Multiple mosquito species serve as competent vectors to carry and transmit numerous flaviviruses1,2. Several long-standing scientific questions remain to be answered, including identification of the fundamental factors that facilitate flavivirus infectivity in mosquitoes and the genetic basis that contributes to the naturally occurring interspecies specificity of mosquitoes to flaviviruses3-8, such as Aedes aegypti mosquitoes to dengue virus (DENV). Here we report that circulating mature virions are inactivated by the acidity of mosquito haemolymph; thus, extracellular vesicles carrying replication-competent viral nucleocapsids serve as the predominant means of intercellular viral dissemination. Mechanistically, mosquito valosin-containing protein (VCP) binds to the viral capsid, thereby allowing the incorporation of nucleocapsids into extracellular vesicles. The capsid of a flavivirus (such as DENV) selectively binds to the VCP of its natural vector (Ae. aegypti), but not to that of an incompetent vector (for example, Culex quinquefasciatus). Replacing the DENV capsid with that of Japanese encephalitis virus (JEV) renders DENV infectious in the haemolymph of the natural JEV vector, Cx. quinquefasciatus. Furthermore, two amino residues in Aedes (D723/N728) and Culex (E723/E728) VCP determine its binding specificity for viral capsid, thus contributing to interspecies specificity of mosquitoes to flaviviruses. In vivo ectopic expression of the Cx. quinquefasciatus VCP mutant E723D/E728N renders Cx. quinquefasciatus susceptible to DENV2 via intrathoracic microinjection. Our study provides a major molecular mechanism contributing to the selectivity and compatibility between mosquito vectors and flavivirus species, enabling systemic virus dissemination after the virus reaches the haemocoel. Upstream mechanisms that determine specificity at the midgut level remain to be determined.

BACKGROUND:Vasculogenic mimicry (VM) is a non-endothelial vascularisation programme sustaining pancreatic ductal adenocarcinoma (PDAC) perfusion and metastasis, yet its regulators and therapeutic vulnerabilities remain unclear. OBJECTIVE:To elucidate the immune and epigenetic mechanisms regulating VM and identify strategies to overcome VM-driven PDAC progression. DESIGN:Histopathology, three-dimensional tissue clearing, spatial transcriptomics and single-cell RNA sequencing were combined to map VM distribution and its immune contexture. Tissue microarrays, co-culture assays and xenograft models were used to assess tumour-associated macrophage (TAM) contributions. Extracellular vesicle (EV) proteomics and mechanistic studies identified cargo molecules and signalling pathways. DOT1L (disruptor of telomeric silencing 1-like) inhibitor EPZ-5676 and vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib were used for therapeutic validation. RESULTS:VM was abundant in PDAC, increased with tumour stage and was preferentially surrounded by TAMs. M2-like TAMs promoted tube formation, invasion and tumour growth, while blockade of TAM-derived EVs abolished these effects. EV proteomics identified caveolin-1 (CAV1) as a key cargo correlating with VM density and TAM infiltration. Mechanistically, EV-delivered CAV1 interacted with DOT1L, promoted DOT1L EV loading and drove H3K79 methylation-dependent autophagy-related 5 (ATG5) transcription, sustaining VM and invasive phenotypes. Notably, while DOT1L inhibition suppressed VM and tumour progression, it paradoxically induced compensatory endothelial angiogenesis. Combined DOT1L and VEGFR blockade overcame this compensatory feedback, achieving superior tumour control without toxicity. CONCLUSION:TAM-derived EVs drive VM through a CAV1-DOT1L-ATG5 axis. We identify a compensatory link between VM and angiogenesis and demonstrate that dual targeting of these two vascular modalities offers a promising therapeutic strategy for PDAC.

