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UNLABELLED: Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

The cell cortex is a dynamic assembly formed by the plasma membrane and underlying cytoskeleton. As the main determinant of cell shape, the cortex ensures its integrity during passive and active deformations by adapting cytoskeleton topologies through yet poorly understood mechanisms. The spectrin meshwork ensures such adaptation in erythrocytes and neurons by adopting different organizations. Erythrocytes rely on triangular-like lattices of spectrin tetramers, whereas in neurons they are organized in parallel, periodic arrays. Since spectrin is ubiquitously expressed, we exploited Expansion Microscopy to discover that, in fibroblasts, distinct meshwork densities co-exist. Through biophysical measurements and computational modeling, we show that the non-polarized spectrin meshwork, with the intervention of actomyosin, can dynamically transition into polarized clusters fenced by actin stress fibers that resemble periodic arrays as found in neurons. Clusters experience lower mechanical stress and turnover, despite displaying an extension close to the tetramer contour length. Our study sheds light on the adaptive properties of spectrin, which participates in the protection of the cell cortex by varying its densities in response to key mechanical features.

Hydrostatic pressure increases with depth in the ocean, but little is known about the molecular bases of biological pressure tolerance. We describe a mode of pressure adaptation in comb jellies (ctenophores) that also constrains these animals depth range. Structural analysis of deep-sea ctenophore lipids shows that they form a nonbilayer phase at pressures under which the phase is not typically stable. Lipidomics and all-atom simulations identified phospholipids with strong negative spontaneous curvature, including plasmalogens, as a hallmark of deep-adapted membranes that causes this phase behavior. Synthesis of plasmalogens enhanced pressure tolerance in Escherichia coli, whereas low-curvature lipids had the opposite effect. Imaging of ctenophore tissues indicated that the disintegration of deep-sea animals when decompressed could be driven by a phase transition in their phospholipid membranes.

The endoplasmic reticulum (ER) undergoes degradation by selective macroautophagy (ER-phagy) in response to starvation or the accumulation of misfolded proteins within its lumen. In yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits acts to displace elements of the ER from their association with the plasma membrane (PM) so they can interact with the autophagosome assembly machinery near the vacuole. A collection of proteins tether the cER to the PM. Of these, Scs2/22 and Ist2 are required for cER-phagy, most likely through their roles in lipid transport, while deletion of the tricalbins, TCB1/2/3, bypasses those requirements. An artificial ER-PM tether blocks cER-phagy in both the wild type (WT) and a strain lacking endogenous tethers, supporting the importance of cER displacement from the PM. Scs2 and Ist2 can be cross-linked to the selective cER-phagy receptor, Atg40. The COPII cargo adaptor subunit, Lst1, associates with Atg40 and is required for cER-phagy. This requirement is also bypassed by deletion of the ER-PM tethers, suggesting a role for Lst1 prior to the displacement of the cER from the PM during cER-phagy. Although pexophagy and mitophagy also require actin assembly, deletion of ER-PM tethers does not bypass those requirements. We propose that within the context of rapamycin-induced cER-phagy, Scs2/22, Ist2, and Lst1 promote the local displacement of an element of the cER from the cortex, while Tcb1/2/3 act in opposition, anchoring the cER to the plasma membrane.

Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ4 exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ4-deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ4. In Gβ4 knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making.

Watermelon (Citrullus lanatus L.) fruit is widely consumed for its sweetness, flavor, nutrition and health-promoting properties. It is commonly commercialized in fresh-cut format, satisfying consumer demand for freshness and convenience, but its shelf-life is limited. Despite the potential for growth in fresh-cut watermelon sales, the industry faces the challenge of maintaining quality attributes during storage. Fresh-cut processing induces a series of physiological and biochemical events that lead to alterations in sensory, nutritional and microbiological quality. A signal transduction cascade involving increases in respiration and ethylene production rates and elevated activities of cell wall and membrane-degrading enzymes compromise cellular and tissue integrity. These responses contribute to the development of quality defects like juice leakage, firmness loss and water-soaked appearance. They also drive the loss of bioactive compounds like lycopene, affecting flesh color and reducing nutritional value, ultimately culminating in consumer rejection, food losses and waste. Although great research progress has been achieved in the past decades, knowledge gaps about the physiological, biochemical and molecular bases of quality loss persist. This review article summarizes the advances in the study of physicochemical, microbiological, nutritional, and sensory changes linked to the deterioration of watermelon after processing and during storage. Different technological approaches for quality improvement and shelf-life extension are summarized: pre- and postharvest, physical, and chemical. We also discuss the advantages, disadvantages and challenges of these interventions and propose alternative directions for future research aiming to reduce qualitative and quantitative fresh-cut watermelon losses. [ABSTRACT FROM AUTHOR]

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Recent advancements in tumor therapy have underscored the potential of biomaterials-mediated biomineralization for tumor blockade. By precisely regulating biomineralization and constructing nanomineralized structures at the cellular level, this therapy achieves multi-dimensional targeted inhibition of tumors. Mineralized precursor molecules are engineered to selectively recognize and bind to proteins on the tumor cell membrane, obstructing signal transduction. Biomineralized materials directly target the tumor cell membrane, disrupting its biological functions and inducing cell apoptosis. Additionally, these materials infiltrate the mitochondria of tumor cells, disrupting energy metabolism through mineralization and significantly impairing tumor viability. This biomaterials-mediated approach enhances treatment precision and efficacy while mitigating side effects, offering a unique approach to tumor therapy. Plain Language Summary An advanced method for cancer therapy, termed "biomaterials-mediated biomineralization-based tumor blockade therapy," has been developed. This technique constructs minute "mineral structures" on the surface of cells to inhibit tumor growth. It identifies unique markers on the surface of tumor cells, similar to finding a keyhole, and creates a "key" that fits these markers precisely. This "key" is a precursor molecule for mineralization that targets and adheres to tumor cells, obstructing their signaling pathways. Moreover, biomineralized materials directly target the tumor cell membrane, disrupting its functions and increasing the cell's susceptibility to death. Additionally, this therapy targets the mitochondria of tumor cells, i.e., the cellular "power plants", using mineralization methods to incapacitate energy production, ultimately leading to the demise of tumor cells. [ABSTRACT FROM AUTHOR]

