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Coal combustion for energy results in the emission of air pollutants such as NOx and SOx, which negatively affect human health and the environment. Reducing toxic gas emissions and ash production is needed to achieve cleaner coal. This study aimed to develop an extraction method for desulfurizing coal with non-toxic solvents before combustion. Mixtures of sub/supercritical carbon dioxide and ethyl lactate (EL) were used at temperatures of 60–80 °C and extraction times of 15–45 min. Box-Behnken design (BBD) was used to assess the influence of the extraction parameters and to optimize the extraction method. The results show that higher temperatures and lower EL content significantly increased desulfurization. The optimal conditions for desulfurization were CO2/EL (95:5, v/v) at 80 °C, 300 bar and 15 min, reducing total sulfur in coal from 1.90 to 0.13% by weight. The extraction was efficient for removing organic sulfur, sulfones and sulfates, whereas there were still traces of sulfoxides and sulfides remaining in the coal after extraction. Moreover, the ash content slightly decreased while the calorific value increased by 8% and 3% by weight, respectively. The use of a temperature less than 100 °C and an extraction time of 15 min make this method ''greener'' in comparison to other proposed ''green'' methods, which use temperatures above 200 °C. Thus, the method has the potential to produce clean coal.

A highly active zinc glutarate-double metal cyanide (DMC) composite catalyst (ZnGA/Zn-CrDMC) was designed for the carbon dioxide (CO2) and propylene oxide (PO) copolymerization reaction. The composite catalyst was synthesized in a rheological phase reaction and characterized using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The synthesized composite catalysed the solvent free reactions of PO and CO2 to afford biodegradable polypropylene carbonate (PPC) copolymer. 1H NMR,13C NMR, FT-IR and ESI-TOF mass spectrometry measurements were employed to confirm the characteristics of the PPC produced. Under optimal reaction conditions (50 bar CO2, 70 °C, 24 h), the ZnGA-Zn3[Cr(CN)6]2 composite displayed higher catalytic activities in the copolymerization reactions than the individual catalysts. The ZnGA:Zn3[Cr(CN)6]2 ratio of 15:1 gave PPC yield of 47.9 g polymer/g cat compared to ZnGA that produced 42.6 g polymer/ g cat in 24 h. In addition, the PPC produced from the composite catalyst displayed higher carbonate linkage content (Fc = 85.4 %) compared to the value of Fc = 33.9 %. obtained using the Zn3[Cr(CN)6]2 catalyst. Similaly, the composite catalsyt produced PPC with molecular weight of 4200 g/mol and narrow polydispersity index of 2.2. The resultant PPC copolymer displayed good thermal stability, exhibiting a high degradation temperatures (TGA-10%) of 229 °C and complete decomposition at 350 °C.

Herein is reported an efficient catalytic system for the direct synthesis of styrene carbonate from styrene and CO2. The preparation and characterization of the catalyst using FTIR, TEM, EDX, XPS, and PXRD is presented. The catalyst comprised of nano-silver modified polyoxometalates (Agx/POM) and n-tetra butyl ammonium bromide (TBAB) was employed in the oxidative carboxylation of styrene with CO2 in water as the solvent using H2O2 oxidant. The catalysed reaction was performed in a stainless steel autoclave reactor and the products were analysed using GC-MS and GC-FID. The oxidative carboxylation process was carried out in a one pot set up without need for subsequent work-up and isolation of the styrene oxide formed from the epoxidation process. The process led to 64.6% styrene conversion in 6 h with 96.9% selectivity towards styrene carbonate at 50 ⁰C and 25 bar CO2. The Agx/POM catalyst and TBAB co-catalyst were both beneficial for the reaction and no cyclic carbonate was formed without the catalyst system. When tested on selected styrene derivatives, the catalyst system showed> 90% conversion and> 90% selectivity to the desired cyclic carbonates. The Agx/POM catalyst could be recovered at the end of the reaction and reused with a fresh amount of TBAB without significant loss in activity.

Abstract Coal combustion greatly contributes to global emissions of toxic gases into the atmosphere, with sulfur emissions as one of the prominent pollutants in addition to carbon dioxide. Nevertheless, Botswana utilizes Morupule's sub‐bituminous coal with average sulfur and ash contents, as determined in this study being 1.9 and 24.4 % by weight with an average calorific value of 22 MJ Kg−1 to generate electricity. We report an optimized extraction method for reducing total sulfur in Morupule coal from 1.9±0.2 to 0.43±0.02 wt.% at optimum conditions of ethanol/water (90/10, v/v %) at 129 °C (105 bars) in 10 minutes. A Box–Behnken experimental design was employed to select the optimal conditions of temperature (100–180 °C), water proportion in ethanol (10–90, v/v %) and extraction time (10–30 minutes), thus reducing the total sulfur under these mild conditions compared to conventional extraction. The optimized conditions were however not efficient in removing ash.

