Food waste-derived carbon dots (CDs) from spent coffee grounds or spinach were synthesized via hydrothermal and solvothermal methods and systematically characterized for their photoluminescence and surface chemical properties. Biological evaluations using human neural progenitor cells (hNPCs) demonstrated efficient cellular uptake and high biocompatibility across all synthesized CDs. Notably, coffee-derived blue-emitting CDs (B-CDs) exhibited robust concentration-dependent antioxidant activity and reduced intracellular reactive oxygen species (ROS) levels. In addition, B-CDs were associated with enhanced astrocytic differentiation of hNPCs. To further evaluate the antioxidative effects of B-CDs under oxidative stress conditions, cells were exposed to H2O2-induced oxidative stress during differentiation. B-CDs alleviated oxidative stress-associated cellular damage and reduced the expression of inflammation-related markers. This antioxidative effect was accompanied by the downregulation of C3, a marker of neurotoxic reactive astrocytes. Further, B-CDs promoted early phosphorylation of STAT3 (Tyr705), a key driver of astrocytic differentiation, and induced sustained expression of a cytoprotective enzyme HO-1, linking intracellular ROS reduction to astrocyte-biased differentiation. This work demonstrates that food waste-derived CDs can function as bioactive nanomaterials capable of modulating neural progenitor cell differentiation and mitigating cellular stress. These findings highlight their potential for applications in neural interface materials, regenerative medicine, and redox-responsive biomaterial systems.

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous inflammatory disease with distinct inflammatory endotypes. This study aimed to identify reliable biomarkers for precise discrimination of eosinophilic CRSwNP (eCRSwNP), and to explore their potential roles in the pathological progression of CRSwNP.MethodsA total of 107 patients with CRS (including 22 CRSsNP and 85 CRSwNP) and 40 healthy controls were enrolled. Differentially expressed proteins related to eCRSwNP were screened via protein microarray combined with the random forest algorithm. The expression of candidate proteins was validated in clinical tissues and serum. Correlation analysis and receiver operating characteristic (ROC) curves were applied to evaluate the association of candidate molecules with eosinophilic inflammation and disease prognosis. Hematoxylin and eosin (HE) staining was performed to assess histopathological changes. Human umbilical vein endothelial cells (HUVECs) were used to explore the regulatory effects of IL-13 on VCAM-1 expression and angiogenesis. siRNA knockdown and tube formation assays were further adopted to verify the functional mechanism.ResultsProtein chip and machine learning analysis identified VCAM-1 as a major molecule associated with CRSwNP endotype. VCAM-1 expression was significantly elevated in both tissue and serum of CRSwNP patients, particularly in eosinophil CRSwNP (eCRSwNP) group. HE staining showed a significant increase in neovascularization in the CRSwNP group compared to the control and CRSsNP groups, especially in the eCRSwNP. Multiplex immunofluorescence revealed increased VCAM-1/CD31 co-expression in vascular regions of eCRSwNP tissues. In vitro, IL-13 induced VCAM-1 expression in HUVECs in a time and dose-dependent manner, while VCAM-1 knockdown reduced CD31 levels and impaired angiogenesis, indicating its functional role in pathological neovascularization.ConclusionVCAM-1 is significantly upregulated in eCRSwNP and closely correlated with eosinophilic inflammation. VCAM-1 may facilitate eosinophil infiltration by participating in IL-13-mediated angiogenesis and vascular remodeling in eCRSwNP.

