Pore Formation Research Articles

Determining the impact of different types of biofuels on the quality of iron ore pellets

The object of this study is the process of roasting iron ore pellets. The study solves the task of replacing fossil fuel with plant-based fuel in order to reduce environmental load and ensure the stable quality of pellets, which is necessary for use in blast furnaces. The influence of biofuel content at a given temperature and air speed on the strength of pellets after roasting was studied. As a result of the research, it was established that the fuel content has a decisive effect on the strength of pellets. Among all types of fuel that were investigated, pellets with the addition of sunflower husks and wood had the highest strength that meets the requirements for blast furnace melting of 200 kilograms. The use of wheat straw and charcoal does not make it possible to completely replace solid fuel in the layer of pellets. The results show that the use of up to 0.36 % of sunflower husk makes it possible to increase the strength of burned pellets compared to samples without biofuel content. Adding all other considered types of fuel reduced the strength of the pellets. These results are explained by the different content of lignin, cellulose, and hemicellulose, which determines the characteristics of the biomass. The high content of cellulose and hemicellulose allows for high hydrophilicity due to the high number of OH groups and positively affects the formation of raw pellets. Volatile substances released during the combustion of biofuel contribute to the formation of spherical pores, as well as their uniform distribution, which prevents the propagation of cracks under load. Research results make it possible to establish the optimal roasting mode, decrease harmful emissions, and bring down costs by reducing fossil fuel consumption

Characteristics and main controlling factors of the Sangonghe tight sandstone reservoirs in the Shengbei Sub-sag of the Turpan-Hami basin, China

The Sangonghe tight sandstone hydrocarbon reservoirs in the Shengbei Sub-sag of the Turpan-Hami Basin are key areas for hydrocarbon exploration. However, previous research has mostly focused on petrological characteristics, physical properties, and pore types. There is a lack of understanding regarding diagenesis, microscopic pore-throat features, and the impact of overpressure on the reservoir. This gap in knowledge poses a disadvantage for future studies and hydrocarbon exploration. This study examines the Sangonghe tight sandstone hydrocarbon reservoirs in the Shengbei Sub-sag of the Turpan-Hami Basin. It combines cast thin sections, physical property tests, high-pressure mercury injection experiments, low-temperature nitrogen adsorption experiments, and well logging overpressure identification to investigate the basic characteristics, diagenesis, and microscopic pore-throat features of these reservoirs. Based on this analysis, the study identifies the main controlling factors of the reservoir properties and presents three key findings. First, the reservoir rocks are primarily composed of lithic sandstone and feldspathic lithic sandstone with porosity ranging from 4% to 10% and permeability ranging between 0.1 and 10 mD, classifying it as a low-porosity, low-permeability tight sandstone reservoir. Second, the reservoir has undergone several diagenetic processes, with significant compaction and common occurrences of cementation and metasomatism. Acidic dissolution is the main dissolution process, but it is relatively weak. The pore-throat system exhibits poor and concentrated sorting, with nanometer-sized pores being predominant. These include 'ink-bottle' pores with narrow necks and wide bodies, and parallel plate-structured fissure pores. Finally, the development of the reservoirs is mainly influenced by sedimentation, dissolution, and overpressure. The parent rock provenance features a high content of stable heavy minerals, larger grain sizes, and thicker sand body layers. These factors enhanced the reservoir's resistance to compaction and promoted the development of primary intergranular pores. Additionally, organic acid fluids caused extensive dissolution of feldspar and lithic fragments, resulting in the formation of numerous secondary dissolution pores. Additionally, under-compaction overpressure helped preserve primary pores, while hydrocarbon generation overpressure extended the hydrocarbon generation period. This extended period provided the driving force for fluid migration, enhanced the transformation of reservoir space, and aided in hydrocarbon accumulation.

Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Liposomes Loaded with STING Agonist Enhances Immune Activation for Breast Cancer Immunotherapy

Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system’s ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy.

Dissecting the Membrane Association Mechanism of Aerolysin Pores at Femtomolar Concentrations Using Water as a Probe.