Cryptosporidium parvum is an obligate intracellular parasite with highly reduced metabolic capacity and strong dependence on host-derived nutrients. Membrane transporters therefore play essential roles in parasite survival and development, yet amino acid transport systems in Cryptosporidium remain poorly characterized. In this study, we focused on CpAAT9 (cgd8_3740), a putative amino acid transporter that lacks recognizable orthologs in most other apicomplexans and instead shows evolutionary affinity to a broader eukaryotic transporter family related to fungal homologs. Phylogenetic analysis suggests that AAT9-like transporters represent an ancient eukaryotic lineage that has been selectively retained in Cryptosporidium in the Phylum Apicomplexa. Using affinity-purified polyclonal antibodies, we examined the expression and subcellular distribution of CpAAT9 across multiple developmental stages by indirect immunofluorescence assays. CpAAT9 is expressed throughout the parasite life cycle. In sporozoites, CpAAT9 localizes primarily to the parasite plasma membrane and displays an irregular punctate distribution beneath the pellicle. Non-permeabilized staining reveals substantial surface exposure of CpAAT9 following excystation, and the protein is shed during sporozoite gliding motility, appearing along gliding trails. During intracellular development, CpAAT9 remains detectable and partially colocalizes with markers of the parasitophorous vacuole membrane (PVM) that faces the intestinal lumen. In contrast, extracellular exposure appears reduced during sexual development. These findings indicate that CpAAT9 is a membrane transporter candidate that undergoes dynamic redistribution and shedding or secretion during parasite development. The unusual localization pattern suggests that CpAAT9 may contribute to nutrient acquisition from the intestinal lumen or interaction with intestinal mucus. This study provides new insight into transporter biology in Cryptosporidium and identifies CpAAT9 as a potential target for future functional investigation.

Autoimmune diseases (ADs) are strongly associated with a significantly increased risk of lymphoma, with the standardised incidence ratio (SIR) markedly elevated in certain conditions, most notably in Sjögren’s disease (SjD) where an SIR as high as 18.8 has been reported. The risk is particularly prominent for diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. This review systematically elucidates the epidemiological features, pathological mechanisms, risk factors, and therapeutic strategies of ADs-associated lymphomas. Epidemiological studies have confirmed strong associations between ADs such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and SjD with specific lymphoma subtypes, and these associations appear to be bidirectional. Core pathogenic mechanisms involve malignant transformation driven by the immune–inflammatory continuum: chronic antigenic stimulation and the inflammatory microenvironment result in regulatory cell (Treg/Breg) dysfunction, tertiary lymphoid structure (TLS) formation, and clonal evolution. Specific autoantibodies directly contribute to oncogenesis by interfering with intracellular signalling pathways, mimicking antigenic stimulation, and forming immune complexes, while infectious agents such as Epstein–Barr virus synergistically promote malignant transformation within immunosuppressive microenvironments. Risk factors encompass intrinsic disease features, treatment-related risks and gene–environment interactions. Clinical management must balance the dual imperatives of “controlling inflammation” and “minimising treatment-related risks”. Targeted therapies, such as rituximab and BTK inhibitors, as well as haematopoietic stem cell transplantation (HSCT), have offered hope, but prognosis remains profoundly influenced by baseline immune status. Future research should focus on risk stratification guided by multi-omics, the application of novel immunotherapies in the autoimmune setting, and the optimisation of multidisciplinary care models.

Abstract The oocyst of Cryptosporidium is a highly resilient transmission stage that protects sporozoites in the environment and mediates infection through a specialized opening known as the suture. While recent studies have identified Cryptosporidium oocyst wall proteins (COWPs) as structural components of the oocyst wall, the functional roles of individual COWPs and the molecular basis of suture biology remain poorly understood. Here, we performed a detailed characterization of two COWP family members, COWP4 and COWP6, combining immunolocalization, ultrastructural analysis, protein interaction assays, and genetic manipulation. We show that COWP4 is strictly localized to the oocyst suture, whereas COWP6 is distributed throughout the oocyst wall inner layer and enriched at the suture. COWP6 is additionally present in sporozoites and is secreted during parasite motility and host cell invasion, where it exhibits high-affinity binding to host cells. Structural analyses indicate that both proteins are cysteine-rich and likely form disulfide-stabilized architectures consistent with roles in wall assembly. Functional analyses reveal that COWP4 is essential for proper suture formation, excystation, and parasite infectivity, establishing the suture as a genetically defined gatekeeper for parasite transmission. In contrast, COWP6 functions as a multifunctional protein linking oocyst wall architecture to host interaction. We further demonstrate that COWP4 and COWP6 interact, suggesting coordinated assembly within the oocyst wall. Together, these findings provide a functional dissection of the Cryptosporidium oocyst suture and reveal distinct, non-redundant roles for individual COWPs. This work advances our understanding of oocyst wall biology and identifies COWP4 as an essential determinant of parasite transmission that may be targeted to disrupt the infectious cycle. Author summary Cryptosporidium is a major cause of diarrheal disease worldwide and is transmitted through environmentally resistant oocysts that protect infectious stages of the parasite. A defining feature of the oocyst is a specialized seam-like structure, called the suture, through which parasites exit to initiate infection. Although oocyst wall proteins (COWPs) have been identified, how individual proteins contribute to the structure and function of the oocyst wall, particularly the suture, has remained unclear. In this study, we investigated two oocyst wall proteins, COWP4 and COWP6, and uncovered distinct roles for each. We found that COWP4 is specifically localized to the suture and is essential for its proper formation, enabling parasites to exit the oocyst and establish infection. In contrast, COWP6 is distributed more broadly in the oocyst wall and also functions beyond it, being secreted during parasite movement and interacting with host cells. These findings reveal that the oocyst wall is composed of specialized proteins with non-redundant functions and identify the suture as a critical control point for parasite transmission. Understanding these mechanisms may help guide the development of new strategies to block infection by disrupting oocyst integrity or parasite release. Highlights COWP4 is a suture-specific protein essential for oocyst excystation and infectivity Genetic disruption of COWP4 produces non-infectious oocysts with impaired viability The oocyst suture is a genetically defined gatekeeper for parasite transmission COWP6 localizes to the wall inner layer and is enriched at the suture COWP6 is secreted by sporozoites and binds host cells with nanomolar affinity · COWP4 and COWP6 directly interact, linking wall architecture to host interaction

