Escalating resistance in Pseudomonas aeruginosa (PA) underscores the need for resistance-agnostic immunotherapies. In this study, we generated a panel of 20 monoclonal antibodies against the flagellin protein FliC and identified 16G10 as a high-affinity lead. Epitope mapping revealed a conserved linear site within the D1 domain (Gly71-Ile88), a region essential for filament assembly. In vitro, 16G10 induced bacterial aggregation, suppressed swimming motility, and significantly reduced adhesion to and invasion of A549 cells, while limiting biofilm biomass by SEM and confocal 3D imaging. In vivo, in murine pneumonia, where 16G10 administered either after pre-incubation with imipenem-resistant PA strain or as post-infection therapy, it improved survival, lowered lung bacterial loads, reduced IL-6 and TNF-α concentrations, and attenuated histologic inflammation. Protection extended across serotype A and B flagellated strains, indicating broad coverage. These data nominate 16G10 as a promising candidate for immunotherapy of drug-resistant PA lung infections and establish a druggable flagellin epitope for future vaccine and antibody designs.

Myofibroblastic cancer-associated fibroblasts (myoCAFs) represent a crucial stromal cell subpopulation associated with tumor growth, relapse, and metastasis. In this study, we identify a noncanonical mechanism through which head and neck cancer cells regulate myoCAF activation. Co-culture with tumor organoids promoted the expression of cytokine interaction-related genes and myoCAF phenotypic markers in paracancerous fibroblasts (PFs). Cytokine and tissue array analyses revealed that upregulation of colony-stimulating factor-2 (CSF2) in tumor cells correlated with overexpression of nicotinamide N-methyltransferase (NNMT) in CAFs. Notably, CSF2 treatment enhanced myoCAF properties in a NNMT-dependent manner, while NNMT overexpression remained largely unaffected by transforming growth factor-β (TGF-β). In both assembled organoid and xenograft models, tumor growth was reduced when either CSF2 in cancer cells or CSF2 receptor subunit CSF2RA in CAFs was knocked down. Mechanistically, CSF2 induced FOS phosphorylation at Ser32, promoting nuclear translocation of phosphorylated FOS (p-FOS) to regulate NNMT transcription. In drug screening assays, CSF2 blockade partially overcame resistance to TGF-β inhibition. These findings establish the CSF2/FOS/NNMT axis as a TGF-β-independent pathway driving myoCAF activation.

Hepatitis B virus (HBV) remains a major global public health challenge, and its early screening is essential for controlling transmission and improving treatment outcomes. We analyzed serum samples from 422 participants via Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a screening model for hepatitis B surface antigen (HBsAg)-positive status. Following multi-bin preprocessing and single-sample spectral aggregation, we assessed three machine learning algorithms—random forest, deep neural network, and light gradient boosting machine (LightGBM). Among them, the LightGBM model achieved the best performance, with an optimized F1 score of 0.87 and an area under the receiver operating characteristic curve (AUC) of 0.94. A 100-iteration ensemble feature stabilization strategy identified twelve distinct m/z peaks as stable biomarkers for HBsAg-positive screening. Independent validation yielded sensitivity of 77.7% and specificity of 76.0%—insufficient for individual diagnosis but potentially suitable for population-level surveillance programs combined with confirmatory testing, particularly in resource-limited settings where conventional methods are impractical. Notably, the method offers a detection time of approximately one minute, a per-sample cost of ~$0.14. In conclusion, the combination of MALDI-TOF MS and machine learning enables a rapid, low-cost screening tool for large-scale HBV detection.