Aerolysin is a bacterial toxin that forms transmembrane pores at the host plasma membrane and has a narrow internal diameter and great stability. These assets make it a highly promising nanopore for detecting biopolymers such as nucleic acids and peptides. Although much is known about aerolysin from a microbiological and structural perspective, its membrane association and pore-formation mechanism are not yet fully understood. Here, we used angle-resolved second harmonic scattering (AR-SHS) and single-channel current measurements to investigate how wild-type (wt) aerolysin and its mutants interact with liposomes in aqueous solutions at femtomolar concentrations. Our AR-SHS experiments were sensitive enough to detect changes in the electrostatic properties of membrane-bound aerolysin, which were induced by variations in pH levels. We reported for the first time the membrane binding affinity of aerolysin at different stages of the pore formation mechanism: while wt aerolysin has a binding affinity as high as 20 fM, the quasi-pore and the prepore states show gradually decreasing membrane affinities, incomplete insertion, and a pore opening signature. Moreover, we quantitatively characterized the membrane affinity of mutants relevant for applications to nanopore sensing. Our study provides a label-free method for efficiently screening biological pores suitable for conducting molecular sensing and sequencing measurements as well as for probing pore-forming processes.

Functional Characterization of the Sterol-Synthesis-Related Gene CgCYP51 in the Poplar Anthracnose-Causing Fungus Colletotrichum gloeosporioides

Poplar is an economically and ecologically valuable tree species. Anthracnose, which severely affects poplar tree growth, is mainly caused by Colletotrichum gloeosporioides. In the infestation cycle of poplar anthracnose, the entry of C. gloeosporioides into the host tissue depends on the formation of an appressorium. The subsequent development of the appressorium determines the pathogenesis of poplar anthracnose and the degree of damage. Previous studies have found that the transcription factor CgSte12 affects appressorium formation and development by regulating the expression of a series of genes, including the sterol-synthesis-related gene CgCYP51, which influences appressorium formation and development. In this study, knockout and functional analyses of CgCYP51 revealed decreases in differentiation, darkening rate, and turgor pressure of appressoria in mutants. Additionally, compared with the wild-type appressorium, mutant appressoria secreted less mucus and exhibited abnormal penetration pore formation, ultimately leading to decreased pathogenicity. Moreover, CgCyp51 affected the sensitivity of C. gloeosporioides to sterol biosynthesis inhibitors. Considered together, the study findings indicate CgCYP51 is a key CgSte12-regulated gene that affects C. gloeosporioides appressorium formation and development. Furthermore, the study data provide new insights into the molecular basis of C. gloeosporioides appressorium formation and development.

Bio-inhibitive corrosion effect of carica papaya leaf extract on cold-rolled mild steel in 0.1 M HCl solution

Plant extracts are prone to microbial growth that can lead to microbial-induced corrosion (MIC), a major setback for their performance and stability as corrosion inhibitors. Hence, this work aims to identify the microbes that may cause the ineffectiveness of carica papaya leaf extract (CPLE) as a bio-corrosion inhibitor of cold-rolled mild steel in 0.1 M HCl solution for 48 days at 28℃. Cold-rolled mild steel coupons were immersed in 100 ml of 0.1 M hydrochloric (HCl) acid solution containing 1 g, 2 g, 3 g, 4 g, and 5 g of carica papaya leaf extract (CPLE) for 48 days at 28℃. The gravimetric method was used to determine the coupons' corrosion rate (CR), surface coverage, and inhibition efficiency (IE%) of the CPLE. The functional groups in the CPLE were identified using Fourier Transform Infrared Spectroscopy (FTIR), and the surface appearance of the coupons after immersion was examined using an atomic force microscope (AFM). Gravimetric data showed the coupons dipped in a 0.1 M HCl solution containing 3 g/100 ml of the inhibitor exhibited the highest inhibition efficiency of 87.73%, surface coverage of 0.88, and lowest corrosion rate of 0.00255 mm/day or 0.93 mm/yr, after 48 days at 28℃. In FTIR, transmittance peaks occurred at 1558 cm−1 for amines (-NH) in alkaloid scissoring, 1452 cm−1 for aromatic -C = C in flavonoids, 2932 cm−1 for aliphatic methylene (-CH2) and aldehyde (RCOH) stretching, 1035 and 1077 cm−1 for aromatic-OR in tannin, and 3280 cm−1 for out-of-plane bending of hydroxyl (-OH) in phenolics. Vitamin C (522,940 μg/g), flavonoids (860 μg/g), saponins (637.9 μg/g), terpenoid (48.4 μg/g), phenol (120%μg/g), alkaloid (4.18 μg/g), tannin (59.84%), and glycosides (9.04%) make up the extract's average phytochemical content. AFM presents pits and ridges on the mild steel coupons immersed in 0.1 M HCl solution without the extract. Those immersed in the solutions with varying concentrations of the extract had a passive layer of the CPLE adhering to the surfaces of the coupons thereby preventing the coupon’s direct contact with the acid solution and weight loss. However, over time, microbial growth decreased the efficiency of CPLE due to metabolites. Microbial tests show creamy, irregular and raised bacterial total colony-forming units per gram (Tcfu/g) as 4.6 × 105 Tcfu/g and 1.9 × 107 Tcfu/g in 2 runs. Also, a mixture of white and fluffy appearance and spore formation of fungi population of 4.8 × 105 Tcfu/g and 3.2 × 107 Tcfu/g in 2 Runs made up of Penicillium spp, Coccidioides immitis, Aspergillus flavus, and Fusarium spp, with hyphae, were seen in the solutions containing CPLE.