Anastasis is a phenomenon observed in cancer cells, where cells that have initiated apoptosis are able to recover and survive. This molecular event is increasingly recognized as a potential contributor to cancer metastasis, facilitating the survival and migration of tumor cells. Nevertheless, the identification of a specific surface marker for detecting cancer cells in anastasis remained elusive. Here we report our observation that the cell surface expression of CD24 is preferentially enriched in a non-adherent FSClowSSChigh melanoma subpopulation, which is generally considered a non-viable population in cultivated melanoma cell lines. More than 90% of non-adherent FSClowSSChighCD24+ve metastatic melanoma cells exhibited bonafide features of apoptosis on the cell surface and in the nucleus, marking apoptotic or seemingly apoptotic subpopulations of the in vitro cultivated metastatic melanoma cell lines. Unexpectedly, however, the CD24+ve subpopulation, despite being apoptotic, showed evidence of metabolic activity and exhibited proliferative capacities, including anchorage-independent growth, when inoculated in soft agarose growth medium. These findings indicate that apoptotic FSClowSSChighCD24+ve melanoma subpopulations are capable of reversing the progression of apoptosis. We report CD24 as the first novel cell surface marker for anastasis in melanoma cells. [ABSTRACT FROM AUTHOR]

Abnormal cholesterol metabolism has become a popular therapeutic target in cancer therapy. In recent years there has been a surge in interest in the anti-tumor activities of saponins, particularly their ability to disrupt cholesterol homeostasis in tumor cells. Cholesterol regulation by saponins is a complex process that involves multiple mechanisms. However, there are now a notable dearth of comprehensive reviews addressing their anti-tumor effects through cholesterol modulation. This review will explore the intricate mechanisms by which saponins regulate cholesterol, including modulation of synthesis, metabolism, and uptake, as well as complex formation with cholesterol. It will also outline how saponins exert their anti-cancer activities through cholesterol regulation, enhancing cytotoxicity, inhibiting tumor cell metastasis, reversing drug resistance, inducing immunotoxin macromolecule escape, and ferroptosis. This comprehensive analysis offers insights into the potential for the use of saponins anti-tumor therapies and their combinations with other drugs, advancing the understanding of their effects on cancer cells. [ABSTRACT FROM AUTHOR]

Proteins found within the fungal cell wall usually contain both N- and O-oligosaccharides. N-glycosylation is the process where these oligosaccharides (hereinafter: glycans) are attached to asparagine residues, while in O-glycosylation the glycans are covalently bound to serine or threonine residues. The PMT family is grouped into PMT1, PMT2, and PMT4 subfamilies. Using bioinformatics analysis within the Botrytis cinerea genome database, an ortholog to Saccharomyces cerevisiae Pmt4 and other fungal species was identified. The aim of this study was to assess the relevance of the bcpmt4 gene in B. cinerea glycosylation. For this purpose, the bcpmt4 gene was disrupted by homologous recombination in the B05.10 strain using a hygromycin B resistance cassette. Expression of bcpmt4 in S. cerevisiae ΔScpmt4 or ΔScpmt3 null mutants restored glycan levels like those observed in the parental strain. The phenotypic analysis showed that Δbcpmt4 null mutants exhibited significant changes in hyphal cell wall composition, including reduced mannan levels and increased amounts of chitin and glucan. Furthermore, the loss of bcpmt4 led to decreased glycosylation of glycoproteins in the B. cinerea cell wall. The null mutant lacking PMT4 was hypersensitive to a range of cell wall perturbing agents, antifungal drugs, and high hydrostatic pressure. Thus, in addition to their role in glycosylation, the PMT4 is required to virulence, biofilm formation, and membrane integrity. This study adds to our knowledge of the role of the B. cinerea bcpmt4 gene, which is involved in glycosylation and cell biology, cell wall formation, and antifungal response. [ABSTRACT FROM AUTHOR]

Biomimetic nanodrug delivery systems based on cell membranes have emerged as a promising approach for targeted cancer therapy due to their biocompatibility and low immunogenicity. Among them, platelet-mediated systems are particularly noteworthy for their innate tumor-homing and cancer cell interaction capabilities. These systems utilize nanoparticles shielded and directed by platelet membrane coatings for efficient drug delivery. This review highlights the role of platelets in cancer therapy, summarizes the advancements in platelet-based drug delivery systems, and discusses their integration with other cancer treatments. Additionally, it addresses the limitations and challenges of platelet-mediated drug delivery, offering insights into future developments in this innovative field. [ABSTRACT FROM AUTHOR]

To explore the antibacterial effect and mechanism of antimicrobial peptide LL-1 against Salmonella, the minimum inhibitory concentration (MIC) was determined by the doubling dilution method, and the antibacterial effect was evaluated by the growth inhibition curve. Then, the bacterial morphology was observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The effect of LL-1 on the cell wall and cell membrane of Salmonella was evaluated by detecting the leakage of intracellular nucleic acids, proteins and alkaline phosphatase (ALP) as well as by conducting propidium iodide (PI) staining experiments. The binding of LL-1 to Salmonella DNA was detected by nucleic acid gel electrophoresis. Finally, the effect of LL-1 on the energy metabolism of Salmonella was evaluated by measuring the activities of intracellular succinate dehydrogenase (SDH), NADP-malate dehydrogenase (NADP-MDH) and ATP levels. The results showed that the MIC was 6.25 μg/mL, and LL-1 had a good antibacterial effect in dose- and time-dependent manners. Salmonella treated with LL-1 showed morphological changes such as cell shrinkage, cell membrane dissolution, and plasmolysis. LL-1 resulted in the leakage of intracellular nucleic acids, proteins and ALP and an increase in the fluorescence intensity of PI-stained bacterial cells. Additionally, LL-1 could bind to bacterial DNA. Increasing LL-1 concentration resulted in a decrease in the intracellular ATP content, SDH and NADP-MDH activities. In conclusion, LL-1 could exert its antibacterial activity against Salmonella by increasing the permeability of the cell membrane and cell wall, thereby causing the leakage of intracellular contents, binding to DNA, and affecting bacterial energy metabolism. This study lays the foundation for further research on the antibacterial mechanism and application of LL-1.

