Strong Activity Research Articles

A novel AA14 LPMO from Talaromyces rugulosus with bifunctional cellulolytic/hemicellulolytic activity boosted cellulose hydrolysis

BackgroundThe recently discovered PcAA14A and B from white-rot basidiomycete Pycnoporus coccineus enriched our understanding of the oxidative degradation of xylan in fungi, however, the unusual mode of action of AA14 LPMOs has sparked controversy. The substrate specificity and functionality of AA14 LPMOs still remain enigmatic and need further investigation.ResultsIn this study, a novel AA14 LPMO was characterized from the ascomycete Talaromyces rugulosus. TrAA14A has a broad substrate specificity with strong oxidative activity on pure amorphous cellulose and xyloglucan. It could simultaneously oxidize cellulose, xylan and xyloglucan in natural hemi/cellulosic substrate such as fibrillated eucalyptus pulp, and released native and oxidized cello-oligosaccharides, xylo-oligosaccharides and xyloglucan oligosaccharides from this substrate, but its cellulolytic/hemicellulolytic activity became weaker as the contents of xylan increase in the alkaline-extracted hemi/cellulosic substrates. The dual cellulolytic/hemicellulolytic activity enables TrAA14A to possess a profound boosting effect on cellulose hydrolysis by cellulolytic enzymes. Structure modelling of TrAA14A revealed that it exhibits a relatively flat active-site surface similar to the active-site surfaces in AA9 LPMOs but quite distinct from PcAA14B, despite TrAA14A is strongly clustered together with AA14 LPMOs. Remarkable difference in electrostatic potentials of L2 and L3 surfaces was also observed among TrAA14A, PcAA14B and NcLPMO9F. We speculated that the unique feature in substrate-binding surface might contribute to the cellulolytic/hemicellulolytic activity of TrAA14A.ConclusionsThe extensive cellulolytic/hemicellulolytic activity on natural hemi/cellulosic substrate indicated that TrAA14A from ascomycete is distinctively different from previously characterized xylan-active AA9 or AA14 LPMOs. It may play as a bifunctional enzyme to decompose some specific network structures formed between cellulose and hemicellulose in the plant cell walls. Our findings shed new insights into the novel substrate specificities and biological functionalities of AA14 LPMOs, and will contribute to developing novel bifunctional LPMOs as the booster in commercial cellulase cocktails to efficiently break down the hemicellulose-cellulose matrix in lignocellulose.

A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA‐induced Sepsis and Chronic Wound Infection

The rising prevalence of global antibiotic resistance evokes the urgent need for novel antimicrobial candidates. Cationic lipopeptides have attracted much attention due to their strong antimicrobial activity, broad‐spectrum and low resistance tendency. Herein, a library of fluoro‐lipopeptide amphiphiles was synthesized by tagging a series of cationic oligopeptides with a fluoroalkyl tail via a disulfide spacer. Among the lipopeptide candidates, R6F bearing six arginine moieties and a fluorous tag shows the highest antibacterial activity, and it exhibits an interesting fluorine effect as compared to the non‐fluorinated lipopeptides. The high antibacterial activity of R6F is attributed to its excellent bacterial membrane permeability, which further disrupts the respiratory chain redox stress and cell wall biosynthesis of the bacteria. By co‐assembling with lipid nanoparticles, R6F showed high therapeutic efficacy and minimal adverse effects in the treatment of MRSA‐induced sepsis and chronic wound infection. This work provides a novel strategy to design highly potent antibacterial peptide amphiphiles for the treatment of drug‐resistant bacterial infections.

