Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with high morbidity and mortality. The molecular mechanisms underlying sepsis-associated renal injury remain incompletely understood. Sinapic acid (SA), a bioactive phenolic compound, exhibits antioxidant, anti-inflammatory, and cytoprotective properties, but its nephroprotective role in LPS-induced AKI has not been clarified. We evaluated the protective effects of SA in an LPS-induced AKI rat model and examined its associations with autophagy-related, apoptotic, inflammatory, and oxidative stress markers. AKI was induced by a single intraperitoneal injection of LPS (5 mg/kg) following 7 days of oral SA pretreatment (40 mg/kg/day). LPS administration caused marked renal tubular injury and significantly increased serum BUN, CREA, and UA levels. SA pretreatment significantly attenuated these alterations. Moreover, LPS increased renal BECN1 immunoreactivity and circulating SQSTM1/p62 levels, indicating alterations in autophagy-related markers, together with increased renal TNF-α and Caspase-3 immunoreactivity. SA pretreatment significantly attenuated the LPS-induced increases in these markers. LPS also increased renal MDA levels and serum total oxidant status. SA pretreatment significantly reduced renal MDA without significantly altering SOD, GPx, or total antioxidant status, indicating attenuation of lipid peroxidation rather than a generalized enhancement of antioxidant defenses. Furthermore, SA attenuated the LPS-induced reductions in serum albumin and total protein and the increase in LDH. Collectively, these findings suggest that SA pretreatment attenuates LPS-induced AKI and that this protective effect is accompanied by changes in autophagy-related markers, reduced renal TNF-α and Caspase-3 immunoreactivity, and decreased renal lipid peroxidation.

Indole-3-acetaldoxime (IAOx) has long been placed in auxin metabolism as a tryptophan-derived precursor that may feed indole-3-acetic acid (IAA) production through indole-3-acetonitrile (IAN) and indole-3-acetamide (IAM). However, recent genetic and biochemical evidence indicates that IAOx-derived IAA formation is not adequately explained by a single obligate linear pathway. Here, we discuss an emerging model in which IAOx acts as a redox-sensitive metabolic branch point. In this model, IAOx can partition into multiple pathways. The peroxidase-dependent oxidative pathway produces nitric oxide (NO) together with indole-3-acetaldehyde (IAAld). Because IAAld can be further oxidized toward IAA, this reaction provides a potential biochemical link between NO production and IAA biosynthesis. We also highlight the upstream role of CYP79 enzymes in defining the spatial and taxonomic distribution of oxime pools, and we compare this modular plant strategy with animal nitric oxide synthase-dependent NO formation. This framework refines the relationship between IAOx metabolism, redox control, NO production, and auxin-dependent development and stress responses.

Neglected tropical diseases (NTDs) affect more than 1.6 billion people worldwide and remain major contributors to morbidity, disability, stigma, and poverty. Metabolomics has emerged as a promising approach for investigating disease-associated biochemical alterations and identifying biomarkers for diagnosis, prognosis, and treatment monitoring. This systematic review evaluated the available evidence on metabolomic profiles in WHO-defined NTDs and their potential clinical applications. MEDLINE/PubMed, Web of Science, and Scopus were searched through March 2026. Observational studies investigating metabolomic profiles in human subjects with NTDs were included, and methodological quality was assessed using a modified QUADOMICS tool. Seventy-four studies met the inclusion criteria. Most were conducted in China and Brazil and focused on dengue, onchocerciasis, schistosomiasis, leprosy, and Chagas disease. Across diseases, metabolomic alterations were predominantly observed in amino acid, lipid, carbohydrate, and energy metabolism pathways. Several candidate biomarkers were identified, including N-acetyltyramine-O-β-glucuronide for onchocerciasis, bile acid derivatives for schistosomiasis, amino acids and peptides for Chagas disease, lipid mediators for leprosy, and lipid- and serotonin-related metabolites for dengue. However, most studies remained exploratory, and only two validated biomarkers in independent populations. Risk-of-bias assessment revealed frequent methodological limitations, including inadequate reporting of pre-analytical procedures, insufficient characterization of study populations, and lack of strategies to address overfitting. Human metabolomics studies were absent for several WHO-defined NTDs, highlighting major research gaps. Future research should prioritize standardized methodologies, multicenter validation studies, and greater inclusion of underrepresented diseases and endemic populations to translate metabolomic discoveries into clinically useful tools for NTD diagnosis, monitoring, and control.