New Insights on the Burst Release Kinetics of Spray-Dried PLGA Microspheres.

Spray drying is one of the leading manufacturing methods for active pharmaceutical ingredients (APIs) owing to its rapid, single-step, and cost-effective nature. It also has the capacity to generate microspheres capable of controlled release of APIs including biomolecules and vaccines. However, one of the key challenges of spray-dried formulations especially with poly(lactic-co-glycolic acid) (PLGA)-based controlled-release injectables is burst release, where a significant fraction of the API is released prematurely within a short period of time following administration, leading to detrimental impact on the performance and quality of end products. This study uses a model API, bovine serum albumin (BSA) protein, to identify the sources of burst release that may affect the kinetics and performance of long-acting injectable microsphere formulations. Spray-dried microspheres with various formulations (i.e., variable BSA/PLGA ratios) were characterized in terms of their morphology, particle size, surface area, thermal properties, moisture content, as well as chemical compositions and their distributions to investigate the impact of spray drying on the burst release phenomenon. The results suggest that a relatively high initial release (85%) observed is mainly attributed to the protein distribution close to the particle surface. Morphology analysis provided evidence that the microspheres retained their spherical structure during the burst release phase. X-ray photoelectron spectroscopy, hard X-ray photoelectron spectroscopy, and argon cluster sputtering-assisted time-of-flight secondary ion mass spectrometry analysis suggest an enrichment of PLGA on particle surfaces with buried BSA protein. The statistically significant difference in particle size and surface area between three different formulations may be responsible for an initial variation in release but did not seem to alter the overall burst release profile. Considering the suggested source of burst release, the two-fluid spray-drying method, characterized by a single liquid feed delivering a preprepared emulsion, generated matrix-type microspheres with a surface layer of PLGA, as evidenced by surface analysis. The PLGA surface layer proved to be prone to degradation and pore formation, allowing for faster diffusion of BSA out of the microspheres, resulting in a burst release. Increasing the polymer concentration did not seem to halt this process.

Air‐Pyrolysis Precision Synthesis of Functional Porous Carbon Materials

AbstractCarbon materials play a pivo tal role across various advanced applications, yet their synthesis traditionally necessitates inert atmospheres to avert oxidation at high temperatures, thus inflating production costs and resource utilization. Achieving precision synthesis of functional porous carbon materials via air‐pyrolysis remains a formidable challenge. Herein, a streamlined, one‐step lava‐like carbonization approach is introduced enabling the fabrication of porous carbons boasting tailored morphologies (0‐3D), elevated specific surface areas (540.7–1047.6 m2g⁻¹), heteroatom doping, and commendable carbon yields (20‐39.1%) through direct pyrolysis within an air environment. Leveraging recyclable boric acid as a reaction medium, a lava‐like flowing protective barrier above 170 °C is engendered that spontaneously creates an oxygen‐free‐like milieu devoid of high pressure or intricate procedures. This boron‐containing lava serves dually as a template and chemical activator, facilitating pore formation and catalyzing porous carbon production. Notably, the method accommodates a spectrum of carbon sources, encompassing sugars, proteins, graphene oxide, and their metal mixtures. The resultant morphologically customizable carbons exhibit excellent performance in areas as diverse as microwave absorption and electrocatalysis. This work pioneers a novel pathway for large‐scale precision synthesis of high‐quality carbon materials via air‐pyrolysis under mild conditions.

