Fenpropathrin disrupted the gills of common carp (Cyprinus carpio L.) through oxidative stress, inflammatory responses, apoptosis, and transcriptional alterations.

Fenpropathrin (FEN) is an extensively utilized synthetic pyrethroid insecticide frequently found in aquatic ecosystems. However, the adverse effects and potential mechanisms of FEN on aquatic species are poorly understood. In this work, common carp were treated with FEN at concentrations of 0.45 and 1.35 µg/L FEN for 14 days, after which the tissue structure, physiological alterations, and mRNA transcriptome of the gills were evaluated. Specifically, FEN exposure caused pathological damage to the gills of carp, downregulated the levels of claudin-1, occludin, and zonula occluden-1 (ZO-1), and inhibited Na+-K+-ATPase activity in the gills. In addition, FEN exposure promoted an increase in reactive oxygen species (ROS) levels and significantly upregulated the levels of malondialdehyde (MDA), 8-hydroxy-2 deoxyguanosine (8-OHdG), and protein carbonyl (PC) in the gills. Moreover, the inflammation-related indices (TNF-α, IL-1ß, and IFN-γ) and the apoptosis-related parameter caspase-3 were generally increased, especially in the 1.35 µg/L FEN group, and these indices were significantly greater than those in the control group. These findings suggest that FEN exposure can cause oxidative stress, the inflammatory response, and apoptosis in carp gills. Importantly, the results of RNA-seq analysis showed that 0.45 and 1.35 µg/L FEN could significantly interfere with multiple immune and metabolic pathways, including the phagosome, NOD-like receptor (NLR) signalling pathway, Toll-like receptor (TLR) signalling pathway, necroptosis, and arachidonic acid metabolism pathways, indicating that the effects of FEN on the gills of fish are intricate. In summary, our findings confirm the toxic effects of FEN on common carp gills and provide additional comprehensive information for evaluating the toxicity and underlying molecular mechanisms of FEN in aquatic organisms.

Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease.

Virus infection and sphingolipid metabolism.

Cellular sphingolipids have vital roles in human virus replication and spread as they are exploited by viruses for cell entry, membrane fusion, genome replication, assembly, budding, and propagation. Intracellular sphingolipid biosynthesis triggers conformational changes in viral receptors and facilitates endosomal escape. However, our current understanding of how sphingolipids precisely regulate viral replication is limited, and further research is required to comprehensively understand the relationships between viral replication and endogenous sphingolipid species. Emerging evidence now suggests that targeting and manipulating sphingolipid metabolism enzymes in host cells is a promising strategy to effectively combat viral infections. Additionally, serum sphingolipid species and concentrations could function as potential serum biomarkers to help monitor viral infection status in different patients. In this work, we comprehensively review the literature to clarify how viruses exploit host sphingolipid metabolism to accommodate viral replication and disrupt host innate immune responses. We also provide valuable insights on the development and use of antiviral drugs in this area.

ESCRT machinery and virus infection.

The endosomal sorting complex required for transport (ESCRT) machinery plays a significant role in the spread of human viruses. However, our understanding of how the host ESCRT machinery responds to viral infection remains limited. Emerging evidence suggests that the ESCRT machinery can be hijacked by viruses of different families to enhance their replication. Throughout their life cycle, these viruses can interfere with or exploit ESCRT-mediated physiological processes to increase their chances of infecting the host. In contrast, to counteract virus infection, the interferon-stimulated gene 15 (ISG15) or the E3 ISG15-protein ligase (HERC5) system within the infected cells is activated to degrade the ESCRT proteins. Many retroviral and RNA viral proteins have evolved "late (L) domain" motifs, which enable them to recruit host ESCRT subunit proteins to facilitate virus transport, replication, budding, mature, and even endocytosis, Therefore, the L domain motifs and ESCRT subunit proteins could serve as promising drug targets for antiviral therapy. This review investigated the composition and essential functions of the ESCRT, shedding light on the impact of ESCRT subunits and viral L domain motifs on the replication of viruses. Furthermore, the antiviral effects facilitated by the ESCRT machinery have been investigated, aiming to provide valuable insights to guide the development and utilization of antiviral drugs.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Newcastle disease virus infection remodels plasma phospholipid metabolism in chickens.

Newcastle disease is a global problem that causes huge economic losses and threatens the health and welfare of poultry. Despite the knowledge gained on the metabolic impact of NDV on cells, the extent to which infection modifies the plasma metabolic network in chickens remains unknown. Herein, we performed targeted metabolomic and lipidomic to create a plasma metabolic network map during NDV infection. Meanwhile, we used single-cell RNA sequencing to explore the heterogeneity of lung tissue cells in response to NDV infection in vivo. The results showed that NDV remodeled the plasma phospholipid metabolism network. NDV preferentially targets infected blood endothelial cells, antigen-presenting cells, fibroblasts, and neutrophils in lung tissue. Importantly, NDV may directly regulate ribosome protein transcription to facilitate efficient viral protein translation. In conclusion, NDV infection remodels the plasma phospholipid metabolism network in chickens. This work provides valuable insights to further understand the pathogenesis of NDV.

Expression and Significance of Programmed Death-1 and Its Ligands in the Accelerated Formation of Atherosclerosis in an Induced Murine Lupus Model.

Atherosclerosis (AS) is a chronic inflammatory disease that occurs in artery walls, which seriously affects the survival and prognosis of patients with systemic lupus erythematosus (SLE). Immune and inflammatory responses have notable effects on all stages of AS. In this study, we modeled SLE combined with AS in vivo via intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) into apolipoprotein E-knockout (ApoE-/- ) mice that had accelerated atherosclerotic lesions compared with wild-type (WT) ApoE-/- mice. In pristane-induced ApoE-/- mice, expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in peripheral blood and on the surfaces of atherosclerotic lesions significantly increased, and levels of proinflammatory cytokines, namely, interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in peripheral blood were elevated. We did not detect expression of programmed death-ligand 2 (PD-L2) in the arterial plaques of either pristane-induced or WT ApoE-/- mice, nor did we observe any significant difference in PD-L2 expression in peripheral blood between the two groups. Taken together, these results suggested that PD-1/PD-L1 signaling pathway might play an important regulatory role in the progression of AS in an induced murine lupus model which implies a potential target for treatment of AS in SLE.