[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Construction of a direct Z-scheme Cs3Bi2Cl9/g-C3N4 heterojunction composite for efficient photocatalytic degradation of various pollutants in water: Performance, kinetics and degradation mechanism.

The use of emerging composite materials has been booming to remove environmental pollutants. The aim of this research is to develop a new composite based on Cs3Bi2Cl9 perovskite and graphitic carbon nitride (g-C3N4) to investigate the photocatalytic performance under visible light irradiation. To achieve this, we produce the Cs3Bi2Cl9/g-C3N4 heterojunctions through a simple self-assembly synthesis. The as-synthesized composites are characterized using XRD, FTIR, FESEM, TEM, BET and EDX techniques. The photocatalytic performance of Cs3Bi2Cl9/g-C3N4 is examined in the degradation of various water contaminants, including 4-nitrophenol (4-NP), tetracycline antibiotic (TC), methylene blue (MB) and methyl orange (MO). The experimental results indicate the superior photocatalytic performance of the composites in the degradation of pollutants compared to pure Cs3Bi2Cl9 and g-C3N4. The 10% Cs3Bi2Cl9/g-C3N4 composite achieves the optimal degradation efficiency of 100, 92, 98.7, and 85.1% of 4-NP, TC, MB, and MO, respectively. This superior photocatalytic activity attributes to improved optical and electrochemical properties, including enhanced absorption ability, narrowing band gap, promoted separation efficiency of photogenerated carriers, and a high redox potential, which is confirmed by UV-vis DRS, PL, EIS, and CV analyses. The 10% Cs3Bi2Cl9/g-C3N4 composite also demonstrates high photocatalytic stability after four consecutive cycles. Radical trapping tests show that superoxide radicals (•O2-), holes (h+), and hydroxyl radicals (•OH) contribute to the photocatalytic process. Based on the obtained data, a direct Z-scheme heterojunction mechanism is proposed. Overall, this research offers a new stable photocatalyst with excellent prospect for photocatalytic applications.

KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway.

BACKGROUND: Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS: DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS: The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION: KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Serendipitous Identification of Azine Anticancer Agents Using a Privileged Scaffold Morphing Strategy.

The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells, showing in five cases acceptable to good anticancer activity associated with low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation.

Bifunctional Sildenafil Diazeniumdiolates Acting as Phosphodiesterase 5 Inhibitors and Nitric Oxide Donors- Towards Wound Healing.

Inefficient wound healing poses a global health challenge with a lack of efficient treatments. Wound healing issues often correlate with low endogenous nitric oxide (NO) levels. While exogenous delivery with NO-releasing compounds represents a promising therapeutic strategy, controlling the release of the highly reactive NO remains challenging. Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, have also been shown to promote wound healing. This study explores hybrid compounds, combining NO-releasing diazeniumdiolates with a sildenafil-derived PDE5 inhibitor. One compound demonstrated a favorable NO-release profile, triggered by an esterase (prodrug), and displayed in vitro nanomolar inhibition potency against PDE5 and thrombin-induced platelet aggregation. Both factors are known to promote blood flow and oxygenation. Thus, our findings unveil promising prospects for effective wound healing treatments.

Development of persulfate-based advanced oxidation processes to remove synthetic azo dyes from aqueous matrices.