As a prevalent metabolic dysfunction, non-alcoholic fatty liver disease (NAFLD) represents an escalating challenge to global healthcare systems. Hepatic carboxylesterases (CES), primarily represented by the CES1 and CES2 isoforms, are important regulators of lipid homeostasis. Emerging evidence suggests that dysregulation of CES1 and CES2 contributes to hepatic lipid accumulation in NAFLD and shows promise as potential biomarkers for NAFLD diagnosis and therapeutic evaluation. Qiwei Gandanqing (QWGDQ), an ethnopharmaceutical preparation rooted in Tibetan and Chinese traditions, has demonstrated significant hepatoprotective properties. However, the precise pathways through which it orchestrates CES activity and re-equilibrates the inflammation-metabolism axis have yet to be fully elucidated. In this study, we engineered OX-CE, a liver-specific near-infrared activatable probe, to track endogenous CES fluctuations in situ. In a high-fat diet-triggered murine model, QWGDQ was found to substantially suppress hepatic steatosis and inflammatory responses. Notably, OX-CE-based imaging revealed a dose-responsive recovery of CES activity, offering a visual confirmation of the formula's therapeutic impact. Mechanistically, QWGDQ alleviates NAFLD by disrupting the antagonistic crosstalk between NF-κB-driven inflammation and PXR-mediated metabolism, thereby restoring enzymatic homeostasis. Our findings emphasize the multi-target therapeutic potential of the formula and concurrently establish the probe as a powerful molecular tool for NAFLD assessment and drug evaluation.

The gut microbiota plays a crucial role in human health, significantly influencing various physiological functions such as amino acid metabolism, which is essential for maintaining homeostasis and preventing disease. Recent progress in gut microbiota research has highlighted the intricate relationships between gut microbial communities and host amino acid metabolism, particularly in the context of cancer. This review focuses on consolidating the latest advances regarding how gut microbiota-mediated amino acid metabolism contributes to cancer development and progression. While dysbiosis has been implicated in various diseases, such as metabolic disorders, autoimmune conditions, and neurodegenerative diseases, this review specifically examines the evidence linking gut microbiota and amino acid metabolism to cancer. Current studies suggest that alterations in gut microbial composition can lead to imbalances in amino acid availability and metabolism, thereby influencing systemic inflammation, oxidative stress, and immune responses that may promote tumorigenesis. Despite these insights, significant challenges remain, including identifying specific microbial strains, deciphering their metabolic pathways, and understanding their complex interactions with host factors in cancer progression. This review aims to summarize recent preclinical and clinical investigations elucidating the mechanisms linking the gut microbiota, amino acid metabolism, and cancer, and to evaluate potential therapeutic strategies targeting the gut microbiome to modulate amino acid metabolism and improve cancer treatment outcomes. By highlighting the gut microbiota as a promising target for innovative oncological therapies, this review provides insights into microbiome-based interventions targeting amino acid-related pathways in cancer.

Chemiluminescence eliminates interference from real-time excitation light, thereby maximizing the signal-to-noise ratio of imaging. However, the reported chemiluminescent scaffolds remain limited, and the development of novel and efficient chemiluminescent scaffolds is critical and urgent. Herein, we synthesized a series of peroxynitrite (ONOO-)-activated chemiluminescent probes based on a hemicyanine scaffold through molecular engineering, and systematically investigated optical properties as well as their response mechanisms. Upon reaction with ONOO-, the vinylene units in the hemicyanine scaffold are oxidatively degraded, thereby emitting a chemiluminescent signal in the 400-650 nm wavelength range. Furthermore, under the defined conditions, it was found that the tissue penetration of ONOO--activated chemiluminescence (up to 12 mm) is deeper than that of 660 nm-activated afterglow luminescence and the fluorescence of hemicyanine scaffolds. In cell imaging, in addition to sensitive ONOO- response via chemiluminescence, it can also respond superiorly to ONOO- through well-separated dual fluorescence channels. In conjunction with satisfactory biocompatibility, the probe showed favorable responsiveness and high sensitivity toward ONOO- levels in lipopolysaccharide-induced inflammation induced. These findings provide solid and reliable experience for the discovery and construction of novel and versatile chemiluminescent scaffolds.

