical activity by chlorophyll as a sensitizer. The functionality, nature and surface compositions of synthesized photo-catalyst have been identified by FTIR, XRD and XPS instrumentation. The internal and surface morphology has been studied using FE-SEM and HR-TEM. The optical activity has been investigated by UV-vis and photoluminescence spectroscopy. The catalytic activity of chlorophyll sensitized BCR have been tested for the photo degradation of Chlorzoxazone (CZX) under simulated visible light for 90 min. The detailed comparison has been studied for the different loading amount of chlorophyll and RGO onto BCR photo-catalyst. The potential of BCR for the photo-degradation of CZX was investigated under various operational parameters such as catalysts dosage, pollutant concentration, effect of pH and ions etc. Approximately, 96.2% of CZX has been degraded over 90 min with the optimum catalyst amount 250 mgL-1 at pH 7. The ●OH radical has been identified as major reactive species using radical scavenging experiment. The mineralization of CZX has been evaluated in terms of HR-MS and TOC-COD analysis.

Comprehensive technological assessment for different treatment methods of leather tannery wastewater.

The leather-making process necessitates large amounts of water and consequently generates tons of liquid waste as leather tannery wastewater (TWW) is disposed of directly in the open environment. Open disposal of untreated TWW into the natural environment causes an accumulation of various polluting compounds, including heavy metals, dyes, suspended solids inorganic matter, biocides, oils, tannins, and other toxic chemicals. It thus poses potential hazards to the environment and human health. This study primarily focuses on providing in-depth insight into the characteristics, treatment strategies, and regulatory frameworks for managing TWW in leather processing industries. Different technologies of conventional physico-chemical (equalization, coagulation, and adsorption), advanced approaches (Fenton oxidation, ozonation, cavitation), thermo-catalytic and biological treatments available to treat TWW, and their integrative approaches were also highlighted. This review also sheds light on the most frequently applied technologies to reduce contaminant load from TWW though there are several limitations associated with it such as being ineffective for large quantities of TWW, waste generation during treatment, and high operational and maintenance (O&M) costs. It is concluded that the sustainable alternatives applied in the current TWW technologies can minimize O&M costs and recirculate the treated water in the environment. The exhaustive observations and recommendations presented in this article are helpful in the industry to manage TWW and recirculate the water in a sustainable manner.

Electrocoagulation treatment of raw palm oil mill effluent: Optimization process using high current application.

In the electrocoagulation wastewater treatment process, extremely polluted water treatment requires an effective technique, and using high current is one of those. This study aims to optimize electrocoagulation parameters such as operation time, electrodes gap and the initial pH by applying high current intensity to treat palm oil mill effluent (POME) via Box-Behnken design (BBD) method. Chemical oxygen demand (COD), biological oxygen demand (BOD), and suspended solids (SS) were used as the response variables in the quadratic polynomial model. Most of the selected models in the analysis of variance (ANOVA) have shown significant results. A high connection between the parameters and dependent variables was surprisingly discovered in this study which the obtained value of R2 for removal percentage of COD, BOD and SS were 0.9975, 0.9984 and 0.9979 respectively. Optimal removal was achieved at 19.07 A of current intensity (equivalent to 542 mA/cm2 of current density), 44.97 min of treatment time, 8.60 mm of inter-electrode distance and 4.37 of pH value, resulted in 97.21%, 99.26% and 99.00% of COD, BOD and SS removal respectively. This optimized scheme of operating parameters combination offers an alternate choice for enhancing the treatment efficiency of POME and also can be a benchmark for other researchers to treat highly polluted wastewater.

Anaerobic digestion of sugarcane bagasse for biogas production and digestate valorization.

