Neoadjuvant immunotherapy is reshaping the treatment of resectable solid tumors, but biomarkers that reflect spatially organized antitumor immunity remain limited. Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that support local antigen presentation, lymphocyte recruitment, T-B cell interaction, germinal center reactions and humoral immunity. Increasing evidence suggests that TLS density, maturation, localization and cellular composition are associated with immune checkpoint blockade response, pathological regression and prognosis. Beyond their biomarker value, TLS may represent modifiable immune niches that can be induced or remodeled by checkpoint blockade, chemotherapy, radiotherapy, vaccines and stromal-vascular strategies. This mini-review discusses the biological basis, biomarker potential, therapeutic targeting and clinical translation of TLS in neoadjuvant cancer immunotherapy, highlighting key challenges and future TLS-guided trial designs.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which environmental factors play an important role in shaping disease risk, activity, and progression. Over the past decade, human and experimental studies have consistently shown alterations in the gut microbiome across the phenotypic spectrum of MS and have linked these changes to immune dysregulation, barrier dysfunction, neuroinflammation, and demyelination. Additionally, emerging evidence indicates that microbial function, particularly metabolite production plays a more direct role in shaping immune responses and associated neuropathology. Evidence from both human studies and experimental autoimmune encephalomyelitis models supports a functional role for microbial metabolites in shaping neuroimmune responses. Bacterially derived metabolites such as short-chain fatty acids, bile acids, polyamines, phytoestrogen metabolites, and tryptophan-derived compounds can influence T-cell differentiation, glial activation, epithelial integrity, and neuroimmune communication. Recent longitudinal studies also show associations between metabolite profiles and disability worsening. Because disease-modifying therapies, diet, and microbiome-directed interventions can reshape microbial metabolism, microbial metabolites may represent promising therapeutic targets in the gut-immune-brain axis. In this Review, we integrate current evidence to propose a mechanistic framework in which microbial metabolites act as central regulators of mucosal and systemic immunity that influence different aspects of MS biology. We discuss how this perspective shifts gut microbiome research from descriptive associations to biological mechanisms that more directly link the gut to immune responses and downstream neuropathology. We then evaluate therapeutic strategies that target microbial metabolism and outline key priorities for longitudinal, multi-omics, and interventional studies that are needed to enable microbiome-informed precision therapies in MS.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of α-synuclein, with increasing evidence implicating environmental factors and neuroimmune dysfunction in its pathogenesis. Micro- and nanoplastics (MNPs), ubiquitous environmental pollutants generated from plastic degradation, have recently emerged as potential biological stressors capable of entering the human body and accumulating in sensitive tissues, including the brain. Due to their small size, environmental persistence, and capacity to carry toxic additives and environmental contaminants, these particles can induce oxidative stress, impair mitochondrial and lysosomal function, and activate both innate and adaptive immune responses. This review summarizes current evidence linking microplastic exposure to neuroinflammatory processes relevant to PD, with a particular focus on microglial activation, astrocyte reactivity, peripheral immune involvement, and dysfunction of the gut-brain axis. Although a direct causal relationship between MNPs and PD has yet to be established, and direct human epidemiological evidence linking MNP exposure to PD is currently absent, the immunotoxic and neuroinflammatory effects of these particles suggest that they may contribute to disease susceptibility and progression. Elucidating the interactions between MNPs and neuroimmune pathways may help refine current frameworks linking environmental exposure, neuroimmune dysfunction, and PD susceptibility.

Epigenetic modifications play a crucial role in cancer, influencing cellular physiology, extracellular matrix (ECM) remodeling, and immune responses. With growing emphasis on chromatin remodeling and the epigenetic regulation of immunity, these regulatory pathways and related players have become focal points of oncological investigations. Epigenetic manipulation of immune system components has emerged as a promising strategy in cancer treatment. Several FDA-approved "epi-drugs" target the epigenome to modulate immune responses and offer new opportunities across different cancers. DNA repair pathways contribute significantly to the avoidance of cancer initiation and also contribute to cellular resistance in cancer treatment. Chromatin remodelers such as INO80, Fun30, and RAD54 play essential roles in DNA damage response (DDR) through homologous recombination and non-homologous end-joining pathways, and their dysregulation leads to genome instability and tumor progression. Chromatin remodeling complexes, including SWI/SNF and CHD families, are frequently altered across various cancer types, further highlighting their role in cancer pathophysiology. Targeting these chromatin modifiers and associated DNA repair mechanisms may provide novel therapeutic options. In addition, combining epigenetic modulators with immunotherapies has shown promise in enhancing responses to immune checkpoint blockade. Epigenetic drugs such as histone deacetylase (HDAC) inhibitors and DNA methylation inhibitors are being explored for their synergistic effects with immunotherapy. While the interplay between chromatin remodeling, DNA repair, and immune responses provides a strong framework for developing targeted oncological strategies, further research is required to better understand these interactions and optimize their clinical application.

