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Despite successfully utilizing anesthetics for over 150 years, the mechanism of action remains relatively unknown. Recent studies have shown promising results, but due to the complex interactions between anesthetics and their targets, there remains a clear need for further mechanistic research. We know that lipophilicity is directly connected to anesthetic potency since lipid solubility relates to anesthetic partition into the membrane. However, clinically relevant concentrations of anesthetics do not significantly affect lipid bilayers but continue to influence various molecular targets. Lipid rafts are derived from liquid-ordered phases of the plasma membrane that contain increased concentrations of cholesterol and sphingomyelin and act as staging platforms for membrane proteins, including ion channels. Although anesthetics do not perturb membranes at clinically relevant concentrations, they have recently been shown to target lipid rafts. In this review, we summarize current research on how different types of anesthetics—local, inhalational, and intravenous—bind and affect both lipid rafts and voltage-gated sodium channels, one of their major targets, and how those effects synergize to cause anesthesia and analgesia. Local anesthetics block voltage-gated sodium channel pores while also disrupting lipid packing in ordered membranes. Inhalational anesthetics bind to the channel pore and the voltage-sensing domain while causing an increase in the number, size, and diameter of lipid rafts. Intravenous anesthetics bind to the channel primarily at the voltage-sensing domain and the selectivity filter, while causing lipid raft perturbation. These changes in lipid nanodomain structure possibly give proteins access to substrates that have translocated as a result of these structural alterations, resulting in lipid-driven anesthesia. Overall, anesthetics can impact channel activity either through direct interaction with the channel, indirectly through the lipid raft, or both. Together, these result in decreased sodium ion flux into the cell, disrupting action potentials and producing anesthetic effects. However, more research is needed to elucidate the indirect mechanisms associated with channel disruption through the lipid raft, as not much is known about anionic lipid products and their influence over voltage-gated sodium channels. Anesthetics’ effect on S-palmitoylation, a promising mechanism for direct and indirect influence over voltage-gated sodium channels, is another auspicious avenue of research. Understanding the mechanisms of different types of anesthetics will allow anesthesiologists greater flexibility and more specificity when treating patients.

Cost-effective heterogeneous catalysts are critical to the ketonization of carboxylic acids for producing biofuels and platform chemicals. Herein, nanocrystalline Cu-loaded CeO2with 1.0–9.0 wt % Cu loadings was synthesized by the precipitation-impregnation method, in which 3.0 wt % Cu/CeO2exhibits the best performance of 72% acetone yield at 330 °C, 97% 3-pentanone yield at 360 °C, and 86% 4-heptanone yield at 400 °C, with good durability up to 10 h on stream. Detailed analyses reveal that 3.0 wt % Cu/CeO2has the highest percentage of O-vacancy sites, more moderate acid–base sites, and better capacity to adsorb and activate carboxylic acids. In situ DRIFT spectra indicate that monodentate, bridging bidentate, and chelating bidentate modes coexist when carboxylic acid is dissociatively adsorbed on 3.0 wt % Cu/CeO2. Based on the above investigations, we propose a mechanism over 3.0 wt % Cu/CeO2through the β-ketoacid intermediate route, which gives more details to help future research into the design and development of catalysts for ketonization.

AbstractMultiple herbicide-resistant (MHR) kochia is a serious concern in the U.S. Great Plains and warrants alternative herbicide mixtures for its control. Greenhouse and field experiments were conducted at Kansas State University research and extension centers near Hays and Garden City, KS, to investigate the interactions of 2,4-D, dichlorprop-p, dicamba, and halauxifen/fluroxypyr premix in various combinations for MHR kochia control. Two previously confirmed MHR (resistant to glyphosate, dicamba, and fluroxypyr) populations and a susceptible population were tested in a greenhouse study. Kochia at the Hays field site was resistant to glyphosate and chlorsulfuron, whereas the population at Garden City was resistant to glyphosate, dicamba, and fluroxypyr. Results from a greenhouse study indicated that 2,4-D, dicamba, dichlorprop-p, and a halauxifen/fluroxypyr premix provided 26% to 69% control of both MHR populations at 28 d after treatment (DAT). However, the control increased to 85% to 97% when these herbicides were applied in three-way mixtures. Synergistic interactions were observed when dicamba was mixed with dichlorprop-p, 2,4-D, dichlorprop-p + 2,4-D, and halauxifen/fluroxypyr + 2,4-D for shoot dry weight reductions (86% to 92%) of both MHR populations. Results from a field study also indicated synergistic interactions when dicamba was mixed with dichlorprop-p + 2,4-D, halauxifen/fluroxypyr + dichlorprop-p, and halauxifen/fluroxypyr + 2,4-D, resulting in 84% to 95% control of MHR kochia at 28 DAT across both sites. These results indicate that synergistic effects of mixing dicamba with other auxinic herbicides in two- or three-way mixtures can help control MHR kochia.

