Tropical fevers, including dengue, malaria, typhoid, chikungunya, leptospirosis, and scrub typhus, impose a substantial and growing public health burden in the tropical and subtropical regions, particularly the Indian subcontinent. Climate change, monsoon season, and inadequate sanitation further exacerbate transmission dynamics and outbreak patterns. Dehydration represents a critical yet frequently underrecognized complication of these infections. It is attributed to high-grade fever, vomiting, excessive sweating, decreased oral intake, and pathophysiological mechanisms, such as plasma leakage in dengue, hemolysis in malaria, and gastrointestinal losses in typhoid. Electrolyte disturbances, specifically hyponatremia, hypokalemia, and hypochloremia, contribute to the severity of these conditions and likelihood of multi-organ failure. Inadequate hydration amplifies underlying physiological dysfunction, including hemoconcentration, hypovolemic shock, acute kidney injury, and cardiovascular compromise, thereby increasing hospitalization rates, morbidity, and mortality. This review explores the disease-specific hydration challenges across diverse tropical fevers and evaluates the current strategies for effective fluid management. The World Health Organization (WHO), United Nations International Children's Emergency Fund (UNICEF), and national guidelines recommend oral rehydration therapy, formulated with optimized sodium and glucose concentrations to promote rehydration through facilitation of the intestinal sodium-glucose co-transporter (SGLT1) mechanism for management of ambulatory and mild-to-moderate cases. Its efficacy in symptom relief, minimizing intravenous fluid requirements, and accelerating clinical recovery is well established. However, individualized and careful calibration of fluid management remains essential to prevent fluid overload and other related complications. Thus, integrating standardized, evidence-based hydration protocols into routine clinical practice holds the potential to be a practical and cost-effective strategy for managing tropical infection in India and other regions with similar climatic and epidemiological settings.

Pulmonary fibrosis (PF) is a fatal respiratory disease characterized by abnormal repair of the pulmonary interstitium and scar formation. Currently, only nintedanib and pirfenidone are approved for clinical use, but their efficacy is limited, and they have significant side effects. The sustained inflammatory microenvironment promotes fibroblast activation and collagen deposition via unresolved inflammation, representing a central pathological mechanism in PF progression. Therefore, anti-inflammatory effects are key in relieving and treating PF. Alkaloids derived from Chinese herbal medicine have become a new hotspot in anti-PF research because of their good anti-inflammatory properties and advantages in multitarget and multipathway approaches. This review elucidates that PF is triggered by multiple factors, such as genetics, the environment, drugs, and infection, and reveals the core mechanism of its pathogenesis from the perspective of the roles of various cell types involved in PF. In this review, we focus on the experimental efficacy and mechanisms of alkaloid drugs that mitigate pulmonary fibrosis through anti-inflammatory actions. We review the research progress of experimental models and signaling pathway regulatory mechanisms to provide a reference for subsequent research. Finally, this review analyzes the transformation bottlenecks faced by alkaloids when applied to PF, such as low active ingredient content, poor target selectivity, and insufficient toxicological and clinical data. Strategies such as structural optimization, nanodelivery, multiomics validation, and real-world research are proposed to overcome these challenges, providing a reference for the development of highly efficient and low-toxicity anti-PF drugs.

