2026年 · 第09卷第02期

The vestibular system contributes to our sense of proprioception and equilibrium, interacting with all body systems through projections to different brain areas. However, the molecular consequences of vestibular disturbance remain unclear. Here, we performed longitudinal multiomics analyses of urine, stool, and saliva from 3 cohorts participating in ocean voyages and their corresponding counterparts who remained on land. On board, proteins involved in the vestibulo-ocular reflex and musculoskeletal systems were down-regulated, and the endocrine and cardiovascular systems exhibited potentially detrimental alterations. Neuronal ephrin receptors and proteins in the endolysosomal system were down-regulated, whereas neuroprotective and neurometabolic processes were up-regulated. Remodeling of the neuronal and immune systems altered host–microbial interactions, reducing neurotransmitter–bacteria associations, suppressing bacteria–host cometabolism, and reducing the Prevotella abundance. Participants in the smaller vessel exhibited more pronounced neuronal and immune alterations. Furthermore, compared with non-seasick individuals, seasick individuals presented lower levels of endolysosomal proteins and a higher Prevotella abundance. This study provides a valuable resource for understanding the transition from living on land to living on the ocean and vestibular stress-related molecular changes.

Background: Artemisinin-based combination therapies remain the first-line treatment for Plasmodium falciparum malaria. However, emerging resistance, often linked to mutations in the Kelch 13 (pfk13) gene, poses a substantial threat to malaria control efforts.This study investigated the molecular profile of pfk13 in P. falciparum isolates from a health facility in Warri, South-South Nigeria. Methods: A total of 284 patients were screened using rapid diagnostic tests. Genomic DNA was extracted from 50 confirmed cases using Whatman filter paper-collected samples. The pfk13 gene was amplified through nested polymerase chain reaction, sequenced, and analyzed using Qiagen CLC Genomics Workbench (v23.0.1). The sequences were aligned to those of the reference P. falciparum 3D7 strain (PF3D7 _1343700), and the translated amino acid sequences were subsequently examined for mutations. Results: Among the 50 isolates, 43 nonsynonymous mutations were identified, including 16 novel and previously unreported variants: E9K, K10N4, K15V, K17R, A21K, S23I, I24E, S25K, F27I, S28V, N40K, D42K, D43K, D44R, S45Y, and G46Y. None of the validated pfk13 mutations known to confer artemisinin resistance were detected. Conclusion: Although no validated resistance-associated mutations were detected, the identification of multiple novel nonsynonymous variants may reflect the ongoing regional evolutionary dynamics of the pfk13 gene in P. falciparum. These findings underscore the need for functional and phenotypic studies to elucidate the potential role of these variants in modulating artemisinin susceptibility.

Objectives: To investigate the diagnostic value of prostate-specific antigen density (PSAD), prostate volume (PV), free prostate-specific antigen (fPSA), total prostate-specific antigen (tPSA), and fPSA/tPSA in prostate cancer (PCa) and to construct a risk prediction model based on analyzed risk factors. Methods: Age, Gleason score of pathological biopsy, PV, fPSA, tPSA, fPSA/tPSA, and PSAD were retrospectively analyzed, and accuracy of the predictive model was evaluated using receiver operating characteristic curve and logistic regression analyses. An age × PSAD product term was introduced to test the interaction between age and PSAD, and the predictive efficacy of PSAD stratified by age was evaluated. Results: Multivariate logistic regression analysis suggested that PV, fPSA, tPSA, fPSA/tPSA, and PSAD were independent risk factors for PCa (P < 0.05). The area under the curve of nomogram model constructed on this basis was 0.855, indicating that the model has good discrimination ability. There was a significant interaction effect between age and PSAD (P for interaction = 0.011). Stratified analysis revealed that predictive effect of PSAD was strongest in the 60-to 70-year-old group (odds ratio [OR] = 46.55, 95% confidence interval [CI]: 24.24 to 89.40) and relatively weaker in the <60-year-old group (OR = 30.93, 95% CI: 10.36 to 92.38) and the >70-year-old group (OR = 33.54, 95% CI: 19.38 to 58.05) (all P < 0.001). Conclusion: The nomogram model constructed based on PV, fPSA, tPSA, fPSA/tPSA, and PSAD can effectively predict the probability of PCa occurrence. Among these factors, the predictive value of PSAD is age dependent and particularly prominent in individuals aged 60 to 70 years.

The prevalence of diabetes mellitus (DM) is increasing because of lifestyle factors including a sedentary lifestyle, poor food choices, and a genetic predisposition. DM has become a major concern in global health. Metabolism, immunological function, and insulin sensitivity are profoundly affected by the complex population of bacteria residing in the gastrointestinal tract, collectively termed the gut microbiota. Many different types of DM, including type 1 DM, type 2 DM, gestational DM, maturity-onset diabetes of the young, and neonatal DM, are intimately linked with the gut microbiota, according to recent research. This review provides a comprehensive overview of how changes in the makeup of the gut microbiota affect the development of DM through insulin resistance, dysregulation of glucose metabolism, and systemic inflammation. This review also discusses how prebiotics, probiotics, nutrition, and fecal microbiota transplantation can modulate the gut microbiota and thus offer therapeutic potential. New possibilities for the prevention and control of diabetes may emerge with a better understanding of the role of the gut microbiota in the pathogenesis of DM. Future studies should aim to elucidate particular microbial signatures of DM and develop targeted interventions that reconstitute microbial homeostasis to improve glycemic control and metabolic well-being.

