Deciphering KDM8 dysregulation and CpG methylation in hepatocellular carcinoma using multi-omics and machine learning.

Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers. Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model. Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891. Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.

Changes in gene function can play a role in causing cancer. In this study, we looked at how a specific gene called KDM8 behaves in liver cancer. By analyzing a large set of liver cancer samples, we investigated how gene interactions are different in this disease and if they can help predict liver cancer risk. Our results show that the KDM8 gene is less active, and its DNA gets chemically modified more often in liver cancer. We also found a group of genes and DNA changes, which are linked to the disease. Using this information, we identified 16 important markers and built a computer model that can accurately predict liver cancer. We found that DNA methylation at a specific spot called cg02871891 is especially important for predicting liver cancer. Overall, our study suggests that high levels of DNA methylation may lead to reduced KDM8 activity in liver cancer, which could be important for future research and better diagnostic tools.

N-to-S Acyl Transfer as an Enabling Strategy in Asymmetric and Chemoenzymatic Synthesis.

The observation of thioester-mediated acyl transfer processes in nature has inspired the development of novel protein synthesis and functionalization methodologies. The chemoselective transfer of an acyl group from S-to-N is the basis of several powerful ligation strategies. In this work, we sought to apply the reverse process, the transfer of an acyl group from N-to-S, as a method to convert stable chiral amides into more reactive thioesters. To this end, we developed a novel cysteine-derived oxazolidinone that serves as both a chiral imide auxiliary and an acyl transfer agent. This auxiliary combines the desirable features of rigid chiral imides as templates for asymmetric transformations with the synthetic applicability of thioesters. We demonstrate that the auxiliary can be applied in a range of highly selective asymmetric transformations. Subsequent intramolecular N-to-S acyl transfer of the chiral product and in situ trapping of the resulting thioester provides access to diverse carboxylic acid derivatives under mild conditions. The oxazolidinone thioester products can also be isolated and used in Pd-mediated transformations to furnish highly valuable chiral scaffolds, such as noncanonical amino acids, cyclic ketones, tetrahydropyrones, and dihydroquinolinones. Finally, we demonstrate that the oxazolidinone thioesters can also serve as a surrogate for SNAC-thioesters, enabling their seamless use as non-native substrates in biocatalytic transformations.

Toxic trespassers: Uncovering phthalates and organophosphate flame retardants in children's rooms and their health implications.

Organophosphate flame retardants (OPEs) and phthalates have garnered significant attention due to their widespread presence in indoor environments. Many recent investigations have reported extensive contamination of indoor dust, air, children's toys, and other environmental compartments with these chemicals. This research aimed to analyze OPEs and phthalates in air (PM10) and dust samples collected from the bedrooms of children (N = 30) residing in various households in Jeddah, Saudi Arabia. High mean levels (ng/g) of phthalates namely DEHP (1438600) and DnBP (159200) were found in indoor dust while TPhP (5620) was the major OPEs in indoor dust. Similarly, DEHP and DnBP were the predominant phthalates in PM10 samples, exhibiting mean levels of 560 and 680 ng/m3, respectively. However, TCPP was the main OPEs with average levels of 72 ng/m3 in PM10 samples. The majority of individual phthalates and OPEs were detected in 90-100 % of the dust samples, whereas in PM10 samples, their presence ranged from 25 % to 100 %. The concentrations of OPEs were notably greater than those of PBDEs and other BFRs previously reported in these samples, suggesting their broader use than alternative BFRs. The estimated long-term non-carcinogenic risk, hazardous index (HI) and daily exposure via dust for children was above threshold levels for DEHP. On the other hand, the cumulative risk of cancer was below the concerning levels. Further research is required to explore diverse groups of chemicals in indoor microenvironments particularly significant for children, such as kindergartens, primary schools, and their rooms at home.

Nicotinamide N-methyltransferase mediates lipofibroblast-myofibroblast transition and apoptosis resistance.