Background:The description of genetic diversity of malaria parasite populations in malaria-endemic areas may help determine the effectiveness of malaria interventions in the region. This study aimed to evaluate the genetic diversity and allele frequencies of the merozoite surface protein 1 gene (Msp1) and merozoite surface protein 2 gene (Msp2) in Plasmodium falciparum populations collected from Paletwa Township in western Myanmar and two regions along the China-Myanmar border (the Myitsone and Bhamo regions of Myanmar). Methods:Between 2013 and 2022, malaria cases in China were predominantly imported, with border counties in Yunnan reporting the highest number of cases nationwide. Furthermore, malaria transmission rates in adjacent townships in Myanmar remained relatively high. A total of 176 P. falciparum-infected blood samples were collected from local residents with infections in Bhamo and Paletwa Township in Myanmar, as well as from migrant malaria patients from Yunnan, China, who had worked in Myitsone, Myanmar. Among them, 96 samples were collected from Paletwa Township, Myanmar in 2015, and 28 from Bhamo, Myanmar in 2018-2019, both from local residents. In 2013, 55 samples were obtained from Chinese migrant workers returning from Myitsone, Myanmar, via the Tengchong border checkpoint in Yunnan, China. The genomic DNA was extracted, and the Msp1 and Msp2 genes were genotyped by nested PCR using allele-specific primers for P. falciparum. Results:A total of 176 and 162 samples were successfully genotyped at the Msp1 and Msp2 genes, respectively. Among them, 54 samples were successfully amplified for the Msp1 allelic families in Myitsone, 27 samples in Bhamo, and 95 samples in Paletwa Township. Additionally, 46 samples were successfully amplified for the Msp2 allelic families in Myitsone, 24 samples in Bhamo, and 92 samples in Paletwa Township. Among the three cities, MAD20 was the most frequent allele in the Msp1 gene, while 3D7 was the most frequent allele in the Msp2 gene. The MAD20 allele predominated with 89% (48/54), 85% (23/27) and 67% (64/95) in Myitsone, Bhamo and Paletwa Township respectively, followed by K1 with 65% (35/54) and 44% (12/27) in Myitsone and Bhamo, respectively. The second most frequent allele in Paletwa Township was RO33, representing 47% (45/95) of the population. In migrant workers, residents of Bhamo and residents of Paletwa Township, the multiplicity of infection (MOI) estimated from Msp1 was 1.87, 1.33 and 1.56, respectively And meanwhile, the MOI estimated from Msp2 was 1.17, 1.29 and 1.35 respectively. Migrant workers harbored MOI and rate of multi-infections more frequently (72%) than residents of Bhamo or Paletwa Township (43% and 45%, respectively) based on Msp1. Conclusions:The Msp1 revealed higher genetic diversity than Msp2. The prevalence of MOI and multi-infections among local residents was lower than that among migrant workers based on Msp1. The migrant workers in Myitsone exhibited higher MOI and the proportion of multi-infections compared to the locals, suggesting that low immunity among the migrant workers might be the primary reason for this observation, or that the transmission level in Myitsone is higher than in the local areas.

Multimodal data integration has emerged as a promising approach for cancer prognosis; however, current methods struggle to effectively address two core scientific challenges: the significant “modal semantic gap” between unstructured pathological images and structured genomic data, and the high “tumor heterogeneity” where the dominance of specific modalities varies across patients. Existing static fusion strategies often fail to align these heterogeneous features or adapt to individual patient differences. To overcome these limitations, this study proposes a Causal-Driven Adaptive Hierarchical Fusion framework (CD-AHF). First, to bridge the semantic gap, we introduce a causal attention fusion module that mimics the biological pathway from genotype to phenotype, enforcing a unidirectional information flow for semantic alignment. Second, to tackle heterogeneity, we design a multi-level adaptive fusion mechanism with dynamic gating that adjusts the integration strategy based on sample-specific data quality. Experimental results on two TCGA cohorts (GBMLGG and KIRC) show that CD-AHF achieves consistent improvements over representative unimodal and multimodal baselines, supporting its effectiveness in mitigating the modal semantic gap and enhancing personalized prognostic prediction.

Abstract Multidrug-resistant Pseudomonas aeruginosa (PA) causes severe infections, with severe burden especially in older adults. Vaccines remain effective and are urgently needed despite immunosenescence. Self-assembling nanoparticles can enhance vaccine immunogenicity, but their translational use is constrained by the useless anticarrier immunity and carrier-induced epitope suppression (CIES). Herein, we developed a protective-antigen-based nanoparticle platform in which the PA chaperonin GroEL, an intrinsically self-assembling protective antigen, serves as the scaffold for a fusion immunogen reGroEL-PO, which displays the PcrV-OprI antigen (rePO). In mice, pre-existing anti-GroEL immunity did not blunt responses but enhanced anti-rePO immunity. Mechanistically, reGroEL-PO increased antigen uptake by antigen-presenting cells, promoted dendritic-cell maturation and accelerated both humoral and cellular immunity. In addition, reGroEL-PO elicited immune responses and conferred protection in adult and aged mice. These data demonstrate reGroEL-PO as a PA vaccine candidate and illustrate a nanoparticle design that leverages protective carriers and circumvents CIES effects.

