Membrane Permeability Research Articles

Responses of glyoxalase system, ascorbate-glutathione cycle, and antioxidant enzymes in Pontederia cordata to lead stress and its capacity to remove lead

A hydroponic experiment was conducted to investigate the variations in membrane permeabilities, chlorophyll contents, antioxidase activities, the ascorbic acid (AsA)-glutathione (GSH) cycle, and the glyoxalase system in the leaves of Pontederia cordata with 0 ∼ 15.0 mg L−1 lead ion (Pb2+) exposure. The concentrations of Pb2+ accumulated in the plant roots, stems, and leaves were also evaluated. After 7 days of exposure, the plants maintained normal growth, and there was a significant increase in ascorbate peroxidase and dehydroascorbate reductase activities. With 5.0 mg L−1 Pb2+ exposure for 28 days, nearly 66.36% of Pb2+ accumulated in the roots, while excess Pb2+ immobilized in the leaves was not observed. Exposure to 10.0 and 15.0 mg L−1 Pb2+ for 28 days significantly increased Pb2+ contents in the leaves. This led to decrease in chlorophyll a, b, and carotenoid contents, and to increase in the methylglyoxal content in the leaves. With 10 and 15 mg L−1 Pb2+ exposure, NPT and PCs contents in leaves increased. however, the glyoxalase system did not function well in the plant tolerant to Pb2+ at higher concentrations. The AsA-GSH cycle did not cooperate with the glyoxalase system in the plant defense against Pb2+ exposure in the present investigation.

A novel α-mangostin derivative synergistic to antibiotics against MRSA with unique mechanisms

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) remains a leading cause of hospital-acquired infections, often linked to complicated treatments, increased mortality risk, and significant cost burdens. Several antibacterial agents have been developed to address MRSA resistance. In this study, potential agents to combat MRSA resistance were explored, with the antibacterial activity of synthesized α-mangostin (α-MG) derivatives being evaluated alongside investigations into their cellular mechanisms against MRSA2. α-MG-4, featuring an allyl group at C3 of the lead compound α-MG, restored the sensitivity of MRSA2 to penicillin, enrofloxacin, and gentamicin, while also demonstrating improved safety profiles. Although α-MG-4 alone was ineffective against MRSA2, it exhibited an optimal synergistic ratio in vitro when combined with these antibiotics. This significant synergistic antibacterial effect was further confirmed in vivo using a mouse skin abscess model. Additionally, the synergistic mechanisms revealed that α-MG-4 was associated with changes in membrane permeability and inhibition of the MepA and NorA genes, which encode the efflux pumps of MRSA2. α-MG-4 also inhibited PBP2a expression, potentially by occupying a crucial binding site in a dose-dependent manner. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA)’s resistance to multiple antibiotics poses significant health and safety concerns. A novel α-mangostin (α-MG) derivative, α-MG-4, was first identified as a xanthone-based PBP2a inhibitor that reverses MRSA2 resistance to penicillin. The synergistic antibacterial effects of α-MG-4 were linked to increased cell membrane permeability and the inhibition of genes involved in efflux pump function.

StaPep: An Open-Source Toolkit for Structure Prediction, Feature Extraction, and Rational Design of Hydrocarbon-Stapled Peptides.

All-hydrocarbon stapled peptides, with their covalent side-chain constraints, provide enhanced proteolytic stability and membrane permeability, making them superior to linear peptides. However, tools for extracting structural and physicochemical descriptors to predict the properties of hydrocarbon-stapled peptides are lacking. To address this, we present StaPep, a Python-based toolkit for generating 3D structures and calculating 21 features for hydrocarbon-stapled peptides. StaPep supports peptides containing two non-standard amino acids (norleucine and 2-aminoisobutyric acid) and six non-natural anchoring residues (S3, S5, S8, R3, R5, and R8), with customization options for other non-standard amino acids. We showcase StaPep's utility through three case studies. The first generates 3D structures of these peptides with a mean RMSD of 1.62 ± 0.86, offering essential structural insights for drug design and biological activity prediction. The second develops machine learning models based on calculated molecular features to differentiate between membrane-permeable and non-permeable stapled peptides, achieving an AUC of 0.93. The third constructs regression models to predict the antimicrobial activity of stapled peptides against Escherichia coli, with a Pearson correlation of 0.84. StaPep's pipeline spans data retrieval, structure generation, feature calculation, and machine learning modeling for hydrocarbon-stapled peptides. The source codes and data set are freely available on Github: https://github.com/dahuilangda/stapep_package.