Azo dyes are largely used in many industries and discharged in large volumes of their effluents into the aquatic environment giving rise to non-esthetic pollution and health-risk problems. Due to the high stability of azo dyes in ambient conditions, they cannot be abated in conventional wastewater treatment plants. Over the last fifteen years, the decontamination of dyeing effluents by persulfate (PS)-based advanced oxidation processes (AOPs) has received a great attention. In these methods, PS is activated to be decomposed into sulfate radical anion (SO4•-), which is further partially hydrolyzed to hydroxyl radical (•OH). Superoxide ion (O2•-) and singlet oxygen (1O2) can also be produced as oxidants. This review summarizes the results reported for the discoloration and mineralization of synthetic and real waters contaminated with azo dyes covering up to November 2023. PS activation with iron, non-iron transition metals, and carbonaceous materials catalysts, heat, UVC light, photocatalysis, photodegradation with iron, electrochemical and related processes, microwaves, ozonation, ultrasounds, and other processes is detailed and analyzed. The principles and characteristics of each method are explained with special attention to the operating variables, the different oxidizing species generated yielding radical and non-radical mechanisms, the addition of inorganic anions and natural organic matter, the aqueous matrix, and the by-products identified. Finally, the overall loss of toxicity or partial detoxification of treated azo dye solutions during the PS-based AOPs is discussed.

Keguizhuia sedimenti gen. nov., sp. nov., isolated from river sediment represents a novel genus of the family Oxalobacteraceae.

A Gram-stain-negative bacterium, designated as R-40T, was isolated from sediment of the Mulong river in Mianyang city, Sichuan province, PR China. The cells of strain R-40T were aerobic non-motile and formed translucent white colonies on R2A agar. Growth occurred at 15-37 °C (optimum 30 °C), pH 5.0-9.0 (optimum 7.0) and salinities of 0-3.0 % (w/v, optimum 0 %). R-40T showed 95.2-96.6 % 16S rRNA gene sequence similarities with the type strains of species of the genera Oxalicibacterium, Herminiimonas, Lacisediminimonas, Paucimonas, Herbaspirillum and Noviherbaspirillum in the family Oxalobacteraceae. The results of phylogenetic analysis based on genome sequences indicated that the strain was clustered with type strains of species of the genera Oxalicibacterium and Herminiimonas in the family Oxalobacteraceae but formed a distinct lineage. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values between R-40T and type strains of species of the genera Oxalicibacterium, Herminiimonas, Lacisediminimonas, Paucimonas, Herbaspirillum and Noviherbaspirillum ranged from 69.3 to 74.1 %, from 18.2 to 21.4 % and from 60.1 to 67.4 %, respectively. The major cellular fatty acids were C16 : 0, C17 : 0 cyclo and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major quinone was ubiquinone-8 (Q-8). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and small amounts of glycophospholipids. The genome size of R-40T was 5.1 Mbp with 54.0 % DNA G+C content. On the basis of the evidence presented in this study, strain R-40T represents a novel species of a novel genus in the family Oxalobacteraceae, for which the name Keguizhuia sedimenti gen. nov., sp. nov. (type strain R-40T=MCCC 1K08818T=KCTC 8137T) is proposed.

Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt.

Although patients with chronic kidney disease (CKD) have a higher risk of colorectal cancer (CRC) aggravation, the connection between these two diseases is not well understood. Recent studies have shown that both CKD and CRC aggravation are closely related to an increased abundance of indole-producing Fusobacterium nucleatum in the gut. The indole absorbed from the gut is eventually metabolized to indoxyl sulfate in the liver. Since indoxyl sulfate is involved not only in accelerating CKD progression but also in the initiation and development of its associated complications, the present study aimed to clarify whether indoxyl sulfate induces the proliferation of CRC cells. This study found that indoxyl sulfate induced the proliferation of CRC-derived HCT-116 cells by activating the aryl hydrocarbon receptor (AhR) and the proto-oncogene Akt. The AhR antagonist CH223191 and Akt inhibitor MK2206 suppressed indoxyl sulfate-induced proliferation of HCT-116 cells. We also found that indoxyl sulfate upregulated epidermal growth factor receptor (EGFR) expression, which is associated with poor prognosis of CRC, whereas CH223191 and MK2206 repressed EGFR expression. Furthermore, indoxyl sulfate increased the sensitivity of CRC cells to EGF by upregulating EGFR expression. These findings suggest that indoxyl sulfate may be an important link between CKD and CRC aggravation.

