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Background Phage holin Hol41 is a membrane protein with broad-spectrum antibacterial potential; however, its high hydrophobicity and prokaryotic expression toxicity severely limit its soluble expression and large-scale production. Results We constructed a synthetic biology-driven secretory expression platform for Hol41 in Komagataella phaffii ( K. phaffii ) by integrating small ubiquitin-related modifier (SUMO) fusion technology and the α-mating factor secretion pathway. This platform avoids prokaryotic toxicity by exploiting the structural differences between the cell membranes of K. phaffii and Escherichia coli . The SUMO tag combined with α-mating factor-mediated secretion enhances protein solubility, reduces toxicity, and inhibits Hol41 aggregation. After scale-up culture in a 2-L fermenter, the yield of SUMO-Hol41 reached 44.95 mg/L, with a yield coefficient ( Y p/s ) of 0.00843 mg protein/mg dry cell weight (DCW). MIC and MBC assays revealed that SUMO-Hol41 exhibited selective antibacterial activity against Gram-positive bacteria among seven standard strains: the MIC values against Staphylococcus aureus ATCC 33,951 and Streptococcus pneumoniae ATCC 49,619 were both 128 µg/mL (MBC: 256 µg/mL), and 64 µg/mL (MBC: 128 µg/mL) for Enterococcus faecalis ATCC 29,212. Among Gram-negative bacteria, only Salmonella enteritidis S4 was susceptible (MIC: 128 µg/mL, MBC: 256 µg/mL). Moreover, the purified protein showed dose- and time-dependent antibacterial activity, whose inhibitory effect increased with elevated dosage and prolonged incubation time. Conclusions This study represents the first successful high-yield functional expression of phage holin Hol41 in K. phaffii. The established K. phaffii -SUMO fusion-secretion strategy effectively overcomes challenges of prokaryotic toxicity and poor solubility, providing a robust platform for developing novel antibacterial agents against drug-resistant bacteria. Graphical Abstract

Multidrug-resistant (MDR) Salmonella enteritidis infections cause high mortality and devastating economic losses in poultry, pose severe threats to animal health and food safety, and create an urgent demand for effective antibiotic alternatives. Herein, we developed a cationic liposome-encapsulated bacteriophage endolysin Lys40 (designated Lys40-Lip), and systematically evaluated its therapeutic efficacy in a chick model challenged with Salmonella enteritidis strain S4. Recombinant Lys40 was encapsulated into cationic liposomes with an encapsulation efficiency (EE) of 34.83%. The resulting Lys40-Lip nanoparticles had a hydrodynamic diameter of 137.3 ± 4.1 nm, a high positive zeta potential of +42.5 ± 0.3 mV, and excellent stability, retaining 78.52% of its initial bactericidal activity after 56 days of storage at 4 °C. Following a three-day oral treatment in Salmonella enteritidis S4-infected chicks, Lys40-Lip significantly increased survival rates in a dose-dependent manner (72.22% to 88.89% for low-to-high dose vs. 44.44% in infected controls, p < 0.05) and reduced ileal Salmonella enteritidis S4 colonization by 28.8% compared to free Lys40. Histopathology revealed Lys40-Lip restored duodenal villus integrity and reduced jejunal and ileal inflammation. Serum cytokine analysis confirmed that Lys40-Lip effectively regulated the host inflammatory response, significantly downregulating the pro-inflammatory cytokines IL-1β and IL-6, and upregulating the anti-inflammatory cytokine IL-10. Crucially, liposomal encapsulation overcame the outer membrane barrier of Gram-negative bacteria via charge-driven fusion mediated by its high positive surface potential (+42.5 ± 0.3 mV), enabling targeted delivery of Lys40 without the need for EDTA or other outer membrane permeabilizers. Lys40-Lip significantly improved the therapeutic outcomes of avian salmonellosis via synergistic direct bactericidal activity, intestinal barrier protection and inflammatory response regulation, offering a promising nanotherapeutic strategy for the control of this disease in veterinary practice.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) poses significant health risks to poultry and humans, with biofilm formation often complicating treatment by enhancing bacterial persistence and resistance. Understanding the genetic mechanisms underlying this lifestyle transition is crucial for controlling infections. This study aimed to investigate the effect of biofilm formation on the transcriptional expression of specific biofilm- and virulence-associated genes in chicken-derived ExPEC strains. Methods: Biofilm formation conditions for three strong biofilm-producing chicken-derived ExPEC strains were optimized using an orthogonal experimental design (L9(33)), evaluating culture medium, incubation time, and initial inoculum concentration. Biofilm biomass was quantified via crystal violet staining. Subsequently, the transcription levels of 10 biofilm-associated genes and 17 virulence-associated genes were compared between planktonic and biofilm states using Reverse Transcription-quantitative PCR (RT-qPCR). Results: Optimal culture conditions varied among strains, though nutrient-rich media consistently promoted rapid biofilm formation. Transcriptional analysis revealed significant reprogramming in the biofilm state. Among biofilm-associated genes, flhC, tolA, qseC, mhpB, and bdcR were consistently and significantly upregulated across all strains (p < 0.05). Regarding virulence determinants, the expression of eaeA, LT, fimH, ompF, and iss was significantly upregulated (p < 0.05), whereas Sta levels were significantly reduced (p < 0.05). Conclusions: Biofilm formation induces a distinct transcriptional shift in chicken-derived ExPEC, simultaneously enhancing the expression of key genes involved in biofilm maintenance and pathogenicity. The conserved upregulation of flhC, tolA, qseC, mhpB, and bdcR suggests these genes are critical drivers of biofilm development. Consequently, they represent potential targets for novel therapeutic strategies aimed at preventing E. coli infections and eradicating biofilms in clinical and agricultural settings.