Extracellular L-asparaginase productive potential of the Priestia megaterium strain GB911 from Khanh Hoa sea of Viet Nam

Currently, L-asparaginase isolated from terrestrial microorganisms has been employed for anticancer industrial production. This enzyme has the function of inhibiting the growth of acute lymphoblastic leukemia, Hodgkin's lymphomas and other cancers. In this study, for the first time, L-asparaginase (ASNase) productive capacity of forty marine bacteria originating from Khanh Hoa sea of Viet Nam was screened and reported. Among those, twenty eight isolates were clarified for their extracellular ASNase activity based on their ability to form a pink zone around colonies on asparagine agar plates. As a result, four strains GB910, GB911, GB976 and GB982 showed high secreted extracellular ASNase activity, ranging from 8.64 to 13.22 IU/mg. Among these four most potential strains, GB911 exhibited better enzyme production capacity and was subjected to taxonomy identification. According to the 16S rRNA gene sequence on the GenBank database, strain GB911 was identified as Priestia megaterium and registered in the GenBank database with accession number MW407014. The purified enzyme obtained from strain GB911 exhibited strong cytotoxic activity against five monolayer and suspension cancerous cell lines with IC50 values ranging from 39 mU/mL to 98 mU/mL. The strain could serve as a promising source for industrial production of ASNase for clinical chemotherapeutic treatment.

Astaxanthin Inhibits STING Carbonylation and Enhances Antiviral Responses.

STING-mediated DNA sensing pathway plays a crucial role in the innate antiviral immune responses. Clarifying its regulatory mechanism and searching STING agonists has potential clinical implications. Although multiple STING agonists have been developed to target cancer, there are few for the treatment of infectious diseases. Astaxanthin, a natural and powerful antioxidant, serves many biological functions and as a potential candidate drug for many diseases. However, how astaxanthin combats viruses and whether astaxanthin regulates the cyclic GMP-AMP synthase-STING pathway remains unclear. In this study, we showed that astaxanthin markedly inhibited HSV-1-induced lipid peroxidation and inflammatory responses and enhanced the induction of type I IFN in C57BL/6J mice and mouse primary peritoneal macrophages. Mechanistically, astaxanthin inhibited HSV-1 infection and oxidative stress-induced STING carbonylation and consequently promoted STING translocation to the Golgi apparatus and oligomerization, which activated STING-dependent host defenses. Thus, our study reveals that astaxanthin displays a strong antiviral activity by targeting STING, suggesting that astaxanthin might be a promising STING agonist and a therapeutic target for viral infectious diseases.

Tribological Behaviors of Electroless Nickel-Boron Coating on Titanium Alloy Surface

Titanium alloys are excellent structural materials in engineering fields, but their poor tribological properties limit their further applications. Electroless plating is an effective method to enhance the tribological performance of alloys, but it is difficult to efficiently apply to titanium alloys, due to titanium alloy’s strong chemical activity. In this work, the electroless Nickel-Boron (Ni-B) coating was successfully deposited on the surface of titanium alloy (Ti-6AL-4V) via a new pre-treatment process. Then, linearly reciprocating sliding wear tests were performed to evaluate the tribological behaviors of titanium alloy and its electroless Ni-B coatings. It was found that the Ni-B coatings can decrease the wear rate of the titanium alloy from 19.89×10−3 mm3 to 0.41×10−3 mm3, which attributes to the much higher hardness of Ni-B coatings. After heat treatment, the hardness of Ni-B coating further increases corresponding to coating crystallization and hard phase formation. However, heat treatment does not improve the tribological performance of Ni-B coating, due to the fact that higher brittleness and more severe oxidative wear exacerbate the damage of heat-treated coatings. Furthermore, the Ni-B coatings heat-treated both in air and nitrogen almost present the same tribological performance. The finding of this work on electroless coating would further extend the practical applications of titanium alloys in the engineering fields.

Analysis of Chemical Constituents of Miao Ethnomedicine Heiguteng Zhuifeng Huoluo Capsule (HZFC) and the Discovery of Active Substances in the Treatment of Rheumatoid Arthritis.