Rapid quantification of Mycobacterium tuberculosis (Mtb) is important for monitoring bacterial load during treatment and in clinical studies. The molecular bacterial load assay detecting Mtb 16S ribosomal RNA (TB-MBLA) can quantify mycobacterial load within hours. As the current TB-MBLA protocol includes highly toxic chemicals and manual RNA extraction, we aimed to optimize TB-MBLA for routine clinical laboratories. We compared several strategies to inactivate Mtb in sputum samples, which would facilitate analysis outside a BSL3 laboratory. Heating at 80°C for 20 min was the most efficient inactivation strategy, whereas GTC-DTT and 1 M NaOH failed to inactivate Mtb sufficiently. We used Mtb-inoculated sputum samples to compare manual phenol-chloroform RNA extraction, as recommended by the TB-MBLA protocol, to an automated magnetic bead-based extraction. Automated RNA extraction reduced total analysis time by 2 h and performed equally to phenol-chloroform extraction, with a detection limit of close to 100 CFU in 10-fold dilution series (mean Ct value: 36.0 ± 1.4 automated versus 33.5 ± 3.6 manual, n = 6). Freezing samples in lysis buffer up to 14 days did not affect TB-MBLA performance (mean Ct value: 22.6 ± 0.3 fresh versus 22.6 ± 0.6 frozen, n = 6). The final TB-MBLA protocol quantified bacterial load up to 11 days faster than time-to-positive culture (TTP) (mean TTP: 11 days, 2-24 days, n = 9) in sputum from patients with pulmonary TB. We adapted the TB-MBLA method for faster throughput in a routine clinical laboratory by using inactivation at 80°C for 20 min, followed by automated RNA extraction, achieving equal sensitivity compared to the original TB-MBLA method, and avoiding manual extraction and toxic reagents.

Tuberculosis (TB) spreads through the air, yet the physical conditions that permit effective airborne transmission remain poorly defined. Although early 20th-century guinea pig studies demonstrated efficient transmission of Mycobacterium tuberculosis (Mtb), this experimental paradigm has not been reestablished in modern high-containment facilities. Here, we show that airflow can impose constraints that suppress or permit biologically effective exposure between infected and susceptible hosts. Using a guinea pig model of animal-to-animal exposure, we combined transmission experiments with quantitative particle tracking and particle transport modeling to explain why some housing configurations fail to support effective exposure. Static environments and excessive unidirectional airflow prevented transmission, whereas controlled low-velocity airflow restored evidence of exposure, including tuberculin skin test conversion, antigen-specific immune responses, and pulmonary inflammation consistent with early infection. These findings identify airflow as a critical constraint on airborne TB transmission and establish a reproducible experimental framework for dissecting host, microbial, and environmental determinants of spread.

Bisphenol A (BPA), a prevalent endocrine disruptor and component of synthetic resins, has recently gained attention for its nephrotoxic potential. Experimental evidence demonstrates that BPA induces kidney injury through oxidative stress, inflammation, and apoptosis. BPA exposure leads to excessive production of reactive oxygen species, increased lipid peroxidation, and decreased levels of key antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, resulting in redox imbalance. Concurrently, BPA activates inflammatory cytokines, including IL-1β, IL-6, and TNF-α, as well as the NF-κB signaling pathway, which contribute to renal inflammation and tissue injury. Histopathological analyses consistently reveal glomerular congestion, tubular degeneration, and necrosis. In vitro studies further demonstrate reduced renal cell viability and enhanced apoptosis mediated by the activation of PI3K/AKT, Bcl2/Bax-caspase, and AMPK/mTOR signaling pathways. Collectively, these findings highlight BPA's ability to cause both structural and functional damage to the kidney through oxidative and inflammatory cascades. Despite advances in understanding BPA-induced nephrotoxicity, translating experimental findings to human health remains challenging due to interspecies variations, differing exposure routes, and inconsistent epidemiological data. Moreover, growing evidence suggests that BPA substitutes, such as bisphenol F and bisphenol S, possess similar endocrine-disrupting and nephrotoxic effects, raising further safety concerns. Future research should focus on elucidating mechanisms underlying BPA-induced cell cycle arrest, its long-term effects on renal repair, and susceptibility factors such as genetic and sex-specific differences. Addressing these gaps is essential for improving risk assessment and guiding regulatory measures to mitigate BPA-related kidney dysfunction.