Metabolism controls cellular phenotype and fate. In this report, we demonstrate that nicotinamide N-methyltransferase (NNMT), a metabolic enzyme that regulates developmental stem cell transitions and tumor progression, is highly expressed in human idiopathic pulmonary fibrosis (IPF) lungs, and is induced by the pro-fibrotic cytokine, transforming growth factor-ß1 (TGF-ß1) in lung fibroblasts. NNMT silencing reduces the expression of extracellular matrix proteins, both constitutively and in response to TGF-ß1. Furthermore, NNMT controls the phenotypic transition from homeostatic, pro-regenerative lipofibroblasts to pro-fibrotic myofibroblasts. This effect of NNMT is mediated, in part, by the downregulation of lipogenic transcription factors, TCF21 and PPARγ, and the induction of a less proliferative but more differentiated myofibroblast phenotype. NNMT confers an apoptosis-resistant phenotype to myofibroblasts that is associated with the downregulation of pro-apoptotic members of the Bcl-2 family, including Bim and PUMA. Together, these studies indicate a critical role for NNMT in the metabolic reprogramming of fibroblasts to a pro-fibrotic and apoptosis-resistant phenotype and support the concept that targeting this enzyme may promote regenerative responses in chronic fibrotic disorders such as IPF.

Nanobiochar Associated Ammonia Emission Mitigation and Toxicity to Soil Microbial Biomass and Corn Nutrient Uptake from Farmyard Manure.

The unique properties of NB, such as its nano-size effect and greater adsorption capacity, have the potential to mitigate ammonia (NH3) emission, but may also pose threats to soil life and their associated processes, which are not well understood. We studied the influence of different NB concentrations on NH3 emission, soil microbial biomass, nutrient mineralization, and corn nutrient uptake from farmyard manure (FM). Three different NB concentrations i.e., 12.5 (NB1), 25 (NB2), and 50% (NB3), alone and in a fertilizer mixture with FM, were applied to corn. NB1 alone increased microbial biomass in soil more than control, but other high NB concentrations did not influence these parameters. In fertilizer mixtures, NB2 and NB3 decreased NH3 emission by 25% and 38%, respectively, compared with FM alone. Additionally, NB3 significantly decreased microbial biomass carbon, N, and soil potassium by 34%, 36%, and 14%, respectively, compared with FM. This toxicity to soil parameters resulted in a 21% decrease in corn K uptake from FM. Hence, a high NB concentration causes toxicity to soil microbes, nutrient mineralization, and crop nutrient uptake from the FM. Therefore, this concentration-dependent toxicity of NB to soil microbes and their associated processes should be considered before endorsing NB use in agroecosystems.

Multicomponent Petasis reaction for the identification of pyrazine based multi-target directed anti-Alzheimer's agents: In-silico design, synthesis, and characterization.

Multi-target directed ligands (MTDLs) have recently attracted significant interest due to their exceptional effectiveness against multi-factorial Alzheimer's disease. The present work described the development of pyrazine-based MTDLs using multicomponent Petasis reaction for the dual inhibition of tau-aggregation and human acetylcholinesterase (hAChE). The molecular structure of synthesized ligands was validated by 1H & 13C NMR and mass spectrometry. The screened compounds were shown to have a strong inhibitory effect at 10 µM concentration against tau-oligomerization and hAChE, but only moderate inhibitory activity against Aß42. Among all the compounds, the half-maximal inhibitory concentration (IC50) for 21 and 24 against hAChE were 0.71 µM and 1.09 µM, respectively, while they displayed half-maximal effective concentrations (EC50) values of 2.21 µM and 2.71 µM for cellular tau-oligomerization, respectively. Additionally, an MTT experiment using tau-expressing SH-SY5Y neuroblastoma cells revealed that 21 was more neuroprotective than the FDA-approved medication donepezil. Furthermore, an MD simulation study was performed to investigate the dynamics and stability of AChE-21 and AChE-24 complexes in an aqueous environment. The MM-PBSA calculations were performed to evaluate the binding of 21 and 24 with AChE, and the relative binding energy was calculated as -870.578 and -875.697 kJ mol-1, respectively. As a result, the study offered insight into the design of new MTDLs and highlighted 21 as a potential roadblock to the development of anti-AD medications.

Environmental evaluation of polyhydroxyalkanoates from animal slaughtering waste using Material Input Per Service Unit.