In this study, the chemical substances of Heiguteng Zhuifeng Huoluo Capsule (HZFC) and its potential active ingredients for the treatment of rheumatoid arthritis (RA) were characterized and analyzed by medicinal chemistry combined with bioinformatics methods. Also, the potential active ingredients of HZFC against RA were verified by lipopolysaccharide (LPS)-induced macrophage activation model. The results showed that 79 chemical constituents were successfully identified, mainly including phenylpropanoids, flavonoids, and alkaloids. Among them, 13 active components were closely related to the nine core targets (FASN, ALOX5, EGFR, MMP1, CYP2D6, CNR1, AR, MAOA, and FKBP5) of HZFC in the treatment of RA. Molecular docking further proved that 13 active components had strong docking activity with 9 core targets. In the verification experiment of the LPS-induced RAW 264.7 macrophage model, the verified components (magnoflorine, N-feruloyltyramine, canadine, rutin, quercetin-3-O-glucoside, and pseudocolumbamine) all showed a clear inhibitory effect on the secretion of inflammatory factors in model cells. The above research results suggest that 13 components such as stepharanine, rutin, quercetin-3-O-glucoside, corydine methyl ether, canadine, 8-oxoepiberberine, disinomenine, deosinomenine glucoside, tuduranine, magnoflorine, isosinomenine, pseudocolumbamine, and N-feruloyltyramine may be the main active substances of HZFC in the treatment of RA.

Lipopeptides from Bacillus velezensis induced apoptosis-like cell death in the pathogenic fungus Fusarium concentricum.

Stem rot caused by Fusarium concentricum is a new disease of Paris polyphylla reported by our research group. The present study investigates the growth inhibitory and apoptotic effects of Bacillus velezensis FJAT-54560 lipopeptide against F. concentricum. HPLC preparation and LC-MS analysis results show that the crude lipopeptides secreted by Bacillus velezensis FJAT-54560 isolated from Jasminum sambac consist of C14-17 iturin A, C14 fengycin B, C16 fengycin A/A2, C18 fengycin A, C20 fengycin B2, C21 fengycin A2, C22-23 fengycin A, C12-16 surfactin A, and C15 surfactin A derivatives. The mass ratios (g/g) of iturin, fengycin, and surfactin in lipopeptides are 2.40, 67.51, and 30.08%, respectively. Through inhibition zone and inhibition rate experiments, we found that crude lipopeptides and purified fengycin exhibit strong antifungal activity against F. concentricum, including accumulation of reactive oxygen species, loss of mitochondrial membrane potential, DNA fragmentation, Ca2+ accumulation, chromatin condensation, and phosphatidylserine externalization. Transcriptomic analysis indicates that crude lipopeptide-induced apoptosis in F. concentricum cells may be mediated by apoptosis-inducing factors and apoptosis mediators and can serve as a metacaspase-independent model. Lipopeptides from Bacillus velezensis FJAT-54560 can control the pathogenic fungus F. concentricum by inducing apoptosis.

Total phenolic and flavonoids content, and antioxidant activity of kratom (Mitragyna speciosa Korth.) leaf ethanol extract

This study aims to determine and compare antioxidant activity, total phenolics, flavonoids, and the relationship of phenolic and total flavonoids with the antioxidant activity of the three kratom variants. The ethanol extract of the third variant of kratom leaves was obtained by maceration. Through the antioxidant activity test using DPPH method, all three extracts showed strong antioxidant activity with IC50 values of 26.39, 30.25, and 30.59 μg/mL. The relationship of total phenolics and flavonoids with antioxidant activity was determined by the Pearson correlation test. Examination of total phenolic content using the Folin-Ciocalteu method with successive results for green, red, and white kratom are 6.11, 8.67, and 9.09 mg GAE/g extract. Examination of total flavonoid content using the colorimetric method for green, red, and white kratom were 0.86, 0.68, and 1.13 mg QE/g extract, respectively. The total phenolic content and antioxidant activity showed a correlation coefficient value of -0.32 (P0.05), and the total flavonoid content to antioxidant activity showed a correlation coefficient value of 0.81 (P0.05). Thus, all three variants of kratom have potency as natural antioxidants, but their total phenolic and flavonoid content does not influence their antioxidant activity.

