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Pellino1 (Peli1) is a highly conserved E3 Ub ligase that exerts its biological functions by mediating target protein ubiquitination. Extensive evidence has demonstrated the crucial role of Peli1 in regulating inflammation by modulating various receptor signaling pathways, including interleukin-1 receptors, Toll-like receptors, nuclear factor−κB, mitogen-activated protein kinase, and phosphoinositide 3-kinase/AKT pathways. Peli1 has been implicated in the development of several diseases by influencing inflammation, apoptosis, necrosis, pyroptosis, autophagy, DNA damage repair, and glycolysis. Peli1 is a risk factor for most cancers, including breast cancer, lung cancer, and lymphoma. Conversely, Peli1 protects against herpes simplex virus infection, systemic lupus erythematosus, esophageal cancer, and toxic epidermolysis bullosa. Therefore, Peli1 is a potential therapeutic target that warrants further investigation. This comprehensive review summarizes the target proteins of Peli1, delineates their involvement in major signaling pathways and biological processes, explores their role in diseases, and discusses the potential clinical applications of Peli1-targeted therapy, highlighting the therapeutic prospects of Peli1 in various diseases.

Neuroinflammation is initiated with an aberrant innate immune response in the central nervous system (CNS) and is involved in many neurological diseases. Inflammasomes are intracellular multiprotein complexes that can be used as platforms to induce the maturation and secretion of proinflammatory cytokines and pyroptosis, thus playing a pivotal role in neuroinflammation. Among the inflammasomes, the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome is well-characterized and contributes to many neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischemic stroke. MS is a chronic autoimmune disease of the CNS, and its hallmarks include chronic inflammation, demyelination, and neurodegeneration. Studies have demonstrated a relationship between MS and the NLRP3 inflammasome. To date, the pathogenesis of MS is not fully understood, and clinical studies on novel therapies are still underway. Here, we review the activation mechanism of the NLRP3 inflammasome, its role in MS, and therapies targeting related molecules, which may be beneficial in MS.

Impedance matching is important for achieving high-efficiency microwave absorbers. The high conductivity of dielectric loss materials such as pure metals and carbon nanomaterials generally results in poor absorption owing to the low impedance matching between the absorbers and air. Carbon nanostructures are very promising candidates for high-efficiency absorption because of their attractive features including low density, high surface area, and good stability. Herein, a new strategy is proposed to improve the impedance matching of dielectric loss materials using electrospun carbon nanofibers as an example. The carbon nanofibers are coated with specifically designed gradient multilayer nanofilms with gradually increasing electroconductibility synthesized by doping ZnO with different A1203 content （AZO） by atomic layer deposition. The gradient nanofilms are composed of five layers of dielectric films, namely, pure A1203, AZO （5：1, the pulse cycle ratio of ZnO to A1203）, pure ZnO, AZO （10：1）, and AZO （20：1）. The versatile gradient films serve as intermediate layers to tune the impedance matching between air and the carbon nanofiber surfaces. Therefore, the carbon nanofibers coated with gradient films of rationally selected thicknesses exhibit remarkably enhanced microwave absorption performance, and the optimal reflection loss reaches -58.5 dB at 16.2 GHz with a thickness of only 1.8 mm. This work can help further understand the contribution of impedance matching to microwave absorption. Our strategy is general and can be applied to improve the absorption properties of other dielectric loss materials and even for applications in other fields.

Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1 -wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10 , for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

Mountain glaciers monitoring is important for water resource management and climate changes but is limited by the lack of a high-quality Digital Elevation Model (DEM) and field measurements. Sentinel 1A/1B satellites provide alternative data for glacier mass balance. In this study, we tried to generate DEMs from C-band Sentinel 1A/1B ascending and descending pass SLC images and evaluate the overall accuracy of INSAR DEMs based on Shuttle Radar Topography Mission (SRTM) DEM and ICESat/GLAS. The low Standard Deviation (STD)and Root Means Square Error (RMSE) displayed the feasibility of Sentinel 1A/1B satellites for DEM generation. Glacier elevation changes and glacier mass balance were estimated based on INSAR DEM and SRTM DEM. The results showed that the most glaciers have exhibited obvious thinning, and the mean annual glacier mass balance between 2000 and 2020 was −0.18 ± 0.1 m w.e.a−1. The south-facing and-east facing aspects, slope and elevation play an important role on glacier melt. This study demonstrates that ascending and descending orbit data of Sentinel-1A/1B satellites are promising for the detailed retrieval of surface elevation changes and mass balance in mountain glaciers.