Spot Overtaking of Dyes of Their Chromatographic Development Associated with Solvent Evaporation.

Infiltration of binary solution of hexane and ethanol into chromatography paper associated with their evaporation was found to generate unexpected initial rapid advancement of wicking front followed by its receding and readvancing in our previous research. In the present study, paper chromatography development of hydrophobic dye, Sudan III, and hydrophilic dye, Acid Blue 9, was carried out using binary solutions of hexane and ethanol in open environment, allowing the developing solvent been evaporated. Sudan III was developed with initial rapid advancing wicking front, while Acid Blue 9 was scarcely developed. On the other hand, Acid Blue 9 was developed with the readvancing second wicking front, while the spot of Sudan III scarcely migrated. Thus, the unexpected illusional phenomenon, overtaking the spot of Sudan III by the spot of Acid Blue 9, was observed. The readvancement of the second wicking front was found to be enhanced as increasing the relative humidity in the environment. Surface temperature of the chromatography paper was measured during the chromatographic development in open environment to show that it became lower than the dew point when the experiments were carried out in relatively high humidity. Solubility of Sudan III in a binary solution of ethanol and water remarkably decreased as increasing the content of water. It was thus suggested that the water vapor condensation to induce water mixing into the mobile phase to decrease the solubility of Sudan III to inhibit its chromatographic development to realize the illusional spot overtaking of dyes of their chromatographic development associated with solvent evaporation.

Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease.

BACKGROUNDS: Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25 % of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD. MiRNAs are potential therapeutic agents that can regulate several genes simultaneously. Therefore, we transfected cell lines with two key miRNAs involved in targeting NAFLD-related genes. METHODS: The suppression effects of the investigated miRNAs (miR-124 and miR-16) and genes (TNF, TLR4, SCD, FASN, SREBF2, and TGFß-1) from our previous study were investigated by real-time PCR in Huh7 and HepG2 cells treated with oleic acid. Oil red O staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were utilized to assess cell lipid accumulation and cytotoxic effects of the miRNAs, respectively. The pro-oxidant-antioxidant balance (PAB) assay was undertaken for miR-16 and miR-124 after cell transfection. RESULTS: Following transfection of miRNAs into HepG2, oil red O staining showed miR-124 and miR-16 reduced oleic acid-induced lipid accumulation by 35.2 % and 28.6 % respectively (p < 0.05). In Huh7, miR-124 and miR-16 reduced accumulation by 23.5 % and 31.3 % respectively (p < 0.05) but without impacting anti-oxidant activity. Real-time PCR in HepG2 revealed miR-124 decreased expression of TNF by 0.13-fold, TLR4 by 0.12-fold and SREBF2 by 0.127-fold (p < 0.05). miR-16 decreased TLR4 by 0.66-fold and FASN by 0.3-fold (p < 0.05). In Huh7, miR-124 decreased TNF by 0.12-fold and FASN by 0.09-fold (p < 0.05). miR-16 decreased SCD by 0.28-fold and FASN by 0.64-fold (p < 0.05). MTT assays showed, in HepG2, viability was decreased 24.7 % by miR-124 and decreased 33 % by miR-16 at 72 h (p < 0.05). In Huh7, miR-124 decreased viability 42 % at 48 h and 29.33 % at 72 h (p < 0.05), while miR-16 decreased viability by 32.3 % (p < 0.05). CONCLUSION: These results demonstrate the ability of miR-124 and miR-16 to significantly reduce lipid accumulation and expression of key pathogenic genes associated with NAFLD through direct targeting. Though this requires further in vivo investigation.

Degradation of Procion brilliant yellow H-E6G using ultrasonic and hydrodynamic cavitation combined with oxidants with demonstration at pilot scale.

