Anti-inflammatory activity and underlying mechanism against sepsis-induced acute lung injury of a low-molecular-weight polysaccharide from the root of Stemona tuberosa Lour.

The root of Stemona tuberosa Lour has been used to treat tuberculosis, scabies, and eczema. Polysaccharides are among its main bioactive ingredients. A low-molecular-weight (1819 Da) polysaccharide (SPS2-A) was obtained from the root of S. tuberosa Lour by optimizing three-phase partitioning, purified using an ion chromatography column, and its effects and mechanisms were investigated. Structural analysis revealed that SPS2-A contained arabinose, galactose (Gal), glucose (Glc), xylose, and mannose. The SPS2-A backbone structure comprised sugar residues →4)-α-D-Glcp-(1→, →4)-α-D-Galp-(1→, and →4,6)-ß-D-Galp-(1→, while the side chain primarily comprised α-D-Glcp-(1 â†’ connected to the O-6 position of the residue →4,6)-ß-D-Galp-(1→. In vitro, SPS2-A downregulated the expression of interleukin-6 in lipopolysaccharide-induced RAW264.7 macrophages. In vivo, SPS2-A significantly downregulated the expression of myeloperoxidase, interleukin-6, interleukin-1ß, and tumor necrosis factor-α in bronchoalveolar lavage fluid and lung tissue. Western blotting analysis indicated that SPS2-A reduced lung inflammation in mice with sepsis-induced acute lung injury by activating the nuclear factor κB pathway. These results suggest that SPS2-A is a potential anti-inflammatory candidate for the treatment of sepsis-induced acute lung injury.

Recent progress in organelle-targeting fluorescent probes for the detection of peroxynitrite.

Peroxynitrite (ONOO-), as an important reactive nitrogen species, plays a pivotal role in the regulation of intracellular redox homeostasis, signal transduction, cell growth and metabolism, and other physiological processes. Organelles are important for regulating ONOO-, and the dysregulation of ONOO- in organelles is closely related to various diseases. Therefore, it is essential to monitor ONOO- in cellular organelles, including mitochondria, lysosome, endoplasmic reticulum (ER), Golgi apparatus, and lipid droplets. However, the latest advances in organelle-targeting ONOO- fluorescent probes have not been reviewed systematically. In this review, we focus on the design, sensing mechanism, and organelle-targeting imaging applications of ONOO- fluorescent probes that were reported since 2018. This review will help to facilitate the comprehension of organelle-targeting fluorescent probes for the detection of ONOO-.

Targeted mutagenesis in Arabidopsis and medicinal plants using transposon-associated TnpB.

The programmable nuclease TnpB is significantly smaller than Cas9, can edit genes in medicinal plants, including Artemisia annua, Salvia miltiorrhiza, Scutellaria baicalensis, Isatis indigotica, and Codonopsis pilosula, and has potential uses in molecular breeding to enhance crop yield and quality.

Parabacteroides goldsteinii enriched by Pericarpium Citri Reticulatae 'Chachiensis' polysaccharides improves colitis via the inhibition of lipopolysaccharide-involved PI3K-Akt signaling pathway.

Epidemiological and preclinical studies have indicated a factual association between gut microbiota dysbiosis and high incidence of colitis. Dietary polysaccharides can specifically shift the composition of gut microbiome response to colitis. Here we validated the preventive role of polysaccharides from Pericarpium Citri Reticulatae 'Chachiensis' (PCRCP), a well-known traditional Chinese medicine, in colitis induced by dextrose sodium sulfate (DSS) in both rats and mice. We found that treatment with PCRCP not only significantly reduced DSS-induced colitis via down-regulating colonic inflammatory signaling pathways including PI3K-Akt, NLRs and NF-κB, but also enhanced colonic barrier integrity in rats. These protective activities of PCRCP against DSS-induced injuries in rats were in part due to the modulation of the gut microbiota revealed by both broad-spectrum antibiotic (ABX)-deleted bacterial and non-oral treatments. Furthermore, the improvement of PCRCP on colitis was impaired by intestinal neomycin-sensitive bacteria in DSS-exposed mice. Specifically, in vivo and in vitro treatment with PCRCP led to a highly sensible enrichment in the gut commensal Parabacteroides goldsteinii. Administration of Parabacteroides goldsteinii significantly alleviated typical symptoms of colitis and suppressed the activation of PI3K-Akt-involved inflammatory response in DSS-exposed mice. The anti-colitic effects of Parabacteroides goldsteinii were abolished after the activation of PI3K-Akt signaling pathway by lipopolysaccharide treatment in mice exposed to DSS. This study provides new insights into an anti-colitic mechanism driven by PCRCP and highlights the potential prebiotic of Parabacteroides goldsteinii for the prevention of ulcerative colitis.

