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As the essential regulators of organ fibrosis, macrophages undergo marked phenotypic and functional changes after organ injury. These changes in macrophage phenotype and function can result in maladaptive repair, causing chronic inflammation and the development of pathological fibrosis. Autophagy, a highly conserved lysosomal degradation pathway, is one of the major players to maintain the homeostasis of macrophages through clearing protein aggregates, damaged organelles, and invading pathogens. Emerging evidence has shown that macrophage autophagy plays an essential role in macrophage polarization, chronic inflammation, and organ fibrosis. Because of the high heterogeneity of macrophages in different organs, different macrophage types may play different roles in organ fibrosis. Here, we review the current understanding of the function of macrophage autophagy in macrophage polarization, chronic inflammation, and organ fibrosis in different organs, highlight the potential role of macrophage autophagy in the treatment of fibrosis. Finally, the important unresolved issues in this field are briefly discussed. A better understanding of the mechanisms that macrophage autophagy in macrophage polarization, chronic inflammation, and organ fibrosis may contribute to developing novel therapies for chronic inflammatory diseases and organ fibrosis.

The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases. Over the long course of evolution, eukaryotic cells have evolved a variety of mechanisms to rescue or eliminate aggregated proteins. Here, we will briefly review the composition and causes of protein aggregation in mammalian cells, systematically summarize the role of protein aggregates in the organisms, and further highlight some of the clearance mechanisms of protein aggregates. Finally, we will discuss potential therapeutic strategies that target protein aggregates in the treatment of aging and age-related neurodegenerative diseases.

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity. In this review, we describe the types of eHSPs, discuss the mechanisms of eHSPs secretion, and then highlight their functions in the modulation of inflammation and immune responses. Finally, we take cancer as an example and discuss the possibility of targeting eHSPs for human disease therapy. A broader understanding of the function of eHSPs in development and progression of human disease is essential for developing new strategies to treat many human diseases that are critically related to inflammation and immunity.

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era. Additionally, the absence of effective antibiotics introduces substantial risks to medical and surgical procedures. The dwindling interest of pharmaceutical industries in developing new antibiotics against MDR pathogens has aggravated the scarcity issue, resulting in an exceedingly limited pipeline of new antibiotics. Given these circumstances, the imperative to devise novel strategies to combat perilous MDR pathogens has become paramount. Contemporary research has unveiled several promising avenues for addressing this challenge. The article provides a comprehensive overview of these innovative therapeutic approaches, highlighting their mechanisms of action, benefits, and drawbacks.

In this study, an eco-friendly superhydrophobic cotton fabric (CF) with water contact angle of 155° was fabricated via a facile two-step approach: imparting surface roughness through hydrothermal growth of ZnO particles, and using stearic acid to create a low-energy surface. ZnO prepared by hydrothermal reaction was in a rod-like shape and had nano- or micro-scale sizes. It was located on the surface in loose aggregates. After modification with stearic acid, the aggregate structure of ZnO particles was changed from loose packing to compact packing. The superhydrophobic CF could be wetted by oil but could not be wetted by water, showing excellent oil/water separation performance. The superhydrophobic CF was able to absorb oils selectively from their mixtures with water and could be used as a filtering membrane to separate oil/water mixtures directly with separation efficiency and oil flux of 96–99% and 2000–9000 L m −2  h −1 , respectively, depending on the intrinsic property of the oils. In addition, the superhydrophobic CF showed excellent mechanical robustness and environmental durability with water contact angle almost remaining unchanged after exposure to sandpaper abrasion, ultrasonication, boiling water treatment and organic solvents erosion. With excellent robustness and durability, the superhydrophobic CF exhibits great potential in oil/water separation even under some harsh conditions. Graphic abstract

Using this system, we can delete the genes of interest in specific cells, tissues, and even the whole organism so as to generate a variety of conditional knockout mouse strains. [...]it is also used to generate cell- or tissue-specific reporter mice for lineage tracing. [...]in order to generate conditional knockout mice efficiently, mating between mice with Cre and floxed genes in the same chromosome should be avoided. When crossed with a mouse strain that contained a loxP site-flanked gene sequence of interest, Cre-mediated recombination will lead to the loss of function of the targeted gene in the myeloid cell lineage, such as monocytes, mature macrophages, and granulocytes. [...]the LysM-Cre strain is believed to be an effective tool for generating macrophage-specific targeted mutants, though LysM is not a specific marker for macrophages. [...]the distance between genes can range from 1 to 50 cM, and the smaller the distance, the closer the genes are to each other on the chromosome.

Strengthening with external prestressing is a kind of reinforcement method which imposes prestress on concrete by setting prestressed steel bar outside concrete, a new strengthening with external prestressing technology can be put forward by using industrial reclaimed steel wire instead of prestressing steel bar. High-quality steel wire is extracted from waste tire after stripping and derusting, and this kind of industrial reclaimed steel wire with high tensile strength and good toughness is applied to building reinforcement by externally prestressing method; it can provide a new research direction for the country’s green, low-carbon, and high-quality development. In this paper, the new strengthening with external prestressing technology is used to study the bending static load test of test beams under different working conditions. The influence of reinforcement material and rotational degree on the bending performance of RC beam is discussed. The results show that the ultimate bearing capacity of the flexural members with industrial recycled steel wire is more effective under the new external prestressed reinforcement method. Under the same reinforcement method, when the reinforcement materials are the same, the increase of prestress can effectively improve the bearing capacity of flexural members in the reinforced beams with prestress of 30%, 40%, and 50%, respectively. In order to verify the reinforcement effect of industrial recycled steel wire on the bending performance of RC beam from multiple perspectives, the numerical simulation was carried out on the concrete specimens reinforced with different degrees of woven reinforced wire, and the simulation results were in good agreement with the experimental results. This study provides a new research direction for the recycling of industrial reclaimed steel wire and the reinforcement of concrete components and has a good promotion, role, and theoretical support for subsequent research.

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger , and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.

Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34 + stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34 + stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34 + CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34 + cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34 + cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34 + cells. These data challenged the dependency of OXPHOS for CML CD34 + cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.

As an evolutionarily conserved cellular process, autophagy plays an essential role in the cellular metabolism of eukaryotes as well as in viral infection and pathogenesis. Under physiological conditions, autophagy is able to meet cellular energy needs and maintain cellular homeostasis through degrading long-lived cellular proteins and recycling damaged organelles. Upon viral infection, host autophagy could degrade invading viruses and initial innate immune response and facilitate viral antigen presentation, all of which contribute to preventing viral infection and pathogenesis. However, viruses have evolved a variety of strategies during a long evolutionary process, by which they can hijack and subvert host autophagy for their own benefits. In this review, we highlight the function of host autophagy in the key regulatory steps during viral infections and pathogenesis and discuss how the viruses hijack the host autophagy for their life cycle and pathogenesis. Further understanding the function of host autophagy in viral infection and pathogenesis contributes to the development of more specific therapeutic strategies to fight various infectious diseases, such as the coronavirus disease 2019 epidemic.