BACKGROUND:Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies, which can occur in any part of the mouth and is highly malignant. DNA Methylation is an epigenetic modification of the genome, which is involved in key cellular processes and has a crucial impact on the occurrence, development, invasion and metastasis of tumors. In this study, we conducted a comprehensive analysis of DNA methylation characteristics in OSCC with the aim of identifying potential diagnostic epigenetic biomarkers and exploring possible mechanisms of methylation's influence on OSCC. METHODS:In this study, genome-wide DNA methylation analysis was performed using Infinium Methylation EPIC arrays, including tumor tissue and adjacent non-tumor tissue from 12 OSCC patients. Differential methylation probes and regions (DMP/DMR) were identified for gene function analysis. Characteristic DMPs and genes were screened according to the specific situation, and OSCC-targeted methylation data from 25 patients in the validation cohort were used to further validate the differential methylation levels of our selected genes. Finally, the expression levels of methylated genes in OSCC were verified by combining RNA-Seq data with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:There were 277,805 DMPs in OSCC tumor tissue. Hypermethylated DMP accounted for 37.4% of all DMPs and hypomethylated DMPs was 62.6%. Functional pathway analysis showed that it was mainly related to passive transmembrane transporter activity, cancer proteoglycan and PI3K-Akt signaling pathway. The methylation level of ZNF880 was emphatically verified in the verification cohort, and the results showed that there was high methylation in ZNF880 in the verification cohort. Subsequently, through RNA-Seq data and qRT-PCR, it was confirmed that the expression of ZNF880 in OSCC tissues was significantly lower than that in normal tissues. This verified the correlation between the high methylation of ZNF880 and gene expression. CONCLUSIONS:This study comprehensively reveals changes in genome-wide DNA methylation patterns in OSCC, indicating that abnormal hypermethylation of the ZNF880 gene plays a catalytic role in the pathogenesis of OSCC.

Apicomplexans encode a single armadillo repeat-only (ARO) protein, exemplified by TgARO and PfARO, that anchors to the rhoptry envelope through N-terminal acylation and supports rhoptry positioning through interaction with an ARO-interacting protein (AIP). These AROs organize rhoptries but are not known to be secreted during invasion. Here, we show that Cryptosporidium parvum ARO (CpARO) localizes to the rhoptry envelope by immunofluorescence assay, ultrastructural expansion microscopy, and structured illumination microscopy. During sporozoite invasion, CpARO-positive rhoptry envelope structures shorten and condense into a discrete punctum after content discharge. Residual rhoptry membrane structures are subsequently detected between the host cell F-actin pad and parasite nucleus in developing trophozoites, consistent with a contribution to nascent feeder organelle formation. In contrast to TgARO and PfARO, CpARO is also detected in secreted fractions during excystation, gliding, invasion, and intracellular development, with no evidence of nuclear localization. Recombinant CpARO binds host cells with high affinity (Kd = 0.189 μM). Although C. parvum encodes an AIP homolog, this protein localizes to the sporozoite cytoplasm rather than to rhoptries; we therefore designate it AIP-like protein (CpAIP-L). Antibodies against both CpARO and CpAIP-L were detected in sera from C. parvum-infected mice. These findings reveal functional divergence of Cryptosporidium ARO-AIP-related proteins and identify CpARO as both a rhoptry envelope marker and a secreted host-interacting factor with potential roles in host interaction and virulence.

