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The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, yielding a wide range of structurally novel and functionally diverse antimicrobial drugs for the treatment of a variety of diseases that are considered good producers of novel antimicrobial drugs. Bacteria produce a wide variety of antimicrobial compounds, and thus, antibiotics derived from natural products still dominate over purely synthetic antibiotics among the antimicrobial drugs developed and introduced over the last four decades. Among them, Pseudomonas aeruginosa secondary metabolites constitute a richly diverse source of antimicrobial substances with good antimicrobial activity. Therefore, they are regarded as an outstanding resource for finding novel bioactive compounds. The exploration of antimicrobial compounds among Pseudomonas aeruginosa metabolites plays an important role in drug development and biomedical research. Reports on the secondary metabolites of Pseudomonas aeruginosa, many of which are of pharmacological importance, hold great promise for the development of effective antimicrobial drugs against microbial infections by drug-resistant pathogens. In this review, we attempt to summarize published articles from the last twenty-five years (2000–2024) on antimicrobial secondary metabolites from Pseudomonas aeruginosa.

The emergence of ciprofloxacin-resistant Salmonella poses a significant challenge to antimicrobial therapy. Probiotics that inhibit ciprofloxacin-resistant Salmonella offer a safer alternative with fewer side effects than conventional antibiotics. In this study, a strain of Companilactobacillus alimentarius Y4, isolated from kimchi, exhibited strong antibacterial activity against Salmonella C1, Escherichia coli , and other intestinal pathogens. Biological characterization showed that C. alimentarius Y4 maintained a relative growth rate of 80% at pH 3.0 and 87.13% in the presence of 0.3% bile salts. It retained over 98.8% antibacterial activity even after exposure to pepsin, trypsin, protease K, and catalase. Additionally, C. alimentarius Y4 downregulated the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), while upregulating the anti-inflammatory cytokine IL-10, which may contribute to alleviating intestinal injury induced by ciprofloxacin-resistant Salmonella C1. Gut microbiota analysis revealed that C. alimentarius Y4 colonized the intestine and increased the abundance of beneficial gut microbes, including Lachnospiraceae bacterium COE1 and Muribaculaceae bacterium CAG-485. Metabolomic profiling further indicated that C. alimentarius Y4 upregulated metabolites such as L-leucine, L-lysine, and tryptophan, contributing to the restoration of intestinal metabolic balance. Collectively, C. alimentarius Y4 may mitigate intestinal inflammation by regulating cytokine expression, repairing mucosal damage, rebalancing gut microbiota composition, and restoring metabolic homeostasis. These findings indicate that C. alimentarius Y4 may contribute to alleviating intestinal inflammatory damage caused by multidrug-resistant Salmonella infection, suggesting its potential as a promising probiotic candidate.

By integrating waste valorization with green extraction, in the current study, the impacts of distinct extraction methods on the extraction yield, structural characterization, in vitro antioxidant abilities and in vitro immunomodulatory activity of polysaccharides from Pholiota nameko residue (PNRP) were determined, providing assistance for the resource utilization of Pholiota nameko. Six PNRPs were obtained by hot water extraction, ultrasonic-assisted extraction, acid-assisted extraction, base-assisted extraction, acid–base extraction and hot water–alkaline-assisted extraction, named PNRP-HWE, PNRP-UAE, PNRP-AE, PNRP-BE, PNAP-ABE and PNRP-HAE, respectively. PNRPs were heteropolysaccharides with similar functional groups, abundant branched chains and a triple helix conformation, but varied monosaccharide molar ratios and molecular weights (382.6–601.7 kDa). PNRP-HAE exhibited the highest yield (3.92%) and superior antioxidant activities, including DPPH, ABTS and hydroxyl radical scavenging capacities, attributed to its low molecular weight and high xylose content. Additionally, PNRP-HAE and PNRP-UAE demonstrated potent immunomodulatory effects by enhancing macrophage phagocytosis and cytokine secretion (NO, IL-1β, IL-6, TNF-α). These findings highlight HAE as an optimal method for extracting high-quality PNRPs, offering a sustainable strategy for valorizing mushroom residue in functional foods and nutraceuticals.

Escherichia coli displays strong adaptability for growth and reproduction at low temperatures, with ribosome biogenesis being a critical process for its growth in cold environments. The cold-shock proteins (CSPs) encompass a protein family that can assist bacterial growth at low temperatures by acting as molecular chaperones. In this study, we investigated whether CSP CspA, CspE, and CspI affect ribosomal RNA (rRNA) transcription. Deletion of the single genes encoding these proteins had only a very marginal effect on cellular growth at low temperatures, and rRNA synthesis was hardly affected. Double and triple deletion of the genes encoding these proteins resulted in a much stronger phenotype providing evidence that CspA, CspE, and CspI play an essential role in maintaining 16S rRNA synthesis and enabling optimal cellular growth at low temperatures. These findings suggest the existence of efficient backup mechanisms able to compensate for the absence of a single CSP.