Vortioxetine (VOX) is a multimodal antidepressant commonly used in long-term therapy, making its sensitive detection in biological samples an important analytical task. Electrochemical detection of VOX on disposable carbon electrodes is often hindered by oxidation at relatively positive potentials, which can lead to background currents, co-oxidation, and surface passivation, thereby reducing analytical reliability. Herein, a fluoride-free alkaline hydrothermal route was adopted to convert MoAlB (MAB) into porous, oxygen-terminated MoAl1-xB (MBene), employed as a functional interfacial modifier on screen-printed electrodes (SPEs). Formation and surface evolution of MBene were confirmed by electron microscopy, XRD, Raman spectroscopy, and XPS. Compared to bare SPE and parent MAB/SPE, MBene/SPE shifted the VOX oxidation response to a lower-potential window centered at 0.70 V vs. Ag/AgCl and generated a markedly stronger faradaic signal under near-neutral pH. Mechanistic evidence from open-circuit potential transients, in situ UV-Vis spectroelectrochemistry, pH and kinetic isotope effect studies, and DFT calculations indicates that the O/OH-rich MBene surface promotes adsorption-assisted VOX preconcentration and interfacial charge redistribution, while the conductive Mo-B framework facilitates charge transfer. Under optimized DPV conditions, the sensor exhibits two linear ranges (0.001-0.090 µM and 0.13-3.80 µM) due to surface-site saturation and diffusion contributions, with high sensitivity evidenced by a 1.0 nM detection limit, repeatability of 0.80% RSD (n = 8), and fabrication reproducibility of 2.9% RSD (n = 5). The platform also demonstrates selectivity against structurally related antidepressants and representative urine interferents, with recoveries of 96.7-109.1% in PBS-diluted urine using a portable potentiostat.

Aberrant glycosylation is a nearly universal hallmark of cancer cells. Tumor-associated glycans can reshape cancer cell biology and act as crucial suppressors of anti-tumor immunity. By engaging immune inhibitory receptors or by modifying the function of immune checkpoints, glycans dampen natural immune responses and immunotherapy efficacy. Therefore, glycans serve both as direct targets for anticancer interventions and as adjuvants aimed at potentiating immunotherapy success. In this Review, we provide an overview of tumor glycosylation and its impact on cancer immune surveillance. Finally, we discuss recent therapeutic developments that highlight the potential of glycans as precision cancer medicines.

