Solid rocket motor propellant health monitoring based on oxide-doped curved long-period fiber grating.

A kind of curved long-period fiber grating(CLPFG) engraved by CO2 laser based on oxide-doped fiber was designed to monitor the structural integrity of propellant. The mechanical damage characteristics of the propellant were analyzed. The sensor model is constructed and the refractive index modulation characteristics of the CLPFG are analyzed. The strain coupling characteristics and the strain transfer efficiency of the interface between the CLPFG and the propellant are clarified. Propellant modules with implanted CLPFG were fabricated. The novel grating sensor has been effectively coated and structurally packaged. Conducted experiments on strain and temperature of propellant modules. The large strain measurement of propellant from 0 µÎµ to 24000 µÎµ is realized. Solved the thorny problem of large strain measurement for propellants. In addition, the temperature discrimination measurement in the temperature range of 30 ℃ to 250 ℃ can be realized. Sensor exhibit extremely high stability characteristics and has good compatibility with propellants. The sensor implantation and extraction structure has been designed to improve the survival rate of the sensor inside the solid rocket motors (SRM). Sensors can accurately measure the mechanical and thermal state parameters of propellants, providing effective data support for the health management of SRM.

Advance Progress in Assembly Mechanisms of Carrier-Free Nanodrugs for Cancer Treatment.

Nanocarriers have been widely studied and applied in the field of cancer treatment. However, conventional nanocarriers still suffer from complicated preparation processes, low drug loading, and potential toxicity of carriers themselves. To tackle the hindrance, carrier-free nanodrugs with biological activity have received increasing attention in cancer therapy. Extensive efforts have been made to exploit new self-assembly methods and mechanisms to expand the scope of carrier-free nanodrugs with enhanced therapeutic performance. In this review, we summarize the advanced progress and applications of carrier-free nanodrugs based on different types of assembly mechanisms and strategies, which involved noncovalent interactions, a combination of covalent bonds and noncovalent interactions, and metal ions-coordinated self-assembly. These carrier-free nanodrugs are introduced in detail according to their assembly and antitumor applications. Finally, the prospects and existing challenges of carrier-free nanodrugs in future development and clinical application are discussed. We hope that this comprehensive review will provide new insights into the rational design of more effective carrier-free nanodrug systems and advancing clinical cancer and other diseases (e.g., bacterial infections) infection treatment.

Chiral FexCuySe nanoparticles as peroxidase mimics for colorimetric detection of 3, 4-dihydroxy-phenylalanine enantiomers.

L-3,4-dihydroxy-phenylalanine (L-dopa) is the most widely used drug in Parkinson's disease treatment. However, development of cost-effective and high-throughput sensors to accurate enantioselective discrimination of L-dopa and D-dopa remains challenging to date. Herein, on the basis of the peroxidase-mimic activity of chiral FexCuySe nanoparticles, we demonstrated a novel colorimetric sensor for determination of chiral dopa. The surface chiral ligand, L/D-histidine (L/D-His), endowed the nanozymes with enantioselectivity in catalyzing the oxidation of dopa enantiomers. According to the values ofkcat/Km, the efficiency of L-His modified nanoparticles (L-FexCuySe NPs) towards L-dopa was 1.56 times higher than that of D-dopa. While, D-His can facilely reverse the preference of the nanozyme to D-dopa. On the basis of high catalytic activity and enantioselectivity of L-FexCuySe NPs in oxidation of L-dopa, the L-FexCuySe NPs-based system can be utilized for detection of L-dopa. The linear ranges for L-dopa determination were 5µM-0.125 mM and 0.125 mM-1 mM with a detection limit of 1.02µM. Critically, the developed sensor has been successfully applied in the quality control of clinical used L-dopa tablets. Our work sheds light on developing simple and sensitive chiral nanomaterials-based sensors for drug analysis.

Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy.

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.

Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus.

