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Suspended particles play a vital role in aquatic environments. We propose a method to rapidly measure the scattered polarization parameters of individual suspended particles with continuously large angular range (PCLAR), from 60° to 120° in one shot. A conceptual setup is built to measure PCLAR with 20 kHz; to verify the setup, 10 μm-diameter silica microspheres suspended in water, whose PCLAR are consistent with those simulated by Mie theory, are measured. PCLAR of 6 categories of particles are measured, which enables high-accuracy classification with the help of a convolutional neural network algorithm. PCLAR of different mixtures of Cyclotella stelligera and silica microspheres are measured to successfully identify particulate components. Furthermore, classification ability comparisons of different angular-selection strategies show that PCLAR enables the best classification beyond the single angle, discrete angles and small-ranged angles. Simulated PCLAR of particles with different size, refractive index, and structure show explicit discriminations between them. Inversely, the measured PCLAR are able to estimate the effective size and refractive index of individual Cyclotella cells. Results demonstrate the method’s power, which intrinsically takes the advantage of the optical polarization and the angular coverage. Future prototypes based on this concept would be a promising biosensor for particles in environmental monitoring.

Stress detection of the conical frustum window is a very important issue to ensure the safety of deep manned submersibles. In this paper, we propose a method based on polarization imaging to evaluate the stress accumulation and recovery in the conical frustum window. An experimental setup of Mueller matrix polarimetry is built, and the samples are made by referring to the typical conical frustum windows in submersibles. By pressurizing different pressures on the samples, we can find the changes of their Mueller matrix images and further derived polarization parameters. The results show that the polarization parameters can characterize the stress transfer process and the elastic–plastic transformation process of the window under different pressurization pressures. We also use a two-layered wave plate model to simulate the stress distribution in the window, which reveals different performances of the former and latter layers of the window under pressurization. Finally, we use a finite element model to simulate and understand some of the above experimental results. This proposed method is expected to provide new possibilities for monitoring the window stress and further ensure the safety of deep manned submersibles.

Abstract Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug‐loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near‐infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti‐inflammatory and antibacterial properties in models of P. aeruginosa‐infected pneumonia and wounds. Hence, this light‐activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

Summary: Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and understanding how NLRP3 inflammasome is regulated can provide strategies to treat inflammatory diseases. Here, we demonstrate that NLRP3 Cys126 is palmitoylated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7), which is critical for NLRP3-mediated inflammasome activation. Perturbing NLRP3 Cys126 palmitoylation by ZDHHC7 knockout, pharmacological inhibition, or modification site mutation diminishes NLRP3 activation in macrophages. Furthermore, Cys126 palmitoylation is vital for inflammasome activation in vivo. Mechanistically, ZDHHC7-mediated NLRP3 Cys126 palmitoylation promotes resting NLRP3 localizing on the trans-Golgi network (TGN) and activated NLRP3 on the dispersed TGN, which is indispensable for recruitment and oligomerization of the adaptor ASC (apoptosis-associated speck-like protein containing a CARD). The activation of NLRP3 by ZDHHC7 is different from the termination effect mediated by ZDHHC12, highlighting versatile regulatory roles of S-palmitoylation. Our study identifies an important regulatory mechanism of NLRP3 activation that suggests targeting ZDHHC7 or the NLRP3 Cys126 residue as a potential therapeutic strategy to treat NLRP3-related human disorders.

Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.

