Nano-energy interference: A novel strategy for blunting tumor adaptation and metastasis.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

Facile Synthesis of Polymer-Reinforced Silica Aerogel Microspheres as Robust, Hydrophobic and Recyclable Sorbents for Oil Removal from Water.

With the rapid development of industry and the acceleration of urbanization, oil pollution has caused serious damage to water, and its treatment has always been a research hotspot. Compared with traditional adsorption materials, aerogel has the advantages of light weight, large adsorption capacity and high selective adsorption, features that render it ideal as a high-performance sorbent for water treatment. The objective of this research was to develop novel hydrophobic polymer-reinforced silica aerogel microspheres (RSAMs) with water glass as the precursor, aminopropyltriethoxysilane as the modifier, and styrene as the crosslinker for oil removal from water. The effects of drying method and polymerization time on the structure and oil adsorption capacity were investigated. The drying method influenced the microstructure and pore structure in a noteworthy manner, and it also significantly depended on the polymerization time. More crosslinking time led to more volume shrinkage, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution and more compact network. Notably, the hydrophobicity increased with the increase in crosslinking time. After polymerization for 24 h, the RSAMs possessed the highest water contact angle of 126°. Owing to their excellent hydrophobicity, the RSAMs via supercritical CO2 drying exhibited significant oil and organic liquid adsorption capabilities ranging from 6.3 to 18.6 g/g, higher than their state-of-the-art counterparts. Moreover, their robust mechanical properties ensured excellent reusability and recyclability, allowing for multiple adsorption-desorption cycles without significant degradation in performance. The novel sorbent preparation method is facile and inspiring, and the resulting RSAMs are exceptional in capacity, efficiency, stability and regenerability.

Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience.

BACKGROUND: Biliary mucinous cystic neoplasms (BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. METHODS: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. RESULTS: Among the 49 patients, 37 were female (75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients (44.9%) had no symptoms. Serum carbohydrate antigen (CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34 (70.8%) had low-grade intraepithelial neoplasms (LGINs), and 14 (29.2%) had high-grade intraepithelial neoplasms (HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin (CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival (OS) of BMCNs was not reached. The longest survival time was 137 months.The 5- and 10-year OS rates were 100% and 85.4%, respectively. The 5- and 10-year recurrence-free survival (RFS) rates were 93.9% and 80.2%, respectively. CONCLUSIONS: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

Preparation and Hydration Properties of Steel Slag-Based Composite Cementitious Materials with High Strength.

Steel slag (SS) has been largely discharged but little utilized, causing an environmental problem in China. In this paper, SS-based composite cementitious materials with high strength were prepared by the high volume of SS (≥40%), granulated blast-furnace slag (GBFS), fly ash (FA), flue gas desulfurization gypsum (FGDG) and cement to promote the effective utilization of SS. The hydration and hardening properties were studied through setting time, compressive strength, length change, isothermal calorimetry (IC), X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS) tests. The results show that SS-based composite cementitious material exhibited a lower hydration heat release, an appropriate setting time, and volume stability. The SS cementitious material with 40% SS could obtain high strength of over 65 MPa at 28 days and 80 MPa at 90 days. The strength value of > 60 MPa is present in the binder, with 50% SS at 56 days. GBFS promotes hydration reactions and the formation of AFt and C-(A)-S-H gel, thus enhancing compressive strength. FA has a beneficial effect on later strength. The small and fine pore structures contribute to the development of strength. The main hydration products of SS composite cementitious materials are C-(A)-S-H gel, and ettringite (AFt), with less Ca(OH)2. The C-(A)-S-H gel with a lower Ca/Si ratio and a higher Al/Ca ratio in cementitious material, promotes mechanical properties.

Development of Regular Hydrophobic Silica Aerogel Microspheres for Efficient Oil Adsorption.