Chemical conversion of carbon dioxide (CO2) into value-added products is an attractive industrial process because it offers several economic and environmental advantages. This review presents advances and challenges in the CO2 and propylene oxide (PO) co-polymerization using heterogeneous catalysts to form poly (propylene carbonate) (PPC), an environmentally friendly polymer with several applications. In the co-polymerization process, CO2 is employed as a green carbon source, an alternative to the toxic phosgene which has numerous negative environmental impacts. However, this route of polycarbonate production, is hindered by the chemical inertness of CO2, and to overcome this, various catalysts have been developed. A number of heterogeneous catalysts including carboxylates, double metal cyanides and composites, have achieved varying success in activating CO2 in the production of polycarbonates. The effect of different reaction conditions including pressure, temperature and solvent has been explored. The limitations faced by various heterogeneous catalysts and improvements made over the past decades have been highlighted. Mechanistic insights for the production of PPC from CO2 and PO have been presented and the differences in both the regioselectivity and stereochemistry of the resultant polymers discussed.

Herbivores and fire are important consumers of plant biomass that influence vegetation structure, nutrient cycling, and biodiversity globally. Departures from historic biomass consumption patterns due to wild herbivore losses, livestock proliferation, and altered fire regimes can have critical ecological consequences. We set out to (i) understand how consumer dominance and prevalence responded to spatial and temporal moisture gradients in Holocene North America and (ii) examine how past and present consumer dominance patterns in North America compare to less altered consumer regimes of modern Sub-Saharan Africa. We developed long-term records of bison abundance and biomass burning in Holocene midcontinent North America and compared these records to reconstructions of moisture availability and vegetation structure. We used these reconstructions to characterize bison and fire prevalence across associated moisture and vegetation gradients. We found that bison herbivory dominated biomass consumption in dry settings whereas fire dominated in wetter environments. Historical distributions of herbivory and burning in midcontinent North America resemble those of contemporary Sub-Saharan Africa, suggesting disturbance feedbacks and interactions regulate long-term consumer dynamics. Comparisons of consumer dynamics in contemporary North America with Holocene North America and Sub-Saharan Africa also reveal that fire is functionally absent from regions where it was once common, with profound ecological implications.

Genetically modified (GM) soybeans expressing Cry1A.105/Cry2Ab2/Cry1Ac (event MON 87701 × MON 89788 × MON 87751 × MON 87708) and Cry1Ac (event MON 87701 × MON 89788) from Bacillus thuringiensis Berliner (Bt) are valuable technologies for managing key lepidopteran pests of soybean in South America, but do not provide stand-alone protection against Spodoptera species. Here, we evaluated the use of these Bt soybeans and their integration with insecticides for managing Spodoptera species. Cry1A.105/Cry2Ab2/Cry1Ac soybean provided reasonable levels of protection against S. cosmioides, S. albula, and S. eridania. However, S. frugiperda had higher survival on this Bt soybean, and Cry1Ac soybean showed low lethality against all species evaluated. Spodoptera larvae that survived on Bt and non-Bt soybean showed comparable susceptibility to flubendiamide and thiodicarb in diet-overlay bioassays. Regardless of soybean plant type, the field doses of flubendiamide and thiodicarb were effective in controlling surviving Spodoptera larvae. We conclude that Cry1A.105/Cry2Ab2/Cry1Ac soybean is effective in controlling S. cosmioides and S. albula, and also has reasonable control of S. eridania, but not S. frugiperda. Cry1Ac soybean provided poor control of all Spodoptera species. Nonetheless, Spodoptera larvae surviving on both Bt and non-Bt soybean were controlled by flubendiamide and thiodicarb. Thus, integrated control tactics would provide effective management of Spodoptera species in Bt soybean fields in South America.

