Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.

While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, we aimed to examine the association between arsenic exposure and MASLD in humans.

Urinary inorganic arsenic data from the National Health and Nutrition Examination Survey, 2011–2020, were used. These were combined with death certificate data from the National Death Index of the National Center for Health Statistics to ascertain mortality rates. Weighted linear regression and chi-squared analysis were performed.

The analysis included 6,386 participants after exclusions. The mean urinary arsenic level was 5.92 µg/L in participants with MASLD versus 5.59 µg/L in those without. Alanine aminotransferase levels exhibited a statistically significant increasing trend across both continuous arsenic levels and arsenic quintiles. A statistically significant upward trend was observed for the income-to-poverty ratio and body mass index but not for education status. MASLD prevalence was highest among the white population, while an increasing trend was observed in the Hispanic population over the years (p < 0.001). The proportion of Mexican Americans increased to 12.6% in the MASLD group versus 8.09% in the non-MASLD cohort (p < 0.001). There was a statistically significant increase in the odds of MASLD across arsenic exposure levels, with individuals in the highest quintile having a 32% greater likelihood compared to those in the lowest quintile (p-trend = 0.002). The odds further increased to 55% in the highest quintile (odds ratio 1.55, 95% confidence interval: 1.19–2.03; p-trend < 0.001). MASLD was more prevalent in females than males (57.9% vs. 47.6%; p < 0.001), and the mean age increased from 46.9 years to 49.9 years (p = 0.016).

Our findings reveal a positive association between urinary arsenic exposure and MASLD, with increasing trends particularly observed among Hispanics and those with higher income-to-poverty ratios and body mass index.

Glioblastoma (GBM) is the most prevalent and aggressive form of primary brain malignancy in adults. Despite continuous advancements in standard treatment modalities, the prognosis for patients remains extremely poor, with a median survival of less than two years. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has achieved revolutionary success in hematologic malignancies, marking a significant breakthrough in the field of immunotherapy. However, the successful application of CAR-T therapy to GBM still faces dual challenges: antigen heterogeneity and the immunosuppressive tumor microenvironment. This review systematically summarizes these challenges encountered in CAR-T therapy for GBM and the innovative strategies currently under development to address these challenges, providing insights for the future clinical translation of CAR-T therapy in GBM.

Spinal cord injury (SCI) significantly impacts the central nervous system, with limited effective treatments available. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal growth, survival, and regeneration after SCI. MicroRNAs, particularly miR-124-3p, have been implicated in SCI pathophysiology. However, the relationship between miR-124-3p and BDNF in the context of SCI remains unclear. This study aimed to investigate the correlation between miR-124-3p expression and BDNF levels in a rat model of spinal cord injury and to assess how the timing of injury affects this relationship.

This study included 72 male Wistar rats divided into three groups: intact (n = 8), sham (n = 32), and SCI (n = 32). SCI diagnosis was confirmed through behavioral-motor function analysis using the Basso, Beattie & Brenham score and histological examination with crystal violet staining. The expression levels of miR-124-3p and BDNF were assessed using real-time polymerase chain reaction in all groups at four time points (one hour, one day, three days, and seven days post-injury).

In the SCI group, a marked reduction in miR-124-3p expression was observed relative to both the sham and intact groups. Conversely, there was a substantial elevation in BDNF expression within the SCI group in comparison to the sham and intact groups. The findings underscore a negative association between miR-124-3p expression and BDNF messenger RNA levels.