Hydrogels are attractive for flexible electronics and wearable sensors, yet their performance is severely limited at subzero temperatures due to ice crystallization, dehydration, and mechanical embrittlement. Here, we report a CaCl2-enhanced double-network (DN) hydrogel (BNP-x) that integrates excellent anti-freezing, mechanical, and adhesive properties with reliable strain-sensing capabilities. The hydrogel combines a covalently crosslinked P(NIPAm-co-HEA) network and an ionically coordinated poly(acrylic acid) network, in which Ca2+ ions regulate water states and suppress ice formation. The optimized BNP-6 hydrogel exhibits excellent low-temperature performance, maintaining a tensile strength of 0.16 MPa and an elongation at break of ∼849% at -30 °C with minimal mass loss and stable properties over repeated freeze-thaw cycles. Owing to the synergistic DN structure and mobile Ca2+ ions, BNP-6 retains high ionic conductivity (44.1 mS cm-1 at -10 °C), representing only a 17.9% decrease compared to its room-temperature value. Moreover, the hydrogel demonstrates stable adhesion, rapid strain response, and reliable sensing performance under subzero conditions-even during cyclic deformation and self-healing processes-highlighting its potential for robust low-temperature wearable electronics and bioelectronic interfaces operating in harsh environments.

Lipid nanoparticles (LNPs) have rapidly emerged as the leading delivery platform for nucleic acid therapeutics due to their high encapsulation efficiency, scalable manufacturing, and clinical success in siRNA and mRNA medicines. Poly(ethylene glycol)-lipids ((PEG)-lipids) have been central to this progress by providing steric stabilization, size control, and tunable biodistribution. However, PEGylation also introduces important limitations, including complement activation, pre-existing and treatment-induced anti-PEG antibodies, and accelerated blood clearance, which increasingly constrain repeated and long-term dosing strategies. This review focuses on recent advances in PEG-alternative LNP designs, including non-PEG polymers, zwitterionic and biomimetic lipids, polypeptides, and structurally modified PEG analogues. We compare how polymer chemistry, anchor geometry, and grafting architecture influence LNP formation, physicochemical properties, biodistribution, cellular uptake, and immunological outcomes. Moreover, we discuss key challenges that remain in translating PEG-free and PEG-modified LNPs toward clinical application and propose future directions to better understand in vivo behavior and enable rational design of next-generation stealth LNPs. Overall, PEG lipid alternatives should not be viewed as simple PEG mimics, but as distinct surface-engineering materials that create new nano-bio interfaces and reshape LNP behavior in biological systems.

Drug resistance hinders treatment success in many cancers. Sunitinib is one of the first-line treatments in renal cell carcinoma (RCC), but resistance develops during treatment. By ameliorating their angiogenic ability, tumor cells finding a different route of escape in RCC is a majorconcern. We aimed to investigate the effects of the succinic acid sunitinib combination on the angiogenesis mechanism in sunitinib-resistant renal cancer cell lines. Gene expression levels of VEGF-A, VEGF-C, PDGF-A, HIF1A, TGF-β, VHL, ANGPT1, and TIE2; protein levels of VEGF-A, HIF1A, and VHL were compared before, and after succinic acid-sunitinib combination treatment in ACHN cells that developed sunitinib resistance. In the sunitinib-resistant group, HIF1A, TGF-β, ANGPT1, and TIE2 gene expression levels were significantly decreased with a combination therapy of succinic acid at 25 µMcompared to the resistant control group. Our study focused on clarifying the increase of angiogenic factors in sunitinib-resistant RCC cells following sunitinib treatment and the subsequent changes in the combination of succinic acid as a secondary treatment agent. It is also anticipated to guide future studies exploring the potential clinical application of the combination of sunitinib and succinic acid.