Even with particular interest in sustainable development, due to the limited types of bioavailable carbon sources that could support heterotrophic/mixotrophic growth, microalgae-derived products still suffer from inconsistent yield and high costs. This study demonstrates a successful cocultivation of the photoautotroph Chlorella vulgariswith a hydrolytic-enzyme-abundant heterotroph, Saccharomycopsis fibuligera, enabling efficient starch upcycling from water/wastewater toward enhancing microalgae-dominant biomass and lipid production. The enzymatic activities of S. fibuligeracontributed to the hydrolysis of starch into glucose, generating a 7-fold higher biomass through mixotrophic/heterotrophic growth of C. vulgaris. Further, scanning transmission electron microscopy (STEM) and quantitative analysis suggested a significantly induced accumulation of lipids in C. vulgaris. Results of meta-transcriptomics revealed the critical regulatory role of illumination in interaction shifting. Gene expression for glycolysis and lipid biosynthesis of C. vulgariswere highly activated during dark periods. Meanwhile, during illumination periods, genes coding for glucoamylase and the sulfur-related activities in S. fibuligerawere significantly upregulated, leading to induced starch hydrolysis and potential increased competition for sulfur utilization, respectively. This study indicates that hydrolytic organisms could collaborate to make starch bioavailable for nonhydrolytic microalgae, thus broadening the substrate spectrum and making starch a novel biotechnological feedstock for microalgae-derived products, e.g., biofuels or single-cell protein.

AbstractThis paper analyzed the chemical constituents of the essential oil (EO) of Kaempferia rotundaL. and the bioactivities of the predominant compounds. Results obtained from GC/MS analysis indicated 14 compounds, which accounted for 96.66% of the total extract. Among them, the most abundant compound was benzyl benzoate (81.13%), followed by bornyl acetate (4.51%). EO from the medicinal plant K. rotundainhibited the potent toxicity of Lasioderma serricorneand Liposcelis bostrychophila(LD50=17.1μg/adult and 18.6 μg/adult). K. rotundaoil also exerted strong repellency against three target insects at high concentrations. Based on the theory of the grey correlation analysis, EO from K. rotundaperformed better than benzyl benzoate but worse than bornyl acetate on the repellency against Tribolium castaneum. Benzyl benzoate possessed excellent contact toxicity with three target insects. Meanwhile, the binary mixture of two main compounds (benzyl benzoate and bornyl acetate) was evaluated for contact toxicity with T.castaneumfor the first time. The synergistic effect in natural ratios has been observed, suggesting that unique mechanisms of action should be responsible for EO toxicity. Plant-derived insecticides appear suitable for developing control means against stored product insects.

Recent studies from Pusan National University in South Korea have explored the role of visfatin in osteoclastogenesis, a process linked to bone loss and osteoporosis. The research found that visfatin, when combined with receptor activator of nuclear factor kappa-B ligand (RANKL), significantly enhanced osteoclast differentiation and activation in vitro. These findings suggest that the RANKL/visfatin signaling axis could be a potential therapeutic target for bone loss-related diseases. [Extracted from the article]

The limitations of conventional strategies in finely controlling the composition and structure demand new promotional effects for upgrading the reverse water–gas shift (RWGS) catalysts for enhanced fuel production. We report the design and synthesis of a hetero-dual-site catalyst for boosting RWGS performance by controllably loading Fe atoms at the neighboring Pt atom on the surface of commercial CeO2. The Fe–Pt/CeO2exhibits a remarkably high catalytic performance (TOFPt: 43,519 h–1) for CO2to CO conversion with ∼100% CO selectivity at a relatively low temperature of 350 °C. Furthermore, the catalyst retains over 80% activity after 200 h of continuous operation. The experimental and computational investigations reveal a “two-way synergistic effect”, where Fe atoms can not only serve as promotors to alter the charge density of Pt atoms but also be activated by the excess active hydrogen species generated by Pt atoms, enhancing catalytic activity and stability.