FORMULATION OF PEEL-OFF GEL MASK OF COCOA SKIN EXTRACT (Theobroma cacao L) WITH VARIED CONCENTRATION GELLING AGENT

Cocoa shells are waste from the plantation industry, with a fairly good potential source of energy and protein. The ethanol extract of cocoa shells contains alkaloids, flavonoids, phenols, and tannins. Cocoa shell extract has strong antioxidant activity with an IC50 value of 17.21 ppm and has sunscreen activity. This study aimed to determine the formulation and physical test of a peel-off gel mask with cocoa shell extract (Theobroma cacao L) and to determine its effect. The research method used was an experimental method with variations in the concentration of a combination of HPMC and PVA of 2%:10%, 3%:9%, 4%:8%, 5%:7%, and 0%:12%. The physical tests used on the peel-off gel mask with cocoa shell extract (Theobroma cacao L) included organoleptic, homogeneity, pH, spreadability, drying time, adhesiveness, viscosity, and cycling tests. Based on the results of the research carried out, peel-off gel mask has the characteristics of a brown color, a distinctive extract smell and a thick texture, homogeneous for F1 and F5, and not homogeneous for F2, F3, and F4, sticking force 4.53±0.24 seconds; 5.45±0.36 seconds; 8.94±0.64 seconds; 11.23±0.72 seconds; 3.87±0.70 seconds; spreadability 3.99 ± 0.18 cm; 3.33±0.31 cm; 3.47±0.78 cm; 3.32±0.50 cm; 3.05±0.42 cm; pH 6.17 ± 0.10; 6.16±0.03; 6.15±0.10; 6.11±0.05; 6.42±0.03; viscosity 19481.10±201.10; 20165.50±1.05; 20165.73±2.02; 20182.53±9.47; 14618.40±158.48. The physical stability of the gel mask preparations after treatment showed that the results of the peel-off gel mask preparations, F1 and F5, were stable. Keywords: peel-off gel mask, cocoa shell, extract, gelling agent

Improving Photoelectron Localization to Significantly Enhanced Broadband Orange‐Light Emission in Hybrid Antimony Halides with Sb─Cl Secondary Bonding

AbstractHybrid ns2 metal halides have attracted extensive attention due to the unique photophysical behavior. However, the reasonable improvement of photoluminescence efficiency by accurate structural modulation remains a great challenge. Herein, two kind of antimony halides with formulae as (S)/(R)‐[C6H16N2]3[SbCl5]2·2Cl ((S)/(R)‐1·2Cl) and (S)/(R)‐[C6H16N2]2[SbCl5]2 ((S)/(R)‐2) ([C6H16N2]2+ = 1,2‐Diaminocyclohexane) are developed, in which 0D [Sb4Cl20]8− clusters and 1D infinite [SbCl5]n2n− polyanion chains are adopted, respectively. The stoichiometric tunability enables metastable (S)/(R)‐1·2Cl being transformed to dynamic stable (S)/(R)‐2. All compounds contain a large number of Sb─Cl secondary bonds because of the strong chemical activity of 5s2 electrons. The obtained compounds exhibit broadband orange‐light emission, while photoluminescence quantum yield of (S)/(R)‐2 is significantly enhanced to ≈76% due mainly to the generation of more localized electrons onto 1D chains. Experimental and computational results reveal that efficient broadband emission derives from the synergistic emission of singlet and triplet states, where the presence of shallow trap energy levels leads to anti‐thermal quenching behavior. Furthermore, the highly efficient photoluminescence property allows (S)‐2 to become excellent down‐conversion phosphor for white‐light emitting diode. This work proves that exploring structure‐property relationship in hybrid systems is helpful in promoting the rapid development of high‐performance broadband emission metal halides.

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes' Relationship to Alterations Identified at the Chromosome 8q Loci.

The MYBL1 gene is a strong transcriptional activator involved in events associated with cancer progression. Previous data show MYBL1 overexpressed in triple-negative breast cancer (TNBC). There are two parts to this study related to further characterizing the MYBL1 gene. We start by characterizing MYBL1 reference sequence variants and isoforms. The results of this study will help in future experiments in the event there is a need to characterize functional variants and isoforms of the gene. In part two, we identify and validate expression and gene-related alterations of MYBL1, VCIP1, MYC and BOP1 genes in TNBC cell lines and patient samples selected from the Breast Invasive Carcinoma TCGA 2015 dataset available at cBioPortal.org. The four genes are located at chromosomal regions 8q13.1 to 8q.24.3 loci, regions previously identified as demonstrating a high percentage of alterations in breast cancer. We identify alterations, including changes in expression, deletions, amplifications and fusions in MYBL1, VCPIP1, BOP1 and MYC genes in many of the same patients, suggesting the panel of genes is involved in coordinated activity in patients. We propose that MYBL1, VCPIP1, MYC and BOP1 collectively be considered as genes associated with the chromosome 8q loci that potentially play a role in TNBC pathogenesis.