The massive production and extensive use of fossil-based non-biodegradable plastics are leading to their environmental accumulation and ultimately cause health threats to animals, humans, and the biosphere in general. The problem can be overcome by developing eco-friendly ways for producing plastics-like biopolymers from waste residues such as of agricultural origin. This will solve two currently prevailing social issues: waste management and the efficient production of a biopolymer that is environmentally benign, polyhydroxyalkanoates (PHA). The current study assesses the environmental impact of biopolymer (PHA) manufacturing, starting from slaughterhouse waste as raw material. The Material Input Per Service Unit methodology (MIPS) is used to examine the sustainability of the PHA production process. In addition, the impact of shifting from business-as-usual energy provision (i.e., electricity from distribution grid network and heat provision from natural gas) to alternative renewable energy sources is also evaluated. As a major outcome, it is shown that the abiotic material contribution for PHA production process is almost double for using hard coal as an energy source than the petro-plastic low-density-poly(ethene) (LPDE), which PHA shall ultimately replace. Likewise, abiotic material contribution is 43 % and 7 % higher when using the electricity from the European electricity mix (EU-27 mix) and biogas, respectively, than in the case of LDPE production. However, PHA production based on wind power for energy provision has 12 % lower abiotic material input than LDPE. Furthermore, the water input decreases when moving from the EU-27 mix to wind power. The reduction in water consumption for various electricity provision resources amounts to 20 % for the EU-27 mix, 25 % for hard coal, 71 % for wind, and 70 % for biogas. As the main conclusion, it is demonstrated that using wind farm electricity to generate PHA is the most environmentally friendly choice. Biogas is the second-best choice, although it requires additional abiotic material input.

Comprehensive review of environmental factors influencing the performance of photovoltaic panels: Concern over emissions at various phases throughout the lifecycle.

Recently, solar photovoltaic (PV) technology has shown tremendous growth among all renewable energy sectors. The attractiveness of a PV system depends deeply of the module and it is primarily determined by its performance. The quantity of electricity and power generated by a PV cell is contingent upon a number of parameters that can be intrinsic to the PV system itself, external or environmental. Thus, to improve the PV panel performance and lifetime, it is crucial to recognize the main parameters that directly influence the module during its operational lifetime. Among these parameters there are numerous factors that positively impact a PV system including the temperature of the solar panel, humidity, wind speed, amount of light, altitude and barometric pressure. On the other hand, the module can be exposed to simultaneous environmental stresses such as dust accumulation, shading and pollution factors. All these factors can gradually decrease the performance of the PV panel. This review not only provides the factors impacting PV panel's performance but also discusses the degradation and failure parameters that can usually affect the PV technology. The major points include: 1) Total quantity of energy extracted from a photovoltaic module is impacted on a daily, quarterly, seasonal, and yearly scale by the amount of dust formed on the surface of the module. 2) Climatic conditions as high temperatures and relative humidity affect the operation of solar cells by more than 70% and lead to a considerable decrease in solar cells efficiency. 3) The PV module current can be affected by soft shading while the voltage does not vary. In the case of hard shadowing, the performance of the photovoltaic module is determined by whether some or all of the cells of the module are shaded. 4) Compared to more traditional forms of energy production, PV systems offer a significant number of advantages to the environment. Nevertheless, these systems can procure greenhouse gas emissions, especially during the production stages. In conclusion, this study underlines the importance of considering multiple parameters while evaluating the performance of photovoltaic modules. Environmental factors can have a major impact on the performance of a PV system. It is critical to consider these factors, as well as intrinsic and other intermediate factors, to optimize the performance of solar energy systems. In addition, continuous monitoring and maintenance of PV systems is essential to ensure maximum efficiency and performance.

Novel mediators of idiopathic pulmonary fibrosis.

