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Breast cancer is the most common cancer in women and the second leading cause of cancer‐related deaths after lung cancer. Metastasis of the central nervous system is a terrible event for breast cancer patients, affecting their survival and quality of life. Compared with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative breast cancer patients, brain metastases are more likely to affect patients with triple‐negative breast cancer and human epidermal growth factor receptor 2‐positive breast cancer. The treatment of breast cancer has improved greatly in the last two decades. However, brain metastases from breast cancer remain the leading cause of morbidity and mortality. Patients with breast cancer brain metastasis have been in an inferior position due to the lack of clinical research in this field, and they are often explicitly excluded from almost all clinical trials. The occurrence and progression of brain metastases will result in severe cognitive impairment and adverse physical consequences, so we must have a good understanding of the molecular mechanisms of breast cancer brain metastasis. In this article, we have retrieved the latest literature of molecules and pathways associated with breast cancer brain metastasis, summarized common therapy strategies, and discussed the prospects and clinical implications of targeting the molecules involved. A portion of cells at the primary site acquired invasive properties by EMT. Invasive cancer cells intravasate into the bloodstream, survive, and arrest the circulatory system. Then these cells extravasate through transendothelial migration, colonize, and form metastatic brain lesions. BBB plays a critical role in ensuring normal brain function. However, as the development of primary or metastatic tumors in the brain, BBB becomes disrupted, and is altered to BTB. At last, new, and aberrant vessels grow during tumor progression.

Cancer poses a severe threat to human health. Although conventional chemotherapy remains a cornerstone of cancer treatment, its significant side effects and the growing issue of drug resistance necessitate the urgent search for more efficient and less toxic anticancer drugs. In recent years, bacteriocins, antimicrobial peptides of microbial origin, have garnered significant attention due to their targeted antitumor activity. This unique activity is mainly attributed to their cationic and amphiphilic nature, which enables bacteriocins to specifically kill tumor cells without harming normal cells. When involving non-membrane-disrupting mechanisms, such as apoptosis induction, cell cycle blockade, and metastasis inhibition, the core mechanism of action is achieved by disrupting cell membranes, which endows bacteriocins with low drug resistance and high selectivity. However, the susceptibility of bacteriocins to hydrolysis and hemolysis in vivo limits their clinical application. To overcome these challenges, structural optimization of bacteriocins or their combination with nanotechnology is proposed for future development. This review aims to study the mechanism of action and current research status of bacteriocins as anticancer treatments, thus providing new insights for their clinical development and application.

Background Basic helix-loop-helix family, member e22 (BHLHE22), a basic helix loop helix transcription factor family member, functions vary in different types of cancer. Currently, its function in triple-negative breast cancer (TNBC) is unclear. Methods The GSE45827 and GSE113865 datasets were used to screen potential TNBC marker. Biological websites were used to analyze BHLHE22 expression in TNBC, its relationship with the prognosis of patients with TNBC, and its potential function. A series of in vitro and in vivo experiments was performed to investigate the function of BHLHE22 in TNBC. The regulatory relationship between OTU domain-containing protein 3 (OTUD3) and BHLHE22 was verified by Co-Immunoprecipitation, ubiquitination assay, and site-specific mutation experiments. The mRNA-seq analysis was performed to identify potential genes for the anti-cancer role of BHLHE22. The transcriptional regulation of DNA replication factor 1 (CDT1) by BHLHE22 was confirmed by dual luciferase reporter assay. Results We identified the downregulation of BHLHE22 in TNBC tissues based on the GSE45827 and GSE113865 datasets. The expression of BHLHE22 in TBNC patients was lower than that in non-TNBC patients, and patients at stages 3 and 4 tended to express lower BHLHE22 expression than patients at stages 1 and 2. Patients with high expression of BHLHE22 had better survival prognosis than those with BHLHE22 low expression. Functional studies revealed that BHLHE22 overexpression impaired cell growth in vitro and in vivo . However, BHLHE22 silencing enhanced the malignant behaviors of cancer cells. OTUD3, a deubiquitinase known to suppress TNBC progression, was found to increase the stability of BHLHE22 protein through deubiquitination regulation. The C76 site mutation of OTUD3 eliminated the catalytic activity of OTUD3 and failed to regulate the protein stability of BHLHE22. Furthermore, BHLHE22 medicated the antitumor effect of OTUD3 in TNBC. The mRNA-seq analysis identified potential genes for the anti-cancer role of BHLHE22, involving CDT1. BHLHE22 was proved to reduce CDT1 RNA expression by blocking CDT1 transcription. The anti-proliferative effect of BHLHE22 overexpression was reversed by CDT1 overexpression. Conclusions Our observations demonstrate that BHLHE22 may be a promising target for TNBC therapy. Graphical abstract