In Vitro Antiviral and Virucidal Activity of Ozone against Feline Calicivirus.

The Caliciviridae family includes several viral pathogens of humans and animals, including norovirus (NoV), genus Norovirus, and feline calicivirus (FCV), genus Vesivirus. Due to their resistance in the environment, NoV and FCV may give rise to nosocomial infections, and indirect transmission plays a major role in their diffusion in susceptible populations. A pillar of the control of viruses resistant to an environment is the adoption of prophylaR1.6ctic measures, including disinfection. Since NoVs are not cultivatable in common cell cultures, FCV has been largely used as a surrogate of NoV for the assessment of effective disinfectants. Ozone (O3), a molecule with strong oxidizing properties, has shown strong microbicidal activity on bacteria, fungi, protozoa, and viruses. In this study, the virucidal and antiviral activities of an O3/O2 gas mixture containing O3 were tested at different concentrations (20, 35, and 50 μg/mL) for distinct contact times against FCV. The O3/O2 gas mixture showed virucidal and antiviral activities against FCV in a dose- and contact time-dependent fashion. Ozonation could be considered as a valid strategy for the disinfection of environments at risk of contamination by FCV and NoV.

Matched Redox Kinetics on Triazine-Based Carbon Nitride/Ni(OH)2 for Stoichiometric Overall Photocatalytic CO2 Conversion.

Mismatched reaction kinetics of CO2 reduction and H2 O oxidation is the main obstacle limiting the overall photocatalytic CO2 conversion. Here, a molten salt strategy is used to construct tubular triazine-based carbon nitride (TCN) with more adsorption sites and stronger activation capability. Ni(OH)2 nanosheets are then grown over the TCN to trigger a proton-coupled electron transfer for a stoichiometric overall photocatalytic CO2 conversion via "3CO2 + 2H2 O = CH4 + 2CO + 3O2 ." TCN reduces the energy barrier of H2 O dissociation to promote H2 O oxidation to O2 and supply sufficient protons to Ni(OH)2 , whereby the CO2 conversion is accelerated due to the enhanced proton-coupled electron transfer process enabled by the sufficient proton supply from TCN. This work highlights the importance of matching the reaction kinetics of CO2 reduction and H2 O oxidation by proton-coupled electron transfer on stoichiometric overall photocatalytic CO2 conversion.

Humic substances mediated superior photochemical pollutant conversion on defective TiO2 in environmentally relevant matrices: The key roles of oxygen vacancy in surface interactions, oxidant activation and radical generation

Ubiquitous humic substances usually exhibit strong interfering effects on target pollutant removal in advanced water purification. This work aims to develop a photochemical conversion system on the nonstoichiometric TiO2 for pollutant removal in environmentally relevant matrices. In this synergistic reaction system, the redox-reactive humic substances and defective oxygen vacancies can serve as the organic electron transfer mediator and the key surface reactive sites, respectively. This system achieves a superior pollutant degradation in real surface water at low oxidant concentrations. Reactive oxygen vacancies on the TiO2 surface and sub-surface are of considerable interest for this photochemical reaction system. By engineering defective oxygen vacancies on high-energy {001} polar facet, the surface and electronic interactions between tailored TiO2 and humic substances are greatly strengthened for the promoted electron transfer and oxidant activation. Rendered by the strong surface affinity and molecular activation, defective oxygen vacancies thermodynamically and dynamically promote reactive chain reactions for free radical formation, including the selective O2 reduction to ·O2− and the H2O2 activation to ·OH. Our findings take new insights into environmental geochemistry, and provide an effective strategy to in-situ boost the humic substances-mediated water purification without secondary pollution. Environmental implicationHumic substances are widely distributed in aquatic environment, thus playing important roles in environmental geochemistry. For example, humic substances can achieve good surface adsorption through electrostatic adsorption, ligand exchange and electronic interactions with typical TiO2 to form reactive ligand-metal charge transfer complexes for pollutant degradation. Inspired by the unique properties of surface and sub-surface oxygen vacancies, the defective TiO2 was designed to refine the humic substances-mediated photochemical reactions. A superior reactivity was measured for pollutant degradation. Our findings provide an effective strategy to boost naturally photochemical decontamination in environmentally relevant matrices.