[Objective] The red pitaya (Hylocereus polyrhizus) HpSWEET7 gene, belonging to the sugar transporter SWEET (sugars will eventually be exported transporter) family, was cloned and its role in fruit sugar accumulation was investigated, which provided a target gene for improving fruit flavor and quality. [Methods] HpSWEET7 gene was isolated from ‘Zihonglong’, and sequence alignment and phylogenetic relationship were analyzed. Gene expression was analyzed by qRT-PCR, and the subcellular localization was detected by fusing fluorescent protein. Sugar transport activity was investigated by the yeast growth complementation and acidification assay. [Results] The ORF of HpSWEET7 was 771 bp, encoding 256 amino acid residues. HpSWEET7 contained two MtN3_saliva (Pfam No. PF03083) and seven transmembrane domains, which was closely related to Arabidopsis AtSWEET6 and AtSWEET7, belonging to SWEET Ⅱ class. Expression of HpSWEET7 in stems was lower than that in fruits at 6 developmental stages. The expression level was the highest in fruits at 20 d after pollination, gradually decreased with fruit development, and was the lowest in ripe fruits (30 d after pollination). Subcellular localization assay showed that HpSWEET7 was located at the cell membrane. HpSWEET7 showed transport activities for glucose, fructose, mannose, sorbitol and galactose. The acidification test further proved that Hp- SWEET7 transported glucose and fructose. [Conclusion] HpSWEET7 transports hexoses across the cell membrane, and participates in sugar accumulation during fruit development in red pitaya.

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated that IDV binds both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac). Bovines produce both Neu5,9Ac2 and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. 9-O-Acetylation of sialic acids is catalyzed by CASD1 via a covalent acetyl-enzyme intermediate. To characterize the role of Neu5,9Ac2 and Neu5Gc9Ac in IDV infection and determine which form of 9-O-acetylated sialic acids drives IDV entry, we took advantage of a CASD1 knockout (KO) MDCK cell line and carried out feeding experiments using synthetic 9-O-acetyl sialic acids in combination with the single-round and multi-round IDV infection assays. The data from our studies show that (i) CASD1 KO cells are resistant to IDV infection and lack of IDV binding to the cell surface is responsible for the failure of IDV replication; (ii) feeding CASD1 KO cells with Neu5,9Ac2 or Neu5Gc9Ac resulted in a dose-dependent rescue of IDV infectivity; and (iii) diverse IDVs replicated robustly in CASD1 KO cells fed with either Neu5,9Ac2 or Neu5Gc9Ac at a level similar to that in wild-type cells with a functional CASD1. These data demonstrate that IDV can utilize Neu5,9Ac2- or non-human Neu5Gc9Ac-containing glycan receptor for infection. Our findings provide evidence that IDV has acquired the ability to infect and transmit among agricultural animals that are enriched in Neu5Gc9Ac, in addition to posing a zoonotic risk to humans expressing only Neu5,9Ac2.IMPORTANCEInfluenza D virus (IDV) has emerged as a multiple-species-infecting pathogen with bovines as a primary reservoir. Little is known about the functional receptor that drives IDV entry and promotes its cross-species spillover potential among different hosts. Here, we demonstrated that IDV binds exclusively to 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac2) and non-human 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac) and utilizes both for entry and infection. This ability in effective engagement of both 9-O-acetylated sialic acids as functional receptors for infection provides an evolutionary advantage to IDV for expanding its host range. This finding also indicates that IDV has the potential to emerge in humans because Neu5,9Ac2 is ubiquitously expressed in human tissues, including lung. Thus, results of our study highlight a need for continued surveillance of IDV in humans, as well as for further investigation of its biology and cross-species transmission mechanism.

The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin β5) as the essential integrin α/β pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the β-propeller domain of ITGAV for integrin αVβ5 dimerization. Combined with in silico compound docking, we developed a CRISPR-Tiling-Instructed Computer-Aided (CRISPR-TICA) pipeline for drug discovery and identified Cpd_AV2 as a lead inhibitor targeting the β-propeller central pocket of ITGAV. Cpd_AV2 treatment led to rapid uncoupling of integrin αVβ5 and cellular apoptosis, providing a unique class of therapeutic action that eliminates the integrin signaling via heterodimer dissociation. We also foresee the CRISPR-TICA approach to be an accessible method for future drug discovery studies.

Many G protein-coupled receptors (GPCRs) initiate a second phase of stimulatory heterotrimeric G protein (Gs)-coupled cAMP signaling after endocytosis. The prevailing current view is that the endosomal signal is inherently β-arrestin-dependent because β-arrestin is necessary for receptor internalization and, for some GPCRs, to prolong the endosomal signal. Here we revise this view by showing that the vasoactive intestinal peptide receptor 1 (VIPR1), a secretin-family polypeptide hormone receptor, does not require β-arrestin to internalize or to generate an endosomal signal. β-Arrestin instead resolves the plasma membrane and endosomal signaling phases into sequential cAMP peaks by desensitizing the plasma membrane phase without affecting the endosomal phase. This appears to occur through the formation of functionally distinct VIPR1-β-arrestin complexes at each location that differ in their phosphorylation dependence. We conclude that endosomal GPCR signaling can occur in the absence of β-arrestin and that β-arrestin sculpts the spatiotemporal profile of cellular GPCR-G protein signaling through location-specific remodeling of GPCR-β-arrestin complexes.