Background Severe steroid-resistant asthma (SSRA) is frequently associated with irreversible airway remodeling (AR), which contributes to persistent airflow limitation and poor therapeutic responsiveness. Celastrol (CEL) exhibits anti-inflammatory and tissue-protective properties; however, its role in steroid-resistant AR remains unclear. Purpose This study aimed to evaluate the therapeutic effects of CEL on SSRA and to determine whether AMOTL1-dependent Hippo/Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling contributes to its anti-remodeling activity. Methods SSRA mice were generated via OVA/CFA/LPS sensitization and challenge and treated with CEL or dexamethasone. Airway hyperresponsiveness (AHR), lung histopathology, inflammatory cell infiltration, mucus secretion, collagen deposition, and lung proteomic profiles were evaluated. Osteopontin (OPN)-stimulated human bronchial smooth muscle cells (HBSMCs) were used to model airway smooth muscle remodeling. AMOTL1 gain- and loss-of-function studies were conducted in HBSMCs, and airway-local Amotl1 knockdown was introduced into SSRA mice. Results CEL improved AHR and suppressed airway inflammation, mucus production, and collagen accumulation in SSRA mice. Proteomic analysis revealed that AMOTL1 was downregulated in SSRA and restored by CEL treatment. In HBSMCs, CEL suppressed OPN-induced proliferation, migration, and extracellular matrix production, accompanied by Hippo pathway reactivation and YAP/TAZ inhibition. AMOTL1 knockdown in HBSMCs attenuated these anti-remodeling effects, whereas AMOTL1 overexpression recapitulated the protective effects of CEL. In vivo, Amotl1 knockdown blunted CEL-mediated improvement in SSRA-associated AR. Conclusion CEL alleviates steroid-resistant AR through AMOTL1-dependent restoration of Hippo/YAP signaling, highlighting the AMOTL1/Hippo/YAP axis as a potential therapeutic target in SSRA.

Drug-resistant epilepsy (DRE) in children remains a major clinical challenge, and environmental contributors to pharmacoresistance are not fully understood. In this study, we quantified polymer-resolved microplastics (MPs) in peripheral blood from pediatric patients with controlled epilepsy (CE), drug-resistant epilepsy (RE), and healthy controls (NC) using pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) with laser direct infrared (LDIR) validation. Eight polymer types were detected. Total circulating polymer-resolved MP burden was observed to be higher in epilepsy patients, with the highest levels in the RE subgroup. Specific polymers, including polystyrene (PS), polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET), were enriched in RE. Self-reported exposure variables did not fully explain these group differences. In a small MRI-negative subgroup, exploratory whole-exome sequencing identified descriptive differences in selected variant categories between controlled and drug-resistant epilepsy patients; however, these findings were not used to infer microplastic uptake, retention, transport, biotransformation, or clearance. Given the small sample size, limited exposure reconstruction, and cross-sectional design, all findings should be interpreted as preliminary and hypothesis-generating. Larger longitudinal studies with standardized contamination control, quantitative exposure assessment, and independent validation cohorts are needed to confirm these observations.