Abstract Vulvovaginal candidiasis (VVC), a common mucosal infection caused by Candida spp., affects approximately 75% of reproductive‐aged women worldwide. Nevertheless, this significant health concern remains understudied. Consequently, novel therapeutic interventions are urgently required. Probiotics have emerged as a viable alternative for VVC management owing to their favorable safety profile and proven efficacy. However, evidence supporting their antifungal properties remains inconclusive, necessitating further elucidation of the underlying mechanisms. Numerous studies have demonstrated that probiotics and their derivatives can effectively counteract Candida by reducing Candida’s virulence factors, modulating immune responses, promoting vaginal barrier, remodeling the metabolic environment and restoring microbiota homeostasis. Providing an updated summary of VVC pathogenesis and its relationship with vaginal microbiota, this review aims to comprehensively elucidate the roles and mechanisms of probiotics and their derivatives in VVC. Additionally, it discusses the existing evidence for probiotic‐based strategies, including probiotics, probiotics derivatives and vaginal microbiome transplants, and provides a better theoretical foundation for interventions targeting VVC based on probiotics.

Adverse inflammatory responses, dominated by macrophages, that are induced by physical cues of implants can threaten the life quality of patients via causing fibrosis. Oriented nanofibers can regulate macrophage phenotypes, reduce inflammatory factors, and inhibit foreign body response (FBR). However, the mechanisms supporting this phenomenon are incompletely understood. Here, we show that oriented nanofiber scaffolds regulate macrophages in respond to FBR and that metabolic rewiring orchestrates function of macrophages. On the oriented nanofibers substrate, the cell membrane is subjected to micro-nano mechanical stimulation, causing conformational change of integrins α4β7. The higher activation state of integrin α4β7 aggravate the calcium-activated, non-selective cationic channel TRPM4, subsequently affects the voltage-gated calcium channel (VGCC), leading to extracellular calcium influx. Intracellular calcium overload further influences macrophage polarization by inhibiting lipid synthesis. Furthermore, rat subcutaneous implantation and skull defect repair experiments have confirmed that oriented nanofibers alleviate the material-induced FBR and provide a favorable immune microenvironment to enhanced bone regeneration during long-term implantation. In summary, our work identifies that lipid synthesis regulated by integrin α4β7-TRPM4 as an essential pathway for meeting the demands of macrophage polarization mediated by oriented nanofibers, and it provides a theoretical foundation for potential transplant therapies to mitigate FBR.

Neural tube defects (NTDs), such as anencephaly and spina bifida, are prevalent congenital anomalies of the central nervous system. These defects can give rise to severe lifelong disabilities and incur substantial healthcare expenses for the affected individuals. The occurrence of NTDs is caused by multiple factors, including molecular regulatory mechanisms and environmental factors. This article comprehensively reviews the underlying mechanisms of three crucial signalling pathways associated with neural tube development: the Wnt/Planar Cell Polarity (PCP) signalling pathway, the Sonic Hedgehog signalling pathway and the Notch signalling pathway, and, on this basis, delves into the potential molecular therapeutic strategies for NTDs. This review is of great significance for comprehensively elucidating the molecular causes of NTDs and expanding prevention and treatment strategies for related congenital anomalies.

Due to the phenotypic and genotypic heterogeneity of tumors, the efficacy of intraoperative indocyanine green (ICG) imaging in lung cancer exhibits significant inter-patient variability. This study identifies macrophage content as a critical predictive biomarker for ICG imaging outcomes, offering both mechanistic, and clinical insights into this variability. Mechanistically, macrophages are demonstrated to serve as the principal ICG reservoirs in tumor tissues, exhibiting seven-fold higher uptake capacity compared to cancer cells. This critical role is confirmed by significantly diminished ICG accumulation following macrophage depletion in patient-derived xenograft (PDX) models. Clinically, a strong correlation is observed between imaging quality and macrophage content, with solid nodules exhibiting superior ICG uptake compared to ground-glass nodules due to higher macrophage infiltration. Furthermore, the strong tumor-to-normal ratio (TNR) association with preoperative maximum Standardized Uptake Value (SUVmax) on PET-CT suggests the feasibility of predicting ICG-guided surgery outcomes through routine imaging. The substantial contribution of macrophages to this predictive capability is a significant discovery, offering a novel biomarker for patient stratification in ICG-guided surgery. These insights not only deepen our comprehension of the intricate interplay between ICG and the lung cancer microenvironment but also open new avenues for the development of more personalized and precise surgical strategies.