Aster proteins mediate the nonvesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). However, the importance of nonvesicular sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss of Aster-B leads to diet-induced obesity in female but not in male mice, and that this sex difference is abolished by ovariectomy. We further demonstrate that Aster-B deficiency impairs nonvesicular cholesterol transport from the PM to the ER in ovaries in vivo, leading to hypogonadism and reduced estradiol synthesis. Female Aster-B-deficient mice exhibit reduced locomotor activity and energy expenditure, consistent with established effects of estrogens on systemic metabolism. Administration of exogenous estradiol ameliorates the diet-induced obesity phenotype of Aster-B-deficient female mice. These findings highlight the key role of Aster-B-dependent nonvesicular cholesterol transport in regulating estradiol production and protecting females from obesity.

G-protein-coupled receptors (GPCRs) mediate many critical physiological processes. Their spatial organization in plasma membrane (PM) domains is believed to encode signaling specificity and efficiency. However, the existence of domains and, crucially, the mechanism of formation of such putative domains remain elusive. Here, live-cell imaging (corrected for topography-induced imaging artifacts) conclusively established the existence of PM domains for GPCRs. Paradoxically, energetic coupling to extremely shallow PM curvature (

Different exogenous electric fields (EF) can guide cell migration, disrupt proliferation, and program cell development. Studies have shown that many of these processes were initiated at the cell membrane, but the mechanism has been unclear, especially for conventionally non-excitable cells. In this study, we focus on the electrostatic aspects of EF coupling with the cell membrane by eliminating Faradaic processes using dielectric-coated microelectrodes. Our data unveil a distinctive biphasic response of the ERK signaling pathway of epithelial cells (MCF10A) to alternate current (AC) EF. The ERK signal exhibits both inhibition and activation phases, with the former triggered by a lower threshold of AC EF, featuring a swifter peaking time and briefer refractory periods than the later-occurring activation phase, induced at a higher threshold. Interestingly, the biphasic ERK responses are sensitive to the waveform and timing of EF stimulation pulses, depicting the characteristics of electrostatic and dissipative interactions. Blocker tests and correlated changes of active Ras on the cell membrane with ERK signals indicated that both EGFR and Ras were involved in the rich ERK dynamics induced by EF. We propose that the frequency-dependent dielectric relaxation process could be an important mechanism to couple EF energy to the cell membrane region and modulate membrane protein-initiated signaling pathways, which can be further explored to precisely control cell behavior and fate with high temporal and spatial resolution.

Androgen binding to the androgen receptor (AR) in the cytoplasm induces the AR to translocate to the nucleus, where it regulates the expression of target genes. Here, we found that androgens rapidly activated a plasma membrane-associated signaling node that enhanced nuclear AR functions. In murine primary osteoblasts, dihydrotestosterone (DHT) binding to a membrane-associated form of AR stimulated plasma membrane-associated protein kinase G type 2 (PKG2), leading to the activation of multiple kinases, including ERK. Phosphorylation of AR at Ser515 by ERK increased the nuclear accumulation and binding of AR to the promoter of Ctnnb1, which encodes the transcription factor β-catenin. In male mouse osteoblasts and human prostate cancer cells, DHT induced the expression of Ctnnb1 and CTNN1B, respectively, as well as β-catenin target genes, stimulating the proliferation, survival, and differentiation of osteoblasts and the proliferation of prostate cancer cells in a PKG2-dependent fashion. Because β-catenin is a master regulator of skeletal homeostasis, these results explain the reported male-specific osteoporotic phenotype of mice lacking PKG2 in osteoblasts and imply that PKG2-dependent AR signaling is essential for maintaining bone mass in vivo. Our results suggest that widely used pharmacological PKG activators, such as sildenafil, could be beneficial for male and estrogen-deficient female patients with osteoporosis but detrimental in patients with prostate cancer.

Invading microbes face a myriad of cidal mechanisms of phagocytes that inflict physical damage to microbial structures. How intracellular bacterial pathogens adapt to these stresses is not fully understood. Here, we report the discovery of a virulence mechanism by which changes to the mechanical stiffness of the mycobacterial cell surface confer refraction to killing during infection. Long-term time-lapse atomic force microscopy was used to reveal a process of "mechanical morphotype switching" in mycobacteria exposed to host intracellular stress. A "soft" mechanical morphotype switch enhances tolerance to intracellular macrophage stress, including cathelicidin. Both pharmacologic treatment, with bedaquiline, and a genetic mutant lacking uvrA modified the basal mechanical state of mycobacteria into a soft mechanical morphotype, enhancing survival in macrophages. Our study proposes microbial cell mechanical adaptation as a critical axis for surviving host-mediated stressors.

All free-living microorganisms homeostatically maintain the fluidity of their membranes by adapting lipid composition to environmental temperatures. Here, we quantify enzymes and metabolic intermediates of the Escherichia coli fatty acid and phospholipid synthesis pathways, to describe how this organism measures temperature and restores optimal membrane fluidity within a single generation after a temperature shock. A first element of this regulatory system is a temperature-sensitive metabolic valve that allocates flux between the saturated and unsaturated fatty acid synthesis pathways via the branchpoint enzymes FabI and FabB. A second element is a transcription-based negative feedback loop that counteracts the temperature-sensitive valve. The combination of these elements accelerates membrane adaptation by causing a transient overshoot in the synthesis of saturated or unsaturated fatty acids following temperature shocks. This strategy is comparable to increasing the temperature of a water bath by adding water that is excessively hot rather than adding water at the desired temperature. These properties are captured in a mathematical model, which we use to show how hard-wired parameters calibrate the system to generate membrane compositions that maintain constant fluidity across temperatures. We hypothesize that core features of the E. coli system will prove to be ubiquitous features of homeoviscous adaptation systems.