Gastric cancer (GC) represents a major global health concern, with over 1 million new cases diagnosed annually worldwide. Emerging studies have highlighted the significant correlation between long noncoding RNAs (lncRNAs) and the progression of GC. The objective of the current study is to investigate the roles and mechanism of lncRNA homeobox A10 antisense RNA (HOXA10-AS) in modulating malignant properties of GC cells. RT-qPCR was employed to detect HOXA10-AS expression in GC cells or human normal gastric epithelium cells. The cellular localization of HOXA10-AS and mRNA HOXA10 were detected using RNA fractionation assays. Colony forming assays and Transwell assays were performed to assess the proliferative, invasive, and migratory capabilities of GC cells. Western blot analysis was used to determine protein levels of epithelial mesenchymal transition (EMT) markers in GC cells. RNA immunoprecipitation, RNA pulldown assays and luciferase assays were conducted to explore gene interaction. As shown by experimental results, HOXA10-AS showed high expression in GC cells. The silencing of HOXA10-AS led to weakened proliferative, invasive, and migratory abilities of GC cells, as well as inhibition of the EMT process. Moreover, HOXA10-AS positively regulated HOXA10 expression by interacting with miR-29a/b/c-3p. Additionally, overexpression of HOXA10 counteracted the repressive impacts on malignant cellular process caused by the knockdown of HOXA10-AS. Furthermore, HOXA10-AS activated the p38 MAPK/STAT3 signaling pathway via upregulation of HOXA10. In conclusion, HOXA10-AS upregulates HOXA10 expression through interaction with miR-29a/b/c-3p. The resultant increase in HOXA10 expression activates the p38 MAPK/STAT3 signaling, thereby promoting GC cell growth, migration, invasion, and EMT process.

To explore the impacts of yeast-derived postbiotic on growth performance and intestinal microbiota of growing pigs, 192 healthy Duroc × Landrace × Yorkshire (initial weights 30 ± 0.6 kg) were subjected to four dietary treatments, with eight replicates per treatment and six pigs per replicate. The diets were: CON: basal diets; YC: CON with 0.5 g/kg yeast-derived postbiotic; RED75–: CON with net energy reduced by 75 kcal/kg; RED75+: RED75– with 0.5 g/kg yeast-derived postbiotic. The results showed that yeast supplementation improved average daily gain in the low energy dietary treatments, tended to improve nutrient digestibility and feed conversion rate. Yeast supplementation in normal energy diets decreased the levels of serum inflammatory factors including IL-1β, IL-10, TNF-α, IFN-γ, and IgA. Yeast in low-energy diets improved antioxidant status by decreasing serum MDA and increasing GSH-Px. Yeast significantly reduced α diversity of the pig feces. Compared to RED75–, Lactobacillus, Faecalibacterium, and Blautia were more prevalent in RED75+, at the family level Christensenellaceae, Rikenellaceae, and inflammatory-related Prevotellaceae were lower in RED75+, the abundance of fiber-digesting bacteria Megaphaera, Subdoligranulum, and Coprococcus were higher in RED75+. Correlation analysis revealed that altered bacterial composition involved glucose/mannose/galactose/fructose metabolism. In vitro, yeast-derived postbiotics promoted the growth of L. amylovorus, L. johnsonii, and L. reuteris at different pH. Our findings provide evidence that supplementation of yeast-derived postbiotics is beneficial to growth performance, anti-inflammatory, antioxidant status, and intestinal microbiota composition of growing pigs by promoting the growth of Lactobacillus.

Breath analysis by direct mass spectrometry faces significant challenges due to the inherent complexities in sample collection, low analyte concentrations, and accurate compound identification. While current breath analysis primarily focuses on volatile organic compounds (VOCs) for disease research, non-volatile organic compounds (nVOCs) remain largely unexplored despite their diagnostic potential. Here, we present a novel breath analysis method for lung cancer diagnosis based on nVOCs, integrating non-invasive breath analysis with machine learning algorithms for comprehensive characterization of 98 clinical breath samples. This study leverages a machine learning-driven database docking methodology to overcome the bottleneck of metabolite direct mass spectrometry conventional identification. This approach enables rapid and precise screening of non-volatile differential metabolites while effectively excluding exogenous confounders (e.g., pharmacological or environmental interference), enhancing nVOC detection in breath. The approach identified 29 statistically significant nVOC biomarkers, including fatty acids and amino acids, achieving a 0.9878 prediction accuracy for lung cancer detection. For distinguishing between NSCLC and SCLC, the area under the curve (AUC) value can reach 0.9, and the out-of-bag error of random forest is 0.00402. Notably, specific nVOCs including fatty acids and amino acids have high diagnostic potential, with an AUC of up to 0.67 of individual metabolites for the differentiation of SCLC from NSCLC. Finally, significantly altered metabolic pathways were explored by metabolite pathway and transcriptome analysis, showing that the fatty acid metabolism is a potentially regulatable pathway. Our approach facilitates rapid, non-invasive discrimination of NSCLC and SCLC in metabolic analysis, showing promise as an efficient, low-cost clinical test.