Hearing loss is a common disease due to sensory loss caused by the diseases in the inner ear. The development of delivery systems for inner ear disease therapy is important to achieve high efficiency and reduce side effects. Currently, traditional drug delivery systems exhibit the potential to be used for inner ear disease therapy, but there are still some drawbacks. As nanotechnology is developing these years, one of the solutions is to develop nanoparticle-based delivery systems for inner ear disease therapy. Various nanoparticles, such as soft material and inorganic-based nanoparticles, have been designed, tested, and showed controlled delivery of drugs, improved targeting property to specific cells, and reduced systemic side effects. In this review, we summarized recent progress in nanocarriers for inner ear disease therapy. This review provides useful information on developing promising nanocarriers for the efficient treatment of inner ear diseases and for further clinical applications for inner ear disease therapy.

ObjectivesDespite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.DesignMeta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.SettingRCTs from any country and healthcare setting.ParticipantsPatients with OC.InterventionsCombination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.Primary and secondary outcome measuresOverall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.ResultsIn total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia.ConclusionsOverall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment.Trial registration numberCRD42020169230.

Artemisia is a large genus encompassing about 400 diverse species, many of which have considerable medicinal and ecological value. However, complex morphological information and variation in ploidy level and nuclear DNA content have presented challenges for evolution studies of this genus. Consequently, taxonomic inconsistencies within the genus persist, hindering the utilization of such large plant resources. Researchers have utilized satellite DNAs to aid in chromosome identification, species classification, and evolutionary studies due to their significant sequence and copy number variation between species and close relatives. In the present study, the RepeatExplorer2 pipeline was utilized to identify 10 satellite DNAs from three species (Artemisia annua, Artemisia vulgaris, Artemisia viridisquama), and fluorescence in situ hybridization confirmed their distribution on chromosomes in 24 species, including 19 Artemisia species with 5 outgroup species from Ajania and Chrysanthemum. Signals of satellite DNAs exhibited substantial differences between species. We obtained one genus-specific satellite from the sequences. Additionally, molecular cytogenetic maps were constructed for Artemisia vulgaris, Artemisia leucophylla, and Artemisia viridisquama. One species (Artemisia verbenacea) showed a FISH distribution pattern suggestive of an allotriploid origin. Heteromorphic FISH signals between homologous chromosomes in Artemisia plants were observed at a high level. Additionally, the relative relationships between species were discussed by comparing ideograms. The results of the present study provide new insights into the accurate identification and taxonomy of the Artemisia genus using molecular cytological methods.