The HIV-1 accessory protein Nef hijacks clathrin adaptors to degrade or mislocalize host proteins involved in antiviral defenses. Here, using quantitative live-cell microscopy in genome-edited Jurkat cells, we investigate the impact of Nef on clathrin-mediated endocytosis (CME), a major pathway for membrane protein internalization in mammalian cells. Nef is recruited to CME sites on the plasma membrane, and this recruitment is associated with an increase in the recruitment and lifetime of the CME coat protein AP-2 and the late-arriving CME protein dynamin2. Furthermore, we find that CME sites that recruit Nef are more likely to recruit dynamin2 and transferrin, suggesting that Nef recruitment to CME sites promotes site maturation to ensure high efficiency in host protein downregulation. Implications of these observations for HIV-1 infection are discussed.

Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP proteins are trafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in the HCC1569 breast cancer cell line, and in undifferentiated, but not differentiated, HC11 cells that serve as a model for mammary lactogenic differentiation. The loss of Vangl2 function results in upregulation of pathways related to STAT5 signaling. We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate recruitment of VANGL2 to specific DNA binding motifs, including one in the Stat5a promoter. Knockdown (KD) of Vangl2 in HC11 cells and primary mammary organoids results in upregulation of Stat5a, Ccnd1 and Csn2, larger acini and organoids, and precocious differentiation; phenotypes are rescued by overexpression of Vangl2, but not Vangl2ΔNLS. Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.

This article focuses on the nuanced interplay between hemodilution and aquaporin, elucidating their collective role in preserving fluid homeostasis within the human body. Hemodilution, which is characterized by a reduction in blood component concentration owing to increased plasma volume, commonly occurs during intravenous fluid administration. Aquaporins, integral transmembrane proteins, facilitate water movement across cell membranes. Hemodilution alters osmotic pressure, influencing fluid balance in tissues. Aquaporins, acting as selective water channels, respond dynamically to these changes to ensure precise cellular hydration. This integrated system prevents cellular dehydration and overhydration in the presence of shifting blood volume. Understanding this relationship is clinically significant, especially in fluid-intensive interventions. Healthcare practitioners must consider the potential effects on cellular hydration and osmoregulation, particularly in patients with underlying conditions affecting water homeostasis. Recognizing the intricate connection between hemodilution and aquaporin provides a foundation for optimizing fluid balance in clinical practice. Further exploration of this nexus could lead to the refinement of therapeutic approaches aimed at maintaining cellular integrity and function.

In order to investigate the action mechanism of proanthocyanidins from the perspective of cell membrane, the effects of 0.5 g/L and 1.0 g/L proanthocyanidins on the characteristics of the cell membrane of Saccharomyces cerevisiae were studied. The changes of extracellular nucleic acid and protein contents, fatty acid composition and malondialdehyde content in different fermentation systems were measured. The results showed that compared with the system without proanthocyanidins, the permeability, integrity and fluidity of the yeast cell membrane treated with proanthocyanidins increased, and 1.0 g/L proanthocyanidins had the greatest effect on cell membrane fluidity, and the addition of 1.0 g/L proanthocyanidins increased the permeability of the cell membrane to 24 ms/cm within 72 h. The content of different fatty acids changed differently, and the change of arachidic acid content was the most obvious. The content of arachidic acid increased by 7% in 1.0 g/L proanthocyanidin group. The analysis results of peroxidation products of membrane lipids showed that the addition of proanthocyanidins decreased the content of malondialdehyde under stress conditions, the change was most obvious in the 1.0 g/L proanthocyanidin group, and the content of malondialdehyde was the lowest on the 5th day (1.3 μmol/L). Therefore, it was concluded that proanthocyanidins increased the exchange rates of substrates and metabolites by enhancing the integrity and permeability of cell membrane during wine fermentation, thus promoting the growth and metabolism of yeast.

In this study, the effects of volatile substances from Trichoderma erinaceum M6-5 on the cell membrane and wall of Alternaria alternata were investigated. To evaluate the antifungal effect, the culture medium inoculated with T. erinaceum and cultured for 5 days was covered with the culture medium containing A. alternata and cultured at 30 ℃ for 3, 5 and 7 days. The mycelia of A. alternata in the treatment and control groups were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and were collected to observe the integrity of the cell membrane by propidiumiodide (PI) staining, and cell membrane-related indexes such as electrical conductivity were measured. The morphological changes of apical growth cells were detected by calcofluor white (CFW) staining, and alkaline phosphatase (AKP) activity and N-acetylglucosamine concentration were determined. The results showed that during the culture period, the volatile substances produced by T. erinaceum had good antifungal effects on A. alternata. SEM and TEM images showed that the mycelia of A. alternata appeared shriveled, swollen and broken partially after the treatment. A greater reduction in cytoplasmic matrix was noted when compared with the control group, which was accompanied by local plasmolysis. For the control group, the mycelium growth was normal, the spore structure was complete, the cross-section structure was clear, the cytoplasm was uniform, and the cell wall and membrane structures were normal. After the treatment, the electrical conductivity, malondialdehyde (MDA) level, protein and nucleic acid leakage significantly increased relative to the control group. PI staining showed that the mycelia of the treated group emitted red fluorescence, indicating that the volatile substances of T. erinaceum damaged the integrity of the cell membrane, thus resulting in the leakage of cellular contents and marked disruption of the normal function of the cell membrane. CFW staining showed no significant differences between the treated and control groups with respect to the fluorescence intensity of mycelia, AKP activity or n-acetylglucosamine concentration indicating that the volatile substances of T. erinaceum did not damage the cell wall of A.alternata, and their major targets were not the cell wall. In conclusion, the antifungal target of volatile substances from T. erinaceum M6-5 is the cell membrane of A. alternata.