Synthesis and biological evaluation of novel aminoguanidine derivatives as potential antibacterial agents

In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2–8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents.

Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications

Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development and maintaining tissue homeostasis and immunological functioning. It is a complex interplay of intrinsic and extrinsic signaling pathways that ultimately converges on executing the apoptotic program. The extrinsic pathway is initiated by the binding of death ligands such as TNF-α and Fas to their respective receptors on the cell surface. In contrast, the intrinsic pathway leads to increased permeability of the outer mitochondrial membrane and the release of apoptogenic factors like cytochrome c, which is regulated by the Bcl-2 family of proteins. Once activated, these pathways lead to a cascade of biochemical events, including caspase activation, DNA fragmentation, and the dismantling of cellular components. Dysregulation of apoptosis is implicated in various disorders, such as cancer, autoimmune diseases, neurodegenerative disorders, and cardiovascular diseases. This article focuses on elucidating the molecular mechanisms underlying apoptosis regulation, to develop targeted therapeutic strategies. Modulating apoptotic pathways holds immense potential in cancer treatment, where promoting apoptosis in malignant cells could lead to tumor regression. This article demonstrates the therapeutic potential of targeting apoptosis, providing options for treating cancer and neurological illnesses. The safety and effectiveness of apoptosis-targeting drugs are being assessed in ongoing preclinical and clinical trials (phase I–III), opening the door for more effective therapeutic approaches and better patient outcomes.

Cuminaldehyde in Combination with Ciprofloxacin Shows Antibiofilm Activity against Clinical Strains of Pseudomonas aeruginosa: A Study to Explore the Underlying Mechanism

Pseudomonas aeruginosa poses a serious threat in healthcare settings. This bacterium can develop resistance to many antibiotics, rendering even last-resort treatments ineffective. Additionally, it forms protective biofilms that shield it from the immune system, making infection treatment challenging. This study investigated the susceptibility of five clinically isolated strains of the test bacteria to a combination of ciprofloxacin and cuminaldehyde. Cuminaldehyde (a natural phytochemical) and ciprofloxacin (an antibiotic) were separately found to show antimicrobial effect against test organism. However, the combination of selected compounds showed an additive effect in their microbial growth inhibitory activity. The mentioned compounds at their sub-MIC doses subjected to test whether they could show any extent of biofilm inhibition or disintegration property against the clinical strains of P. aeruginosa. The chosen concentrations of the compounds demonstrated significant antibiofilm activity against all the tested clinical strains. Additionally, it was observed that the compounds not only accumulated reactive oxygen species (ROS) but also enhanced the cell membrane permeability of the clinical strains. These findings suggest that the combination of ciprofloxacin and cuminaldehyde could explore new directions in fighting P. aeruginosa-linked infections.

Cefiderocol in Combating Carbapenem-Resistant Acinetobacter baumannii: Action and Resistance

Acinetobacter baumannii (A. baumannii) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, active antibiotic efflux, and enzymatic hydrolysis via different β-lactamases are the main resistance mechanisms displayed by A. baumannii, and they are all effective against successful treatment approaches. This means that alternate treatment approaches, such as combination therapy that incorporates beta-lactams, β-lactamase inhibitors, and novel antibiotics like cefiderocol, must be investigated immediately. Cefiderocol, a new catechol-substituted siderophore cephalosporin, improves antibacterial activity by allowing for better bacterial membrane penetration. Due to its unique structure, cefiderocol can more efficiently target and destroy resistant bacteria by using iron transport systems. Through its inhibition of peptidoglycan formation through binding to penicillin-binding proteins (PBPs), cefiderocol avoids conventional resistance pathways and induces bacterial cell lysis. The possibility of resistance development due to β-lactamase synthesis and mutations in PBPs, however, emphasizes the need for continued investigation into cefiderocol’s efficacy in combination treatment regimes. Cefiderocol’s siderophore mimic mechanism is especially important in iron-limited conditions because it can use ferric-siderophore transporters to enter cells. Additionally, its passive diffusion through bacterial porins increases its intracellular concentrations, making it a good option for treating carbapenem-resistant A. baumannii, especially in cases of severe infections and ventilator-associated diseases (IVACs). Cefiderocol may reduce MDR infection morbidity and mortality when combined with customized antimicrobial treatments, but further investigation is needed to improve patient outcomes and address A. baumannii resistance issues.