Intracellular protein degradation is essential for the survival of all organisms, but its role in interspecies interaction is unknown. Here, we show that the ClpXP protease of Pseudomonas aeruginosa suppresses its antimicrobial activity against Staphylococcus aureus, a common pathogen co-isolated with P. aeruginosa from polymicrobial human infections. Using proteomic, biochemical, and molecular genetic approaches, we found that this effect is due to the inhibitory effects of ClpXP on the quorum sensing (QS) of P. aeruginosa, mainly by degrading proteins (e.g., PhnA, PhnB, PqsR, and RhlI) which are critical for the production of QS signal molecules PQS and C4-HSL. We provide evidence that co-culturing with S. aureus induces a decrease in the activity of ClpXP in P. aeruginosa, an effect which was also achieved by the treatment of P. aeruginosa with N-acetylglucosamine (GlcNAc), a widespread chemical present on the surface of diverse cell types from bacteria to humans. These findings extend the range of biological events governed by proteolytic machinery to microbial community structure, thus also suggesting that a chemical-induced alteration of protein homeostasis is a mechanism for interspecies interactions.

Colorimetric determination of amyloid-ß peptide using MOF-derived nanozyme based on porous ZnO-Co3O4 nanocages.

A sensitive and rapid colorimetric biosensor has been developed for determination of amyloid-ß peptide (Aß) and study of amyloidogenesis based on the high peroxidase-like activity of porous bimetallic ZnO-Co3O4 nanocages (NCs). Due to the high binding ability of Aß monomer to ZnO-Co3O4 NCs, the catalytic activity of ZnO-Co3O4 NCs can be significantly suppressed by Aß monomer. This finding forms the basis for a colorimetric assay for Aß monomer detection. The detection limit for Aß monomer is 3.5 nM with a linear range of 5 to 150 nM (R2 = 0.997). The system was successfully applied to the determination of Aß monomer in rat cerebrospinal fluid. Critically, the different inhibition effects of monomeric and aggregated Aß species on the catalytic activity of ZnO-Co3O4 NCs enabled the sensor to be used for tracking the dynamic progress of Aß aggregation and screening Aß inhibitors. Compared with the commonly used thioflavin T fluorescence assay, this method provided higher sensitivity to the formation of Aß oligomer at the very early assembly stage. Our assay shows potential application in early diagnosis and therapy of Alzheimer's disease (AD).

Portal vein ligation alters coding and noncoding gene expression in rat livers.

Portal vein occlusion increases the resectability of initially unresectable liver cancer by inducing hypertrophy in non-occluded liver lobes. However, the mechanisms of how portal vein occlusion induces hepatic hypertrophy remain unclear. A cDNA microarray was used to identify the gene expression signatures of ligated (LLLs) and nonligated liver lobes (NLLLs) at different time points after portal vein ligation (PVL). The results of a bioinformatics analysis revealed that LLLs and NLLLs displayed different gene expression profiles. Moreover, the expression levels of both coding and noncoding RNA were different between LLLs and NLLLs at different time points after PVL. A series test of cluster analysis revealed that the No. 22 and No. 5 expression patterns, which showed altered expression at 24 h and maintained this altered expression over the following 14 days, had the lowest P values and the highest number of differentially expressed genes in both the LLLs and NLLLs. The results of a GO analysis showed the activation of hypoxia pathways in LLLs and the activation of cell proliferation and cell-cycle pathways in NLLLs, suggesting the involvement of these pathways in PVL-induced hepatic hypertrophy and regeneration. These results provide insight into the molecular mechanisms underlying hepatic hypertrophy and regeneration induced by portal vein occlusion, and they identify potential targeting pathways that can promote the clinical application of PVL in liver cancer therapy.

Rapid Construction of PVA@CDs/SiO2 Fluorescent/Structural Color Dual-Mode Anti-Counterfeiting Labels via Spray-Coating Method.