Fibrosis involving the lung may occur in many settings, including in association with known environmental agents, connective tissue diseases, and exposure to drugs or radiation therapy. The most common form is referred to as 'idiopathic' since a causal agent or specific association has not been determined; the strongest risk factor for idiopathic pulmonary fibrosis is aging. Emerging studies indicate that targeting certain components of aging biology may be effective in mitigating age-associated fibrosis. While transforming growth factor-ß1 (TGF-ß1) is a central mediator of fibrosis in almost all contexts, and across multiple organs, it is not feasible to target this canonical pathway at the ligand-receptor level due to the pleiotropic nature of its actions; importantly, its homeostatic roles as a tumor-suppressor and immune-modulator make this an imprudent strategy. However, defining targets downstream of its receptor(s) that mediate fibrogenesis, while relatively dispenable for tumor- and immune-suppressive functions may aid in developing safer and more effective therapies. In this review, we explore molecular targets that, although TGF-ß1 induced/activated, may be relatively more selective in mediating tissue fibrosis. Additionally, we explore epigenetic mechanisms with global effects on the fibrogenic process, as well as metabolic pathways that regulate aging and fibrosis.

Analysis and Modeling of Air Pollution in Extreme Meteorological Conditions: A Case Study of Jeddah, the Kingdom of Saudi Arabia.

Air pollution has serious environmental and human health-related consequences; however, little work seems to be undertaken to address the harms in Middle Eastern countries, including Saudi Arabia. We installed a continuous air quality monitoring station in Jeddah, Saudi Arabia and monitored several air pollutants and meteorological parameters over a 2-year period (2018-2019). Here, we developed two supervised machine learning models, known as quantile regression models, to analyze the whole distribution of the modeled pollutants, not only the mean values. Two pollutants, namely NO2 and O3, were modeled by dividing their concentrations into several quantiles (0.05, 0.25, 0.50, 0.75, and 0.95) and the effect of several pollutants and meteorological variables was analyzed on each quantile. The effect of the explanatory variables changed at different segments of the distribution of NO2 and O3 concentrations. For instance, for the modeling of O3, the coefficients of wind speed at quantiles 0.05, 0.25, 0.5, 0.75, and 0.95 were 1.40, 2.15, 2.34, 2.31, and 1.56, respectively. Correlation coefficients of 0.91 and 0.92 and RMSE values of 14.41 and 8.96, which are calculated for the cross-validated models of NO2 and O3, showed an acceptable model performance. Quantile analysis aids in better understanding the behavior of air pollution and how it interacts with the influencing factors.

Recent advancements in chromone as a privileged scaffold towards the development of small molecules for neurodegenerative therapeutics.

Neurodegenerative disorders, i.e., Alzheimer's or Parkinson's disease, involve progressive degeneration of the central nervous system, resulting in memory loss and cognitive impairment. The intensification of neurodegenerative research in recent years put some molecules into clinical trials, but still there is an urgent need to develop effective therapeutic molecules to combat these diseases. Chromone is a well-identified privileged structure for the design of well-diversified therapeutic molecules of potential pharmacological interest, particularly in the field of neurodegeneration. In this short review, we focused on the recent advancements and developments of chromones for neurodegenerative therapeutics. Different small molecules were reviewed as multi-target-directed ligands (MTDLs) with potential inhibition of AChE, BuChE, MAO-A, MAO-B, Aß plaque formation and aggregation. Recently developed MTDLs emphasized that the chromone scaffold has the potential to develop new molecules for the treatment of neurodegenerative diseases.

Biofuel supply chain management in the circular economy transition: An inclusive knowledge map of the field.

Investment in biofuels, as sustainable alternatives for fossil fuels, has gained momentum over the last decade due to the global environmental and health concerns regarding fossil fuel consumption. Hence, effective management of biofuel supply chain (BSC) components, including biomass feedstock production, biomass logistics, biofuel production in biorefineries, and biofuel distribution to consumers, is crucial in transitioning towards a low-carbon and circular economy (CE). The present study aims to render an inclusive knowledge map of the BSC-related scientific production. In this vein, a systematic review, supported by a keywords co-occurrence analysis and qualitative content analysis, was carried out on a total of 1,975 peer-reviewed journal articles in the target literature. The analysis revealed four major research hotspots in the BSC literature, namely (1) biomass-to-biofuel supply chain design and planning, (2) environmental impacts of biofuel production, (3) biomass to bioenergy, and (4) techno-economic analysis of biofuel production. Besides, the findings showed that the following subject areas of research in the BSC research community have recently attracted more attention: (i) global warming and climate change mitigation, (ii) development of the third-generation biofuels produced from algal biomass, which has recently gained momentum in the CE debate, and (iii) government incentives, pricing, and subsidizing policies. The provided insights shed light on the understanding of researchers, stakeholders, and policy-makers involved in the sustainable energy sector by outlining the main research backgrounds, developments, and tendencies within the BSC arena. Looking at the provided knowledge map, potential research directions in BSCs towards implementing the CE model, including (i) integrative policy convergence at macro, meso, and micro levels, and (ii) industrializing algae-based biofuel production towards the CE transition, were proposed.