Most proteins are organized in macromolecular assemblies, which represent key functional units regulating and catalyzing most cellular processes. Affinity purification of the protein of interest combined with liquid chromatography coupled to tandem mass spectrometry (AP-MS) represents the method of choice to identify interacting proteins. The composition of complex isoforms concurrently present in the AP sample can, however, not be resolved from a single AP-MS experiment but requires computational inference from multiple time- and resource-intensive reciprocal AP-MS experiments. Here we introduce deep interactome profiling by mass spectrometry (DIP-MS), which combines AP with blue-native-PAGE separation, data-independent acquisition with mass spectrometry and deep-learning-based signal processing to resolve complex isoforms sharing the same bait protein in a single experiment. We applied DIP-MS to probe the organization of the human prefoldin family of complexes, resolving distinct prefoldin holo- and subcomplex variants, complex-complex interactions and complex isoforms with new subunits that were experimentally validated. Our results demonstrate that DIP-MS can reveal proteome modularity at unprecedented depth and resolution., (© 2024. The Author(s).)

Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense by attacking intracellular pathogens and by inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression in the absence of IFN-γ killed the cells and induced Golgi fragmentation. IFN-γ exposure improved macrophage survival through the activity of the kinase PIM1. PIM1 phosphorylated GBP1, leading to its sequestration by 14-3-3σ, which thereby prevented GBP1 membrane association. During Toxoplasma gondii infection, the virulence protein TgIST interfered with IFN-γ signaling and depleted PIM1, thereby increasing GBP1 activity. Although infected cells can restrain pathogens in a GBP1-dependent manner, this mechanism can protect uninfected bystander cells. Thus, PIM1 can provide a bait for pathogen virulence factors, guarding the integrity of IFN-γ signaling.

Skin cancer is the most common malignant disease worldwide and, therefore, also poses a challenge from a pharmacotherapeutic perspective. Derivatives of indirubin are an interesting option in this context. In the present study, the effects of 3-[3'-oxo-benzo[ b ]thiophen-2'-( Z )-ylidene]-1-(β-d-glucopyranosyl)-oxindole (KD87), a thia-analogous indirubin N -glycoside, on the viability and mitochondrial properties of melanoma (A375) and squamous cell carcinoma cells (A431) of the skin were investigated. In both cell lines, KD87 caused decreased viability, the activation of caspases-3 and -7, and the inhibition of colony formation. At the mitochondrial level, a concentration-dependent decrease in both the basal and ATP-linked oxygen consumption rate and in the reserve capacity of oxidative respiration were registered in the presence of KD87. These changes were accompanied by morphological alterations in the mitochondria, a release of mitochondrial cytochrome c into the cytosol and significant reductions in succinate dehydrogenase complex subunit B (SDHB, subunit of complex II) in A375 and A431 cells and NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8, subunit of complex I) in A375 cells. The effect of KD87 was accompanied by a significant upregulation of the enzyme heme oxygenase-1, whose inhibition led to a partial but significant reduction in the metabolic-activity-reducing effect of KD87. In summary, our data show a mitochondria-targeting effect of KD87 as part of the cytotoxic effect of this compound on skin cancer cells, which should be considered in future studies with this class of compounds.

Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log-transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population-specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir-associated ALT elevations appear to be multifactorial, and further studies are needed., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Phytocannabinoids represent a promising approach in glioblastoma therapy. Previous work has shown that a combined treatment of glioblastoma cells with submaximal effective concentrations of psychoactive Δ 9 -tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD) greatly increases cell death. In the present work, the glioblastoma cell lines U251MG and U138MG were used to investigate whether the combination of THC and CBD in a 1:1 ratio is associated with a disruption of cellular energy metabolism, and whether this is caused by affecting mitochondrial respiration. Here, the combined administration of THC and CBD (2.5 µM each) led to an inhibition of oxygen consumption rate and energy metabolism. These effects were accompanied by morphological changes to the mitochondria, a release of mitochondrial cytochrome c into the cytosol and a marked reduction in subunits of electron transport chain complexes I (NDUFA9, NDUFB8) and IV (COX2, COX4). Experiments with receptor antagonists and inhibitors showed that the degradation of NDUFA9 occurred independently of the activation of the cannabinoid receptors CB 1 , CB 2 and TRPV1 and of usual degradation processes mediated via autophagy or the proteasomal system. In summary, the results describe a previously unknown mitochondria-targeting mechanism behind the toxic effect of THC and CBD on glioblastoma cells that should be considered in future cancer therapy, especially in combination strategies with other chemotherapeutics.