Prostate cancer is a serious global health issue, particularly among older males, with genetic susceptibility playing a critical role in its development and progression. This review synthesizes recent advances in understanding the genetic factors contributing to prostate cancer risk, including both hereditary and somatic mutations. A detailed literature search was conducted using databases such as PubMed, Scopus, ProQuest, and Web of Science. Genome-wide association studies have identified numerous single-nucleotide polymorphisms associated with increased susceptibility, while rare variants in genes such as BRCA1, BRCA2, HOXB13, and DNA mismatch repair genes have been linked to more aggressive disease phenotypes. Moreover, insights into polygenic risk scores offer potential for improved risk stratification and personalized screening strategies. Emerging evidence also highlights the influence of racial and ethnic disparities in the genetic risk of prostate cancer and how genetic profiling can be used to facilitate the use of targeted treatments, such as poly(adenosine-diphosphate-ribose) polymerase inhibitors, which are particularly effective in patients harboring BRCA mutations. This review underscores the importance of integrating genetic information into clinical practice to enhance early detection, tailor treatment approaches, and improve outcomes in patients with prostate cancer.

Background: Autologous adipose tissue transfer has evolved from simple volumetric augmentation to sophisticated regenerative procedures. Understanding the biological principles underlying fat grafting success is essential for optimal clinical outcomes. Objective: The aim to this study is o provide a comprehensive narrative review of adipose tissue biology, technical variations in fat grafting (macrofat, microfat, nanofat, and microfiltrate), and their clinical applications, with an emphasis on microfiltration parameters that preserve tissue progenitor cells. Methods: A narrative review was conducted by searching the PubMed, Scopus, and Web of Science databases (2010–2025) using terms related to autologous fat grafting, adipose-derived stem cells, and regenerative medicine. Both original research and review articles were included to provide a comprehensive overview of the current evidence. Key Findings from Literature: Current evidence demonstrates that adipose tissue contains approximately 4,500 adiposederived stem cells per milliliter, representing a 45-fold higher concentration than the bone marrow. Studies indicate that macrofat and microfat provide volumetric restoration with 30% to 60% longterm retention, whereas nanofat improves tissue quality through mechanical emulsification. Emerging evidence supports microfiltration at 20 to 40 microns for the selective isolation of tissue progenitors (17.9 to 30.4 microns), while excluding inflammatory debris that activates Toll-like receptor 4-mediated fibrotic pathways. Graft survival depends critically on atraumatic harvesting, minimal processing, and adequate revascularization within the first 7 d posttransplantation. Conclusion: Successful fat grafting requires biology-based technical choices. Understanding adipose tissue components, cellular viability parameters, and size-selective processing enables rational treatment selection across volumetric, regenerative, and tissue quality applications. Microfiltration at 20 to 40 microns represents an evidence-based approach for regenerative procedures requiring high progenitor concentrations without a volumetric contribution.

As a revolutionary breakthrough in cancer treatment, messenger RNA(mRNA)-based nanomedicine provides a versatile and programmable platform to elicit strong antitumor responses. In contrast to conventional treatments, mRNA can encode therapeutic proteins, immune activators, or tumor antigens, allowing for highly individualized treatment plans. However, efficient delivery is still a major problem that has been solved by the creation of nanocarriers such as lipid nanoparticles, polymeric vectors, and exosome mimics. These systems reduce off-target effects while improving stability, cellular uptake, and tumor targeting. With an emphasis on delivery methods, clinical pharmacokinetics, tumor penetration, metabolism, and immune pharmacodynamics, this review offers a thorough summary of mRNA nanomedicine in oncology. The safety profiles and efficacy signals of important clinical trials, including Moderna’s mRNA-4359 for NSCLC treatment and BNT111 for melanoma treatment, have been analyzed. Practical considerations for real-world integration, such as the preparation, monitoring, and patient education responsibilities of pharmacists and oncologists, are also covered. Clinical decision-making is supported by the use of visual aids such as radar charts and comparative summary tables, which help to simplify complex datasets. The development of adherence support tools for pharmaceutical practice, artificial intelligence-driven immune response prediction, and customized mRNA design are highlighted as future directions. Success in the journey of mRNA nanomedicine from bench to bedside will rely on interdisciplinary cooperation, strong regulatory frameworks, and medical staff prepared to handle these cutting-edge treatments. The purpose of this article is to help physicians, researchers, and pharmacy professionals navigate the rapidly changing field of mRNA therapeutics in oncology.

Acute myeloid leukemia (AML), a hematologic malignancy characterized by poor prognosis, frequent relapse, and resistance to standard therapies, remains challenging to treat. Recent advances in targeted therapy have offered limited success because of the incomplete eradication of leukemic stem cells and the emergence of drug resistance. Proteolysis-targeting chimeras (PROTACs) represent a novel therapeutic paradigm that facilitates the selective degradation of oncogenic proteins through the recruitment of E3 ubiquitin ligases. Unlike traditional inhibitors, PROTACs operate via an event-driven mechanism, enabling catalytic and often more durable suppression of disease-driving proteins. This review explores the mechanistic foundation of PROTACs and highlights their application against key molecular targets in AML, including BRD4, FLT3, CDK9, BCL-xL, and MLL fusion co-factors. Preclinical data demonstrate that PROTACs not only enhance therapeutic efficacy but also overcome the limitations of conventional inhibitors. Challenges such as pharmacokinetic limitations, tissue specificity, off-target effects, and manufacturing complexity are discussed alongside emerging strategies such as dual degraders, conditional activation, and biomarker-guided precision therapy. With ongoing advances, PROTACs hold substantial promise as next-generation agents capable of transforming AML treatment, particularly for relapsed and refractory cases.