The current study focuses on the degradation of Procion brilliant yellow H-E6G, an azo dye, using ultrasonic and hydrodynamic cavitation (HC), evaluating the impact of various parameters on the extent of degradation. The use of only ultrasound showed less oxidation capacity as indicated by only 19.1% degradation at an optimized power of 140 W, pH of 2.5, temperature of 40°C, and initial dye concentration of 15 ppm. The effectiveness of hybrid approaches involving US + H2 O2 , US + Fenton, and US + H2 O2 + potassium persulfate (KPS) was subsequently evaluated under optimized conditions. A notable enhancement in decolorization extent was observed for combined operations, including US + H2 O2 , US + Fenton, and US + H2 O2 + KPS (dual oxidant scheme) with the actual decolorization extents as 80.6%, 85%, and 92.2% respectively. An optimized scheme of US + H2 O2 + KPS was also utilized to decolorize the dye at a pilot scale using a US flow cell and also an HC reactor that yielded 91.8% and 88% reductions in initial concentration. The dye decolorization was elucidated to follow first-order kinetics for all the individual and combination approaches. The obtained values of the rate constants were also utilized for the evaluation of the synergistic index. A toxicity analysis was also performed on the dye, both before and following treatment, utilizing two bacterial strains. A comparative analysis of various treatment approaches has been presented focusing on factors such as cavitational yield, operational expenses, and energy requirements. The study elucidated that the combination of US + H2 O2 + KPS effectively removes Procion brilliant yellow H-E6G giving 92.2% as the maximum degradation at an operating cost of 0.1862 $/L. PRACTITIONER POINTS: First depiction of cavitative degradation of Procion brilliant yellow H-E6G Optimizing the equipment operating parameters and chemical oxidants Demonstration of optimized treatment scheme at pilot scale Evaluation of various approaches based on synergy and costs of treatment US + H2 O2  + KPS is the best approach for dye degradation.

[Risdiplam for the treatment of spinal muscular atrophy]. / Risdiplam pri lechenii spinal'noi myshechnoi atrofii.

Spinal muscular atrophy (SMA) is a devastating disease that is the leading genetic cause of death in infants and young children. It includes a broad spectrum of phenotypes that are classified into clinical groups based on the age of onset and maximum motor function achieved. The most common form of SMA is due to a defect in the survival motor neuron 1 gene (SMN1) localized to 5q11.2-q13.3. The development of clinical symptoms and disease progression is thought to be due to decreased levels of survival motor neuron (SMN) protein. SMA type 1 results in almost inevitable mortality within the first 2 years of life. The first two drugs approved globally for the treatment of SMA were the antisense oligonucleotide nusinersen (Spinraza), and the gene therapy onasemnogene abeparvovec-xioi (Zolgensma). Both interventions have approval and restrictions on use in different countries around the world. Despite these approved therapies, the medical unmet need in SMA (the majority of patients with SMA are not on a disease-modifying therapy) remains high with therapies in the pipeline to address some of the remaining limitations. The third and more recently approved drug for SMA is risdiplam (Evrysdi), an orally administered, centrally and peripherally distributed small molecule that modulates SMN2 pre-mRNA splicing toward the production of full-length SMN2 mRNA to increase functional SMN protein levels. In Russia the drug risdiplam was approved for use on November 26, 2020 with indications for the treatment of SMA in patients aged 2 months and older, and in 2023 the indications were expanded - use is allowed starting from the birth. Risdiplam is widely distributed into the CNS and peripheral tissues including muscles. Following risdiplam administration, SMN protein levels compared with baseline levels increase between 2- and 6-fold depending on the SMA phenotype treated. The risdiplam clinical development program currently has four ongoing clinical trials assessing its safety and efficacy. Clinical trials included more than 450 patients receiving risdiplam to date, has been well tolerated and no treatment-related safety findings leading to study withdrawal have been observed. Data from real clinical practice - more than 11.000 patients worldwide receive therapy with risdiplam, also confirm the safety and good tolerability of the drug.