Enhancing CO2/N2 and CO2/CH4 Separation Properties of PES/SAPO-34 Membranes Using Choline Chloride-Based Deep Eutectic Solvents as Additives

CO2 separation is an important environmental method mainly used in reducing CO2 emissions to mitigate anthropogenic climate change. The use of mixed-matrix membranes (MMMs) arrives as a possible answer, combining the high selectivity of inorganic membranes with high permeability of organic membranes. However, the combination of these materials is challenging due to their opposing nature, leading to poor interactions between polymeric matrix and inorganic fillers. Many additives have been tested to reduce interfacial voids, some of which showed potential in dealing with compatibility problems, but most of them lack further studies and optimization. Deep eutectic solvents (DESs) have emerged as IL substitutes since they are cheaper and environmentally friendly. Choline chloride-based deep eutectic solvents were studied as additives in polyethersulfone (PES)/SAPO-34 membranes to improve CO2 permeability and CO2/N2 and CO2/CH4 selectivity. SAPO-34 crystals of 150 nm with a high surface area and microporosity were synthesized using dry-gel methodology. The PES/SAPO-34 membranes were optimized following previous work and used in a defined composition, using 5 or 10 w/w% of DES during membrane preparation. All MMMs were characterized by their ideal gas permeability using N2 and CO2 pure gasses. Selected membranes were also tested using CH4 pure gas. The results presented that 5 w/w%, in polymer mass, of ChCl–glycerol presented the best result over the synthesized membranes. An increase of 200% in CO2 permeability maintains the CO2/N2 selectivity for the non-modified PES/SAPO-34 membrane. A CO2/CH4 selectivity of 89.7 was obtained in PES/SAPO-34/ChCl-glycerol membranes containing 5 w/w% of this DES, which is an outstanding ideal separation performance for MMMs when compared to other results in the literature. FTIR analysis reiterates the presence of glycerol in the membranes prepared. Dynamic Mechanical Thermal Analysis (DMTA) shows that the addition of 5 w/w% of DES does not impact the membrane flexibility or polymer structure. However, in concentrations higher than 10 w/w%, the inclusion of DES could lead to high membrane rigidification without impacting the overall thermal resistance. SEM analysis of DES-enhanced membranes presented asymmetric final membranes and reaffirmed the results obtained in DMTA about rigidified structures and lower zeolite–polymer interaction with higher concentrations of DES.

Enhanced Antibacterial, Anti-Inflammatory, and Antibiofilm Activities of Tryptophan-Substituted Peptides Derived from Cecropin A-Melittin Hybrid Peptide BP100

The emergence of multidrug-resistant pathogens necessitates the development of novel antimicrobial agents. BP100, a short α-helical antimicrobial peptide (AMP) derived from cecropin A and melittin, has shown promise as a potential therapeutic. To enhance its efficacy, we designed and synthesized 16 tryptophan-substituted BP100 analogs based on helical wheel projections. Among these, BP5, BP6, BP8, BP11, and BP13 exhibited 1.5- to 5.5-fold higher antibacterial activity and improved cell selectivity compared to BP100. These analogs demonstrated superior efficacy in suppressing pro-inflammatory cytokine release in LPS-stimulated RAW 264.7 cells and eradicating preformed biofilms of multidrug-resistant Pseudomonas aeruginosa (MDRPA). Additionally, these analogs showed greater resistance to physiological salts and serum compared to BP100. Mechanistic studies revealed that BP100 and its analogs exert their antibacterial effects through membrane disruption, depolarization, and permeabilization. Notably, these analogs showed synergistic antimicrobial activity with ciprofloxacin against MDRPA. Our findings suggest that these tryptophan-substituted BP100 analogs represent promising candidates for combating multidrug-resistant bacterial infections, offering a multifaceted approach through their antibacterial, anti-inflammatory, and antibiofilm activities.