Outcomes for patients with acute myeloid leukemia (AML) remain poor due to the inability of current therapeutic regimens to fully eradicate disease-initiating leukemia stem cells (LSC). Previous studies have demonstrated that oxidative phosphorylation (OXPHOS) is an essential process that is targetable in LSC. Sirtuin 3 (SIRT3), a mitochondrial deacetylase with a multi-faceted role in metabolic regulation, has been shown to regulate OXPHOS in cancer models; however, it has not yet been studied in the context of LSC. Thus, we sought to identify if SIRT3 is important for LSC function. Using RNAi and a SIRT3 inhibitor (YC8-02), we demonstrate that SIRT3 is a critical target for the survival of primary human LSC but is not essential for normal human hematopoietic stem and progenitor cell function. In order to elucidate the molecular mechanisms by which SIRT3 is essential in LSC we combined transcriptomic, proteomic, and lipidomic approaches, showing that SIRT3 is important for LSC function through the regulation of fatty acid oxidation (FAO) which is required to support OXPHOS and ATP production in human LSC. Further, we discovered two approaches to further sensitize LSC to SIRT3 inhibition. First, we found that LSC tolerate the toxic effects of fatty acid accumulation induced by SIRT3 inhibition by upregulating cholesterol esterification. Disruption of cholesterol homeostasis sensitizes LSC to YC8-02 and potentiates LSC death. Second, SIRT3 inhibition sensitizes LSC to the BCL-2 inhibitor venetoclax. Together, these findings establish SIRT3 as a regulator of lipid metabolism and potential therapeutic target in primitive AML cells.

Succinylation is a metabolism-associated post-translational protein modification. Here the authors describe changes to the succinylation of proteins in the brain of individuals with Alzheimer’s disease.

Sirtuins use NAD+ to remove various acyl groups from protein lysine residues. Through working on different substrate proteins, they display many biological functions, including regulation of cell proliferation, genome stability, metabolism, and cell migration. There are seven sirtuins in humans, SIRT1-7, each with unique enzymatic activities, regulatory mechanisms, subcellular localizations, and substrate scopes. They have been indicated in many human diseases, including cancer, neurodegeneration, microbial infection, metabolic and autoimmune diseases. Consequently, interests in development of sirtuin modulators have increased in the past decade. In this brief review, we specifically summarize genetic and pharmacological modulations of sirtuins in cancer, neurological, and cardiovascular diseases. We further anticipate this review will be helpful for scrutinizing the significance of sirtuins in the studied diseases.

Lysine fatty acylation is an important protein posttranslational modification but mammalian lysine fatty acyl transferases have remained unknown so far. Here the authors report that the human N-terminal glycine myristoyltransferases 1 and 2 catalyze the addition of myristoyl chains to specific lysine residues and show that they myristoylate ARF6 lysine 3, which explains the unusual membrane binding properties of ARF6.

Post-translational acylation of lysine side chains is a common mechanism of protein regulation. Modification by long-chain fatty acyl groups is an understudied form of lysine acylation that has gained increasing attention recently due to the characterization of enzymes that catalyze the addition and removal this modification. In this review we summarize what has been learned about lysine fatty acylation in the approximately 30 years since its initial discovery. We report on what is known about the enzymes that regulate lysine fatty acylation and their physiological functions, including tumorigenesis and bacterial pathogenesis. We also cover the effect of lysine fatty acylation on reported substrates. Generally, lysine fatty acylation increases the affinity of proteins for specific cellular membranes, but the physiological outcome depends greatly on the molecular context. Finally, we will go over the experimental tools that have been used to study lysine fatty acylation. While much has been learned about lysine fatty acylation since its initial discovery, the full scope of its biological function has yet to be realized.

Large quantities of phthalic acid esters (PAEs) are released and migrate into the environment continuously and become ubiquitous in soil, surface water, groundwater and other areas, eventually leading to serious environmental pollution. Therefore, the methods of PAEs mineralization have become a hot research topic. In this study, a highly efficient dimethyl phthalate (DMP)-degrading bacterium capable of utilizing DMP as the sole source of carbon and energy was isolated from frozen soil collected from a refuse disposal station. The DMP-degrading bacterium was identified as Pseudomonas sp. QDF12 according to the phylogeny of 16S rDNA sequence. The degradation process well fitted a first-order kinetic model, with a half-life of 9.8 h and the highest degradation rate of 20.19 mg/L•h at 15.0 °C. The fermentation conditions that enhanced the fermentation of biomass were optimized via Plackett-Burman design and response surface methodology. Finally, the carbon-nitrogen ratio, CaCO3, temperature and shaking speed were identified as key factors. Verification experiments indicated that the maximal biomass was 1.85 × 109 cfu/mL under the optimized conditions, which was 134.18% and 66.67% higher than those obtained under the Luria broth medium and the basic fermentation conditions, respectively. The time and temperature of fermentation were reduced to 12 h and 12.0 °C respectively. In conclusion, the strain QDF12 is more suitable for application in low-temperature areas owing to its fast, efficient fermentation and low-temperature resistance. Because of the shorter fermentation period and lower fermentation temperature, the large-scale commercial application of strain QDF12 will reduce the production costs and accelerate the fermentation speed.