A novel regulator CdsR negatively regulates cell motility in Bacillus thuringiensis

Cell motility increases the fitness of bacterial cells. Previous research focused on the transcriptional regulator CdsR, which represses cellular autolysis and promotes spore formation in Bacillus thuringiensis. However, the targets of CdsR are mostly unknown. Here, we reported a new function of CdsR in regulating cell motility. Mutation of cdsR results in increase of cell mobility, and a number of related genes were upregulated compared to wild type HD73. Thus, we investigated the transcription of the fla/che gene cluster, which involves in cell mobility and comprises eight operons/genes, including motAB1, cheY-yrhK, lamB-cheR, yaaR-fliG2, cheV-mogR, hag1, hag2, and yjbJ-flgG. Additionally, the motAB2 operon was discovered, which consists of homologs genes motA2 and motB2 that are like motA1 and motB1. Through promoter-lacZ fusion assays and EMSA experiments, it was discovered that CdsR directly regulates the motAB1, cheY-yrhK, lamB-cheR, yaaR-fliG2, cheV-mogR, hag1, hag2, yjbJ-flgG, and motAB2 operons by binding to their promoter regions. Importantly, it was confirmed that CdsR is a metalloregulator and the binding to promoter can be inhibited by Cu (II) ions. This research enhances our understanding of the regulation of cell mobility in B. thuringiensis.

Caspase-1 in Cx3cr1-expressing cells drives an IL-18-dependent T cell response that promotes parasite control during acute Toxoplasma gondii infection.

Inflammasome activation is a robust innate immune mechanism that promotes inflammatory responses through the release of alarmins and leaderless cytokines, including IL-1α, IL-1β, and IL-18. Various stimuli, including infectious agents and cellular stress, cause inflammasomes to assemble and activate caspase-1. Then, caspase-1 cleaves targets that lead to pore formation and leaderless cytokine activation and release. Toxoplasma gondii has been shown to promote inflammasome formation, but the cell types utilizing caspase-1 and the downstream effects on immunological outcomes during acute in vivo infection have not been explored. Here, using knockout mice, we examine the role of caspase-1 responses during acute T. gondii infection globally and in Cx3cr1-positive populations. We provide in vivo evidence that caspase-1 expression is critical for, IL-18 release, optimal interferon-γ (IFN-γ) production, monocyte and neutrophil recruitment to the site of infection, and parasite control. Specifically, we find that caspase-1 expression in Cx3cr1-positive cells drives IL-18 release, which potentiates CD4+ T cell IFN-γ production and parasite control. Notably, our Cx3cr1-Casp1 knockouts exhibited a selective T cell defect, mirroring the phenotype observed in Il18 knockouts. In further support of this finding, treatment of Cx3cr1-Casp1 knockout mice with recombinant IL-18 restored CD4+ T cell IFN-γ responses and parasite control. Additionally, we show that neutrophil recruitment is dependent on IL-1 receptor accessory protein (IL-1RAP) signaling but is dispensable for parasite control. Overall, these experiments highlight the multifaceted role of caspase-1 in multiple cell populations contributing to specific pathways that collectively contribute to caspase-1 dependent immunity to T. gondii.

Effect of peptide hydrophilicity on membrane curvature and permeation.