HPIDF (High Purity Insoluble Dietary Fiber from Soybean Dregs) is characterized by a high degree of toughness and insolubility, which limits its potential applications. This study aimed to develop an HPIDF-microcapsule (HPIDF-MIC), a composite microcapsule. This microcapsule comprises HPIDF, sodium alginate (SA), and fructooligosaccharide (FOS) to facilitate more effective HPIDF product development. Scanning electron microscopy and three-dimensional laser microscopy revealed that the HPIDF-MIC exhibited smoother surfaces and higher mechanical strength than the Simple-MIC (only SA and FOS as wall materials). X-ray diffraction and Fourier transform infrared spectroscopy analyses demonstrated that HPIDF-MIC exhibited robust structural integrity and strong hydrogen bonding capabilities, which enhanced the protection and control of probiotics. Long-term storage and digestion tests revealed that HPIDF-MIC effectively preserved probiotics, maintaining 6 Log CFU/mL live bacteria after simulated digestion, thereby ensuring their survival and probiotic function. The findings of this research offer new insights and avenues for the advancement and commercialization of HPIDF in the food industry.

We summarize the design strategies for improving the ECL of metal nanoclusters, including 1. aggregation-induced emission; 2. anodic pre-oxidation; 3. aggregation-induced self-loading; 4. Anionic substitution; 5. ion doping; 6. valence engineering.

Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) include primary central nervous system large B-cell lymphoma (PCNSL), primary vitreoretinal large B-cell lymphoma (PVRL), and primary testicular large B-cell lymphoma (PTL). These tumors not only have a unique anatomical distribution but also exhibit specific biological and clinical characteristics. Given the high biological overlap between intravascular large B-cell lymphoma (IVLBCL) and IP-LBCLs, and the fact that IVLBCL is confined to the intravascular microenvironment, IVLBCL is currently included in the category of IP-LBCLs. IP-LBCLs are associated with suboptimal prognosis. However, advancements in biomarker detection technologies have facilitated novel therapeutic approaches for this disease entity. This review aims to summarize and analyze the latest research progress in IP-LBCLs, with a focus on new treatment strategies in the era of targeted therapy and immunotherapy. It is intended to further understand the biological characteristics, treatment, and latest advancements of this disease.

Astrocytes undergo a reactive transformation in central nervous system (CNS) disorders, manifesting significant heterogeneity in morphology, molecules, function, and spatial distribution. Just like all cells, astrocytes necessitate energy for their basic functions. Energy production proves critical for the survival and development of astrocytes, as well as their fate determination and functional diversity. The activation process of astrocytes involves a metabolic shift in energy, yet our understanding of how this change impacts the heterogeneity of reactive astrocytes remains limited. In this comprehensive review, we begin by outlining the advancements in research on reactive astrocytes in CNS disorders, establishing a crucial association between the energy metabolism of reactive astrocytes and their molecular and functional aspects. Following this, we delve into a thorough analysis of the energy metabolic transitions of reactive astrocytes within the context of CNS diseases. Starting from the essential pathways of energy metabolism, we present a novel perspective, shedding light on the molecular and functional heterogeneity of reactive astrocytes by considering the heterogeneity in energy metabolism. In conclusion, we propose that the modulation of energy metabolism in reactive astrocytes, coupled with the promotion of their functionality toward disease recovery, represents a cutting-edge and promising strategy for the treatment of CNS diseases.

Klebsiella pneumoniae is a major pathogen responsible for severe pulmonary infections, yet the early mechanisms of infection remain incompletely understood. This study investigates the role of exosomes derived from K. pneumoniae in polarizing macrophages to the M1 phenotype, thereby facilitating early lung infections. Utilizing single-cell Raman spectroscopy, we rapidly detected K. pneumoniae within host cells and observed significant lipid expression changes. Metabolomic analysis of exosomes from infected epithelial cells uncovered an elevation of phosphatidylcholine, which disrupted endothelial tight junctions and promoted M1 macrophage recruitment and polarization. This process activated the NF-κB signaling pathway, increasing inflammatory responses and attracting neutrophils. Our findings, validated in infected tissue models, suggest that these exosomal mechanisms significantly contribute to the early stages of pulmonary infection by K. pneumoniae. This study offers crucial insights into potential therapeutic targets for controlling K. pneumoniae infections.