Priming immunity via herbal components and their nanomedicines for the treatment of cancer

Recently, immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system. Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development, reduce pain, and prolong patient survival. However, the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability, poor membrane permeability, and low bioavailability. To address this issue, nanotechnology has been used to enhance the activity of active compounds. Therefore, this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems, challenges in their delivery, and the application of nanocarriers for the effective delivery of these herbal components.

In vitro antibacterial activity of photoactivated flavonoid glycosides against Acinetobacter baumannii

Acinetobacter baumannii’s extensive antibiotic resistance makes its infections difficult to treat, so effective strategies to fight this bacterium are urgently needed. This study aims to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) mediated by Rutin-Gal(III) complex and Quercetin against A. baumannii. Absorbance spectra, fluorescence spectra, and minimum inhibitory concentration (MIC) of Rutin-Gal(III) complex and Quercetin were determined. The intracellular reactive oxygen species (ROS), extracellular polymeric substances (EPS), cell membrane permeability, expression of ompA and blaOXA−23, anti-biofilm activity, and anti-metabolic activity of Rutin-Gal(III) complex- and Quercetin-mediated aPDT were measured. Rutin-Gal(III) complex and Quercetin revealed absorption peaks in the visible spectra. Quercetin and Rutin-Gal(III) complex displayed fluorescence peaks at 524 nm and 540 nm, respectively. MIC values for the Rutin-Gal(III) complex and Quercetin were 64 µg/mL and 256 µg/mL, respectively. Quercetin- and Rutin-Gal(III) complex-mediated aPDT significantly reduced the colony forming units/mL (58.4% and 67.5%), EPS synthesis (47.4% and 56.5%), metabolic activity (30.5% and 36.3%), ompA (5.5- and 10.5-fold), and blaOXA−23 (4.1-fold and 7.8-fold) genes expression (respectively; all P < 0.05). Quercetin- and Rutin-Gal(III) complex-mediated aPDT enhanced notable biofilm degradation (36.2% and 40.6%), ROS production (2.55- and 2.90-folds), and membrane permeability (10.8– and 9.6-folds) (respectively; all P < 0.05). The findings indicate that Rutin-Gal(III) complex- and Quercetin-mediated aPDT exhibits antibacterial properties and could serve as a valuable adjunctive strategy to conventional antibiotic treatments for A. baumannii infections. One limitation of this study is that it was conducted solely on the standard strain; testing on clinical isolates would allow for more reliable interpretation of the results.

Mechanical, thermal and gas separation properties of copolyimides and their thermal rearrangement copolymer membranes with spirobisindane structures

In this work, two kinds of dimaine monomers with spirocyclic structures, including 3,3,3′,3′-tetramethyl-6,6′-bis[3-amino-4-hydroxyphenoxy]-1,1′-spirobisindane (TBAHS) and 3,3,3′,3′-tetramethyl-bis(5-amino-6-hydroxyphenyl)-1,1′-spirobisindane (TBHAS) are firstly synthesized. Then, the two diamines TBAHS and TBHAS are copolymerized in different molar ratios with equimolar 4,4′-(hexafluoroisopropenyl)diphthalic anhydride (6FDA) to synthesize poly(amic acid) (PAA) solution, followed by thermal imidization to obtain a series of copolyimide (coPI) membranes. Next, these coPI(TBAHS-TBHAS) specimens are subjected to thermal rearrangement (TR) treatment at 450°C to obtain the corresponding coTR(TBAHS-TBHAS) copolymer membranes. The influences of the molar ratio of TBAHS to TBHAS, thermal treatment temperature and time on the microstructures and properties of the PI and TR copolymers are investigated. With the increase of rigid TBHAS molar ratio, the glass transition temperature ( Tg) and d-spacing value of the coPI(TBAHS-TBHAS) samples are significantly enhanced. Furthermore, as the thermal treatment temperature increases, the mechanical properties of the copolymer membranes display a sharply decline trend, but the d-spacing values are obviously increased. When the molar ratio of TBAHS to TBHAS is 7:3, the gas permeabilities of the coTR membrane reach 1140.5, 1180.6, 306.6, and 44.9 Barrer for H2, CO2, O2, and N2, respectively. Meanwhile, the ideal selectivity of O2/ N2 is 6.82, suggesting a superior separation performance close to the 2015 upper limit. Furthermore, with the increase of thermal treatment temperature and time, the gas permeabilities are also improved.