Indirubin was identified as an active component of Danggui Longhui Wan, an herbal mixture used in traditional Chinese medicine, and showed anticancer activity in clinical trials in patients with chronic leukemia. Investigations on the mechanisms of antitumor action of indirubins have mainly focused on the indirubin derivative indirubin-3'-monoxime (I3M). Meanwhile, antiproliferative and cytotoxic properties on cancer cells have also been demonstrated for several synthetic indirubin N -glycosides. In the present study, we demonstrate cytotoxic activity of the thia-analogous indirubin N -glycosides KD87 (3-[3'-oxo-benzo[ b ]thiophen-2'-( Z )-ylidene]-1-(β-d-glucopyranosyl)-oxindole) and KD85 (3-[3'-oxo-benzo[ b ]thiophen-2'-( Z )-ylidene]-1-(β-d-mannopyranosyl)-oxindole) against melanoma and squamous cell carcinoma cells as well as lung cancer and glioblastoma cells. The advanced state of preclinical studies on the effects of indirubins conducted to date underscores the need for pharmacokinetic data from cellular, animal, and human studies for which reliable quantification is required. Therefore, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous measurement of KD87, KD85, and I3M in plasma and cell culture medium. Experimental conditions for sample preparation were optimized for human plasma protein precipitation and liquid-liquid extraction from plasma and cell culture medium. The methods were successfully validated in accordance with the U.S. Food and Drug Administration Bioanalytical Method Validation and evaluated for selectivity, sensitivity, matrix effect, recovery, carryover, calibration curve linearity, accuracy, precision, and stability. The applicability of the methods was demonstrated by the determination of KD87 in mouse plasma after prior intraperitoneal administration to mice.

Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates., Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease. We tested the hypothesis that the APOL1 high-risk group is associated with a higher-risk of COVID-19-associated AKI and death., Design, Setting, and Participants: This retrospective cohort study included 990 participants with African ancestry enrolled in the Million Veteran Program who were hospitalized with COVID-19 between March 2020 and January 2021 with available genetic information., Exposures: The primary exposure was having 2 APOL1 risk variants (RV) (APOL1 high-risk group), compared with having 1 or 0 risk variants (APOL1 low-risk group)., Main Outcomes and Measures: The primary outcome was AKI. The secondary outcomes were stages of AKI severity and death. Multivariable logistic regression analyses adjusted for preexisting comorbidities, medications, and inpatient AKI risk factors; 10 principal components of ancestry were performed to study these associations. We performed a subgroup analysis in individuals with normal kidney function prior to hospitalization (estimated glomerular filtration rate ≥60 mL/min/1.73 m2)., Results: Of the 990 participants with African ancestry, 905 (91.4%) were male with a median (IQR) age of 68 (60-73) years. Overall, 392 (39.6%) patients developed AKI, 141 (14%) developed stages 2 or 3 AKI, 28 (3%) required dialysis, and 122 (12.3%) died. One hundred twenty-five (12.6%) of the participants were in the APOL1 high-risk group. Patients categorized as APOL1 high-risk group had significantly higher odds of AKI (adjusted odds ratio [OR], 1.95; 95% CI, 1.27-3.02; P = .002), higher AKI severity stages (OR, 2.03; 95% CI, 1.37-2.99; P < .001), and death (OR, 2.15; 95% CI, 1.22-3.72; P = .007). The association with AKI persisted in the subgroup with normal kidney function (OR, 1.93; 95% CI, 1.15-3.26; P = .01). Data analysis was conducted between February 2021 and April 2021., Conclusions and Relevance: In this cohort study of veterans with African ancestry hospitalized with COVID-19 infection, APOL1 kidney risk variants were associated with higher odds of AKI, AKI severity, and death, even among individuals with prior normal kidney function.

Drugs targeting the endocannabinoid system are of interest as potential systemic chemotherapeutic treatments and for palliative care in cancer. In this context, cannabinoid compounds have been successfully tested as a systemic therapeutic option in preclinical models over the past decades. Recent findings have suggested an essential function of the endocannabinoid system in the homeostasis of various skin functions and indicated that cannabinoids could also be considered for the treatment and prophylaxis of tumour diseases of the skin. Cannabinoids have been shown to exert their anticarcinogenic effects at different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy. This review provides an insight into the current literature on cannabinoid compounds as potential pharmaceuticals for the treatment of melanoma and squamous cell carcinoma.

The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOG). By using SOG-coupled antibodies, small molecule drugs, biologics and intact viral particles, we demonstrate the ability of LUX-MS to decode ligand receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. Furthermore, by coupling SOG to antigens we achieved light-controlled molecular mapping of intercellular signaling within functional immune synapses between antigen-presenting cells and CD8 +  T cells providing insights into T cell activation with spatiotemporal specificity. LUX-MS based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies., (© 2021. The Author(s).)