Exploring the novel antioxidant peptides in low-salt dry-cured ham: Preparation, purification, identification and molecular docking

Dry-cured ham is important source of bioactive peptides. In this study, the antioxidant activities of peptides and components from low and fully salted dry-cured hams were compared by peptidomics. And novel antioxidant peptides were identified and characterized. The results showed that the peptides (<3 KDa) extracted from low-salt dry-cured ham had higher antioxidant activity. Therefore, the antioxidant peptides in low-salt dry-cured ham were further characterized and the mechanism of their antioxidant activity was investigated. From the five candidate peptides selected, we found DWPDARGIWHND (DD12) to be highly stable, non-sensitizing, and non-toxic with the highest free radical scavenging activity. Molecular docking predicted that DD12 interacted with Keap1 through hydrogen-bond formation and hydrophobic interactions, suggesting that DD12 had good cellular antioxidant activity. DD12 peptide can bind to DPPH• and ABTS•+, resulting in strong free radical scavenging activity. Our findings support the development and application of natural antioxidant peptides in dry-cured ham.

Rational design and synthesis of 2,4-dichloro-6-methyl pyrimidine derivatives as potential selective EGFRT790M/L858R inhibitors for the treatment of non-small cell lung cancer.

Many patients with non-small cell lung cancer (NSCLC) initially benefit from epidermal growth factor receptor (EGFR) targeted therapy. Unfortunately, varying degrees of resistance or side effects eventually develop. Overcoming and preventing the resistance and side effects of EGFR inhibitors has become a hot topic of research today. Based on the previous studies on AZD-9291, we designed and synthesized two series of 2,4-dichloro-6-methylpyrimidine derivatives, 19 compounds in total, as potential inhibitors of the EGFR kinase. The most promising compound, L-18, showed better inhibitory activity (81.9%) and selectivity against EGFRT790M/L858R kinase. In addition, L-18 showed strong antiproliferative activity against H1975 cells with an IC50 value of 0.65 ± 0.06 μM and no toxicity to normal cells (LO-2). L-18 was able to dose-dependently induce the apoptosis of H1975 cells and produced a cell-cycle-blocking effect, and it can also dose-dependently inhibit the migration and invasion of H1975 cells. L-18 also showed in vivo anticancer efficacy in H1975 cells xenograft mice. We also performed a series of in vivo and in vitro toxicological evaluations of compound L-18, which did not cause obvious injury in mice during administration. These results suggest that L-18 may be a promising drug candidate that warrants further investigation.

Antagonistic Effects of Lactic Acid Bacteria Isolated from Ethiopian Traditional Fermented Foods and Beverages Against Foodborne Pathogens.