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

Colonization by the endophytic fungus Phyllosticta fallopiae combined with the element Si promotes the growth of Dendrobium nobile.

Endophytic fungi can promote plant growth and development, particularly of Orchidaceae species. Previously, we found that the endophytic fungus Phyllosticta fallopiae DN14, collected from Dendrobium nobile growing on rocks in a wild habitat, significantly promoted growth of its host plant D. nobile, an important herb in Chinese traditional medicine that contains the bioactive component dendrobine. Phyllosticta was positively correlated with FW and dendrobine content of D. nobile and with Si content of the epiphytic matrix. Si is also highly beneficial for the growth and productivity of many plants. Here, we co-cultured D. nobile with P. fallopiae DN14 in half-strength Murashige and Skoog medium with and without various concentrations of Si to investigate the effects of DN14 and Si on plant fresh weight and dendrobine content. We also explored the effects of DN14 infection and colonization on host plant growth, Si accumulation and transport, and expression of key genes, as well as the interaction between DN14 and Si. The combination of DN14 and Si promoted the lignification of D. nobile roots, stems, and leaves and markedly increased the thickening of xylem cell walls. Co-culture with DN14 increased transport of Si from roots to stems and from stems to leaves. Transcriptome sequencing and qRT-PCR analyses showed that enhancement of D. nobile growth by DN14 and Si may involve upregulation of plant hormone-related genes (AUX/IAA and MYC) and lignin biosynthesis genes (HCT, PAL1, and PAL2). Insoluble Si promoted the growth of DN14, perhaps through downregulation of genes (e.g., FBP, MPI, RPIAD) related to carbohydrate metabolism, and DN14 in turn promoted the transformation of insoluble Si into soluble Si for plant uptake. These findings demonstrate that endophytic fungi and Si can improve the growth of D. nobile and therefore show promise as organic amendments for commercial cultivation.

Radiomics analysis using magnetic resonance imaging of bone marrow edema for diagnosing knee osteoarthritis.

This study aimed to develop and validate a bone marrow edema model using a magnetic resonance imaging-based radiomics nomogram for the diagnosis of osteoarthritis. Clinical and magnetic resonance imaging (MRI) data of 302 patients with and without osteoarthritis were retrospectively collected from April 2022 to October 2023 at Longhua Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. The participants were randomly divided into two groups (a training group, n = 211 and a testing group, n = 91). We used logistic regression to analyze clinical characteristics and established a clinical model. Radiomics signatures were developed by extracting radiomic features from the bone marrow edema area using MRI. A nomogram was developed based on the rad-score and clinical characteristics. The diagnostic performance of the three models was compared using the receiver operating characteristic curve and Delong's test. The accuracy and clinical application value of the nomogram were evaluated using calibration curve and decision curve analysis. Clinical characteristics such as age, radiographic grading, Western Ontario and McMaster Universities Arthritis Index score, and radiological features were significantly correlated with the diagnosis of osteoarthritis. The Rad score was constructed from 11 radiological features. A clinical model was developed to diagnose osteoarthritis (training group: area under the curve [AUC], 0.819; testing group: AUC, 0.815). Radiomics models were used to effectively diagnose osteoarthritis (training group,: AUC, 0.901; testing group: AUC, 0.841). The nomogram model composed of Rad score and clinical characteristics had better diagnostic performance than a simple clinical model (training group: AUC, 0.906; testing group: AUC, 0.845; p < 0.01). Based on DCA, the nomogram model can provide better diagnostic performance in most cases. In conclusion, the MRI-bone marrow edema-based radiomics-clinical nomogram model showed good performance in diagnosing early osteoarthritis.