The downregulation of miR-124-3p and concurrent upregulation of BDNF suggest a potential regulatory role of miR-124-3p in modulating BDNF expression during SCI. These findings provide new insights into the molecular mechanisms underlying SCI and suggest that miR-124-3p and BDNF could serve as potential therapeutic targets. Further research is needed to explore the translational potential of these findings for developing novel diagnostic and therapeutic strategies for SCI.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disorder worldwide, results from multidimensional network dysregulation involving lipid metabolism imbalance, insulin resistance, oxidative stress, chronic inflammation, and gut-liver axis disruption. Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, functions as a central regulator of metabolic homeostasis and a key mediator in immune microenvironment remodeling and inter-organ communication. This review systematically describes the multi-target mechanisms of SIRT1 in MASLD pathogenesis through its regulation of critical factors, including peroxisome proliferator-activated receptor gamma coactivator 1-α, Forkhead Box O, and nuclear factor kappa-light-chain-enhancer of activated B cells, which govern hepatocyte lipid remodeling, mitochondrial quality control, autophagy–endoplasmic reticulum stress balance, and Kupffer cell/T cell polarization. This work introduces, for the first time, the concept that SIRT1 mediates systemic regulation of MASLD via coordinated “metabolism–inflammation–organ axis” interactions. Recent studies indicate that natural compounds (e.g., resveratrol, curcumin) improve gut-liver barrier function through microbiota–SIRT1 interactions, while synthetic activators (SRT1720) and NAD+ precursors (NMN) enhance hepatocyte antioxidant capacity and fatty acid β-oxidation. This innovative analysis highlights the spatiotemporal specificity of various SIRT1 activators, emphasizing that tissue-selective delivery and dynamic dosage optimization are crucial for overcoming clinical translation challenges. By integrating mechanistic and translational insights, this review provides a novel foundation for precision intervention strategies targeting SIRT1 network reprogramming.

The incidence of early-onset pancreatic cancer (EOPC) is rising, yet optimal treatment strategies remain unclear. While adjuvant chemotherapy (ACT) has shown survival benefits in pancreatic ductal adenocarcinoma, its specific role in EOPC patients following neoadjuvant chemotherapy (NACT) and surgery remains underexplored. This study aimed to assess the clinical benefit of ACT in EOPC patients after NACT.

This retrospective cohort study analyzed pancreatic ductal adenocarcinoma patients from the SEER database (2006–2019) who received NACT followed by curative resection. Propensity score matching (1:1) was used to balance covariates such as tumor, lymph node, metastasis stage, chemotherapy, and radiotherapy. Overall survival (OS) and cancer-specific survival (CSS) were compared between patients with EOPC (<50 years) and average-onset pancreatic cancer (AOPC, ≥50 years). Multivariate Cox regression analysis was performed to identify prognostic factors.

After propensity score matching (124 EOPC vs. 124 AOPC), EOPC patients had significantly longer median OS (41.0 vs. 29.0 months, P = 0.042) and CSS (48.0 vs. 30.0 months, P = 0.016). ACT was an independent prognostic factor for EOPC (OS: hazard ratio = 0.495, 95% confidence interval 0.271–0.903, P = 0.022; CSS: hazard ratio = 0.419, 95% confidence interval 0.219–0.803, P = 0.009), but not for AOPC (P > 0.05). Subgroup analysis revealed that EOPC patients with tumor, lymph node, metastasis stage II disease or those receiving ACT derived the greatest survival benefit.

EOPC patients exhibit superior survival following NACT and surgical resection compared to AOPC, with ACT further enhancing outcomes in this subgroup. These findings support the use of tailored ACT for EOPC and underscore the need for prospective validation.

Multimodal applications combining electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) are widely used in cognitive neuroscience and have progressively been applied to clinical applications, such as the joint diagnosis of amyotrophic lateral sclerosis, Alzheimer’s disease, and pediatric epilepsy. This study conducted a bibliometric analysis of EEG-fNIRS synchronization techniques over the past 20 years. The aim was to clarify their diagnostic and therapeutic value in clinical applications, particularly in the neurological system, and to guide future research and development trends.

This study utilized the Web of Science Core Collection database to analyze documents published between January 1, 2005, and May 13, 2024. CiteSpace and VOSviewer were employed for visual analyses of co-author relationships, keywords, citation patterns, and journal distributions. By overlaying dual-map diagrams and analyzing annual publication trends, the study identified research hotspots, development trends, and the evolution of EEG-fNIRS technology.