Effects of SNP, MgSO4, and MgO-NPs foliar application on Spinacia oleracea L. growth and physio-biochemical responses under cadmium stress

The effects of foliar application of sodium nitroprusside (SNP), magnesium sulfate (MgSO4) and magnesium oxide nanoparticles (MgO-NPs) on the growth, physiology, and gas exchange parameters of two varieties of spinach (Spinacia oleracea L.) under cadmium (Cd) stress were examined. The experiment was arranged in a completely randomized design with 72 pots. Two varieties of S. oleracea (Desi Palak & Lahori Palak) were used. Two concentrations of Cd (0 µM and 150 µM) in the form of cadmium chloride (CdCl2) were used. Two levels of SNP (0 ppm and 100 ppm) and two levels for each form of Mg i.e. MgSO4 and MgO-NPs (0 and 200 ppm) were foliar sprayed on plants in control and Cd stress. Both varieties behaved similarly under Cd stress and caused reductions in growth, physiology, gas exchange, water content parameters and inorganic ion uptake. However, the biochemical parameters like relative membrane permeability (RMP), malondialdehyde (MDA), and hydrogen peroxide (H2O2) contents were increased. However, all foliar spray treatments increased growth, physiological and gas exchange parameters, water content and inorganic ion uptake. However, this reduced the MDA, RMP, and H2O2 contents. Desi Palak showed the more positive results under foliar application of MgO-NPs. However, Lahori palak showed more positive results under the SNP + MgO-NP treatment. It is concluded that foliar application of SNP, MgSO4 and MgO-NPs could be an innovative approach to alleviated the heavy metals (Cd) toxicity in crop plants.

Design of Self-Standing Chiral Covalent-Organic Framework Nanochannel Membrane for Enantioselective Sensing.

Nanochannel membranes are promising materials for enantioselective sensing. However, it is difficult to make a compromise between the selectivity and permeability in traditional nanochannel membranes. Therefore, new types of nanochannel membranes with high enantioselectivity and excellent permeability should be explored for chiral analysis. Here, asymmetric catalysis strategy is reported for interfacial polymerization synthesis of chiral covalent-organic framework (cCOF) nanochannel membrane for enantioselective sensing. Chiral phenylethylamine (S/R-PEA) and 2,4,6-triformylphloroglucinol (TP) are used to prepare chiral TP monomer. 4,4',4″-triaminotriphenylamine (TAPA) is then condensed with chiral TP to obtain cCOF nanochannel membrane via a C═N Schiff-base reaction. The molar ratio of TP to S/R-PEA is adjusted so that S/R-PEA is bound to the aldehyde only or both the aldehyde and hydroxyl groups on TP to obtain chiral-induced COF (cCOF-1) or both chiral-induced and modified COF (cCOF-2) nanochannel membrane, respectively. The prepared cCOF-2 nanochannel membrane showed two times more selectivity for limonene enantiomers than cCOF-1 nanochannel membrane. Furthermore, cCOF-2 nanochannel platform exhibited excellent sensing performance for other chiral molecules such as limonene, propanediol, methylbutyric acid, ibuprofen, and naproxen (limits of detection of 19-42ngL-1, enantiomer excess of 63.6-86.3%). This work provides a promising way to develop cCOF-based nanochannel enantioselective sensor.

Insight into the Antibacterial Activities of Pyridinium-Based Cationic Pillar[5]arene with Controllable Hydrophobic Chain Lengths against Staphylococcus aureus.