N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

GhVIM28, a negative regulator identified from VIM family genes, positively responds to salt stress in cotton.

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

Chemical Composition of Essential Oil from Citrus reticulata Blanco cv. Chachiensis (Chachi) and Its Anti-Mosquito Activity against Pyrethroid-Resistant Aedes albopictus.

The overuse of synthetic insecticides has led to various negative consequences, including insecticide resistance, environmental pollution, and harm to public health. This may be ameliorated by using insecticides derived from botanical sources. The primary objective of this study was to evaluate the anti-mosquito activity of the essential oil (EO) of Citrus reticulata Blanco cv. Chachiensis (Chachi) (referred to as CRB) at immature, semi-mature, and mature stages. The chemical compositions of the CRB EO were analyzed using GC-MS. The main components were identified to be D-limonene and γ-terpinene. The contents of D-limonene at the immature, semi-mature, and mature stages were 62.35%, 76.72%, and 73.15%, respectively; the corresponding contents of γ-terpinene were 14.26%, 11.04%, and 11.27%, respectively. In addition, the corresponding contents of a characteristic component, methyl 2-aminobenzoate, were 4.95%, 1.93%, and 2.15%, respectively. CRB EO exhibited significant larvicidal activity against Aedes albopictus (Ae. albopictus, Diptera: Culicidae), with the 50% lethal doses being 65.32, 61.47, and 65.91 mg/L for immature, semi-mature, and mature CRB EO, respectively. CRB EO was able to inhibit acetylcholinesterase and three detoxification enzymes, significantly reduce the diversity of internal microbiota in mosquitoes, and decrease the relative abundance of core species within the microbiota. The present results may provide novel insights into the utilization of plant-derived essential oils in anti-mosquitoes.

Anticancer efficacy triggered by synergistically modulating the homeostasis of anions and iron: Design, synthesis and biological evaluation of dual-functional squaramide-hydroxamic acid conjugates.

Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron. Among them, compound 16 exhibited the most potent antiproliferative activity against a panel of selected cancer cell lines, and strong in vivo anti-tumor efficacy. This compound effectively elevated lysosomal pH through anion transport, and reduced the levels of intracellular iron. Compound 16 could disturb autophagy in A549 cells and trigger robust apoptosis. This compound caused cell cycle arrest at the G1/S phase, altered the mitochondrial function and elevated ROS levels. The present findings clearly demonstrated that synergistic modulation of anion and iron homeostasis has high potentials in the development of promising chemotherapeutic agents with dual action against cancers.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Research on Fault Prediction Method of Elevator Door System Based on Transfer Learning.

The elevator door system plays a crucial role in ensuring elevator safety. Fault prediction is an invaluable tool for accident prevention. By analyzing the sound signals generated during operation, such as component wear and tear, the fault of the system can be accurately determined. This study proposes a GNN-LSTM-BDANN deep learning model to account for variations in elevator operating environments and sound signal acquisition methods. The proposed model utilizes the historical sound data from other elevators to predict the remaining useful life (RUL) of the target elevator door system. Firstly, the opening and closing sounds of other elevators is collected, followed by the extraction of relevant sound signal characteristics including A-weighted sound pressure level, loudness, sharpness, and roughness. These features are then transformed into graph data with geometric structure representation. Subsequently, the Graph Neural Networks (GNN) and long short-term memory networks (LSTM) are employed to extract deeper features from the data. Finally, transfer learning based on the improved Bhattacharyya Distance domain adversarial neural network (BDANN) is utilized to transfer knowledge learned from historical sound data of other elevators to predict RUL for the target elevator door system effectively. Experimental results demonstrate that the proposed method can successfully predict potential failure timeframes for different elevator door systems.

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A.

Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Baicalin-2-ethoxyethyl ester alleviates gentamicin-induced acute kidney injury via NF-κB signaling pathway.