Abstract Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins. Graphical abstract

Abstract Drug-carrying nanoparticles can be recognized and captured by macrophages and cleared away by the immune system, resulting in reduced drug efficacy and representing the main drawbacks. Biomimetic nanoparticles, which are coated with cell membranes from natural resources, have been applied to address this problem. This type of nanoparticle maintains some specific biological activities, allowing them to carry drugs reaching designated tissues effectively and have a longer time in circulation. This review article aims to summarize recent progress on biomimetic nanoparticles based on cell membranes. In this paper, we have introduced the classification of biomimetic nanoparticles, their preparation and characterization, and their applications in inflammatory diseases and malignant tumors. We have also analyzed the shortcomings and prospects of this technology, hoping to provide some clues for basic researchers and clinicians engaged in this field.

The limitations of traditional drug therapy have driven the creation and development of novel cell membrane-coated nanoparticle (CMNP) platforms. Since the introduction of the CMNP concept and method in 2011, an increasing number of studies focusing on this field have been widely conducted. Despite the growing body of literature, comprehensive bibliometric analysis in this field is still lacking. This study conducted a bibliometric analysis of CMNP-related publications sourced from the Web of Science Core Collection database, covering the period from January 1, 2011, to December 31, 2023. The analysis included co-authorships, co-citations, and co-occurrences of countries, institutions, authors, references, and keywords. Visualized tools such as Citespace, VOSviewer, and R Package Bibliometrix were employed to present the data. A total of 780 studies were included, with China contributing the highest number of publications (75.64%, n = 590). The number of annual publications increased consistently from 2011 to 2023, indicating a growing global interest in the CMNP field. Prof. Liangfang Zhang from the United States is recognized as the founder and leading figure in this area. The top three academic journals in this field, based on publication volume, are ACS Nano (32 publications, IF 2022 = 17.1), ACS Applied Materials Interfaces (32 publications, IF 2022 = 9.5), and Advanced Functional Materials (31 publications, IF 2022 = 19) among 185 scholarly journals. Reference and keyword analysis revealed that erythrocytes and macrophage membranes are significant research hotspots. The primary diseases targeted by CMNP research are cancer and pulmonary inflammation. In addition, CMNPs are frequently studied in conjunction with photothermal and photodynamic therapy. Furthermore, this study also summarized the timelines for various cell membrane coating methods and the three-step preparation process for CMNP. This comprehensive bibliometric analysis provides valuable insights to guide future research in the CMNP field, highlighting the importance of clinical application. Research on cell membrane-coated nanomaterials, particularly those related to cancer and pulmonary inflammation, is expected to remain a focal point. In addition, there is a need for the further development of other potential cell membrane-coated nanomaterials. This bibliometric analysis serves as a resource for researchers to quickly and comprehensively understand the current hotspots and emerging frontiers in this field.

Dietary restriction (DR) has been reported to be a significant intervention that influences lipid metabolism and potentially modulates the aging process in a wide range of organisms. Lipid metabolism plays a pivotal role in the regulation of aging and longevity. In this review, we summarize studies on the significant role of lipid metabolism in aging in relation to DR. As a potent intervention to slow down aging, DR has demonstrated promising effects on lipid metabolism, influencing the aging processes across various species. The current review focuses on the relationships among DR-related molecular signaling proteins such as the sirtuins, signaling pathways such as the target of rapamycin and the insulin/insulin-like growth factor (IGF)-1, lipid metabolism, and aging. Furthermore, the review presents research results on diet-associated changes in cell membrane lipids and alterations in lipid metabolism caused by commensal bacteria, highlighting the importance of lipid metabolism in aging. Overall, the review explores the interplay between diet, lipid metabolism, and aging, while presenting untapped areas for further understanding of the aging process. [ABSTRACT FROM AUTHOR]

ABSTRACT We explore the potential of using magnetic cues as a novel approach to modulating ion channel expression, which could provide an alternative to traditional pharmacological interventions. Ion channels are crucial targets for pharmacological therapies, and ongoing research in this field continues to introduce new methods for treating various diseases. However, the efficacy of ion channel drugs is often compromised by issues such as target selectivity, leading to side effects, toxicity, and complex drug interactions. These challenges, along with problems like drug resistance and difficulties in crossing biological barriers, highlight the need for innovative strategies. In this context, the proposed use of magnetic cues to modulate ion channel expression may offer a promising solution to address these limitations, potentially improving the safety and effectiveness of treatments, particularly for long‐term use. Key developments in this area are reviewed, the relationships between changes in ion channel expression and magnetic fields are summarized, knowledge gaps are identified, and central issues relevant to future research are discussed. [ABSTRACT FROM AUTHOR]

The quality of dehydrated vegetables is affected by the degree to which they are returned to their original state during rehydration (restorability). At present, whether this mechanism occurs at the cell-wall or cell-membrane level is unclear. This paper reviews the important factors affecting the mechanism of dehydration–rehydration, focusing on the analysis of the composition and structure of the cell wall and cell membrane, and summarizes the related detection and analytical techniques that can be used to explore the mechanisms of dehydration–rehydration at the cell-wall and cell-membrane levels. The integrity and permeability of the cell membrane affect water transport during the dehydration–rehydration process. The cell wall and cell membrane are supporting materials for tissue morphology. The arabinan side chains of the primary structure and fibers are important for water retention. Water transport may be classified as symplastic and apoplastic. Cell membrane disruption occurs with symbiotic transport but increases the drying rate. An in-depth analysis of the dehydration–rehydration mechanism of vegetables will help develop and improve their processing methods and inspire new applications. [ABSTRACT FROM AUTHOR]