A study conducted at Mohammed First University in Oujda, Morocco, aimed to evaluate the chemical composition and antibacterial effectiveness of essential oil from Clinopodium nepeta subs ascendens (CNEO) against various bacteria. The researchers found that CNEO exhibited significant antibacterial activity, particularly against antibiotic-resistant bacteria. They also discovered that CNEO had synergistic interactions with antibiotics, enhancing their efficacy. These findings are important for developing new approaches to combat bacterial infections that are resistant to conventional treatments. [Extracted from the article]

The application of arbuscular mycorrhizal fungi (AMF), plant growth promoting rhizobacteria (PGPR) and compost (C) is a biological approach to boost growth of plants. The aim of the study was to evaluate the impact of AMF, PGPR and compost on growth, physiology and biochemical traits of date palm in the absence and the presence of microorganisms in soil. Date palm seedlings were transplanted in sterile (SS) and non-sterile soils (NSS) in the presence and absence of the biostimulants/biofertilizers. After 6 months, the application of AMF combined with compost (AMF + C) revealed significant increments in shoot dry weight (SDW), root dry weight (RDW), stomatal conductance and chlorophyll aby 122, 114, 95 and 119%, respectively in SS. Moreover, PGPR treatment significantly improved the SDW by 482%, while AMF + C + PGPR treatment significantly increased the RDW, chlorophyll band carotenoids concentration by 864, 211 and 145%, respectively in NSS compared to the control. In addition, the sugar and protein concentrations were significantly enhanced in plants treated with AMF + C + PGPR for SS and NSS, respectively compared to their respective controls. It was revealed that the organic matter, available phosphorus and glomalin were enhanced in soils amended with compost alone and/or combined with AMF and/or PGPR under SS and NSS. This study revealed the positive synergy of the tested native biostimulants with in NSS compared to SS in improving the growth, physiology and biochemical traits of date palm as well as soil fertility.

A recent study conducted at the University of Life Sciences in Timisoara, Romania, explored the antibacterial properties of essential oils derived from Romanian lavender. The study found that these oils contain compounds such as linalool, linalyl acetate, 1,8-cineole, lavandulyl acetate, trans-b-ocimene, and camphor. The oils exhibited higher efficacy against Gram-positive bacteria compared to Gram-negative bacteria and showed potential synergistic interactions with the antibiotic ampicillin. In addition, in silico protein-ligand docking studies revealed notable binding interactions between the lavender oil compounds and bacterial protein targets. These findings suggest that Romanian lavender essential oils possess antioxidant and antibacterial properties that could enhance antibiotic therapies. [Extracted from the article]

Researchers from Zhejiang Wanli University in Ningbo, China have conducted a study on the inhibitory effects of vine tea and its key compounds on alpha-glycosidase, a therapeutic target in type 2 diabetes mellitus. The study found that vine tea extracts inhibited alpha-glycosidase in a dose-dependent manner, with dihydromyricetin (DHM) identified as the main compound in vine tea. The researchers also discovered that the combination of DHM and the antidiabetic drug acarbose significantly enhanced inhibitory effectiveness, offering a promising option for safer and more effective diabetes therapy. The study provides a comprehensive analysis of the synergistic interactions between DHM and acarbose in vine tea extracts. [Extracted from the article]

Background: One of the main reasons for the poor survival rates of pancreatic cancer patients is the development of gemcitabine resistance, indicating that novel treatment strategies that have the ability to improve gemcitabine sensitivity are in need to combat this devastating disease. Methods: TCGA PAAD data was used to determine the clinicopathological significance of high RRM2 (Ribonucleotide reductase subunit M2) expression for Pancreatic Ductal Adenocarcinoma (PDAC). The effects of GW8510 and gemcitabine on PANC-1 cell viability were determined using WST-8 assay. The potential synergistic interaction between GW8510 and gemcitabine was evaluated by the Combination Index (CI) analysis. The effects of GW8510 treatment on apoptosis, cell cycle, and cell migration, either in combination with gemcitabine or alone, were investigated. The effect of GW8510 on RRM2 protein levels was evaluated using ELISA assay. Results: RRM2 is significantly over-expressed in PDAC compared to healthy pancreatic tissues (p <0.0001). RRM2 mRNA expression was found to be significantly correlated with the overall survival rate of patients (HR=2.17 [1.44-3.27], p=0.00016) and the pathological stages of the disease (p=0.0054). GW8510 significantly decreased the RRM2 protein levels compared to the control. Cell viability analysis showed that GW8510 has a similar effect to gemcitabine in inhibiting PANC-1 cell viability. GW8510 was found to synergize with gemcitabine to inhibit PANC-1 cell viability and migration. However, the effects of GW8510 on PANC-1 cells could not be explained by induction of apoptosis or cell cycle arrest. Conclusion: Targeting RRM2 using GW8510 may have the potential to increase gemcitabine sensitivity in pancreatic cancer.