Cell-based drug delivery systems have shown tremendous advantages in cancer treatment due to their distinctive properties. For instance, delivery of therapeutics using tumor-tropic cells like neutrophils, lymphocytes and mesenchymal stem cells can achieve specific tumor targeting due to the “Trojan Horse” effect. Other circulatory cells like erythrocytes and platelets can greatly improve the circulation time of nanoparticles due to their innate long circulation property. Adipocytes, especially cancer-associated adipocytes, play key roles in tumor development and metabolism, therefore, adipocytes are regarded as promising bio-derived nanoplatforms for anticancer targeted drug delivery. Nanomaterials are important participants in cell-based drug delivery because of their unique physicochemical characteristics. Therefore, the integration of various nanomaterials with different cell types will endow the constructed delivery systems with many attractive properties due to the merits of both. In this review, a number of strategies based on nanomaterial-involved cell-mediated drug delivery systems for cancer treatment will be summarized. This review discusses how nanomaterials can be a benefit to cell-based therapies and how cell-derived carriers overcome the limitations of nanomaterials, which highlights recent advancements and specific biomedical applications based on nanomaterial-mediated, cell-based drug delivery systems.

The KRAS gene encodes two isoforms, KRas4a and KRas4b. Differences in the signaling functions of the two KRas proteins are poorly understood. Here we report the comparative and nucleotide-dependent interactomes of KRas4a and KRas4b. Many previously unknown interacting proteins were identified, with some interacting with both isoforms while others prefer only one. For example, v-ATPase a2 and eIF2Bδ interact with only KRas4b. Consistent with the v-ATPase interaction, KRas4b has a significant lysosomal localization. Comparing WT and constitutively active G12D mutant KRas, we examined differences in the effector proteins of the KRas4a and KRas4b. Interestingly, KRas4a binds RAF1 stronger than KRas4b. Correspondingly, KRas4a can better promote ERK phosphorylation and anchorage-independent growth than KRas4b. The interactome data represent a useful resource to understand the differences between KRas4a and KRas4b and to discover new function or regulation for them. A similar proteomic approach would be useful for studying numerous other small GTPases.

Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation.

The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty acylation promotes the plasma membrane localization of R-Ras2 and its interaction with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased cell proliferation. Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor.

Recent advancements in bone implant materials have led to the development of various alloys. In this study, the degradation behavior of the as-cast Mg-3 wt% Zn-1 wt% Ca-0.5 wt% Sr alloy in vitro was investigated using x-ray diffraction (XRD), scanning Kelvin probe force microscopy (SKPFM), and scanning electron microscopy (SEM). Our results demonstrated that the alloy microstructure was composed of α-Mg, a Ca _2 Mg _6 Zn _3 phase, and a Mg _17 Sr _2 phase. The Ca _2 Mg _6 Zn _3 phase, which had the smallest absolute potential, was shown to have cathodic protection, while the α-Mg, which had the largest absolute potential, was shown to prefer corrosion. The in vitro corrosion products of the as-cast alloy were Mg(OH) _2 , a Ca-P compound, and HA. At the beginning of the corrosion, the hydrogen evolution rate of the alloy was fast due to the thin corrosion product layer. With the extension of the corrosion time, the corrosion layer thickened and the hydrogen evolution rate slowed down and stabilized to 1.25 × 10 ^−5 mol cm ^−2 · h . Due to the high concentration of Ca and Mg ions near the second phase, HA was quickly deposited and an ion exchange channel between the solution and the alloy was formed, making it easier for the Mg, Ca, and Sr ions to enter the solution and promote the formation of HA. The hysteresis effect of Sr element was found, that is, Sr ions were released into the solution after etching for a period of time, which promoted the formation of HA and HA-containing Sr (Sr/HA).