Previous studies on artificial diet domestication in mandarin fish (Siniperca chuatsi) have mainly focused on feeding adaptation, digestive physiology, and basal metabolic regulation. However, whether artificial diet feeding modifies host responses to bacterial infection remains unclear. In this study, Aeromonas hydrophila was used as a bacterial challenge model to compare the responses of mandarin fish fed live bait or an artificial diet. Four groups were established: L, live bait-fed control; AL, live bait-fed infected; A, artificial diet-fed control; and AA, artificial diet-fed infected. Compared with their corresponding controls, both AL and AA showed increased lymphocyte-related indices, reduced neutrophil counts, elevated serum immune-antioxidant indices, and hepatic inflammatory cell infiltration. Compared with A, AA showed significant reductions in red blood cell percentage, mean corpuscular volume, and mean corpuscular hemoglobin. Histological observations further revealed indistinct hepatocyte boundaries and loosely arranged cytoplasm in AA compared with AL. Gene expression analysis showed that interleukin-1β was upregulated, whereas apolipoprotein B and interleukin-8 were downregulated in AA compared with A. Metabolomic analysis identified more differential metabolites in AA vs A (893) than in AL vs L (208). Shared differential metabolites were mainly enriched in nucleotide metabolism, pyrimidine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism. Metabolites specific to AL vs L were associated with amino acid metabolism, glutathione metabolism, and ABC transporters, whereas those specific to AA vs A were enriched in nucleotide metabolism, one-carbon metabolism, cofactor biosynthesis, and steroid hormone biosynthesis. Collectively, these findings demonstrate that mandarin fish fed different diets exhibit distinct immunophysiological and metabolic responses to A. hydrophila infection, with AA showing more pronounced hepatic injury and broader metabolic remodeling.

High prevalence of metabolic disease among coal workers has attracted particular attention. This study aims to investigate the relationship between urinary polycyclic aromatic hydrocarbons metabolites (OH-PAHs) and the risk of hyperuricaemia (HUA) by the baseline survey of the China-Northern Anhui Coal Workers Cohort (C-NACWC) study and explore the possible molecular mechanism. Basic information, lifestyle and occupational exposure of 2043 participants were collected via questionnaires. Serum and morning urine samples were collected simultaneously, and their urinary OH-PAHs were measured using GC-MS. In this study, 480 (23.5%) participants were diagnosed with HUA. Participants in the HUA group were younger and had a shorter work tenure, higher BMI and smoking index, and showed a dietary preference for heavy oil and salt. Logistic regression analysis suggested that 1-OHNA, 2-OHNA, 2-OHFLu and 1-OHPh contributed significantly to elevated risk of HUA after adjusting for confounding factors and false discovery rate (FDR) correction. Multivariate linear regression analysis showed that 2-OHNA and 2-OHFLu were positively correlated with uric acid concentration in serum. Notably, 1-OHNA and 2-OHNA had the highest weights among PAH metabolites in the weighted quantile sum (WQS) model and the Bayesian kernel machine regression (BKMR) model. Subgroup analysis revealed that elevated OH-PAHs were positively associated with the risk of HUA among tunneling, mining and underground auxiliary workers. Furthermore, network toxicology highlighted inflammation-related genes and IL-17 pathway as possible toxicological mechanism linking PAHs exposure and HUA. In conclusion, our findings underscore the significance of understanding the potential health risks associated with PAHs and emphasize that inflammation-related genes may be involved in the adverse effect of PAHs on HUA risk among coal workers.

Atractylodes lancea is an important medicinal crop, but viral diseases have become increasingly severe in recent years. Viruses in the genus Carlavirus are common plant pathogens that are primarily transmitted by aphids and can cause stunted growth and reduced yields in their host plants. In this study, a novel carlavirus, tentatively named Atractylodes virus A (AVA), was identified from A. lancea plants exhibiting virus-like symptoms. The full-length genome of AVA is 8,817 nt in length and contains six open reading frames, displaying the typical genomic organization of the genus Carlavirus. The replicase and CP exhibit 53.43% and 56.72% amino acid identity, respectively, with those of previously characterized carlaviruses, indicating that AVA represents a novel species in the genus Carlavirus. This study expands our understanding of viral diversity in A. lancea and provides a scientific foundation for the prevention and control of viral diseases as well as for resistance breeding.