A method of sequential spraying of polyvinyl alcohol with carbon quantum dots (PVA@CDs) aqueous suspension and SiO2 aqueous suspension is proposed to rapidly prepare multicolor dual-mode anti-counterfeiting labels. With the optimization of the concentration (15%) of colloidal microspheres in the SiO2 aqueous suspension as well as the spraying process parameters (spray distance of 10 cm, spray duration of 3 s, and assembly temperature of 20 °C), different-sized SiO2 microspheres (168 nm, 228 nm, and 263 nm) were utilized to rapidly assemble red, green, and blue photonic crystals. Furthermore, the tunable fluorescence emission of carbon quantum dots endows the labels with yellow, green, and blue fluorescence. The constructed dual-mode labeling was used to develop an anti-counterfeiting code with dual-channel information storage capabilities and also to create dual-mode multicolor anti-counterfeiting labels on various packaging substrates. This work provides a novel solution for anti-counterfeiting packaging and information storage.

RNA-Seq Analysis Reveals Potential Neuroprotective Mechanisms of Pachymic Acid Toward Iron-Induced Oxidative Stress and Cell Death.

Iron dysregulation is a crucial factor in the development of neurological diseases, leading to the accumulation of reactive oxygen species (ROS) and oxidative stress, triggering inflammatory responses, and ultimately causing neurological impairment. Pachymic acid (PA) is an active ingredient extracted from the medicinal fungus Poria cocos, which has been reported with multiple pharmacological effects, including anti-inflammatory, anti-ischemia/reperfusion, and anticancer actions. In this study, we test whether PA have neuroprotection effect aganist ferrous ions induced toxicity in SH-SY5Y cells. It was found that pre-treatment with PA reduced intracellular ROS levels, increased mitochondrial membrane potential, and protected cells from apoptotic death. RNA-seq and qRT-PCR results indicated that PA can regulate the key genes IL1B, CXCL8, CCL7, and LRP1 on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as NF-κB signaling pathway, IL-17 signaling pathway, to prevent Fe2+-induced apoptotic cell death. Our research indicated that PA has potential therapeutic effects on the neuroprotection by regulating neuroinflammation and oxidative stress damage.

Discovery of an Ortho-Substituted N-Cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.

Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor.

Tumor microenvironment (TME) with the particular features of severe hypoxia, insufficient endogenous H2O2, and overexpression of glutathione (GSH) markedly reduced the antitumor efficacy of monotherapy. Herein, a TME-responsive multifunctional nanoplatform (Bi2S3@Bi@PDA-HA/Art NRs) was presented for synergistic photothermal therapy (PTT), chemodynamic therapy (CDT), and photodynamic therapy (PDT) to achieve better therapeutic outcomes. The Z-scheme heterostructured bismuth sulfide@bismuth nanorods (Bi2S3@Bi NRs) guaranteed excellent photothermal performance of the nanoplatform. Moreover, its ability to produce O2 and reactive oxygen species (ROS) synchronously could relieve tumor hypoxia and improve PDT outcomes. The densely coated polydopamine/ammonium bicarbonate (PDA/ABC) and hyaluronic acid (HA) layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ "bomb-like" release of Art. The CDT treatment was achieved by activating the released Art through intracellular Fe2+ ions in an H2O2-independent manner. Furthermore, decreasing the glutathione peroxidase 4 (GPX4) levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs. Owing to the synergistic effect, this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo. Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.

Hierarchical structure design of sea urchin Shell-Based evaporator for efficient omnidirectional Solar-Driven steam generation.

Solar-driven steam generation (SSG) is regarded as a feasible solution to the problem of fresh water scarcity. Although several attempts have been devoted to increase the efficiency of solar-to-steam conversion, it remains difficult to fabricate cost-effective, steady, and multi-angle sunlight-absorbing evaporators from readily available biomass materials. Herein, a novel hierarchical structured SSG evaporator (PDA@Shell-NaClO) is developed through a simple, low-cost, and scalable etching treatment on discarded sea urchin (SU) shells. Attributing to the dedicatedly designed microneedles array structure and porous skeleton structure of the SU shell, this PDA@Shell-NaClO evaporator shows an outstanding average light absorption performance (>90%) in a broad range of angles from 0° to 60° and exceedingly high evaporation rate of 2.81 kg m-2 h-1 under one sun condition. Furthermore, the prepared evaporator also maintains an overall stable evaporation performance and exhibits an excellent durability for a long time of up to two weeks in actual seawater. This full-ocean biomass-based SSG evaporator with plentiful raw material availability offers innovative opportunities for large-scale fresh water production.