Ribosomal DNA (rDNA) is an excellent cytogenetic marker owing to its tandem arrangement and high copy numbers. However, comparative studies have focused more on the number of rDNA site variations within the Chrysanthemum genus, and studies on the types of rDNA sites with the same experimental procedures at the species levels are lacking. To further explore the number and types of rDNA site variations, we combined related data to draw ideograms of the rDNA sites of Chrysanthemum accessions using oligonucleotide fluorescence in situ hybridization (Oligo-FISH). Latent variations (such as polymorphisms of 45S rDNA sites and co-localized 5S-45S rDNA) also occurred among the investigated accessions. Meanwhile, a significant correlation was observed between the number of 5S rDNA sites and chromosome number. Additionally, the clumped and concentrated geographical distribution of different ploidy Chrysanthemum accessions may significantly promote the karyotype evolution. Based on the results above, we identified the formation mechanism of rDNA variations. Furthermore, these findings may provide a reliable method to examine the sites and number of rDNA variations among Chrysanthemum and its related accessions and allow researchers to further understand the evolutionary and phylogenetic relationships of the Chrysanthemum genus.

Though the concept of Berry force was proposed thirty years ago, little is known about the practical consequences of this force as far as chemical dynamics are concerned. Here, we report that when molecular dynamics pass near a conical intersection, a massive Berry force can appear as a result of even a small amount of spin-orbit coupling (<10 −3 eV), and this Berry force can in turn dramatically change pathway selection. In particular, for a simple radical reaction with two outgoing reaction channels, an exact quantum scattering solution in two dimensions shows that the presence of a significant Berry force can sometimes lead to spin selectivity as large as 100%. Thus, this article opens the door for organic chemists to start designing spintronic devices that use nuclear motion and conical intersections (combined with standard spin-orbit coupling) in order to achieve spin selection. Vice versa, for physical chemists, this article also emphasizes that future semiclassical simulations of intersystem crossing (which have heretofore ignored Berry force) should be corrected to account for the spin polarization that inevitably arises when dynamics pass near conical intersections. Spin polarization is at the basis of quantum information and underlies some natural processes, but many aspects still need to be explored. Here, the authors, by quantum mechanical computations, show that even a weak spin-orbit coupling near a conical intersection can induce large spin selection, with consequences for spin manipulation in photochemical or electrochemical reactions.

This paper mainly concentrated on how the anxiety affects impulse control and decision-making patterns in adolescents. Through investigating the psychological and neurocognitive research.the paper suggests that high level of anxiety is strongly associated with reduced impulse control and a tendency toward impulsive decisions. Especially among the adolescents, whose cognitive control systems are still maturing, are particularly affected to these negative effects. The study also investigated some current findings to discover that anxiety may make adolescents toward risk-avoidant or irrational decision styles, especially under stress. By integrating multiple perspectives, this study further comprehends the emotional cognitive interaction during adolescence and stresses the need to implement certain intervention measures to support the behavioral regulation and decision-making needs of adolescents facing anxiety-related challenges.

We obtain L p estimates for fractional parabolic equations with space-time non-local operators ∂ t α u - L u + λ u = f in ( 0 , T ) × R d , where ∂ t α u is the Caputo fractional derivative of order α ∈ ( 0 , 1 ] , T ∈ ( 0 , ∞ ) , and L u ( t , x ) : = ∫ R d ( u ( t , x + y ) - u ( t , x ) - y · ∇ x u ( t , x ) χ ( σ ) ( y ) ) K ( t , x , y ) d y is an integro-differential operator in the spatial variables. Here we do not impose any regularity assumption on the kernel K with respect to t and y . We also derive a weighted mixed-norm estimate for the equations with operators that are local in time, i.e., α = 1 , which extend the previous results in Mikulevičius and Pragarauskas (J Differ Equ 256(4):1581–1626, 2014) and Zhang (Annales l’IHPAnalyse Nonlinéaire 30:573–614, 2013) by using a quite different method.