With the development of nanosystems, they are gradually utilized to ameliorate diverse cancer therapies. Specifically for immunotherapy, most nanosystems are elaborately designed to initiate the self‐sustaining "cancer immunity cycle (CIC)" to elicit the immune response. However, owing to the highly complex circulatory environment, nanosystems may face issues like nonspecific nanoparticle uptake and rapid clearance, leaving enormous room for advancement. For employing the biomimetic design in nanosystems, biomimetic nanosystems based on cell membranes (BNCMs) inherit various functional molecules from source cells, permitting precise tumor targeting, enhancing blood circulation, and conferring more desired functionality for a more robust immune response. To take full advantage of the BNCMs, understanding their functions in cancer immunotherapy is essential. In this review, the unique properties of BNCMs derived from various cells and main preparation strategies are introduced. Subsequently, the recent advances of BNCMs for improving cancer immunotherapy are discussed from the aspects of their roles in particular stages of the CIC, and the working mechanisms of the outer cell membranes are highlighted. Finally, along with the analysis of existing bottlenecks for clinical translation, some suggestions for the future development of BNCMs are put forward. [ABSTRACT FROM AUTHOR]

Bombyx mori cecropin A (Bmcecropin A) has antibacterial, antiviral, anti‐filamentous fungal and tumour cell inhibition activities and is considered a potential succedaneum for antibiotics. We clarified the antibacterial mechanism and structure–activity relationships and then directed the structure–activity optimization of Bmcecropin A. Firstly, we found Bmcecropin A shows a strong binding force and permeability to cell membranes like a detergent; Bmcecropin A could competitively bind to the cell membrane with the cell membrane‐specific dye DiI, then damaged the membrane for the access of DiI into the cytoplasm and leading to the leakage of electrolyte and proteins. Secondly, we found Bmcopropin A could also bind to and degrade DNA; furthermore, DNA library polymerase chain reaction (PCR) results indicated that Bmcecropin A inhibited DNA replication by non‐specific binding. In addition, we have identified C‐terminus amidation and serine‐lysine‐ glycine (SLG) amino acids of Bmcecropin A played critical roles in the membrane damage and DNA degradation. Based on the above results, we designed a mutant of Bmcecropin A (E9 to H, D17 to K, K33 to A), which showed higher antibacterial activity, thermostability and pH stability than ampicillin but no haemolytic activity. Finally, we speculated that Bmcecropin A damaged the cell membrane through a carpet model and drew the schematic diagram of its antibacterial mechanism, based on the antibacterial mechanism and the three‐dimensional configuration. These findings yield insights into the mechanism of antimicrobial peptide–pathogen interaction and beneficial for the development of new antibiotics. [ABSTRACT FROM AUTHOR]

The severe threat of microbial contamination to human life and health safety necessitates urgent research and development of antimicrobial materials capable of inhibiting or eradicating pathogens. Cyclodextrin metal-organic framework (CD-MOF) was utilized as a carrier to encapsulate gold nanoparticles (AuNPs), resulting in a composite material (Au@CD-MOF) that exhibited remarkable antibacterial properties. The antibacterial study revealed that Au@CD-MOF completely eradicated Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes) at a concentration of approximately 1 × 105 CFU/mL after 48 h and 36 h, respectively. Moreover, Au@CD-MOF also demonstrated the complete elimination of Escherichia coli O157:H7 (E. coli O157:H7), Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), and Salmonella typhimurium (S. typhimurium) at a concentration of approximately 1 × 105 CFU/mL after 48 h. Moreover, the antibacterial mechanism of Au@CD-MOF was investigated using E. coli O157:H7 and S. aureus as model organisms. The findings revealed that Au@CD-MOF disrupted the integrity of cell membranes and diminished their potential, consequently impeding the normal functions of the bacteria. Additionally, the heightened permeability of cell membranes induced by Au@CD-MOF resulted in substantial leakage of nucleic acids and proteins, ultimately leading to bacterial eradication. Highlights: Cyclodextrin metal-organic framework loaded with AuNPs has an excellent antibacterial ability. Antibacterial mechanism of cyclodextrin metal-organic framework loaded with AuNPs was investigated. [ABSTRACT FROM AUTHOR]

Several therapeutic drugs including heptamethine cyanine dye (IR‐780), doxorubicin (DOX), and others have exhibited positive outcomes in the treatment of multiple myeloma (MM). However, curing MM is still hampered by undesired off‐target effects and uncontrolled release of the therapeutics. Herein, we present novel MM‐mimicking nanocarriers by integration of DOX, IR‐780, and MM cell membrane with zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles (D/INPs@CM) for MM treatment. The nanocarriers were fabricated by co‐loading DOX and IR‐780 into ZIF‐8 and further coated with the cell membrane. After intravenous injection, the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane. Once accumulating in the tumor site, ZIF‐8 decomposed under the acid microenvironment and released the encapsulated DOX and IR‐780. As a result, D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs, without displaying noticeable systemic toxicity. All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies. [ABSTRACT FROM AUTHOR]

In neurons and myocytes, selective ion channels in the plasma membrane play a pivotal role in transducing chemical or sensory stimuli into electrical signals, underpinning neural and cardiac functionality. Recent advancements in biomedical research have increasingly spotlighted the interaction between ion channels and electromagnetic fields, especially terahertz (THz) radiation. This review synthesizes current findings on the impact of THz radiation, known for its deep penetration and non-ionizing properties, on ion channel kinetics and membrane fluid dynamics. It is organized into three parts: the biophysical effects of THz exposure on cells, the specific modulation of ion channels by THz radiation, and the potential pathophysiological consequences of THz exposure. Understanding the biophysical mechanisms underlying these effects could lead to new therapeutic strategies for diseases. [ABSTRACT FROM AUTHOR]