Type 2 diabetes mellitus (T2D) is no longer viewed solely as a metabolic disorder but rather as a chronic, low-grade inflammatory disease shaped by the interplay of immune signaling and metabolic stress across key organs. This study explored inflammatory molecular signatures in pancreatic islets, adipose tissue (AT), and liver associated with T2D. Publicly available human genomic and transcriptomic datasets were identified through a PubMed search. Differentially expressed genes and all identified non-coding RNAs (ncRNAs) from the three tissues were subjected to bioinformatic and enrichment analyses to identify tissue-specific and common inflammatory mediators. Through integrative multi-omics and functional analyses, we delineated both shared and tissue-specific inflammatory circuits in pancreatic islets, liver, and AT, highlighting the convergence of cytokine networks, particularly TNF-α, IL-6 and IL-17, as potential mediators of inter-organ dysfunction. These cytokines can contribute to a pathological feedback loop whereby inflammatory cues originating in AT propagate to pancreatic and hepatic compartments, compounding insulin resistance and β-cell failure. AKT1, MAPK3, and CCL2 may represent key cross-tissue effectors linking inflammatory signaling and metabolic control, whose activity is also sensitive to age-related molecular drift and stress response imbalances. Additionally, ncRNAs such as miR-3064 and miR-21 emerged as potential key post-transcriptional regulators of NF-κB, IL-6 and IL-17 signaling pathways, supporting the notion that epigenetic and transcriptomic reprogramming is involved in metabolic inflammation. Overall, our findings suggest a multi-layered inflammatory architecture underlying T2D, highlighting inflammatory mediators and regulatory RNAs as potential targets for precision therapeutic strategies.

Despite significant advancements in biomaterial-guided in situ bone regeneration, treating osteoporotic bone defects remains a substantial challenge in clinical practice. The imbalance in osteoblast/osteoclast function, coupled with attenuated vascularization, leads to delayed bone repair or even nonunion, whereas the acidic, hydrogen peroxide (H2O2)-rich osteoporotic microenvironment dampens macrophage immunological responses, creating a vicious cycle of inflammation and oxidative stress that inhibits bone regeneration. To address these challenges, a versatile coordination chemistry-driven tannic acid-functionalized calcium carbonate microsphere (TCM) was tailored and incorporated into 3,4-dihydroxyphenylalanine-modified hyaluronic acid (HA-DOPA)/phenylboronic acid-modified alginate (Alg-PBA)-based dynamically crosslinked hydrogel (HDAP/TCM) to promote the reconstruction of osteoporotic bone defects through integrated immune regulation, osteoblast/osteoclast homeostasis, and revascularization. Owing to the dual-crosslinking strategy of dynamic boronate bonds and metal coordination bonds, the resulting hydrogel exhibited an interconnected porous structure, injectability, tissue adhesion, self-healing behavior, enhanced mechanical properties, and pH/ROS-responsive degradation and release under the tested conditions. The TCM incorporated into the hydrogel functions as a naturally derived photothermal stimulator to induce osteogenesis, vascular network reconstruction, and M2 macrophage polarization, as well as to neutralize acidic inflammatory conditions in the osteoporotic bone microenvironment. Moreover, the developed HDAP/TCM hydrogel platform can respond intelligently to the pathological microenvironment (pH and ROS) of osteoporosis for the on-demand release of bioactive agents (i.e., polyphenols and Ca2+), combine spatiotemporally controlled mild local hyperthermia with synergistic free-radical scavenging, alleviate inflammation, protect osteoblasts and endothelial cells from oxidative stress damage, and inhibit excessive osteoclast activation in the alkaline microenvironment generated by TCM degradation. Transcriptomic analysis revealed that HDAP/TCM improved the inflammatory microenvironment by inhibiting NF-κB signaling and altering inflammation- and macrophage polarization-related gene expression in LPS-stimulated RAW264.7 cells, thereby significantly accelerating the repair and functional reconstruction of osteoporotic bone defects. In conclusion, these findings suggest that injectable microenvironment-responsive HDAP/TCM hydrogels can be promising alternative materials for the treatment of osteoporotic bone defects.