Efficiency of thermostable purified laccase isolated from Physisporinus vitreus for azo dyes decolorization.

Laccases are versatile biocatalysts that are prominent for industrial purposes due to their extensive substrate specificity. Therefore, this research investigated producing laccase from Physisporinus vitreus via liquid fermentation. The results revealed that veratryl alcohol (4mM) was the most effective inducer 7500U/L. On the other hand, Zn ions inhibited laccase production. The optimum carbon and nitrogen sources were glucose and tryptone by 5200 and 3300 U/L, respectively. Moreover, solvents exhibited various impacts on the enzyme activity at three different solvent concentrations (5%, 10% and 20%), however, it showed a highest activity at 5% of the investigated solvent. Ferric ions inhibited the enzyme activity. In addition, the enzyme has a high ability to decolorize azo dyes when using syringaldehyde as a mediator. The purified laccase from Physisporinus vitreus is a promising substance to be used for industrial and environmental applications due to its stability under harsh conditions and efficiency in decolorization of dyes.

Pillar[5]arene/albumin biosupramolecular systems for simultaneous native protein preservation and encapsulation of a water-soluble substrate.

The growing resistance of pathogens, bacteria, viruses, and fungi to a number of drugs has encouraged researchers to use natural and synthetic biomimetic systems to overcome this challenge. Multicomponent systems are an attractive approach for drug design and multitarget therapy. In this study, we report the assembly of a three-component (pillar[5]arene, bovine serum albumin, and methyl orange) biosupramolecular system as a potential drug delivery system. We estimated the cytotoxic activity and transfection ability of pillar[5]arene derivatives and investigated the effect of the nature of macrocycle functions (L-phenylalanine, glycine, L-alanine) on the native conformation of serum albumin in a three-component system. NMR, UV-vis, fluorescence, CD spectroscopy, DLS, and molecular docking studies were performed in order to confirm the structure and possible pillar[5]arene/bovine serum albumin/methyl orange interactions occurring during the association process. Results indicate that pillar[5]arene with L-phenylalanine fragments retains the native form of BSA to the maximum extent and forms more stable associates.

A novel premixing strategy for highly sensitive detection of nitrite on paper-based analytical devices.

BACKGROUND: Nitrite has been involved in many food processing techniques and its excessive consumption is closely related to the development of different diseases. Therefore, highly sensitive detection of nitrite is significant to ensure food safety. RESULT: This study presents a simple and novel strategy for the highly sensitive detection of nitrite in food using paper-based analytical devices (PADs). In this proposed strategy, the nitrite present in the sample undergoes efficient diazotization when initially mixed with sulfanilamide solution before reacting with N-(1-naphthyl) ethylenediamine dihydrochloride (NED) coated on the detection region of the PAD, leading to the maximum production of colored azo compounds. Specifically, within the concentration range of 0.1-20 mg/L, the LOD and LOQ for the nitrite assay using the premixing strategy are determined as 0.053 mg/L and 0.18 mg/L, respectively which significantly surpass the corresponding values of 0.18 mg/L (LOD) and 0.61 mg/L (LOQ) achieved with the regular Griess reagent analysis. SIGNIFICANCE: The study highlights the critical importance of the premixing strategy in nitrite detection. Under optimized conditions, the strategy demonstrates an excellent limit of detection (LOD) and limit of quantification (LOQ) for nitrite detection in eight different meat samples. In addition to its high precision, the strategy is applicable in the field of nitrite analysis. This strategy could facilitate rapid and cost-effective nitrite analysis in real food samples, ensuring food safety and quality analysis.

Adsorption of azo dye by biomass and immobilized Yarrowia lipolytica; equilibrium, kinetic and thermodynamic studies.