Wound healing remains a critical global healthcare challenge, with an annual treatment cost exceeding $50 billion worldwide. Over the past decade, significant advances in wound care have focused on developing sophisticated biomaterials that promote tissue regeneration and prevent complications. Despite these developments, there remains a crucial need for multifunctional wound healing materials that can effectively address the complex, multiphase nature of wound repair while being cost effective and easily applicable in various clinical settings. This review systematically analyzes the latest developments in wound healing materials, examining their chemical composition, structural design, and therapeutic mechanisms. We comprehensively evaluate various bioactive components, including natural polymers, synthetic matrices, and hybrid composites, along with their different forms, such as hydrogels, powders, and smart dressings. Special attention is given to emerging strategies in material design that integrate multiple therapeutic functions, including sustained drug delivery, infection prevention, and tissue regeneration promotion. The insights provided in this review illuminate the path toward next‐generation wound healing materials, highlighting opportunities for developing more effective therapeutic solutions that can significantly improve patient outcomes and reduce healthcare burden. This paper reviews the current status and latest advancements in the field of hemostatic materials, focusing on the mechanism of hemostasis and wound healing, the chemical design principles and physiological mechanisms of hemostatic materials, and the comparison of different active ingredients and dosage forms. In addition, considering the subsequent needs of wound healing posthemostasis, this review also discusses the main challenges and future directions of hemostatic materials for wound healing .

To explore the differences of vaginal microbes in women with preterm birth (PTB), and to construct prediction model. We searched for articles related to vaginal microbiology in preterm women and obtained four 16S rRNA-sequence datasets. We analyzed that for species diversity and differences, and constructed a random forest model with 20 differential genera. We introduce an independent whole genome-sequencing (WGS) data for validation. In addition, we collected vaginal and cervical swabs from 33 pregnant women who delivered spontaneously full-term and preterm infants, performed WGS in our lab to further validate the model. Compared to term birth (TB) samples, PTB women vagina were characterized by a decrease in Firmicutes , Lactobacillus , and an increase in diversity accompanied by the colonization of pathogenic bacteria such as Gardnerella , Atopobium and Prevotella . Twenty genus markers, including Lactobacillus , Prevotella , Streptococcus , and Gardnerella performed well in predicting PTB, with study-to-study transfer validation and LODO validation, different gestation validation showing good results, and in two independent cohorts (external WGS cohorts and woman samples WGS cohorts) in which the accuracy was maintained. PTB women have unique vaginal microbiota characteristics. A predictive model of PTB was constructed and its value validated from multiple perspectives. Importance This study integrates current data on the vaginal microbiome of women with preterm birth to comprehensively investigate the unique vaginal microbiome of women with preterm birth. A preterm birth risk prediction model based on 20 characteristic genera was constructed, and its effectiveness was verified by internal, external, and collected whole genome sequencing data.

Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2− breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2− breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.

Aroma compounds in fruits and related products are known to occur in free and glycosidically bound forms. In this study, free and bound volatiles in juices and wines of two kiwifruit cultivars, Actinidia deliciosa ‘Hayward’ and A. chinensis ‘Hort16A’, were analyzed by solid-phase microextraction-gas chromatography-mass spectrometry. Results showed that 67 free and 79 bound volatiles were found in juices and wines. Alcohols were the most abundant free volatiles, while the most representative bound volatiles were terpenoids. β-Damascenone and 4-methyl-3-penten-2-one released from aroma precursors were found in ‘Hort16A’ juice for the first time. Fruity, floral, and sweet flavors appeared to be the characteristic aroma in kiwifruit juices and wines. Principal component analysis showed that kiwifruit wines had a great aroma potential. Cluster analysis revealed that juices and wines had different profile of free volatiles, while similar bound volatile compositions were found. Moreover, abundant bound volatiles were discovered in these two kiwifruit pomace for the first time, indicating their potential applications in food and cosmetics industry.