The objective of this research was to develop new hydrophobic silica aerogel microspheres (HSAMs) with water glass and hexmethyldisilazane for oil adsorption. The effects of the hexmethyldisilazane concentration and drying method on the structure and organic liquid adsorption capacity were investigated. The hexmethyldisilazane concentration of the modification solution did not influence the microstructure and pore structure in a noteworthy manner, which depended more on the drying method. Vacuum drying led to more volume shrinkage of the silica gel microsphere (SGM) than supercritical CO2 drying, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution, and more compact network. Owing to the large pore volume and pore size, the HSAMs synthesized via supercritical CO2 drying had a larger organic liquid adsorption capacity. The adsorption capacities of the HSAMs with pore volumes of 4.04-6.44 cm3/g for colza oil, vacuum pump oil, and hexane are up to 18.3, 18.9, and 11.8 g/g, respectively, higher than for their state-of-the-art counterparts. The new sorbent preparation method is facile, cost-effective, safe, and ecofriendly, and the resulting HSAMs are exceptional in capacity, stability, and regenerability.

Ethoxy-erianin phosphate and afatinib synergistically inhibit liver tumor growth and angiogenesis via regulating VEGF and EGFR signaling pathways.

The therapeutic efficacy of tyrosine kinase inhibitors (TKIs) on solid tumors is limited by drug resistance and side effects. Currently, the combination therapy comprises of TKIs and angiogenesis inhibitors have been corroborated as an effective approach in cancer therapy. Ethoxy-erianin phosphate (EBTP) is an anti-angiogenic compound with low toxicity obtained by structural modification of the natural product erianin. Here, we aimed to evaluate whether EBTP can cooperate with TKIs to inhibit the proliferation and angiogenesis of tumor cells and reduce toxic effects. First, CCK-8 results showed that EBTP can effectively inhibit the proliferation of liver cancer cell line HepG2. We combined EBTP with four TKIs (Bosutinib, Apatinib, Afatinib and Erlotinib) to treat HepG2 cells and CompuSyn software analysis suggested that EBTP/Afatinib(Afa)shows the best synergistic inhibitory effect. Meanwhile, EBTP/Afa can significantly suppress the proliferation, invasion, migration and angiogenesis of HepG2 and HUVECs. ELISA results revealed that EBTP/Afa inhibits the secretion of VEGF in HepG2. EBTP/Afa down-regulates the expression of VEGF, p-VEGFR1, p-VEGFR2 and p-EGFR in both HepG2 and HUVECs. Further, the supernatant of HepG2 cells treated with EBTP/Afa blocks the intracellular downstream signal transduction shared by VEGF and EGFR in HUVECs. Finally, EBTP/Afa significantly inhibits tumor growth and angiogenesis in vivo. To conclude, EBTP/Afa targets VEGF and EGFR signaling pathways in liver cancer cells and tumor vasculature, thereby inhibiting the proliferation, motion and angiogenesis of liver cancer cells. Overall, this study provides a new combined strategy for the clinical treatment of hepatocellular carcinoma.

Discovery of 2-(Ortho-Substituted Benzyl)-Indole Derivatives as Potent and Orally Bioavailable RORγ Agonists with Antitumor Activity.

RORγ is a dual-functional drug target, which involves not only induction of inflammation but also promotion of cancer immunity. The development of agonists of RORγ promoting Th17 cell differentiation could provide a novel mechanism of action (MOA) as an immune-activating anticancer agent. Herein, we describe new 2-(ortho-substituted benzyl)-indole derivatives as RORγ agonists by scaffold hopping based on clinical RORγ antagonist VTP-43742. Interestingly, subtle structural differences of the compounds led to the opposite biological MOA. After rational optimization for structure-activity relationship and pharmacokinetic profile, we identified a potent RORγ agonist compound 17 that was able to induce the production of IL-17 and IFNγ in tumor tissues and elicit antitumor efficacy in MC38 syngeneic mouse colorectal tumor model. This is the first comprehensive work to demonstrate the in vivo antitumor efficacy of an RORγ agonist.