Sugarcane bagasse is an abundantly available agricultural waste having high potential that is still underutilized and mostly burnt as fuel. There are various processes available for bagasse utilization in improved ways and one such process is anaerobic digestion (AD) of bagasse for biogas production. The complex structure of biomass is recalcitrant to degradation and is a major hindrance for the anaerobic digestion, so different pretreatment methods are applied to deconstruct the bagasse for microbial digestion. In this review, different processes developed for the pretreatment of bagasse and their effect on biogas production have been extensively covered. Moreover, combination of pretreatment methods, co-digestion of bagasse with other waste (nitrogen rich or easily digestible) for enhanced biogas production and biomethane generation along with other value-added products has also been reviewed. The digestate contains a significant amount of organics with partial recovery of energy and products and is generated in huge amount that further creates disposal problem. Therefore, integration of digestate valorization with AD through gasification, pyrolysis, hydrothermal carbonization and use of microalgae for maximum recovery of energy and value-added products have also been evaluated. Thus, this review highlights major emerging area of research for improvement in bagasse based processes for enhanced biogas production along with digestate valorization to make the overall process economical and sustainable.

Leveraging artificial intelligence in bioelectrochemical systems.

Bioelectrochemical systems (BESs) are highly evolved and sophisticated systems that produce bioenergy via exoelectrogenic microbes. Artificial intelligence (AI) helps to understand, relate, model, and predict both process parameters and microbial diversity, resulting in higher performance. This approach has revolutionized BESs through highly advanced computational algorithms that best suit the systems' architecture.

Repurposing Combination Therapy of Voacamine With Vincristine for Downregulation of Hypoxia-Inducible Factor-1α/Fatty Acid Synthase Co-axis and Prolyl Hydroxylase-2 Activation in ER+ Mammary Neoplasia.

The current study investigated the role of combination therapy with voacamine and vincristine in preventing mammary gland carcinoma through prolyl hydroxylase-2 activation. Prolyl hydroxylase-2 activation leads to the downregulation of hypoxia-inducible factor-1α and fatty acid synthase. Overexpression of hypoxia-inducible factor-1α and fatty acid synthase has been previously reported in solid tumors of the mammary gland. After screening a battery of natural compounds similar to vincristine, voacamine was selected as a possible prolyl hydroxylase-2 activator, and its activity was evaluated using a 7,12-dimethylbenz[a]anthracene-induced rat model. The combination therapy was evaluated for cardiac toxicity using a hemodynamic profile. Angiogenic markers were evaluated by carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity using hematoxylin and eosin staining. The antioxidant potential was delineated using oxidative stress markers. The serum metabolomic profile was studied using NMR spectroscopy, and the disruption of fatty acids was evaluated using gas chromatography. Western blotting of proteins involved in hypoxic pathways was performed to decipher the action of therapy at the molecular level. Immunoblotting analysis validated that combination therapy has potential toss with prolyl hydroxylase-2 activity and thus initiates proteolytic degradation of hypoxia-inducible factor-1α and its consequent effects. Combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells. The present study explored the role of voacamine inactivation of prolyl hydroxylase-2, which can decrease the overexpression of hypoxia-inducible factor-1α and fatty acid synthase in mammary gland carcinoma cells.

Bio-synthesized Cu-ZnO hetro-nanostructure for catalytic degradation of organophosphate chlorpyrifos under solar illumination.

In present study, a simple, effective and rapid green method using leaf extract of Melia azedarach was explored for the synthesis of Cu-ZnO nano heterojunction particles. The leaf extract of Melia azedarach acts as a reducing agent and prevents the agglomeration of nanoparticles. Different standard analytical techniques were used to study the morphology and size of synthesized nanocomposite. The efficiency of the synthesized material was tested as a photocatalyst for the degradation of simulated wastewater having chlorpyriphos pesticide. The different factors have been investigated such as pH of the solution, catalyst dosage and conact time. Approximately, 81% of chlorpyrifos was degraded after 240 min of solar illumination. The generation of hydroxyl radicals at the catalysts surface owing to photo-irradiation contributed to the chlorpyrifos degradation. The maximum photo-degradation (91%) of pesticides was observed at 6.0 pH. The pathway for the degradation of chlorpyriphos has been checked by LC-MS and this hinting the absence of any harmfull side product. The COD removal and TOC was found to be 32.4% and 28.5%, respectively. The photodegradation of chlorpyriphos using Cu-ZnO nanocomposite was followed the pseudo-first-order kinetic with higher value of regressiuon coefficient (0.99).