A Fe-containing N-doped graphene nanosheet-modified glassy carbon electrode (Fe/N-Gr/GCE) was developed for the sensitive electrochemical determination of apremilast (APRE), a phosphodiesterase-4 inhibitor used in the treatment of psoriatic arthritis. The electrochemical response of APRE was investigated using differential pulse voltammetry (DPV), showing a well-defined oxidation peak in Britton-Robinson buffer (pH 2.0). The enhanced performance of the sensor is attributed to the high surface area and favorable electron-transfer properties of the Fe/N-Gr nanomaterial. Under optimized conditions, a linear range of 0.1-22.0 μM (R2 = 0.998) was obtained, with a detection limit of 0.008 μM and a quantification limit of 0.029 μM. The sensor exhibited good repeatability (RSD = 2.4%) and reproducibility (RSD = 2.1%), confirming its precision and fabrication reliability. Its applicability was demonstrated in synthetic human serum, urine, and pharmaceutical tablets, with recoveries of 97.41-102.71% and RSDs of 1.25-2.36%. Overall, the proposed method offers a simple, sensitive, and environmentally friendly approach for APRE determination in pharmaceutical and biological samples.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by joint involvement, significant impact on quality of life and frequently linked with obesity, metabolic syndrome and cardiovascular comorbidities. Despite advances in PsA management, obesity remains a critical factor influencing disease severity, treatment response and patient outcomes. We examine the interplay between PsA and obesity, the current clinical guidelines, gaps in clinical practice, research on shared inflammatory pathways, treatment implications and the potential of weight-loss interventions to modify disease progression. This comprehensive narrative review uses a non-systematic search of PubMed, Embase and Scopus databases and analyses literature on PsA, obesity, cytokine signalling and therapeutic outcomes, with priority to clinical trials, meta-analyses and large cohort studies. Obesity exacerbates PsA through systemic inflammation, adipokine dysregulation and mechanical joint stress, contributing to worse clinical outcomes, increased comorbidity and poorer response to biologics. Weight management improves disease activity and therapeutic efficacy, although its effects on PsA pathophysiology remain underexplored. Our review highlights that obesity should be recognised as a risk factor and comorbidity in PsA for the integral management of patients. Further research is needed to elucidate the cytokine and molecular changes induced by weight management, generate more clinical data and optimise personalised management strategies. While clinical guidelines recommend a coordinated care approach to optimising the management of PsA in patients with obesity, emerging clinical data support further focus on the role of targeting inflammation, obesity and metabolic dysfunction to improve long-term PsA outcomes and quality of life, mitigate complications and provide better cardiovascular and overall health to patients.

Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors, such as ribociclib (RB), limits breast cancer therapy. Although PEG10 siRNA (siPEG10) can counteract this resistance, achieving targeted, synchronized co-delivery to reshape the immunosuppressive tumor microenvironment (TME) remains a formidable challenge. By loading RB and siPEG10 into PEG-β-CD-modified mesoporous silica nanoparticles (PMSNs) and coating them with breast cancer cell membranes (CM), the nanocomposite RB/siPEG10@PMSNs-CM was synthesized. The nanomaterials were characterized for size, charge, drug loading, and pH-responsive release. Therapeutic efficacy, immunotherapy-related potentials, and underlying mechanisms were evaluated using in vitro functional assays, an anoikis resistance model, and in vivo breast cancer models. Toxicity was assessed in liver and kidney tissue. The nanodrug RB/siPEG10@PMSNs-CM (<200 nm) exhibited enhanced cellular uptake and pH-dependent drug release. The zeta potential of the RB/siPEG10@PMSNs-CM was negative. The nanodrug significantly inhibited tumor cell growth, migration, invasion, and metastasis, while inducing apoptosis. Crucially, the nanodrug overcame anoikis resistance, upregulated cleaved caspase-3 and cleaved PARP, reversed epithelial-mesenchymal transition (EMT) markers (increased E-cadherin and decreased Vimentin), and inhibited p-STAT3 and p-ERK signaling. Furthermore, the nanodrug exhibited lower toxicity to liver and kidney than RB. In Conclusion, the developed biomimetic nano-delivery system RB/siPEG10@PMSNs-CM successfully co-delivers RB and siPEG10 and exhibits a favorable safety profile. This platform exhibits anti-primary tumor and anti-metastatic efficacy and effectively overcomes anoikis resistance in breast cancer, which correlated with the suppression of the MEK/ERK and STAT3 signaling pathways, offering a promising combination strategy for advanced breast cancer immunotherapy and targeted treatment.