The type II histidine triad protein HtpsC facilitates invasion of epithelial cells by highly virulent Streptococcus suis serotype 2.

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after co-cultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.

LncRNA CRNDE Promotes ATG4B-Mediated Autophagy and Alleviates the Sensitivity of Sorafenib in Hepatocellular Carcinoma Cells.

Autophagy is closely related to the growth and drug resistance of cancer cells, and autophagy related 4B (ATG4B) performs a crucial role in the process of autophagy. The long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) promotes the progression of hepatocellular carcinoma (HCC), but it is unclear whether the tumor-promoting effect of CRNDE is associated with the regulation of ATG4B and autophagy. Herein, we for the first time demonstrated that CRNDE triggered autophagy via upregulating ATG4B in HCC cells. Mechanistically, CRNDE enhanced the stability of ATG4B mRNA by sequestrating miR-543, leading to the elevation of ATG4B and autophagy in HCC cells. Moreover, sorafenib induced CRNDE and ATG4B as well as autophagy in HCC cells. Knockdown of CRNDE sensitized HCC cells to sorafenib in vitro and in vivo. Collectively, these results reveal that CRNDE drives ATG4B-mediated autophagy, which attenuates the sensitivity of sorafenib in HCC cells, suggesting that the pathway CRNDE/ATG4B/autophagy may be a novel target to develop sensitizing measures of sorafenib in HCC treatment.

A Pyrite Iron Disulfide Cathode with a Copper Current Collector for High-Energy Reversible Magnesium-Ion Storage.

Owing to its low cost, high theoretical capacity, and environmentally friendly characteristics, pyrite FeS2 demonstrates promise as a cathode material for high-energy metal-anode-based rechargeable batteries. When it is used in a rechargeable magnesium battery (RMB), the electrode couple exhibits an extremely low theoretical volume change upon full discharge. However, its electrochemical Mg-ion storage is considerably hindered by slow reaction kinetics. In this study, a high-performance FeS2 cathode for RMBs using a copper current collector is reported, which is involved in cathode reactions via a reversible redox process between copper and cuprous sulfide. This phase transformation with the formation of copper nanowires during discharge activates the redox reactions of FeS2 via a two-step and four-electron Mg-ion transfer that dominates the cathode reactions. As a result, the as-prepared FeS2 nanomaterial cathode delivers a significantly enhanced reversible capacity of 679 mAh g-1 at 50 mA g-1 . The corresponding energy density of 714 Wh kg-1 is superior to those of all previously reported metal chalcogenide cathodes in RMBs or hybrid batteries using a Mg metal anode. Notably, the as-assembled FeS2 -Mg battery can operate over 1000 cycles with a good capacity retention at 400 mA g-1 .

Micelle enabled C(sp2)-C(sp3) cross-electrophile coupling in water via synergistic nickel and copper catalysis.

A robust and sustainable C(sp2)-C(sp3) cross-electrophile coupling was developed via nickel/copper synergistic catalysis under micellar conditions. This protocol provided a general method to access alkylated arenes with good to excellent yields on a very large scale.

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer. This trial did not reach its efficacy end point in the intention-to-treat population. Here we show that ctDNA testing at the start of therapy (cycle 1 day 1) identified 214 (37%) patients who were positive for ctDNA and who had poor prognosis (observation arm hazard ratio = 6.3 (95% confidence interval: 4.45-8.92); P < 0.0001). Notably, patients who were positive for ctDNA had improved disease-free survival and overall survival in the atezolizumab arm versus the observation arm (disease-free survival hazard ratio = 0.58 (95% confidence interval: 0.43-0.79); P = 0.0024, overall survival hazard ratio = 0.59 (95% confidence interval: 0.41-0.86)). No difference in disease-free survival or overall survival between treatment arms was noted for patients who were negative for ctDNA. The rate of ctDNA clearance at week 6 was higher in the atezolizumab arm (18%) than in the observation arm (4%) (P = 0.0204). Transcriptomic analysis of tumours from patients who were positive for ctDNA revealed higher expression levels of cell-cycle and keratin genes. For patients who were positive for ctDNA and who were treated with atezolizumab, non-relapse was associated with immune response signatures and basal-squamous gene features, whereas relapse was associated with angiogenesis and fibroblast TGFß signatures. These data suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in patients who are positive for ctDNA and who are at a high risk of relapse. These findings, if validated in other settings, would shift approaches to postoperative cancer care.