The aim of this study is to compare the azole synergy across an insect, Chironomus riparius, and a crustacean species, Daphnia magna. We use a combination of in vivomeasurements of cytochrome P450 monooxygenase (CYP) biotransformation potential and toxicokinetic (TK) and toxicodynamic (TD) modeling to understand the mechanism behind the synergy of two azole fungicides: the imidazole prochloraz and the triazole propiconazole on the pyrethroid insecticide α-cypermethrin. For both species, the synergistic effect of prochloraz was well-described by its effect on in vivoCYP activity, which corresponded to the biotransformation rate of the TK model parameterized on the survival data of the mixture experiment. For propiconazole, however, there were 100-fold and 50-fold differences between the 50% effect concentration of in vivoCYP activity and the modeled biotransformation rate for C. ripariusand D. magna, respectively. Propiconazole, therefore, seems to induce synergy through a mechanism that cannot be quantified solely by the CYP activity assay used in this study in either of the two species. We discuss the differences between prochloraz and propiconazole as synergists across the two species in the light of the type and time dynamics of affected biotransformation processes.

A researcher from the Medical University of Silesia in Poland has published new data on antibiotics. The study focused on the antibacterial effects of cinnamic acid and its derivatives, as well as their combinations with b-lactam antibiotics, on Staphylococcus epidermidis strains. The research found that cinnamic acid and its derivatives have weak antibacterial activity, but when combined with b-lactam antibiotics, their effectiveness increased. This study is significant as it explores potential new substances with antimicrobial activity to combat infections associated with the implantation of various implants. [Extracted from the article]

A recent study conducted by researchers at the State Key Laboratory has revealed new findings on liver cancer. The study focused on the use of CRISPR/Cas12a-based combinational screening to identify genetic interactions. The researchers developed a rapid and efficient double-knockout screening system using a dual-CRISPR RNA library, which showed promising results in inhibiting hepatocellular carcinoma (HCC) cell growth. This screening system has the potential to identify genetic interactions and combinations of FDA-approved drugs for clinical translational medicine in the future. [Extracted from the article]

A recent study conducted by the Indian Council of Agricultural Research (ICAR) Indian Veterinary Research Institute has found that baicalein, a phytochemical derived from the traditional Chinese herb Scutellaria baicalensis, has an inhibitory effect on methicillin-resistant Staphylococcus aureus (MRSA). The study investigated the synergistic effect of baicalein in combination with b-lactam antibiotics (amoxicillin and ampicillin) against MRSA. The results showed that the combination of baicalein and amoxicillin exhibited potent synergy against MRSA in vitro, suggesting potential therapeutic implications for MRSA infections. This research provides valuable evidence for the development of new treatment options for MRSA. [Extracted from the article]

Sensitization of wide-gap metal oxides by the porphyrins has been promising to utilize the major fraction of solar light for photocatalytic reactions. In this context, rutile-SnO2was anchored with hemin complex and their performance was evaluated for the 4-nitro phenol (4-NP) degradation under UV/visible light. Driven by the significant interactions between -COOH and surface -OH functional groups of hemin and SnO2respectively, a new linkage O=CO-Sn was formed at the interface, which was vital for charge carrier transfer between them. Both X-ray diffraction studies and scanning electron microscope analysis confirmed that the surface hemin adsorption did not alter the crystal structure and the morphology of pristine SnO2. The light absorption properties revealed a red shift in the optical response of the composite, which facilitated the photocatalytic reactions to operate under visible light. The electrochemical and photoluminescence measurements collectively attested to the enhanced charge carrier separation in the composite compared to pure SnO2. The synergism arising from the photo-Fenton and photocatalytic reactions was derived from the cyclic reactions of Fe(II)/Fe(III) and oxidation of hydroxyl radicals by the valence band holes of SnO2with H2O2under UV light. In contrast, the sensitization process resulted in electron transfer from the excited state of hemin to the conduction band (CB) of SnO2under visible light. Such distinct mechanistic pathways by the metal oxide-porphyrin composite would be promising for wastewater purification under UV–visible light region in near future.