Using a well-developed reaction coordinate in umbrella sampling, we studied the single peptide permeation through a model cancerous cell membrane, varying the hydrophilicity and the charge of the peptides. Two peptides, melittin and pHD108, were studied. The permeation mechanism differs from a barrel-stave-like mechanism to toroidal pore and vesicle formation based on the number and the placement of the hydrophilic amino acids in the peptide. Membrane curvature changes dynamically as the permeation process occurs. In the case of vesicles, the peptide traverses along a smooth, homogenous pathway, whereas a rugged, steep pathway was found when lipid molecules did not line up along the wall of the membrane (barrel-stave-like mechanism). A mechanism similar to a toroidal pore consists of multiple minima. Higher free energy was found for the permeating terminal containing charged amino acid residues. Vesicle formation was found for pHD108 peptide N-terminal with a maximum membrane thinning effect of 54.4% with free energy cost of 8.20 ± 0.10kcal mol-1 and pore radius of 2.33 ± 0.07nm. Insights gained from this study can help to build synthetic peptides for drug delivery.

Endosomal membrane budding patterns in plants

Multivesicular endosomes (MVEs) sequester membrane proteins destined for degradation within intralumenal vesicles (ILVs), a process mediated by the membrane-remodeling action of Endosomal Sorting Complex Required for Transport (ESCRT) proteins. In Arabidopsis, endosomal membrane constriction and scission are uncoupled, resulting in the formation of extensive concatenated ILV networks and enhancing cargo sequestration efficiency. Here, we used a combination of electron tomography, computer simulations, and mathematical modeling to address the questions of when concatenated ILV networks evolved in plants and what drives their formation. Through morphometric analyses of tomographic reconstructions of endosomes across yeast, algae, and various land plants, we have found that ILV concatenation is widespread within plant species, but only prevalent in seed plants, especially in flowering plants. Multiple budding sites that require the formation of pores in the limiting membrane were only identified in hornworts and seed plants, suggesting that this mechanism has evolved independently in both plant lineages. To identify the conditions under which these multiple budding sites can arise, we used particle-based molecular dynamics simulations and found that changes in ESCRT filament properties, such as filament curvature and membrane binding energy, can generate the membrane shapes observed in multiple budding sites. To understand the relationship between membrane budding activity and ILV network topology, we performed computational simulations and identified a set of membrane remodeling parameters that can recapitulate our tomographic datasets.

Biocontrol Ability of Strain Bacillus amyloliquefaciens SQ-2 against Table Grape Rot Caused by Aspergillus tubingensis.

Bacillus amyloliquefaciens strain SQ-2, isolated from a cured product, has been demonstrated to exhibit a highly efficacious performance against phytopathogens, including Stemphylium solani, Fusarium moniliforme, Fusarium graminearum, and Aspergillus tubingensis. In particular, with regard to A. tubingensis, which causes summer bunch rot, SQ-2 has been observed to suppress the mycelial growth of all tested grape cultivars by over 40%. Especially on Kyoho grapes, it has the highest inhibition rate of 53%. Scanning electron microscopy (SEM) confirms that SQ-2 is an effective agent for suppressing the mycelia proliferation, differentiation, and spore formation of A. tubingensis. Furthermore, an LC/MS analysis revealed that SQ-2 produces two principal lipopeptides, namely, bacillibactin and surfactin, in addition to a polyketide, bacillaene. Further analysis through gas chromatography-mass spectrometry (GC/MS) identified 41 distinct volatile organic compounds secreted by SQ-2. Transcriptomic analysis indicated that exposure to the metabolite of SQ-2 induced substantial gene expression alterations in A. tubingensis. These data suggest that B. amyloliquefaciens strain SQ-2 exhibits promising crop protection potential of inhibiting plant pathogens through the secretion of bacillibactin, surfactin, bacillaene, and VOCs.

Apolipoprotein-L1 (APOL1): From Sleeping Sickness to Kidney Disease.