Background The modification of single or multiple genes via metabolic engineering can lead to the dysregulation of central metabolism and affect bacterial growth and metabolite accumulation. Meanwhile, transcription factor engineering can trigger metabolic network reprogramming at the global or systemic level, redirecting metabolic flux toward the synthetic pathways of target metabolites. In this study, we modulated pyrimidine and carbon-nitrogen metabolism in Bacillus subtilis through transcription factor engineering to promote the synthesis of cytidine, a drug intermediate. Results First, cytidine synthesis was enhanced by knocking out the transcriptional regulator PyrR, which increased the cytidine titer during shake flask fermentation to 0.67 g/L. Second, mutations in the transcriptional regulator catabolite control protein A (CcpA) significantly promoted cytidine synthesis, increasing the shake flask titer to 2.03 g/L. Finally, after culture in a 5 L fermenter, the cytidine titer reached 7.65 g/L, which was 3.77-fold that of shake flask fermentation. Moreover, a cytidine yield and productivity of 0.06 g/g glucose and 0.16 g/L/h, respectively, were achieved. Subsequently, the regulatory mechanisms through which PyrR and CcpA modification affect cytidine biosynthesis were explored through multi-omics analysis. Transcriptome and metabolome analysis revealed that coordinated alterations in carbon, nitrogen, nucleotide, and amino acid metabolism were essential to promote cytidine synthesis. However, the increased cytidine production in recombinant strains was attributed to the enhancement of pyrimidine metabolism, the Phosphotransferase (PTS) system, the tricarboxylic acid (TCA) cycle, the pentose phosphate (PP) pathway, and nitrogen metabolism. Conclusions These results indicate that PyrR knockdown can enhance pyrimidine metabolic pathway and promote cytidine synthesis. CcpA mutation can reprogram the central carbon-nitrogen metabolic network, change the metabolic flow to de novo synthesis pathway of pyrimidine nucleoside, increase the supply of cytidine synthesis precursors and promote the accumulation of cytidine. Overall, regulation of engineered carbon and nitrogen metabolic networks is essential for improving the efficiency of microbial cell factories.

The gut microbiota is associated with the response to immunotherapy in cutaneous melanoma (CM). However, gut fungal biomarkers and bacterial-fungal interactions have yet to be determined. Metagenomic sequencing data of stool samples collected before immunotherapy from three independent groups of European ancestry CM patients were collected. After characterizing the relative abundances of bacteria and fungi, Linear Discriminant Analysis Effect Size (LEfSe) analysis, Random Forest (RF) model construction, and SHapley Additive exPlanations (SHAP) methodology were applied to identify biomarkers and key bacterial-fungal interactions associated with immunotherapy responders in CM. Diversity analysis revealed significant differences in the bacterial and fungal composition between CM immunotherapy responders and non-responders. LEfSe analysis identified 45 bacterial and 4 fungal taxa as potential biomarkers. After constructing the RF model, the AUC of models built using bacterial and fungal data separately were 0.64 and 0.65, respectively. However, when bacterial and fungal data were combined, the AUC of the merged model increased to 0.71. In the merged model, the following taxa were identified as important biomarkers: , , , , , , , and , which were associated with responders, whereas was associated with non-responders. Moreover, the positive correlation interaction between and is considered a key bacterial-fungal interaction associated with CM immunotherapy response. Our results provide valuable insights for the enrichment of responders to immunotherapy in CM patients. Moreover, this study highlights the critical role of bacterial-fungal interactions in CM immunotherapy.

The aim of this study was to evaluate probiotic properties of ten Streptococcus thermophilus strains (st1 to st10) isolated from pickles in China. These strains all had β-galactosidase activity, which laid foundation for studying their probiotic properties. In this study, the bile salt hydrolase activity, lysozyme resistance, tolerance to simulated gastric juice, bile salt tolerance, and bacterial adhesion capacity to the Caco-2 cells of these selected strains were detected in vitro conditions. The results indicated that the bile salt hydrolase activities of st2, st6, and st9 were higher than that for other strains. St10 showed the greatest lysozyme resistance (> 80% survival), followed by st9, st8, st7, st5, and st6. As for the tolerance to simulated gastric juice, st5 possessed the highest survival rate (35%), followed by st6 (30%). St6 was the best performer in both bile salt tolerance and bacterial adhesion capacity to the Caco-2 cells. The results of fluorescence microscope and electron microscope further confirmed previous studies and more intuitively demonstrated the st6 strain's tolerance to harsh environments. Overall, these strains were expected to possess beneficial properties and have the potentiality to be probiotics.