Lactic acid bacteria (LAB) found in Ethiopian traditional fermented foods and beverages have potential antagonistic effects against foodborne pathogens due to their capacity to produce various antimicrobial metabolites. This study evaluated the antagonistic activity of LAB isolated from Ethiopian traditional fermented foods and beverages against foodborne pathogens and characterized their antimicrobial substances. A total of 180 traditional fermented foods and beverages were collected, and the antagonistic activities of LAB were evaluated against selected foodborne pathogens. The effects of pH, temperature, enzymes, and food additives on the antagonistic effects of cell-free supernatant produced by LAB were investigated. LAB identification and characterization were conducted using an integrated phenotypic approach and MALDI TOF MS spectrum analysis, and data were analyzed using one-way ANOVA and Tukey post hoc analysis. A total of 956 LAB were isolated, of which seventeen (17 LAB) isolates of Pediococcus pentosaceus (Pc. pentosaceus (n = 7)), Pediococcus acidilactici (Pc. acidilactici (n = 2)), Enterococcus faecium (Ec. faecium (n = 6)), and Lactococcus lactis (Lc. lactis (n = 2)) were screened for antagonistic activity based on their ability to produce bacteriocins, probiotic activity, and preservative potential. Pc. pentosaceus JULABB16, Pc. pentosaceus JULABB01, and Ec. faecium JULABBr39 showed strong antagonistic activity against all pathogens, with mean inhibition zone diameters ranging from 23.50 to 35.50mm. Lc. lactis, Pc. pentosaceus, Pc. acidilactici, and Ec. faecium produced bioactive metabolites that were sensitive to proteolytic enzymes and capable of withstanding high temperatures (80-100°C) and acid concentrations (pH 2-10). The CFS produced by Lc. lactis, Pc. pentosaceus, Pc. acidilactici, and Ec. faecium showed the most impending antagonistic activity against all pathogens. The bioactive substances produced by LAB isolates had promising effects against food spoilage and pathogenic bacteria, making them potential natural food preservatives.

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.

Construction of an aptamer sensor for sensitive detection of AOH based on the enhancement of light/electric dual signaling response of Ru/Cu-THQ by Ag NCs

Precise detection of food safety is a hotspot and challenging aspect in contemporary scientific research. This study utilized Ag nanocubes (Ag NCs) to augment the electrogenerated chemiluminescence (ECL) and electrochemical (EC) dual-response signals of Ru/Cu-tetrahydroxybenzoquinone (Ru/Cu-THQ). Consequently, a novel aptamer sensor was developed for the trace detection of Alternariol (AOH). This dual-mode sensor offers several advantages: (1) The output of dual-channel signals significantly reduces the likelihood of false-positive and false-negative detection results, which are common in traditional single-mode sensing. (2) Ru/Cu-THQ effectively coordinates dual-channel outputs and exhibits excellent ECL and EC behavior. (3) Ag NCs, due to their strong K2S2O8 activation ability and excellent conductivity, further amplify the sensor's response signal. This sensor demonstrates effective detection performance for AOH in the concentration range of 0.01–100 ng/mL, offering a novel approach for accurate food safety detection and potential application in real sample analysis.

Ultrasound assisted biogenic synthesis of Palladium nanoparticles using Cocculus hirsutus leaf extract: Antimicrobial, anti-inflammatory and catalytic activities

We have synthesized palladium nanoparticles (PdNPs) from aqueous leaf extract of Cocculus hirsutus (CH) by ultra-sonication in an easy, non-toxic, and eco-friendly manner. PdNPs synthesized were analyzed using UV–vis, FT-IR, powder XRD, TEM, and DLS instruments. From UV–vis spectra, the Surface Plasmon Resonance (SPR) signal indicated that the formation of PdNPs. The synthesized PdNPs shows spherical shape, crystalline and polydispersibility nature with a mean particle size of 10±3 nm was observed from XRD and TEM. FTIR analysis reveals the active role of phenolic constituents from CH leaf extract in reduction and surface functionalization of nanoparticles. The stability of the PdNPs was assessed by devious the Zeta potential analysis. The as-prepared PdNPs showed antibacterial efficacy (maximum zone of inhibition is 11.20 mm for S. typhimurium) and antifungal efficacy (maximum zone of inhibition is 32.80 mm for C. albicans) against disease causing human pathogens, strong anti-inflammatory activity for BSA denaturation and blistering catalytic activity against 4-NP reduction up to 5 cycles (6 min; 100 % reduction, rate constant is 0.532 min−1). The potency of the anti-inflammatory activity was found to be 90 % using PdNPs against the standard drug Diclofenac sodium (90 %) for 500 µg/mL. The above mentioned activities were used to evaluate the effectiveness of the PdNPs in treating bacterial, inflammation related conditions and also as an effective catalyst in wastewater treatment.