Placental malaria (PM), driven by sequestration of Plasmodium falciparum-infected erythrocytes within the placental intervillous space, remains a major contributor to adverse maternal and fetal outcomes in endemic regions. Increasing evidence suggests that PM may also contribute to the development of preeclampsia (PE), a leading cause of maternal and perinatal morbidity and mortality worldwide. Although PM and PE arise from distinct initiating events, Plasmodium falciparum sequestration in PM and defective spiral artery remodeling in PE, both conditions converge on shared placental and systemic biological pathways. In PM, P. falciparum-infected red blood cells (iRBCs) sequester within the placental intervillous space through binding of parasite-expressed variant surface antigen 2-chondroitin sulfate A (VAR2CSA) adhesion to chondroitin sulfate A (CSA) on the syncytiotrophoblast. This sequestration, together with the accumulation of parasite derived products such as hemozoin, promotes local inflammation, syncytiotrophoblast stress, and disruption of placental vascular homeostasis. In PE, placental hypoperfusion and ischemia-reperfusion injury induce oxidative stress and abnormal trophoblast turnover. Despite these different origins, both conditions produce some overlapping patterns of placental injury including angiogenic dysregulation, characterized by elevated anti-angiogenic factors and reduced pro-angiogenic mediators. This convergence is further marked by activation of inflammatory signalling through NF-κB and inflammasome pathways, oxidative injury, complement activation, and systemic endothelial dysfunction. This review synthesizes current evidence on the shared biological pathways linking PM and PE and explores how malaria-induced placental injury may increase susceptibility to PE. We also examine the implications of overlapping biomarker signatures for diagnosis and risk stratification in malaria-endemic settings. Key knowledge gaps are highlighted, and priorities for future research are proposed to inform integrated strategies for malaria control and improved clinical management of PE in malaria-endemic settings.

Metabolic diseases and age-related disorders represent a major global health burden driven by the increasing prevalence of obesity and obesity-associated complications. These disorders are characterized by chronic disturbances in energy homeostasis. A key feature linking metabolic disease and aging is the activation of stress-related pathways, which contribute to progressive metabolic dysfunction. Among the endocrine mediators of cellular stress, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) have emerged as key regulators of metabolic homeostasis. Both are induced by similar stress conditions, including nutrient imbalance, inflammation, oxidative and endoplasmic reticulum (ER) stress and mitochondrial dysfunction, and are elevated in pathophysiological conditions such as obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD) and aging. FGF21 and GDF15 also share overlapping regulatory pathways and complementary functions, suggesting a potential coordinated regulation and functional interplay. However, the extent and physiological relevance of this possible interrelationship remain incompletely understood. This review summarizes current knowledge on the regulation, tissue sources, and signaling mechanisms of FGF21 and GDF15 across metabolic diseases and aging, with particular attention to their roles as mediators of adaptive metabolic responses and their overlapping biological actions. We further discuss their context-dependent effects under acute and chronic stress and their relevance as biomarkers of metabolic dysfunction and disease progression. Collectively, this work highlights FGF21 and GDF15 as integrated stress signals linking cellular stress to systemic metabolic adaptation, providing a conceptual framework for understanding their cooperative roles and regulation in metabolic and age-related diseases, which may have therapeutic potential.

Aggression in mental disorders is a clinically and societally highly relevant transdiagnostic phenomenon with heterogeneous developmental trajectories in childhood and adolescence: Aggressive behaviors may occur transiently and decline, but they may also stabilize across adolescence and persist into adulthood. The Collaborative Research Center Transregio 379 "Neuropsychobiology of Aggression: A Transdiagnostic Approach in Mental Disorders" investigates the biological, psychological, and social mechanisms that explain these divergent trajectories. The guiding framework is a developmental model in which aggressive biosignatures emerge from an imbalance between the developing negative valence system and cognitive control. During adolescence, reactivity to social threat, rejection, frustration, and status loss increases, while cognitive control systems continue to mature. Peers, exclusion, victimization, bullying, and puberty-related hormonal changes may shape these maturational processes. This article describes the child and adolescent developmental projects of TRR 379 and the longitudinal cohort. Understanding transdiagnostic biosignatures opens new opportunities for preventive and mechanism-based therapeutic interventions during critical windows of developmental plasticity.