CPPU treatment increased the supply of carbohydrates in the fruiting branches, and the upregulation of genes related to lignin synthesis improved the tensile strength of the AZ, thereby inhibiting fruitlet abscission in A. catechu. Forchlorfenuron (CPPU) is a synthetic plant growth regulator with cytokinin activity that effectively promotes cell division and expansion, thereby enhancing fruit set rate and improving fruit quality. In this study, CPPU has been verified to effectively suppress fruitlet abscission in A. catechu. The CPPU treatment resulted in a notable increase in the levels of total sugar, starch, sucrose, glucose, and lignin in the abscission zones (AZs) of A. catechu fruitlets. Concurrently, the levels of ACC (1-aminocyclopropane-1-carboxylic acid) and ABA (abscisic acid) significantly decreased, while the levels of ZR (zeatin riboside) and GA3 (gibberellic acid) significantly increased. Furthermore, totally 1,503 differentially expressed genes (DEGs) between the AZs treated by CPPU and control have been identified through RNA-Seq, including 778 upregulated and 725 downregulated genes. Within the phytohormone signaling pathways, two genes involved in GA3 signaling transduction, AcCXE and AcGAST, were significantly upregulated, while AcABI, a gene related to ABA signaling, was significantly downregulated. Additionally, genes involved in sucrose and starch metabolism pathways, such as AcSUS4 and AcFRK, and genes associated with lignin biosynthesis, including AcPAL, AcC4H, AcOMT, and AcF5H, were significantly upregulated. These results suggest that CPPU may accelerate the transport of carbohydrates in the leaves and increasing the carbohydrate supply in fruit-bearing branches, and the elevated lignin content improves the tensile strength of the AZ, thereby suppressing fruitlet abscission. These results not only provide preliminary insights into the regulatory mechanisms underlying the suppression of CPPU on fruitlet abscission, but also offer a practical strategy for improving the management of A. catechu industrial.

Postoperative nocardial infection after cranial surgery is rare and difficult to diagnose because Nocardia spp. grow slowly in conventional culture. Metagenomic next-generation sequencing (mNGS) can shorten the interval to microbial detection, but read abundance is influenced by commensal DNA and by contamination during sampling, laboratory processing, and sequencing. mNGS findings therefore require correlation with conventional microbiology and with the clinical context. An 84-year-old woman developed purulent surgical wound discharge with epidural empyema approximately 2 weeks after resection of a World Health Organization grade 4 glioblastoma and postoperative corticosteroid exposure. Revision surgery comprised extensive debridement, removal of the infected bone flap and fixation screw, and evacuation of the empyemas. Direct Gram and modified acid-fast stains of the operative specimen showed branching, acid-fast filamentous organisms on day 1. mNGS of abscess fluid reported 196,785 reads assigned to Nocardia cyriacigeorgica on day 7, and culture on buffered charcoal yeast extract agar yielded N. cyriacigeorgica on day 18, confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. More than 20 million reads were assigned to Corynebacterium tuberculostearicum, yet no corresponding coryneform predominance was seen microscopically; its significance was therefore interpreted cautiously as a possible skin-derived or background contribution, although a true polymicrobial contribution could not be excluded. Surgical source control with intravenous meropenem and amikacin was followed by resolution of the infection. Additionally, three multimodal artificial intelligence systems were each queried five times with the same prompt. mNGS enabled earlier species-level recognition of N. cyriacigeorgica than culture, but direct microscopy gave the earliest diagnostic clue and culture remained essential for confirmation and isolate recovery. Taxonomic read abundance must not be equated with causality. The artificial intelligence outputs were discordant between systems and, in one system, incorrect in a stable and reproducible way; this illustrates current limitations rather than clinical readiness and supports the need for prespecified, blinded, multi-case validation before clinical deployment.