The increasing number of infections caused by pathogenic bacteria has severely affected human society. More and more deaths were originated from Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) infection each year. The potential and excellent bacteriostatic activity and resistance to biofilm formation of pillar[5]arene with different functional groups attract important attention to further study the relationship between antimicrobial activity and cytotoxicity by varying the length of the hydrophobic chain, the number of positive charges, and the hydrophobic/hydrophilic balance of the molecule. In this work, four pyridinium-based cationic pillar[5]arene (PPs) with linear aliphatic chains of different lengths were synthesized. After systematic characterization, their inhibition activities against S. aureus were investigated. It revealed that PP6 (six methylenes in each linker) exhibited excellent inhibition activity against S. aureus (ATCC 6538) with a minimum inhibitory concentration (MIC) of 3.91 μg/mL and a minimum bactericidal concentration (MBC) of 62.50 μg/mL. As expected, PP6 exhibited the strongest antibiofilm ability and negligible antimicrobial resistance even after the 20th passage. A study of the action mechanism of selected PPs on the bacterial membrane depolarization and permeability by transmission electron microscopy (TEM) disclosed that the cationic pyridine groups of PPs inserted into the negatively charged bacterial membranes, thereby leading to membranolysis, cytoplasmic content leakage, and cell death. Importantly, PPs all showed very low toxicity to mammalian cells (L929 and HBZY-1), which provided a significant reference for the construction of hypotoxic antibacterial biomaterials for multiple drug-resistant bacteria based on pyridinium-grafted cationic macrocycles with controllable hydrophobic chain lengths.

Harnessing anti-infective efficacy of Cinnamomum verum in synergy with β-lactam and fluoroquinolones drugs to combat virulence and biofilms of Pseudomonas aeruginosa PAO1

Multidrug resistance (MDR) Gram-negative bacteria are increasingly resistant to multiple antibiotics, posing a serious challenge to infection control and treatment. Combining plant-derived bioactives with antibiotics offers a promising approach to overcome the challenges posed by MDR pathogens like Pseudomonas aeruginosa. This study investigated the synergistic effects of Cinnamomum verum with beta-lactam and fluoroquinolones against P. aeruginosa PAO1. The ethyl acetate fraction of C. verum (CVEF) was obtained through fractionation in organic solvents with progressively higher polarity. The interaction of CVEF with selected antibiotics was assessed by checkerboard synergy assay. The effects of synergistic combinations on pyocyanin, pyoverdine, protease, EPS production, and biofilm development were measured using spectroscopic assays. CVEF combined with cefepime, ceftazidime, and levofloxacin significantly enhanced antibacterial efficacy with FICIs between 0.156 to 0.5. The most active combinations i.e., CVEF-cefepime and CVEF-ceftazidime inhibited viable cell count of growth by 3.6 and 4.2 log10 CFU/ml respectively. The combination also inhibited virulence factors (>75%) and biofilms (>80%) at lower 1/2×FICs. The viable count of biofilm cells was also reduced from 6.4 to 3.3 and 3.6 log10 CFU/ml. Membrane permeability was decreased by 60.34% and biofilm cell viability by 22.53-38.44%. Key phytochemicals analyzed by GC/MS and LC/MS/MS, include cinnamaldehyde, trans-chlorogenic acid, quercetin, and quercetin 3'-O-glucuronide. In molecular docking investigations, quercetin 3'-O-glucuronide had the highest binding affinity with quorum sensing (QS) and biofilm-associated protein. The findings suggest CVEF, in combination with antibiotics, effectively targets resistance phenotypes of P. aeruginosa, impairing growth, virulence, and biofilms. This supports further research into natural compounds alongside antibiotics to treat drug-resistant infections.

Enhanced removal of fluoride ions using lanthanum-doped coconut shell biochar in PVDF ultrafiltration membranes

Fluoride contamination in surface and ground water poses significant health risks, necessitating a low-energy, cost-effective removal method. Herein, an ultrafiltration (UF) adsorptive membrane doped with lanthanum (La)-based coconut shell biochar was synthesized to effectively remove fluoride ions. Based on the results of adsorption and membrane separation performance, it was found that La-based biochar showed a significantly higher adsorption capacity (126.7 mg F/g) compared to bare biochar (27.41 mg F/g), due to the oxygen-containing functional groups from La2O2CO3 that enhance binding sites and electrostatic attraction for fluoride ions. Furthermore, the addition of La-modified adsorbent to the polyvinylidene fluoride (PVDF) UF membrane markedly altered its structure and surface properties, changing the pore structure to porous, narrowing pore size, increasing active adsorption sites, and improving hydrophilicity. These changes boosted fluoride ion rejection from 9.53 % to 62.07 % with tiny effect on membrane permeability. More important, this UF adsorptive membrane exhibited excellent antifouling ability with the lowest flux decline (J/J0 =0.450) compared to pristine PVDF membrane (J/J0 =0.142), which was owing to the better improved surface properties. In all, this study provides a novel strategy for efficient, economic and selective separation of fluoride ions and further extends the application of UF to the field of ion removal.