Sustainable microalgal biomass valorization to bioenergy: Key challenges and future perspectives.

The global trend is shifting toward circular economy systems. It is a sustainable environmental approach that sustains economic growth from the use of resources while minimizing environmental impacts. The multiple industrial use of microalgal biomass has received great attention due to its high content of essential nutrients and elements. Nevertheless, low biomass productivity, unbalanced carbon to nitrogen (C/N) ratio, resistant cellular constituents, and the high cost of microalgal harvesting represent the major obstacles for valorization of algal biomass. In recent years, microalgae biomass has been a candidate as a potential feedstock for different bioenergy generation processes with simultaneous treating wastewater and CO2 capture. An overview of the appealing features and needed advancements is urgently essential for microalgae-derived bioenergy generation. The present review provides a timely outlook and evaluation of biomethane production from microalgal biomass and related challenges. Moreover, the biogas recovery potential from microalgal biomass through different pretreatments and synergistic anaerobic co-digestion (AcoD) with other biowastes are evaluated. In addition, the removal of micropollutants and heavy metals by microalgal cells via adsorption and bioaccumulation in their biomass is discussed. Herein, a comprehensive review is presented about a successive high-throughput for anaerobic digestion (AD) of the microalgal biomass in order to achieve for sustainable energy source. Lastly, the valorization of the digestate from AD of microalgae for agricultural reuse is highlighted.

Conductive Polymers and Their Nanocomposites as Adsorbents in Environmental Applications.

Proper treatment and disposal of industrial pollutants of all kinds are a global issue that presents significant techno-economical challenges. The presence of pollutants such as heavy metal ions (HMIs) and organic dyes (ODs) in wastewater is considered a significant problem owing to their carcinogenic and toxic nature. Additionally, industrial gaseous pollutants (GPs) are considered to be harmful to human health and may cause various environmental issues such as global warming, acid rain, smog and air pollution, etc. Conductive polymer-based nanomaterials have gained significant interest in recent years, compared with ceramics and metal-based nanomaterials. The objective of this review is to provide detailed insights into different conductive polymers (CPs) and their nanocomposites that are used as adsorbents for environmental remediation applications. The dominant types of CPs that are being used as adsorbent materials include polyaniline (PANI), polypyrrole (Ppy), and polythiophene (PTh). The various adsorption mechanisms proposed for the removal of ODs, HMIs, and other GPs by the different CPs are presented, together with their maximum adsorption capacities, experimental conditions, adsorption, and kinetic models reported.

A Compressed Sensing Approach to Pooled RT-PCR Testing for COVID-19 Detection.

We propose 'Tapestry', a single-round pooled testing method with application to COVID-19 testing using quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) that can result in shorter testing time and conservation of reagents and testing kits, at clinically acceptable false positive or false negative rates. Tapestry combines ideas from compressed sensing and combinatorial group testing to create a new kind of algorithm that is very effective in deconvoluting pooled tests. Unlike Boolean group testing algorithms, the input is a quantitative readout from each test and the output is a list of viral loads for each sample relative to the pool with the highest viral load. For guaranteed recovery of [Formula: see text] infected samples out of [Formula: see text] being tested, Tapestry needs only [Formula: see text] tests with high probability, using random binary pooling matrices. However, we propose deterministic binary pooling matrices based on combinatorial design ideas of Kirkman Triple Systems, which balance between good reconstruction properties and matrix sparsity for ease of pooling while requiring fewer tests in practice. This enables large savings using Tapestry at low prevalence rates while maintaining viability at prevalence rates as high as 9.5%. Empirically we find that single-round Tapestry pooling improves over two-round Dorfman pooling by almost a factor of 2 in the number of tests required. We evaluate Tapestry in simulations with synthetic data obtained using a novel noise model for RT-PCR, and validate it in wet lab experiments with oligomers in quantitative RT-PCR assays. Lastly, we describe use-case scenarios for deployment.

Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells.

Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or 'alveolospheres' with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology.

Many tissues in the body are capable of regenerating by replacing defective or worn-out cells with new ones. This process relies heavily on stem cells, which are precursor cells that lack a set role in the body and can develop into different types of cells under the right conditions. Tissues often have their own pool of stem cells that they use to replenish damaged cells. But as we age, this regeneration process becomes less effective. Many of our organs, such as the lungs, are lined with epithelial cells. These cells form a protective barrier, controlling what substances get in and out of the tissue. Alveoli are parts of the lungs that allow oxygen and carbon dioxide to move between the blood and the air in the lungs. And alveoli rely on an effective epithelial cell lining to work properly. To replenish these epithelial cells, alveoli have pockets, in which a type of epithelial cell, known as AEC2, lives. These cells can serve as stem cells, developing into a different type of cell under the right conditions. To work properly, AEC2 cells require close interactions with another type of cell called L-MSC, which supports the maintenance of other cells and also has the ability to differentiate into several other cell types. Both cell types can be found close together in these stem cell pockets. So far, it has been unclear how aging affects how these cells work together to replenish the epithelial lining of the alveoli. To investigate, Chanda et al. probed AEC2s and L-MSCs in the alveoli of young and old mice. The researchers collected both cell types from young (2-3 months) and aged (22-24 months) mice. Various combinations of these cells were grown to form 3D structures, mimicking how the cells grow in the lungs. Young L-MSCs formed normal 3D structures with both young and aged AEC2 cells. But aged L-MSCs developed abnormal, loose structures with AEC2 cells (both young and old cells). Aged L-MSCs were found to have higher levels of an enzyme (called Nox4) that produces oxidants and other 'pro-aging' factors, compared to young L-MSCs. However, reducing Nox4 levels in aged L-MSCs allowed these cells to form normal 3D structures with young AEC2 cells, but not aged AEC2 cells. These findings highlight the varying effects specific stem cells have, and how their behaviour is affected by pro-aging factors. Moreover, the pro-aging enzyme Nox4 shows potential as a therapeutic target ­ downregulating its activity may reverse critical effects of aging in cells.

Emerging challenges of air pollution and particulate matter in China, India, and Pakistan and mitigating solutions.

This study examines point and non-point sources of air pollution and particulate matter and their associated socioeconomic and health impacts in South Asian countries, primarily India, China, and Pakistan. The legislative frameworks, policy gaps, and targeted solutions are also scrutinized. The major cities in these countries have surpassed the permissible limits defined by WHO for sulfur dioxide, carbon monoxide, particulate matter, and nitrogen dioxide. As a result, they are facing widespread health problems, disabilities, and causalities at extreme events. Populations in these countries are comparatively more prone to air pollution effects because they spend more time in the open air, increasing their likelihood of exposure to air pollutants. The elevated level of air pollutants and their long-term exposure increases the susceptibility to several chronic/acute diseases, i.e., obstructive pulmonary diseases, acute respiratory distress, chronic bronchitis, and emphysema. More in-depth spatial-temporal air pollution monitoring studies in China, India, and Pakistan are recommended. The study findings suggest that policymakers at the local, national, and regional levels should devise targeted policies by considering all the relevant parameters, including the country's economic status, local meteorological conditions, industrial interests, public lifestyle, and national literacy rate. This approach will also help design and implement more efficient policies which are less likely to fail when brought into practice.

Restoration of SIRT3 gene expression by airway delivery resolves age-associated persistent lung fibrosis in mice.