Apolipoprotein-L1 (APOL1) is a membrane-interacting protein induced by inflammation, which confers human resistance to infection by African trypanosomes. APOL1 kills Trypanosoma brucei through induction of apoptotic-like parasite death, but two T. brucei clones acquired resistance to APOL1, allowing them to cause sleeping sickness. An APOL1 C-terminal sequence alteration, such as occurs in natural West African variants G1 and G2, restored human resistance to these clones. However, APOL1 unfolding induced by G1 or G2 mutations enhances protein hydrophobicity, resulting in kidney podocyte dysfunctions affecting renal filtration. The mechanism involved in these dysfunctions is debated. The ability of APOL1 to generate ion pores in trypanosome intracellular membranes or in synthetic membranes was provided as an explanation. However, transmembrane insertion of APOL1 strictly depends on acidic conditions, and podocyte cytopathology mainly results from secreted APOL1 activity on the plasma membrane, which occurs under non-acidic conditions. In this review, I argue that besides inactivation of APOL3 functions in membrane dynamics (fission and fusion), APOL1 variants induce inflammation-linked podocyte toxicity not through pore formation, but through plasma membrane disturbance resulting from increased interaction with cholesterol, which enhances cation channels activity. A natural mutation in the membrane-interacting domain (N264K) abrogates variant APOL1 toxicity at the expense of slightly increased sensitivity to trypanosomes, further illustrating the continuous mutual adaptation between host and parasite.

Molecular Characterization of Ancient Prosaposin-like Proteins from the Protist Dictyostelium discoideum.

To combat the permanent exposure to potential pathogens every organism relies on an immune system. Important factors in innate immunity are antimicrobial peptides (AMPs) that are structurally highly diverse. Some AMPs are known to belong to the saposin-like proteins (SAPLIPs), a group of polypeptides with a broad functional spectrum. The model organism Dictyostelium discoideum possesses a remarkably large arsenal of potential SAPLIPs, which are termed amoebapore-like peptides (Apls), but the knowledge about these proteins is very limited. Here, we report about the biochemical characterization of AplE1, AplE2, AplK1, and AplK2, which are derived from the two precursor proteins AplE and AplK, thereby resembling prosaposins of vertebrates. We produced these Apls as recombinant polypeptides in Escherichia coli using a self-splicing intein to remove an affinity tag used for purification. All recombinant Apls exhibited pore-forming activity in a pH-dependent manner, as evidenced by liposome depolarization, showing higher activities the more acidic the setting was. Lipid preference was detected for negatively charged phospholipids and in particular for cardiolipin. Antimicrobial activity against various bacteria was found to be inferior in classical microdilution assays. However, all of the Apls studied permeabilized the cytoplasmic membrane of live Bacillus subtilis. Collectively, we assume that the selected Apls interact by their cationic charge with negatively charged bacterial membranes in acidic environments such as phagolysosomes and eventually lyse the target cells by pore formation.

Gladiolin produced by pathogenic Burkholderia synergizes with amphotericin B through membrane lipid rearrangements.

Amphotericin B (AmpB) is one of the oldest antifungal drugs in clinical use. It is an effective therapeutic, but it comes with toxicity issues due to the similarities between its fungal target (the membrane lipid ergosterol) and its mammalian counterpart (cholesterol). One strategy to improve its activity/toxicity relationship is by combinatorial therapy with potentiators, which would enable a lower therapeutic dose of AmpB. Here, we report on the discovery of the antibiotic gladiolin as a potentiator of AmpB against several priority human fungal pathogens and fungal biofilms, with no increased toxicity against mammalian cells. We show that gladiolin potentiates AmpB by increasing and accelerating membrane damage. Our findings also provide insights into the on-going debate about the mechanism of action of AmpB by indicating that both proposed mechanisms, extraction of ergosterol from membranes and pore formation, are potentiated by gladiolin.

Altruistic feeding and cell-cell signaling during bacterial differentiation actively enhance phenotypic heterogeneity.

Starvation triggers bacterial spore formation, a committed differentiation program that transforms a vegetative cell into a dormant spore. Cells in a population enter sporulation nonuniformly to secure against the possibility that favorable growth conditions, which put sporulation-committed cells at a disadvantage, may resume. This heterogeneous behavior is initiated by a passive mechanism: stochastic activation of a master transcriptional regulator. Here, we identify a cell-cell communication pathway containing the proteins ShfA (YabQ) and ShfP (YvnB) that actively promotes phenotypic heterogeneity, wherein Bacillus subtilis cells that start sporulating early use a calcineurin-like phosphoesterase to release glycerol, which simultaneously acts as a signaling molecule and a nutrient to delay nonsporulating cells from entering sporulation. This produced a more diverse population that was better poised to exploit a sudden influx of nutrients compared to those generating heterogeneity via stochastic gene expression alone. Although conflict systems are prevalent among microbes, genetically encoded cooperative behavior in unicellular organisms can evidently also boost inclusive fitness.