Background and objective Droplet digital polymerase chain reaction (ddPCR) is increasingly being applied in clinical practice, with absolute quantification as one of its key advantages. This study aims to explore the significance of pathogen DNA load in evaluating the therapeutic efficacy of bloodstream infection (BSI). Methods A total of 25 hospitalized patients with bloodstream infection were enrolled as research subjects. These patients were confirmed by ddPCR testing in the Department of Infectious Diseases, Fuyang People's Hospital, and admitted between November 2024 and April 2025. All patients showed clinical improvement after treatment and were discharged. Based on ddPCR results, they were divided into the Escherichia coli (E. coli) group (n=15) and the Klebsiella pneumoniae (K. pneumoniae) group (n=10). Each patient underwent consecutive ddPCR testing three times, and data including general clinical information, laboratory test results, and sequential organ failure assessment (SOFA) scores were collected and analyzed. The study further aimed to investigate the value of dynamic changes in pathogen DNA load for evaluating efficacy of treatment in BSI and other potential clinical implications. Results Among the baseline data of two groups, the alanine aminotransferase（ALT）level in the K. pneumoniae group (52.8 U/L) was higher than that in the E. coli group (21.0U/L), and the medianl DNA load in the K.pneumoniae group(8329.2 copies/mL,[IQR]: 291.8–47722.4 copies/mL) was higher than that in the E. coli group (310.2 copies/mL,[IQR]: 129.0–1838.0 copies/mL). Meanwhile, Pearson correlation analysis showed no strong correlation between the initial DNA load and SOFA score in patients of the two groups. Dynamic observation indicated that the pathogen DNA load of BSI patients in both groups showed a decreasing trend; at the same time, the proportion of patients with normalized body temperature increased in each group. Further verification demonstrated a strong correlation between the changing trend of DNA load and C-reactive protein(CRP) as well as procalcitonin(PCT)(r ＞0.9).In addition, the rate of reduction in pathogen DNA load in the two groups was comparable to CRP and PCT. Finally, in the K. pneumoniae group, it was found when the DNA load cut-off value was set at 8329.23 copies/mL, it exhibited high sensitivity and high specificity for identifying the formation of secondary abscesses(AUC=1). Conclusion Our study demonstrates that DNA load levels of BSI vary significantly among different pathogens. More importantly, the dynamic changes in pathogen DNA load closely correlate with clinical outcomes, serving as a reliable and objective indicator to directly evaluate therapeutic efficacy in BSI patients. This highlights the practical clinical value of pathogen DNA load monitoring for real-time assessment of treatment response and optimization of clinical management strategies. Clinical trial number Not applicable.

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl , has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo , we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.

Background Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease. Methods In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice. Results The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl − efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model. Conclusions Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.

Calcium alginate (CA) beads as a green sorbent were easily fabricated in this study using sodium alginate crosslinking with CaCl2, and the crosslinking pathway was the exchange between the sodium ion of α-L-guluronic acid and Ca(II). The experimental study was conducted on Cu(II), Cd(II), Ni(II) and Zn(II) as the model heavy metals and the concentration was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The characterization and sorption behavior of the CA beads were analyzed in detail via using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adsorption experiments demonstrated that the CA beads exhibited a high removal efficiency for the selective adsorption of Cu(II) from the tetra metallic mixture solution and an excellent adsorption capacity of the heavy metals separately. According to the isotherm studies, the maximum uptake of Cu(II) could reach 107.53 mg/g, which was significantly higher than the other three heavy metal ions in the tetra metallic mixture solution. Additionally, after five cycles of adsorption and desorption, the uptake rate of Cu(II) on CA beads was maintained at 92%. According to the properties mentioned above, this material was assumed to be applied to reduce heavy metal pollution or recover valuable metals from waste water.

Background Ovarian cancer (OC) is recognized as one of the deadliest forms of gynecological cancer, approximately two-thirds of patients have already developed metastasis when they are diagnosed. The function of transmembrane protein 176B (TMEM176B) in the progression of OC remains elusive. This study aimed to investigate the role and molecular mechanism of TMEM176B on OC proliferation and metastasis. Method Expression of TMEM176B in OC and normal tissues were determined from the TCGA, GTEx, and CPTAC databases, and verified by patient-derived tissue samples. We analysed the prognostic relevance of TMEM176B in OC via Kaplan‒Meier (K‒M) survival curves and receiver operating characteristic (ROC) curves. Subsequent in vitro assays, including the CCK8 assay, colony formation assay, wound healing assay, and transwell assay, were performed to detect the influence of TMEM176B on cell proliferation and metastasis. Furthermore, a tumorigenesis study in nude mice was conducted to confirm the suppressive impact of TMEM176B on OC. RNA sequencing (RNA-seq) was utilized to uncover the mechanisms of TMEM176B on OC progression. Spearman correlation analysis was used to calculate the correlations between TMEM176B and cell adhesion, DNA replication, and the Wnt/β-catenin pathway. Finally, the role of TMEM176B in regulating the epithelial-mesenchymal transition (EMT) depending on the Wnt/β-catenin pathway was evaluated using LiCl agonist. Result The mRNA expression of TMEM176B was significantly downregulated in OC tissues, with lower TMEM176B correlating with a worse prognosis. Moreover, higher tumor stage and tumor grade were associated with a lower TMEM176B protein level. Consistent with these findings, OC tissues exhibited significantly reduced of TMEM176B compared to normal ovarian tissue from patients. In vitro studies indicated that TMEM176B knockdown increased both the proliferation, metastasis and EMT levels of OC cells, while TMEM176B overexpression had the opposite effects. In vivo investigations reinforced that TMEM176B significantly inhibited the progression of OC. RNA-seq analysis demonstrated that TMEM176B enhanced cell adhesion, diminished DNA replication, and suppressed EMT through the regulation of the Wnt/β-catenin signaling pathway, effectively obstructing the proliferation and metastasis of OC cells and impeding the disease’s progression. Conclusions TMEM176B inhibited EMT in OC cells by controlling the activation of the Wnt/β-catenin pathway. This mechanism underscored the diagnostic and prognostic potential of TMEM176B for OC and highlights its tumor-suppressive properties as a promising therapeutic candidate.