The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

Effects of NaCl Concentration on the Behavior of Vibrio brasiliensis and Transcriptome Analysis.

The growth of Vibrio bacteria is affected by environmental conditions, and unfavorable conditions will produce different degrees of stress on Vibrio. The cells respond to the stress on the bacteria through changes in biological characteristics and transcriptomes. To study the effect of NaCl concentration on Vibrio brasiliensis, we have determined the biological characteristics of the 0%, 1%, 2%, 3%, 5%, and 7% NaCl concentrations cultured V. brasiliensis to research the salt stress to bacteria. We found that the biological properties of V. brasiliensis cultured with different NaCl concentrations were different, and the expression of outer membrane proteins of V. brasiliensis changed when it was grown under different NaCl concentrations. When bacteria cultured in higher NaCl concentrations (3%, 5% and 7% NaCl), the sodium-type flagellar protein MotY was found. Finally, the transcriptome analysis of V. brasiliensis cultured with 0% NaCl and 7% NaCl was carried out to find out the differentially expressed genes. We found that the same gene have opposite up-regulated and down-regulated expression in two treatments, indicating that these types of genes are regulated different in low and high osmotic stress.

Ion channel-targeting near-infrared photothermal switch with synergistic effect for specific cancer therapy.

Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.

Multicomponent carrier-free nanodrugs for cancer treatment.

Nanocarriers can be used to deliver insoluble anticancer drugs to optimize therapeutic efficacy. However, the potential toxicity of nanocarriers cannot be ignored. Carrier-free nanodrugs are emerging safe drug delivery systems, which are composed of multiple components, such as drugs, bioactive molecules and functional ingredients, avoiding the usage of inert carrier materials and offering advantages that include high drug loading, low toxicity, synergistic therapy, versatile design, and easy surface functionalization. Therefore, how to design multicomponent carrier-free nanodrugs is becoming a priority. In this review, the common strategies for rapid construction of multicomponent carrier-free nanodrugs are briefly explored from the perspective of methodology. The properties of organic-organic, organic-inorganic and inorganic-inorganic multiple carrier-free nanosystems are analyzed according to wettability and in-depth understanding is provided. Further advances in the applications of multiple carrier-free nanodrugs are outlined in anticipation of grasping the intrinsic nature for the design and development of carrier-free nanodrugs.

The LINC00261/MiR105-5p/SELL axis is involved in dysfunction of B cell and is associated with overall survival in hepatocellular carcinoma.

Background: Previous studies have been reported the immune dysfunction of various live tissues. However, the potential molecular mechanism of post-transcriptional regulation of immune related genes in hepatocellular carcinoma (HCC) is still not clear. We tried to identify crucial immune related biomarkers associated with HCC patients' outcomes and to reveal the transcriptional regulation. Method: The fractions of 22 immune cells in tumor and adjacent tissues were estimated by CIBERSORT. Kruskal-Wallis test and differentially expressed analyzes were used for comparative studies. Cox proportional hazard regression model, Kaplan-Meier estimates and Log-rank test were used for survival analyses. Results: From The Cancer Genome Atlas (TCGA), the gene, lncRNA and miRNA expression profiles of 379 HCC samples with clinical information were used for comparative studies. Eleven adaptive and innate immune cell types were significantly altered in HCC samples, including B cell memory, regulatory T cells and follicular helper T cells. Differentially expressed competing endogenous RNA (ceRNA) network associated with patients' overall survival was identified. Then, the novel pathway, including LINC00261, MiR105-5p and selectin L(SELL) was found and may be potential novel biomarkers for patients' outcomes and immunotherapy. Furthermore, SELL was significantly positively correlated (correlation coefficients: 0.47-0.69) with 12 known gene signatures of immunotherapy except for programmed cell death 1 (PDCD1). Conclusions: Our findings could provide insights into the selection of novel LINC00261/MiR105-5p/SELL pathway which is associated with overall survival and may impact on efficacy of immunotherapy in HCC.