A total of 645 articles and reviews from 55 countries were analyzed. The USA contributed the most publications. The team led by Michela Balconi at the Catholic University of the Sacred Heart published the highest number of papers. Frontiers in Human Neuroscience had the greatest number of publications, while NeuroImage had the highest citation impact. Recent research has primarily focused on the application of neuroimaging and neurophysiological techniques (e.g., EEG, fNIRS, functional magnetic resonance imaging), brain activation, and brain-computer interface.

This study highlights the applications and developmental trends of dual-modality EEG-fNIRS technology. Specifically, this approach can assist in diagnosing neurological disorders, assessing activation and connectivity within functional brain regions, and evaluating therapeutic neuromodulation in clinical neurology. Overall, multimodal fusion is poised to advance neuroscience research significantly.

Sepsis involves a complex cascade of inflammatory reactions and immune system dysregulation. Neutrophils play a crucial role in modulating the anti-inflammatory response, which is vital for managing sepsis. Impaired chemotaxis of granulocytes can significantly impact the outcome of sepsis. Shenfu Decoction, by tonifying Qi and warming Yang, enhances the propelling function of Qi for promoting the chemotactic function of neutrophils. This study aimed to investigate the effects of Shenfu Decoction on the chemotactic function of neutrophils in septic mice and the underlying mechanisms.

Thirty 10-week-old specific-pathogen-free male C57BL/6J mice were randomly divided into five groups: sham operation, model, and low-, medium-, and high-dose Shenfu Decoction treatment groups (n = 6 in each group). Sepsis was induced using cecum ligation and puncture procedures. The sham-operated group served as the control. The drug was administered 6 h after surgery; the sham-operated and model groups received saline, while the treatment groups were gavaged every 12 h with the respective concentrations of Shenfu Decoction. Four hours after the last gavage, the mice were euthanized, and samples were collected to determine neutrophil counts and related indices. Primary neutrophils were extracted from the peripheral blood of septic mice and divided into blank control, sham-operated, low-dose, and high-dose groups. These cells were cultured with serum containing the respective treatments to measure neutrophil chemotactic distance, intracellular calcium ion concentration, and the expression levels of chemokine receptors and P2X1 receptors.

Compared with the sham-operated group, the total number of colonies and the number of neutrophils in the peritoneal lavage fluid were increased in the model group (P < 0.05). In the treatment groups, the number of neutrophils in the peritoneal lavage fluid was significantly increased (P < 0.05), while the number of neutrophils in the blood was decreased. Compared with the blank control group, the neutrophil chemotaxis distance was significantly prolonged in the sham-operated group. Additionally, the expression levels of P2X1 and FPR1 receptors were decreased, the expression levels of CXCR1 and CXCR2 receptors were increased (P < 0.05), and the calcium ion concentration was decreased (P > 0.05). Compared with the sham-operated group, the treatment groups exhibited a prolonged neutrophil chemotaxis distance, significantly decreased expression levels of P2X1 and FPR1 receptors, significantly increased expression levels of CXCR1 and CXCR2 receptors (P < 0.05), and significantly decreased calcium ion concentrations (P < 0.05). These effects were positively correlated with the Shenfu Decoction dosage.

Shenfu Decoction can improve the chemotactic function of neutrophils, possibly through the downregulation of P2X1 receptor expression. Its effects are positively correlated with the dosage.

Immunoinflammatory skin diseases are characterized by an imbalance in immune homeostasis, and their chronic inflammatory processes involve a complex regulatory network of CD4+ T cell differentiation. With the widespread use of biologics (e.g., interleukin-17/interleukin-23 inhibitors) in psoriasis, atopic dermatitis, and other diseases, the adverse effects triggered by the phenomenon of CD4+ T cell-mediated immune drift have attracted significant attention, with the skin being the primary target as an immune organ. In this paper, we provide a review of the clinical features of the skin and the mechanisms of immune drift caused by different types of biologics, as well as the therapeutic modalities.