Pulmonary hypertension (PH) is a malignant and progressive disease lacking effective treatments, characterized primarily by pulmonary vascular remodeling resulting from endothelial cells (ECs) dysfunction. The increase of reactive oxygen species (ROS) in a pathological state is the pivotal factor that triggers ECs dysfunction, primarily through the induction of DNA damage. Currently, there is a significant scarcity of drugs capable of reducing ECs DNA damage by eliminating ROS in the microenvironment. Therefore, we synthesis hydrogen-generated metal-organic framework nanoparticles (PdH/ZIF-8), which can not only release hydrogen continuously for over 24 h, but also has efficiently ROS scavenging activity. In vitro, PdH/ZIF-8 inhibits hypoxia-induced dysfunction of pulmonary microvascular ECs. In vivo models PdH/ZIF-8 accumulates in lungs rapidly and steadily, effectively alleviating pulmonary vascular remodeling, and ultimately significantly improving cardiac function. Further, PdH/ZIF-8 decreases expression of inflammatory factors. At the same time, PdH/ZIF-8 regulates the expression of poly ADP-ribose polymerase (PARP1), reduced ataxia telangiectasia mutated and Rad3 related (ATR)/cell cycle checkpoint kinase 1 (CHK1) phosphorylation. In conclusion, this work provides a novel and effective nano-technology with the synergistic therapy of innocuous gas to the treatment of PH.

Helicobacter pylori (H. pylori), a proven carcinogenic microbe, necessitates antimicrobial treatment once infected. However, H. pylori worldwide currently faces serious antibiotic resistance (AMR), requiring infected patients to undergo antibiotic susceptibility testing (AST) to guide therapy. Currently, the recommended ASTs for H. pylori are culture-based methods, which are time-consuming, complicated, and expensive, impeding their widespread application. With in-depth researches on the AMR mechanisms of H. pylori, specific gene mutations and novel proteins have been confirmed as the cause of AMR and can serve as targets of ASTs. Accordingly, molecular biology detection has been developed and tremendously shortened the time and reduced difficulty of AST. However, these assays still struggle to meet the enormous testing demand and need for even faster, simpler, and more accurate methods. In recent years, researchers have developed various new platforms based on biosensors, transcriptomics, proteomics, and single-cell analysis. This review introduces the AMR mechanisms of H. pylori and summarizes the current ASTs from the working principles to application characteristics. Additionally, we draw attention to the potentially applicable techniques for AST of H. pylori from DNA, RNA, protein, and cell perspectives. By systematically recapitulating the past, present, and future of AST for H. pylori, this review provides valuable insights for developing novel assays.

H. pylori induces gastritis and promotes gastric carcinogenesis. Antimicrobial therapy against H. pylori often causes gastrointestinal dysbiosis, with side effects like vomiting, diarrhea, and antibiotic resistance, hindering effective eradication. This study investigated the effects and mechanisms of probiotics in balancing microbiota to alleviate H. pylori-related gastritis. Using in vivo and in vitro gastritis models with various H. pylori virulence strains, the study employed 16S rRNA amplicon sequencing and qPCR to link gastric microbiota with inflammation. Genomic mining and microbiota reconstruction identified Lactococcus garvieae LG3092 and GarQ as key microecological-targeting regulators. Results showed that different H. pylori induce varying levels of gastritis in vivo, with elevated IL-1β, IL-6, and TNF-α levels linked to pro-inflammatory bacteria. LG3092 secretes GarQ, specifically targeting Man-PTS receptors on pro-inflammatory bacteria, disrupting their membranes and modulating the gastric microbiota, highlighting the potential of probiotics in combination with other therapies to managing H. pylori infection and related gastritis.

The gut microbiota of centenarians plays a vital role in promoting healthy longevity. We performed a cross-sectional study of 224 people from Jiaoling, China, which is globally recognised for the longevity of its residents. Compared with younger people, centenarians showed significantly increased alpha-diversity, enrichment of the beneficial bacteria Lactobacillus, Akkermansia, and Christensenella, and increased redox capacity in the gut microbiota. Serum metabolomics of centenarians showed significant enrichment of antioxidant metabolites, including L-ascorbic acid 2-sulphate and lipoic acid. Finally, we isolated and screened a strain of Lactobacillus plantarum 124 (LP124) with a good antioxidant effect on the gut microbiota of centenarians. Animal experiments further verified that mesaconic acid from LP124 regulates the gut microbiota, is anti-inflammatory, relieves oxidative stress, maintains the intestinal barrier, and is the best-known anti-aging molecule. LP124 derived from the gut microbiota of centenarians and its metabolite mesaconic acid, have a significant positive effect on health and longevity.