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC–MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.

In recent years, multidrug resistance in pathogenic bacteria has become increasingly serious, causing serious harm to the livestock and poultry breeding industries and posing severe challenges to its clinical prevention and treatment; therefore, the development of new antibacterial agents is urgently needed. We previously isolated Bacillus velezensis CB6, which exhibits broad-spectrum antibacterial activity, from Changbaishan in China. In this study, multidrug-resistant Escherichia coli B2(MDR E. coli B2) was used as an indicator bacterium. Ammonium sulfate precipitation, dextran gel chromatography, and Diethylaminoethyl Bestarose High Performance was used to isolate antibacterial protein with strong activity against MDR E. coli B2. SDS–PAGE combined with liquid chromatography-mass spectrometry was used to obtain the antibacterial protein CB6-E, which has a molecular weight of 54.537 kDa. Our study found that CB6-E has a strong inhibitory effect on Gram-negative bacteria such as Pseudomonas aeruginosa Z1, Salmonella H9812, and Shigella castellani Z1; among them, the minimum inhibitory concentration for MDR E. coli B2 was 32 µg/mL. In addition, CB6-E is stable under various conditions including exposure to various temperatures, organic reagents, pH values, and proteolytic enzymes. The hemolytic activity test and cytotoxicity test also showed that CB6-E is safe. Research on antibacterial mechanisms showed that CB6-E destroys cell membranes in a dose-dependent manner and can inhibit the growth of MDR E. coli B2 by targeting lipopolysaccharides on the cell membrane, showing good therapeutic effects in model animals. In summary, CB6-E is a newly discovered antibacterial protein with a high therapeutic index that is safe, nontoxic, and stabile, and is expected to be an effective antibacterial agent.

Ophiolites are fragments of ancient oceanic lithosphere, serving as geological indicators for reconstructing ocean-continent transitions, plate convergence and paleo-ocean evolution in orogenic belts. The Kekedieba ophiolite was recently identified during a 1:50,000 regional geological survey. To constrain its formation age, material source and tectonic setting, this study conducted systematic petrological observations, geochemical testing and zircon U-Pb geochronological analyses on the ophiolite. This ophiolite consists of typical end-members, such as cumulate gabbro and diabase dykes. Trace element analyses and geochemical discrimination diagrams reveal that the basalts exhibit geochemical characteristics typical of mid-ocean ridge basalt (MORB), and the ophiolite suite as a whole belongs to the low-K tholeiite series. Differences in the degree of partial melting in the source region among various end-member rocks further indicate the complexity of its tectonic setting. LA-ICP-MS zircon U-Pb dating shows that the formation age of the gabbro is 321.4 ± 2.7 Ma, indicating that the Kekedieba ophiolite formed in the late Early Carboniferous. Combined with its tectonic slice-association relationship with Early Carboniferous island-arc volcanic rocks, it is identified as fragments of a SSZ-type supra-subduction zone ophiolite, which provides direct evidence for the subduction evolution of regional paleo-plates. Although some extrusive units retain MORB-like geochemical signatures inherited from early seafloor spreading, the island-arc affinities of the full lithological suite and subduction imprints in cumulates confirm a dominant SSZ origin.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 μg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.

The antimicrobial peptide LR (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LR and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LR , and the resulting corresponding fusion protein GFP-LR was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LR was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LR displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 μg/mL. Compared to the chemically synthesized LR the prokaryotic-expressed LR exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LR showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a infection model. The mechanism by which LR causes bacterial death was found to be the disruption of the Gram-negative cell membrane.

Multinational enterprise (MNE) subsidiaries abroad are important organizations in their own rights. They typically hold some of the MNE’s most critical resources, and operate at the forefront of complex international environments. In this review, we identify and organize theoretical and empirical research on subsidiary management based on over 600 articles in leading academic journals. We develop a conceptual framework that integrates complementary streams of theoretical and empirical research with the subsidiary as its focal unit of analysis. In particular, we review six lines of research on subsidiary scope, practices, knowledge management, engagement with local market and nonmarket actors, performance, and individuals within subsidiaries. We highlight theoretical perspectives that have contributed to, and been advanced by, research on MNE subsidiaries. Based on the review, we explore future research agendas, linking the contemporary research themes with two main thrusts. First, subsidiary management is a multi-level phenomenon that would benefit from more microfoundational research. Second, subsidiary management operates at key interfaces of technology paradigm shifts, and of disruptions in the political and institutional environment. Research into the dynamics of subsidiary management would thus enhance our understanding of international business in a volatile global economy.