One of the major environmental problems we have today is dye pollution, primarily caused by the textile industry. This pollution has detrimental effects on aquatic life, soil fertility, and human health. Many microbial biosorbents have been documented in the literature for the removal of a wide range of azo dyes commonly employed in the textile industry. However, Yarrowia lipolytica NBRC1658 is firstly used as both free and immobilized sorbents for the removal of Reactive yellow 18 (RY18), acid red 18 (AR18) and basic blue 41 (BB41) in this study. The effect of experimental conditions such as pH, biosorbent quantity, dye concentration, contact time, and temperature on dye removal capacity are examined. The research findings demonstrate that the adsorption capacity is higher in biomass compared to immobilized cells. The highest adsorption capacities are observed at pH 2 for RY18 and AR18, while pH 9 is optimal for BB41. Increasing the adsorbent dosage and initial concentration significantly improves the adsorption capacity. The Langmuir model best describes the adsorption process, indicating that the dye attaches to the biosorbent in a single layer, with a uniform biosorbent surface. The removal of the dye occurs through a chemical process on the biosorbent surface, as evidenced by the pseudo-second-order kinetic model. According to thermodynamic analysis, higher temperatures promote greater adsorption of dyes. Our study shows the effectiveness of Yarrowia lipolyica NBRC1658 as a biosorbent in the removal of a wide range of industrial dyes.

Revealing soil microbial ecophysiological indicators in acidic environments laden with heavy metals via predictive modeling: Understanding the impacts of black diamond excavation.

Appraising the activity of soil microbial community in relation to soil acidity and heavy metal (HM) content can help evaluate it's quality and health. Coal mining has been reported to mobilize locked HM in soil and induce acid mine drainage. In this study, agricultural soils around coal mining areas were studied and compared to baseline soils in order to comprehend the former's effect in downgrading soil quality. Acidity as well as HM fractions were significantly higher in the two contaminated zones as compared to baseline soils (p < 0.01). Moreover, self-organizing and geostatistical maps show a similar pattern of localization in metal availability and soil acidity thereby indicating a causal relationship. Sobol sensitivity, cluster, and principal component analyses were employed to enunciate the relationship between the various metal and acidity fractions with that of soil microbial properties. The results indicate a significant negative impact of metal bioavailability, and acidity on soil microbial activity. Lastly, Taylor diagrams were employed to predict soil microbial quality and health based on soil physicochemical inputs. The efficiency of several machine learning algorithms was tested to identify Random Forrest as the best model for prediction. Thus, the study imparts knowledge about soil pollution parameters, and acidity status thereby projecting soil quality which can be a pioneer in sustainable agricultural practices.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3ß, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.

Computational analysis into the potential of azo dyes as a feedstock for actinorhodin biosynthesis in Pseudomonas putida.

Fermentation-based biosynthesis in synthetic biology relies heavily on sugar-derived feedstocks, a limited and carbon-intensive commodity. Unconventional feedstocks from less-noble sources such as waste are being utilized to produce high-value chemical products. Azo dyes, a major pollutant commonly discharged by food, textile, and pharmaceutical industries, present significant health and environmental risks. We explore the potential of engineering Pseudomonas putida KT2440 to utilize azo dyes as a substrate to produce a polyketide, actinorhodin (ACT). Using the constrained minimal cut sets (cMCS) approach, we identified metabolic interventions that optimize ACT biosynthesis and compare the growth-coupling solutions attainable on an azo dye compared to glucose. Our results predicted that azo dyes could perform better as a feedstock for ACT biosynthesis than glucose as it allowed growth-coupling regimes that are unfeasible with glucose and generated an 18.28% higher maximum ACT flux. By examining the flux distributions enabled in different carbon sources, we observed that carbon fluxes from aromatic compounds like azo dyes have a unique capability to leverage gluconeogenesis to support both growth and production of secondary metabolites that produce excess NADH. Carbon sources are commonly chosen based on the host organism, availability, cost, and environmental implications. We demonstrated that careful selection of carbon sources is also crucial to ensure that the resulting flux distribution is suitable for further metabolic engineering of microbial cell factories.