Copyright of Bagcilar Medical Bulletin / Bağcılar Tıp Bülteni is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In recent years, plant essential oils have been confirmed as natural inhibitors of foodborne pathogens. Citrus reticulata Blanco cv. Tankan peel essential oil (CPEO) showed anti-Listeria monocytogenes (LM) activities, and this study investigated the associated mechanisms by using high-resolution electron microscope, fluorescence spectrometer, flow cytometer, potentiometer, and transcriptome sequencing. The results showed that CPEO restrained LM growth at a minimum inhibitory concentration of 2% (v/v). The anti-LM abilities of CPEO were achieved by disrupting the permeability of the cell wall, damaging the permeability, fluidity, and integrity of the cell membrane, disturbing the membrane hydrophobic core, and destroying the membrane protein conformation. Moreover, CPEO could significantly inhibit the LM aggregation from forming biofilm by reducing the extracellular polymeric substances' (protein, polysaccharide, and eDNA) production and bacterial surface charge numbers. The RNA sequencing data indicated that LM genes involved in cell wall and membrane biosynthesis, DNA replication and repair, quorum sensing and two-component systems were expressed differently after CPEO treatment. These results suggested that CPEO could be used as a novel anti-LM agent and green preservative in the food sector. Further studies are needed to verify the anti-LM activities of CPEO in real food. [ABSTRACT FROM AUTHOR]

Nanopores offer significant advantages in biosensing. Conventional nanopore sensors require probe modification within the pore, and there are two major obstacles: inhomogeneity of probe modification within the pore, and distortion of the detection signal due to the uncontrollable dynamics of the target within the pore. Here, we constructed a cell‐sensing analogue nanopore (CeSa‐nanopore), by coating the outer surface of the nanopore with cell membrane. The inhomogeneity of probe modification and the uncontrollable kinetics of target‐probe binding were also addressed. Specific cells are selected to prepare CeSa‐nanopore, for example, cells with high expression of angiotensin‐converting enzyme 2 (ACE2) are used to achieve the detection of SARS‐CoV‐2. When SARS‐CoV‐2 binds to CeSa‐nanopore the surface potential changes, causing a change in the ionic current, thus enabling its detection with a detection rate of 100 %. In addition, the detection of different proteins, such as follicle‐stimulating hormone (FSH), can be achieved by changing the cell membrane coating. The identification of cancer cells in ascites can also be achieved by utilizing homologous targeting between cancer cells. Importantly, the use of CeSa‐nanopores for the detection of these targets eliminates the need for pre‐processing and significantly reduces detection time. [ABSTRACT FROM AUTHOR]

The copper transport (COPT/Ctr) family plays an important role in maintaining metal homeostasis in organisms, and many species rely on Ctrs to achieve transmembrane transport via copper (Cu) uptake. At present, the Ctr family is widely studied in plants. However, there are few reports on the use of Ctrs in edible mushrooms. In this study, the Pleurotus ostreatus CCMSSC00389 strain was used as the research object, and the addition of exogenous copper ions (Cu2+) increased the temperature tolerance of mycelia, maintained the integrity of cell membranes, and increased mycelial density. In addition, four PoCtr genes were further identified and subjected to bioinformatics analysis. Further research revealed that there were differences in the expression patterns of the PoCtr genes under different temperature stresses. In addition, the biological function of PoCtr4 was further explored by constructing transformed strains. The results showed that OE-PoCtr4 enhanced the tolerance of mycelia to heat stress and H2O2. After applying heat stress (40 °C), OE-PoCtr4 promoted the recovery of mycelia. Under mild stress (32 °C), OE-PoCtr4 promoted mycelial growth, maintained cell membrane integrity, and reduced the degree of cell membrane damage caused by heat stress. It is speculated that OE-PoCtr4 may maintain the integrity of the cell membrane and enhance the heat resistance of mycelia by regulating the homeostasis of Cu2+. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of China Brewing is the property of China Brewing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Drug-carrying nanoparticles can be recognized and captured by macrophages and cleared away by the immune system, resulting in reduced drug efficacy and representing the main drawbacks. Biomimetic nanoparticles, which are coated with cell membranes from natural resources, have been applied to address this problem. This type of nanoparticle maintains some specific biological activities, allowing them to carry drugs reaching designated tissues effectively and have a longer time in circulation. This review article aims to summarize recent progress on biomimetic nanoparticles based on cell membranes. In this paper, we have introduced the classification of biomimetic nanoparticles, their preparation and characterization, and their applications in inflammatory diseases and malignant tumors. We have also analyzed the shortcomings and prospects of this technology, hoping to provide some clues for basic researchers and clinicians engaged in this field. [ABSTRACT FROM AUTHOR]

A novel series of 23-hydroxybetulinic acid derivatives were designed and synthesized, in which some compounds displayed good antibacterial activity with MIC values of 4–16 μg/mL against gram-positive bacteria and moderate inhibitory activity (16–32 μg/mL) against gram-negative bacteria. 23-O-6-Aminohexyl[3,2-b]pyrazine oleanan-28,19β-lactone demonstrated the most potent antibacterial activity against S. aureus, B. subtilis, E. coli, and P. aeruginosa with MICs ranging from 4 to 16 μg/mL. Additional testing against drug-resistant bacteria (MRSA and K. pneumonia) showed 23-O-6-aminohexyl[3,2-b]pyrazine oleanan-28,19β-lactone also possessed good antibacterial activity (4–32 μg/mL). In addition, this lactone interacted effectively with cell membranes, posed negligible cytotoxicity to mammalian cells, and rapidly curbed the growth of MRSA and E. coli, while not significantly enhancing bacterial resistance. The subsequent assay of bactericidal time-kill kinetics revealed that 23-O-6-aminohexyl[3,2-b]pyrazine oleanan-28,19β-lactone showed excellent bactericidal activity against MRSA at 3MIC (> 6 log10 CFU/mL reduction) after 9 h, whereas the positive control group only demonstrated inhibitory activity. Additionally, study of drug-likeness properties suggest that these molecules may have drug-likeness characteristics, potentially improving membrane absorption and bioavailability. [ABSTRACT FROM AUTHOR]

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins. [ABSTRACT FROM AUTHOR]

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small‐ and ultra‐small‐angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10−6 Å−2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane‐matching medium, estimated droplet diameters are 770 nm (RBC/PFH) and 1.5 µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble–droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation. [ABSTRACT FROM AUTHOR]