At the base of stream food webs, photoautotrophic biofilms supply essential polyunsaturated fatty acids (PUFAs) to higher trophic levels. Xenobiotics can alter biofilm structure and function, potentially impairing this vertical interaction. Here we assess how biofilms respond to the herbicide propyzamide and the antibiotic ciprofloxacin, individually and in mixture, and whether effects of these xenobiotics are transferred to higher trophic levels, represented by the grazing snail Potamopyrgus antipodarum. Biofilms were grown in indoor stream microcosms, exposed to xenobiotics for 14 days and subsequently used in a 21-day feeding assay. Biofilm responses were ash-free dry weight, chlorophyll content, and fatty acid (FA) composition, whereas grazer responses were determined as biomass and FA composition as fitness proxies. Xenobiotic exposure had negligible effects on biofilm biomass and chlorophyll content, but FA analyses revealed treatment-specific reductions. In particular, PUFAs decreased by up to 39% under xenobiotic exposure. Correspondingly, grazers biomass was reduced across all xenobiotic treatments. Grazer FA composition differed markedly, with control individuals exhibiting the highest PUFA levels. Propyzamide and the mixture caused the strongest PUFA reductions in grazers (-30% and -45%, respectively), while ciprofloxacin exposure led to increased saturated fatty acids (+25%) and a pronounced PUFA decline (-24%). These results demonstrate that even when biofilm functions appear unaffected, subtle biochemical shifts seem to propagate across trophic levels, reducing consumer growth and modifying energy allocation. Our findings highlight the importance of evaluating direct and indirect effects of xenobiotics when assessing ecological risks in aquatic ecosystems.

Lead (Pb) contamination in agricultural soils reduces crop productivity and threatens food safety, highlighting the need for in situ amendments that lower Pb bioavailability while supporting soil functioning and plant performance. This study upgraded poultry manure-derived biochar through microwave activation and genipin-crosslinked chitosan modification (MPBCH), then evaluated its performance in a greenhouse pot experiment with Brassica napus grown in field-collected Pb-contaminated soil. Six treatments were compared: untreated Pb-stressed soil (CK), chitosan (CH), poultry manure biochar (PBC), microwave-prepared biochar (MPBC), chitosan-modified PBC (PBCH), and MPBCH. The MPBCH produced the strongest overall response, increasing soil pH from 5.84 to 6.95 and reducing DTPA-extractable Pb by 62.0%. Root and shoot Pb concentrations decreased by 52.1% and 57.9%, respectively, while immobilization-related indices consistently indicated lower Pb mobility and restricted soil-to-plant transfer. MPBCH also increased β-glucosidase, phosphomonoesterase, catalase, and urease activities by 43.74%, 40.22%, 60.24%, and 40.48%, respectively. Rhizosphere bacterial analysis showed the highest Shannon diversity (4.52) and Chao richness (1882.12) under MPBCH, with clear community separation in principal coordinates analysis, significant divergence by PERMANOVA (F = 3.73, R2 = 0.599, p = 0.0005), and enrichment of bacterial biomarkers. These belowground responses coincided with improved biomass, photosynthetic pigments, gas-exchange traits, nutrient status, antioxidant defense, and lower oxidative stress markers. Transcriptomic and qRT-PCR analyses supported reduced Pb-stress status under MPBCH, with shifts in carbon metabolism, glutathione metabolism, photosynthesis, and metal transport-related genes. Multivariate integration identified MPBCH as the strongest-performing treatment across the measured Pb immobilization, plant physiological, and soil biochemical responses.

Although polyethylene microplastics (PE-MPs) have been documented to adsorb heavy metals, such as cadmium (Cd) in aquatic environments, the effects of their combined ingestion on marine organisms remain scarcely understood. This study evaluated the individual and combined effects of spherical PE-MPs (53-63 μm) and Cd on survival, growth, and bioaccumulation in juvenile shrimps Litopenaeus vannamei exposed via feeding for 21 days. Individual (300 mg kg-1 PE-MPs and 30 mg kg-1 Cd) and combined exposures did not affect survival rates. However, the final weight was significantly lower in the combined treatment (3.8 ± 0.1 g) compared to the control (4.3 ± 0.2 g), suggesting that co-exposure to PE-MPs and Cd adversely affected growth. The highest PE-MPs accumulation at 21 days under the combined treatments was observed in the gastrointestinal tract (GIT) (981.7 ± 70.8 MP g-1). Cadmium (Cd) accumulation followed the order hepatopancreas (HP) > GIT > gills (GL) > exoskeleton (EX) > muscle (MU), reaching its highest concentration in the HP of the combined treatment (91.7 ± 1.4 μg g-1), even higher than in the treatment with Cd alone (80.5 ± 5.6 μg g-1). Overall, dietary co-exposure to PE-MPs and Cd for 21 days reduced growth and increased the bioaccumulation of both contaminants, suggesting that combined exposure may modify contaminant bioavailability and retention. Further studies are needed to elucidate the metabolic mechanisms associated with this response.