Lipidomics-guided screening of unexplored natural product chemical space provides access to small molecules that globally reprogram cellular lipid profiles. Here, we show that the meroterpenoid cyclosmenospongine from Spongia sp. reshapes immune cell lipidomes, shifting them from pro-inflammatory toward anti-inflammatory and pro-resolving mediators. Structural variation yielded derivatives that context-dependently inhibit leukotriene biosynthesis to varying extents while upregulating pro-resolving lipid mediators, epoxyeicosatrienoic acids, endocannabinoids, sphingosine-1-phosphate, and others in resting and activated innate immune cells in vitro, as well as in self-resolving murine peritonitis and fibrosis in vivo. Mechanistically, meroterpenoids target 5-lipoxygenase or 5-lipoxygenase-activating protein, promote 15-lipoxygenase-1 translocation to particulate sites, and inhibit monoacylglycerol lipase. They also redirect arachidonic acid from neutral lipids to specific phospholipids while increasing free arachidonic acid levels. Furthermore, meroterpenoids reprogram immune cell lipid metabolism by reducing neutral lipid, triacylglycerol, and cholesteryl ester levels, a shift that correlates with a lower capacity for leukotriene biosynthesis and is phenocopied by inhibiting sterol-O-acyltransferase, which catalyzes cholesterol esterification for storage, and diacylglycerol acyltransferase-1/2, which catalyze the final step in triacylglycerol biosynthesis. In conclusion, specific meroterpenoids exert anti-inflammatory effects by rewiring lipid mediator biosynthesis through structure-controlled switches in lipid mediator classes, and an unexpected link between lipogenesis and inflammation.

The advancement of precision medicine depends critically on well-defined molecular targets. Pathologically activated fibroblasts drive disease progression in cancer, fibrosis and chronic inflammation through sustained inflammation, extracellular matrix remodeling and pathological microenvironment formation. Among available markers, fibroblast activation protein (FAP) stands out due to its selective overexpression in diseased tissues versus minimal expression in healthy organs. This unique profile makes FAP a promising target for molecular imaging and targeted therapy, enabling precision theranostics across both oncological and nononcological diseases. FAP-targeted theranostics originated from the lead compound PT-100, which established the core pharmacophore. Subsequent key advance was the replacement of the boronic acid warhead with a cyano group, along with the introduction of fluorine and quinoline moieties, yielding the UAMC-1110 scaffold. This scaffold exhibits improved bioactivity and favorable pharmacokinetics. Systematic modification of the quinoline side chain and conjugation with chelators have allowed efficient radiolabeling, positioning radiolabeled FAP inhibitors as promising tools for precision theranostics. However, continued optimization of UAMC-1110-derived probes to enhance their stability, affinity, tumor retention, and cellular uptake, together with integration into advanced strategies such as nanomedicine, remains essential not only for refining FAP-targeted precision medicine but also for expanding its applications beyond oncology to nononcological diseases. Unlike previous reviews, this Account organizes the field around a unified chemical design language, following a "rational design-pharmacokinetics-translational validation" paradigm. After delineating the core biological functions of FAP-expressing fibroblasts in disease pathogenesis, we systematically examine the rapid advancement of radionuclide-labeled FAPIs, including optimization of linkers, chelators, and albumin-binding moieties, along with multimerization strategies, which significantly enhanced the pharmacokinetic profiles. Key innovations in the field include three strategic approaches. First, the albumin-binding therapeutic agent [177Lu]Lu-EB-FAPI achieves prolonged tumor retention and promising efficacy. Second, multimerization strategies have yielded bivalent and tetrameric FAPI constructs, which exhibit superior tumor accumulation. Third, heterodimeric probes such as [68Ga]Ga-FAPI-RGD and [68Ga]Ga-FAPI-LM3 enable dual targeting of FAP along with integrin αvβ3 or somatostatin receptor SSTR2, thereby addressing tumor heterogeneity and enhancing lesion detectability. Subsequently, the application scope of FAPI-based imaging has been expanded from oncology to nononcological diseases. The value of this technique in visualizing dynamic remodeling processes across key pathologic conditions has been established, offering quantitative assessment beyond the reach of standard modalities. Furthermore, we review recent advances in diverse FAP-targeted therapeutic strategies, including nanomaterials, CAR-T cells, and vaccines, and offer a forward-looking perspective on both the potential and the ongoing challenges of FAP as a cross-disease precision theranostic platform.