A lipid signature of BAK-driven apoptotic pore formation.

Apoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken. Firstly, the lipids released during BAK-mediated pore formation were measured with targeted lipidomics, revealing enrichment of long chain polyunsaturated lysophospholipids (LPLs) in the released fraction. In contrast, the BAK protein was not released suggesting that BAK and LPLs locate to distinct microdomains. Secondly, added cholesterol not only prevented pore formation but prevented the clustering of BAK homodimers. Our data lead us to a model in which BAK clustering triggers formation of a separate microdomain rich in LPLs that can progress to lipid shedding and the opening of a lipid-lined pore. Pore stabilisation and growth may be due to BAK dimers then moving to the pore edge. Our BAK-lipid microdomain model supports the heterogeneity of BAK assemblies, and the observed lipid-release signature gives new insight into the genesis of the apoptotic pore.

Developing High-Performance Ceramics from Multicomponent Grain Boundary Entropy Design.

Grain boundary (GB) glassy phase often results in poor ceramic performances. Here, a Multicomponent Grain Boundary Entropy (MGBE) descriptor extracted from high-throughput first-principle calculations is proposed to capture the nature of high-entropy GB phases in ceramics. In a Si3N4 ceramic model system, MGBE is found to have a direct correlation with GB phase crystallinity, element segregation, and formation of pores. The predicted highest MGBE sintering additive combination (MgO-Y2O3-Er2O3-Yb2O3) leads to high-performance ceramics of homogenous microstructure and pure GB (YErYb)2Si3O3N4 phase without observable glassy film. Conversely, low MGBE additives result in a substantial amount of GB glassy phase, element segregation, and pore clusters. The MGBE descriptor can make a rapid screening of multicomponent sintering additives, offering a novel approach for rational designing of ceramics with targeted microstructure and performances.

Mechanical properties and corrosion behavior of SiC reinforced high entropy alloy (Ni-Co-Fe-Ti) matrix composites produced by microwave and conventional sintering techniques

Abstract The aim of this work is to synthesize SiC reinforced Ni-Co-Fe-Ti composite using powder metallurgy (PM) method. Two sintering methods, conventional sintering (CS) using a tubular furnace and microwave sintering (MWS), are employed to synthesize three different weight percentages of SiC (3 wt.%, 6 wt.%, and 9 wt.%) within a Ni-Co-Fe-Ti matrix. The densification behavior of synthesized Ni-Co-Fe-Ti-SiC composites are studied using sinterability function. The highest sinterability of 0.89 was achieved for Ni-Co-Fe-Ti-0 wt.wt.% SiC alloy. The densification rate was found to be higher in MW sintered composites compared to those sintered conventionally. 3.5 wt.% NaCl solution was considered for corrosion examination and it was determined that Ni-Co-Fe-Ti- 9 wt.% SiC MW sintered composite exhibit highest corrosion resistance. Ni-Co-Fe-Ti-9 wt.%SiC MW sintered composite exhibits higher compressive strength of 1050 MPa than conventional sintered Ni-Co-Fe-Ti-9 wt.%SiC (625MPa). Ni-Co-Fe-Ti-6wt.% SiC MW sintered composite possess highest hardness of 58 HRC among other prepared composites. Interestingly, decreasing trend in hardness was observed for further inclusion of SiC with Ni-Co-Ti-Fe matrix. Scanning electron microscopy (SEM) and microstructural characterization technique shows the formation of pores in the conventional sintered composites. But, there is no formation of pores in the MW sintered composite of all the composition. Tribological studies were conducted using pin on disc method. Worn surface morphology was analyzed and it shows that severe pullout was observed in the worn surface of conventional sintered Ni-Co-Fe-Ti- 6wt.%SiC.The best optimum set of parameters (Sliding Speed 1146 rpm, SiC inclusion 6 wt.%, Applied Load 20 N) were found out using Taguchi method.