Lactobacillus plantarum Antimicrobial Peptide Y8-2: A New strategy against Toxoplasma gondii

Toxoplasma gondii is an important foodborne zoonotic parasite that is estimated to have infected one-third of the world's population. However, there are no specific drugs or vaccines to treat toxoplasmosis in humans. Therefore, there is an urgent need to develop safe and effective ways for toxoplasmosis. The antimicrobial peptide Y8-2 was isolated from the supernatant of Lactobacillus plantarum Y8 fermentation that was involved in this study. Flow cytometry analysis showed that Y8-2 had a significant killing effect on tachyzoites; this result, combined the results of SEM and TEM, suggested that Y8-2 could deform cells, disrupt the integrity and permeability of tachyzoite cell membranes, resulting in cytoplasmic vacuolization and extravasation. In addition, Y8-2 significantly inhibited the proliferation of tachyzoites at 12 h and 24 h and elevated the levels of IL-12p70 and TNF-α after infection with Ana-1 cells. Plaque experiments verified that Y8-2 can inhibit tachyzoites invasion and proliferation and significantly reduce the plaque area. Our study provides a new strategy for developing a safe and effective method for the treatment of toxoplasmosis and provides data to support the treatment of toxoplasmosis with LAB metabolites, thus broadening the prospects for the development and utilization of LAB.

Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity.

The advancement of antimicrobial peptides (AMPs) as therapeutic agents is hindered by their poor selectivity. Recent evidence indicates that controlled disruption of the amphipathicity of α-helical AMPs may increase the selectivity. This study investigated the role of imperfect amphipathicity in optimizing AMPs with varied sequences to enhance their activity and selectivity. Among these, the lead peptide RI-18, characterized by an imperfectly amphipathic α-helical structure, demonstrated potent and broad-spectrum antibacterial activity without inducing hemolytic or cytotoxic effects. RI-18 effectively eliminated planktonic and biofilm-associated bacteria as well as persister cells and exhibited high bacterial plasma membrane affinity, inducing rapid membrane permeabilization and rupture. Notably, RI-18 significantly reduced bacterial loads without promoting bacterial resistance, highlighting its therapeutic potential. Overall, this study identified RI-18 as a promising antimicrobial candidate. The rational strategy of tuning imperfect amphipathicity to enhance the AMP activity and selectivity may facilitate the design and development of AMPs.

Caspase-2 kills cells with extra centrosomes.

Centrosomes are membrane-less organelles that orchestrate a wide array of biological functions by acting as microtubule organizing centers. Here, we report that caspase-2-driven apoptosis is elicited in blood cells failing cytokinesis and that extra centrosomes are necessary to trigger this cell death. Activation of caspase-2 depends on the PIDDosome multi-protein complex, and priming of PIDD1 at extra centrosomes is necessary for pathway activation. Accordingly, loss of its centrosomal adapter, ANKRD26, allows for cell survival and unrestricted polyploidization in response to cytokinesis failure. Mechanistically, cell death is initiated upstream of mitochondria via caspase-2-mediated processing of the BCL2 family protein BID, driving BAX/BAK-dependent mitochondrial outer membrane permeabilization (MOMP). Remarkably, BID-deficient cells enforce apoptosis by engaging p53-dependent proapoptotic transcriptional responses initiated by caspase-2. Consistently, BID and MDM2 act as shared caspase-2 substrates, with BID being kinetically favored. Our findings document that the centrosome limits its own unscheduled duplication by the induction of PIDDosome-driven mitochondrial apoptosis to avoid potentially pathogenic polyploidization events.