Large Amino Acid Mimicking Selenium-Doped Carbon Quantum Dots for Multi-Target Therapy of Alzheimer's Disease.

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer's disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid ß peptides (Aß) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aß aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aß, leading to the ability of SeCQDs to inhibit Aß aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aß induced memory deficits, reduce Aß accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.

A New Prognostic Algorithm Predicting HCC Recurrence in Patients With Barcelona Clinic Liver Cancer Stage B Who Received PA-TACE.

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) is effective in preventing the recurrence of hepatocellular carcinoma (HCC) in patients treated with surgery. However, there is a lack of reports studying the risk factors associated with recurrence in HCC patients who received PA-TACE. In this study, we identified the independent risk factors for recurrence of HCC patients who received PA-TACE. We also developed a novel, effective, and valid nomogram to predict the individual probability of recurrence, 1, 3, and 5 years after PA-TACE. METHODS: A retrospective study was performed to identify the independent risk factors for recurrence of HCC in a group of 502 patients diagnosed in stage B based on the Barcelona Clinic Liver Cancer (BCLC) evaluation system for HCC that underwent curative resections. Then, subgroup analysis was performed for 184 patients who received PA-TACE, who were included in the training cohort. The other 147 HCC patients were included in a validation cohort. A recurrence-free survival (RFS)-predicting nomogram was constructed, and results were assessed using calibration and decision curves and a time-dependent AUC diagram. RESULTS: PA-TACE was shown to be a significant independent prognostic value for patients with BCLC stage B [p < 0.001, hazard ratio (HR) = 0.508, 95% CI = 0.375-0.689 for OS, p = 0.002; HR = 0.670, 95%CI = 0.517-0.868 for RFS]. Alpha fetoprotein (AFP), tumor number, tumor size, microvascular invasion (MVI), and differentiation were considered as independent risk factors for RFS in the training cohort, and these were further confirmed in the validation cohort. Next, a nomogram was constructed to predict RFS. The C-index for RFS in the nomogram was 0.721 (95% CI = 0.718-0.724), which was higher than SNACOR, HAP, and CHIP scores (0.587, 0.573, and 0.607, respectively). Calibration and decision curve analyses and a time-dependent AUC diagram were used. Our nomogram showed stronger performance than these other nomograms in both the training and validation cohorts. CONCLUSIONS: HCC patients diagnosed as stage B according to BCLC may benefit from PA-TACE after surgery. The RFS nomogram presented here provides an accurate and reliable prognostic model to monitor recurrence. Patients with a high recurrence score based on the nomogram should receive additional high-end imaging exams and shorter timeframes in between follow-up visits.

Phenformin inhibits cell proliferation and induces cell apoptosis and autophagy in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignant tumor and the prognosis of patients with advanced stage disease remains poor. Therefore, the identification of novel treatment agents for CCA is required. In the present study, the biological effects of the diabetes therapeutic agent, phenformin, in CCA cell lines was investigated. Cell Counting Kit­8 cell viability, cellular clone formation and subcutaneous tumor formation assays were performed, which revealed that phenformin inhibited CCA cell proliferation and growth both in vitro and in vivo. In addition, phenformin induced CCA cell apoptosis and autophagy. Phenformin partly activated the liver kinase B1 (LKB1)/5' AMP­activated protein kinase signaling pathway to exert its biological effects on CCA cell lines, as demonstrated by knockdown of LKB1, which reversed these effects. In conclusion, the present study demonstrated the biological effects of phenformin in CCA and suggested that phenformin may be a potential novel agent for CCA treatment.