Drug nephrotoxicity has high fatality rates and complications. To study this conditional, traditionally, Gentamicin (GM) is used to induce acute injury and establish a nephrotic syndrome model. Baicalin, a flavonoid derived from baicalin with potent anti-inflammatory and antioxidant activity, has been used to treat various inflammatory diseases. This study aims to investigate the process of baicalin-2-ethoxyethyl ester (BAE) synthesis and its therapeutic effect on GM-induced acute kidney injury (AKI). Briefly, baicalin was processed by various reactions to yield BAE. A GM-induced AKI model was established for in vivo evaluation of the protective effect and mechanism of BAE. The results indicated that BAE reduced serum creatinine and urea nitrogen levels and improved pathological alterations, inflammatory responses, and oxidative stress in renal tissues. Furthermore, it was revealed that BAE might exert anti-inflammatory and anti-oxidative responses during AKI via the NF-κB signaling pathway regulation. The findings imply that BAE has a protective impact on the kidneys and might serve as a potent medicine for treating renal damage.

Prognostic nomogram model for selecting between transarterial chemoembolization plus lenvatinib, with and without PD-1 inhibitor in unresectable hepatocellular carcinoma.

OBJECTIVES: To establish and verify a prognostic nomogram model for selecting in unresectable hepatocellular carcinoma (uHCC) treated by transarterial chemoembolization plus lenvatinib (TACE-L) with or without PD-1 inhibitor. METHODS: Data of 241 uHCC patients who underwent TACE-L (n = 128) and TACE-L plus PD-1 inhibitor (TACE-L-P, n = 113) were retrospectively reviewed. The differences in tumour responses, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between two groups were compared, and a prognostic nomogram model was established based on independent clinical-radiologic factors and confirmed by Cox regression analysis for predicting PFS and OS. The treatment selection for uHCC patients was stratified by the nomogram score. RESULTS: Compared to TACE-L, TACE-L-P presented prolonged PFS (14.0 vs. 9.0 months, P < .001), longer OS (24.0 vs. 15.0 months, P < .001), and a better overall objective response rate (54.0% vs. 32.8%, P = .001). There was no significant difference between the rate of AEs in the TACE-L-P and the TACE-L (56.64% vs. 46.09%, P = .102) and the rate of grade ≥ 3 AEs (11.50% vs. 9.38%, P = .588), respectively. The nomogram model presented good discrimination, with a C-index of 0.790 for predicting PFS and 0.749 for predicting OS. Patients who underwent TACE-L and obtained a nomogram score >9 demonstrated improved 2-year PFS when transferred to TACE-L-P, and those with a nomogram ≤25 had better 2-year OS when transferred to TACE-L-P. CONCLUSIONS: TACE-L-P showed significant improvements in efficiency and safety for uHCC patients compared with TACE-L. The nomogram was useful for stratifying treatment decisions and selecting a suitable population for uHCC patients. ADVANCES IN KNOWLEDGE: Prognostic nomogram model is of great value in predicting individualized survival benefits for uHCC patients after TACE-L or/and TACE-L-P. And the nomogram was helpful for selection between TACE-L-P and TACE-L among uHCC patients.

A novel donor-acceptor fluorescent probe for the fluorogenic/ chromogenic detection and bioimaging of nitric oxide.

Nitric oxide (NO) plays an essential role in regulating various physiological and pathological processes. This has spurred various efforts to develop feasible methods for the detection of NO. Herein we designed and synthesized a novel donor-acceptor fluorescent probe Car-NO for the selective and specific detection of NO. Reaction of Car-NO with NO generated a new donor-acceptor structure with strong intramolecular charge transfer (ICT) effect, and led to remarkable chromogenic change from yellow to blue and dramatic fluorescence quenching. Car-NO exhibited high selectivity, excellent sensitivity, and rapid response for the detection of NO. In addition, the nanoparticles prepared from Car-NO (i.e., Car-NO NPs) showed strong NIR emission and high selectivity/sensitivity. Car-NO NPs was successfully employed to image both endogenous and exogenous NO in HeLa and RAW 264.7 cells. The present findings reveal that Car-NO is a promising probe for the detection and bioimaging of NO.