Aging is a risk factor for progressive fibrotic disorders involving diverse organ systems, including the lung. Idiopathic pulmonary fibrosis, an age-associated degenerative lung disorder, is characterized by persistence of apoptosis-resistant myofibroblasts. In this report, we demonstrate that sirtuin-3 (SIRT3), a mitochondrial deacetylase, is downregulated in lungs of IPF human subjects and in mice subjected to lung injury. Over-expression of the SIRT3 cDNA via airway delivery restored capacity for fibrosis resolution in aged mice, in association with activation of the forkhead box transcription factor, FoxO3a, in fibroblasts, upregulation of pro-apoptotic members of the Bcl-2 family, and recovery of apoptosis susceptibility. While transforming growth factor-ß1 reduced levels of SIRT3 and FoxO3a in lung fibroblasts, cell non-autonomous effects involving macrophage secreted products were necessary for SIRT3-mediated activation of FoxO3a. Together, these findings reveal a novel role of SIRT3 in pro-resolution macrophage functions that restore susceptibility to apoptosis in fibroblasts via a FoxO3a-dependent mechanism.

Baf45a Mediated Chromatin Remodeling Promotes Transcriptional Activation for Osteogenesis and Odontogenesis.

Chromatin remodeling, specifically the tissue-specific regulation in mineralized tissues, is an understudied avenue of gene regulation. Here we show that Baf45a and Baf45d, two Baf45 homologs belong to ATPase-dependent SWI/SNF chromatin remodeling complex, preferentially expressed in osteoblasts and odontoblasts compared to Baf45b and Baf45c. Recently, biochemical studies revealed that BAF45A associates with Polybromo-associated BAF (PBAF) complex. However, the BAF45D subunit belongs to the polymorphic canonical BRG1-associated factor (cBAF) complex. Protein profiles of osteoblast and odontoblast differentiation uncovered a significant increase of BAF45A and PBAF subunits during early osteoblast and odontoblast maturation. Chromatin immunoprecipitation sequencing (ChIP-seq) during the bone marrow stromal cells (BMSCs) differentiation showed higher histone H3K9 and H3K27 acetylation modifications in the promoter of Baf45a and Baf45d and increased binding of bone and tooth specific transcription factor RUNX2. Overexpression of Baf45a in osteoblasts activates genes essential for the progression of osteoblast maturation and mineralization. Furthermore, shRNA-mediated knockdown of Baf45a in odontoblasts leads to markedly altered genes responsible for the proliferation, apoptosis, DNA repair, and modest decrease in dentinogenic marker gene expression. Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) assay in Baf45a knockout osteoblasts revealed a noticeable reduction in chromatin accessibility of osteoblast and odontoblast specific genes, along with transcription factor Atf4 and Klf4. Craniofacial mesenchyme-specific loss of Baf45a modestly reduced the mineralization of the tooth and mandibular bone. These findings indicated that BAF45A-dependent mineralized tissue-specific chromatin remodeling through PBAF-RUNX2 crosstalk results in transcriptional activation is critical for early differentiation and matrix maturation of mineralized tissues.

Sustainability Evaluation of Polyhydroxyalkanoate Production from Slaughterhouse Residues Utilising Emergy Accounting.

High raw material prices and rivalry from the food industry have hampered the adoption of renewable resource-based goods. It has necessitated the investigation of cost-cutting strategies such as locating low-cost raw material supplies and adopting cleaner manufacturing processes. Exploiting waste streams as substitute resources for the operations is one low-cost option. The present study evaluates the environmental burden of biopolymer (polyhydroxyalkanoate) production from slaughtering residues. The sustainability of the PHA production process will be assessed utilising the Emergy Accounting methodology. The effect of changing energy resources from business as usual (i.e., electricity mix from the grid and heat provision utilising natural gas) to different renewable energy resources is also evaluated. The emergy intensity for PHA production (seJ/g) shows a minor improvement ranging from 1.5% to 2% by changing only the electricity provision resources. This impact reaches up to 17% when electricity and heat provision resources are replaced with biomass resources. Similarly, the emergy intensity for PHA production using electricity EU27 mix, coal, hydropower, wind power, and biomass is about 5% to 7% lower than the emergy intensity of polyethylene high density (PE-HD). In comparison, its value is up to 21% lower for electricity and heat provision from biomass.