Cryptosporidium is a genus of apicomplexan parasites that causes diarrheal disease in humans and animals worldwide. The primary species affecting humans are C. parvum and C. hominis, while other species may also infect humans, specially immunocompromised individuals. Infections are particularly severe in people with weakened immune systems and malnourished children in developing countries. In livestock, especially young ruminants, C. parvum leads to significant economic losses. The parasite occupies a unique epicellular niche and undergoes a complex life cycle involving both asexual and sexual stages. While the mechanisms of parasite invasion, replication, immune evasion, and tissue damage have been challenging to unravel due to earlier technical limitations and lack of genetic tools, recent advances have transformed our understanding. Innovations in genomics, transcriptomics, and molecular genetics have identified key virulence factors and clarified intricate host-parasite interactions. The parasite's secretory organelles (micronemes, rhoptries, dense granules, and small granules) play central roles by releasing molecules that facilitate host cell attachment, invasion, and modulation of host defenses. This review provides an up-to-date overview of the biology and pathogenic mechanisms of Cryptosporidium, highlighting structural features, invasion strategies, and host immune responses. It also covers recent progress in experimental models, vaccine development, and identification of new molecular targets for treatment and prevention. By synthesizing recent discoveries with previous research, this review offers a current perspective linking fundamental biology to disease outcomes and potential control strategies.

Histone deacetylases (HDACs) are a class of epigenetic regulators that play pivotal roles in key biological processes such as cell proliferation, differentiation, metabolism, and immune regulation. Based on this, HDAC inhibitors (HDACis), as novel epigenetic-targeted therapeutic agents, have demonstrated significant antitumor potential by inducing cell cycle arrest, activating apoptosis, and modulating the immune microenvironment. Current research is focused on developing highly selective HDAC isoform inhibitors and combination therapy strategies tailored to molecular subtypes, aiming to overcome off-target effects and resistance issues associated with traditional broad-spectrum inhibitors. This review systematically elaborates on the multidimensional regulatory networks of HDACs in tumor malignancy and assesses the clinical translation progress of next-generation HDACis and their prospects in precision medicine, providing a theoretical framework and strategic reference for the development of epigenetic-targeted antitumor drugs.

The high-performance electrochemical detection relies on sensing material with highly active structure, which requires the development of advanced synthesis technique and the study of its structure-activity mechanism. Herein, the few-layer Ti3C2Tx 3 C 2 T x nanosheets densely coated zeolitic imidazole framework-8 nanoparticles (Ti3C2Tx@ZIF-8) 3 C 2 T x @ZIF-8) have been successfully prepared as a unique precursor, which combines the structural advantages of two-dimensional Ti3C2Tx 3 C 2 T x and porous ZIF-8 nanoparticles, leading to the vast interior spaces for loading electrocatalytic nanomaterials. For this purpose, Ti3C2Tx@Au 3 C 2 T x @Au nanoparticles-ZnO nanoparticles@N-doped carbon (Ti3C2Tx@AuNPs-ZnO@NC) 3 C 2 T x @AuNPs-ZnO@NC) has been obtained for the simultaneous electrochemical detection of pharmaceutical molecules including dopamine (DA), acetaminophen (AC), and xanthine (XA). The materials characterization and sensing analysis results of Ti3C2Tx@AuNPs-ZnO@NC 3 C 2 T x @AuNPs-ZnO@NC reveal the structure-activity relationship of Ti3C2Tx, 3 C 2 T x , AuNPs and NC resulting in the high-performance behaviors, which can be summed up as stable electrochemical active sites and efficient electron transport channels. First, the abundant anchor points are offered by NC for immobilizing AuNPs, which ensure the electrochemical activity of such material. Second, the close combination of few-layer Ti3C2Tx 3 C 2 T x nanosheets and NC provides an ideal channel for electron transmission along with the electrochemical reaction process. The potential application of Ti3C2Tx@AuNPs-ZnO@NC 3 C 2 T x @AuNPs-ZnO@NC is displayed to develop the electrochemical medical sensor. The detection limits are 41 nM towards DA, 59 nM towards AC, and 67 nM towards XA. The linear ranges are 3-200 mu M for DA, 15-500 mu M for AC, and 8-350 mu M for XA.