Ferroptosis, a regulated cell death mechanism characterized by iron dependency and lipid peroxidation, has been identified as a pivotal driver of tumor evolution and treatment resistance. Our findings reveal a previously unrecognized ubiquitination-driven mechanism in esophageal squamous cell carcinoma (ESCC), whereby F-box protein 10 (FBXO10) modulates ferroptosis susceptibility and oncogenic aggressiveness by orchestrating acyl-CoA synthetase long-chain family member 4 (ACSL4) degradation. Co-immunoprecipitation and immunofluorescence colocalization assays confirmed specific physical interaction between FBXO10 and ACSL4. Mechanistically, FBXO10 silencing stabilized ACSL4 by suppressing ubiquitination degradation, thereby potentiating ferroptosis through amplified lipid peroxidation and Fe2⁺ accumulation. Functional studies revealed that FBXO10 ablation suppressed ESCC cell proliferation, migration, and invasion via ACSL4-dependent ferroptosis activation. In vivo validation demonstrated that FBXO10 knockdown attenuated xenograft tumor growth while elevating ferroptotic markers. Crucially, this regulatory axis operates independently of the canonical glutathione peroxidase 4 (GPX4) pathway, as evidenced by preserved GPX4/solute carrier family 7 member 11 (SLC7A11) expression. Our experimental results establish the FBXO10-ACSL4 axis as a core signal axis in ESCC, proposing targeted disruption of this ubiquitination switch to restore ferroptotic susceptibility.

Anomalous systemic arterial supply to the left basal segment of the lung is a rare congenital pulmonary vascular malformation, historically classified as a variant of intra-lobar pulmonary sequestration. The standard surgical approach has typically involved ligation of the anomalous artery in combination with lobectomy or segmentectomy. We present three cases of anomalous systemic arterial supply to the left basal segment of the lung, all successfully treated with thoracoscopic anomalous arterial ligation alone. In one case, indocyanine green was used to assess the blood supply, enhancing procedural safety. Thoracoscopic ligation of the anomalous artery alone may be a safe and lung-preserving surgical option for patients with this rare anomaly. The use of indocyanine green can further improve the safety of the procedure.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

There have been numerous studies on collective behavior, among which communication between agents can have a great impact on both the payoff and the cost of making decisions. Research usually focuses on how to improve the collective synchronization rate or accelerate the process of cooperation under given communication cost constraints. In this context, evolutionary game theory (EGT) and reinforcement learning (RL) arise as essential frameworks for tackling this intricate problem. In this study, an adapted Vicsek model is introduced, wherein agents exhibit varying movement patterns contingent on their chosen strategies. Each agent gains a payoff determined by the advantages of collective motion juxtaposed with the cost of communicating with neighboring agents. Individuals choose the objective agents based on the Q-learning strategy and then adapt their strategies following the Fermi rule. The research reveals that the utmost level of cooperation and synchronization can be attained at an optimal communication radius after applying Q-learning. Similar conclusions have been drawn from research on the influence of random noise and relative cost. Different cost functions were considered in the study to demonstrate the robustness of the proposed model and conclusions under a wide range of conditions. (https://github.com/WangchengjieT/VM-EGT-Q)

Traditional detection methods for Helicobacter pylori (H. pylori) infection are complex and time-consuming, which hinders their large-scale application. In recent years, advances in multi-omics techniques have expanded the detection targets for H. pylori. Simultaneously, the development of technologies such as CRISPR/Cas systems, biosensors and artificial intelligence image recognition systems has also promoted the development of detection technology. Therefore, systematic summary and in-depth description of the latest technology will facilitate the advancement of H. pylori detection. In this paper, the existing H. pylori detection methods are divided into four categories according to detection targets: pathological detection, metabolic detection, proteomic detection and nucleic acid detection. The working principles and application characteristics are reviewed, and their advantages and limitations are compared. This article is not exhaustive, but it also discusses potential techniques that could inspire the development of faster, more accurate, and more convenient detection systems for H. pylori infection.

Artemether-lumefantrine (AL) is the most widely used antimalarial drug for treating uncomplicated falciparum malaria. This study evaluated whether the K65Q mutation in the Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) gene was associated with alternated susceptibility to lumefantrine using clinical parasite samples from Ghana and the China-Myanmar border area. Parasite isolates from the China-Myanmar border had significantly higher IC50 values to lumefantrine than parasites from Ghana. In addition, the K65 allele was significantly more prevalent in the Ghanaian parasites (34.5%) than in the China-Myanmar border samples (6.8%). However, no difference was observed in the lumefantrine IC50 value between the Pfnfs1 reference K65 allele and the non reference 65Q allele in parasites from the two regions. These data suggest that the Pfnfs1 K65Q mutation may not be a reliable marker for reduced susceptibility to lumefantrine.