Chemical Surface Adsorption and Trace Detection of Alcohol Gas in Graphene Oxide-Based Acid-Etched SnO2 Aerogels.

An acidified SnO2/rGO aerogel (ASGA) is an attractive contributor in ethanol gas sensing under ultralow concentration because of the sufficient active sites and adsorption pores in SnO2 and the rGA, respectively. Furthermore, a p-n heterojunction is successfully constructed by the high electron mobility between ASP and rGA to establish a brand-new bandgap of 2.72 eV, where more electrons are released and the surface energy is decreased, to improve the gas sensitivity. The ASGA owns a specific surface area of 256.1 m2/g, far higher than SnO2 powder (68.7 m2/g), indicating an excellent adsorption performance, so it can acquire more ethanol gas for a redox reaction. For gas-sensing ability, the ASGA exhibits an excellent response of Ra/Rg = 137.4 to 20 ppm of ethanol at the optimum temperature of 210 °C and can reach a response of 1.2 even at the limit detection concentration of 0.25 ppm. After the concentration gradient change test, a nonlinear increase between concentration and sensitivity (S-C curve) is observed, and it indirectly proves the chemical adsorption between ethanol and ASGA, which exhibits charge transfer and improves electron mobility. In addition, a detailed energy band diagram and sensor response diagram jointly depict the gas-sensitive mechanism. Finally, a conversed calculation explains the feasibility of the nonlinear S-C curve from the atomic level, which further verifies the chemical adsorption during the sensing process.

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial.

Atezolizumab is an anti-PD-L1 immune checkpoint inhibitor recommended for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) after prior platinum-containing chemotherapy, regardless of PD-L1 status, among other treatment settings. We conducted a long-term follow-up to the exploratory analysis of overall survival (OS) and safety for the IMvigor211 intent-to-treat (ITT) population. Patients with mUC and disease progression during or following platinum-based chemotherapy were randomised 1:1 to receive atezolizumab 1200 mg or chemotherapy (vinflunine 320 mg/m2, paclitaxel 175 mg/m2, or docetaxel 75 mg/m2 according to investigator choice) intravenously every 3 wk. Although the primary analysis did not demonstrate statistically significant longer OS for patients receiving atezolizumab versus chemotherapy, updated OS showed long-term durable remission. With a median of 33 mo of follow-up, the 24-mo OS rate was 23% with atezolizumab and 13% with chemotherapy. Safety findings were consistent with the primary analysis, with no new signals detected. Chemotherapy-treated patients experienced more grade 3/4 treatment-related adverse events (AEs; 43% vs 22%) and more AEs leading to treatment discontinuation (18% vs 9%). Atezolizumab-treated patients experienced more AEs of special interest (35% vs 20%), which tended to be grade 1-2. Our findings support the use of atezolizumab in platinum-treated patients with mUC regardless of PD-L1 status. PATIENT SUMMARY: We report follow-up results from a study of an immunotherapy treatment, atezolizumab, in patients with bladder cancer who had already received platinum-containing chemotherapy. This analysis compared the effectiveness of atezolizumab with chemotherapy over 2.5 years after starting treatment. The results show that patients who received atezolizumab lived longer and had manageable side effects compared with patients who received chemotherapy. This trial is registered at ClinicalTrials.gov as NCT02302807.

LncRNA NKX2-1-AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR-2 signaling pathway in gastric cancer.

Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, tube formation and co-culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR-145-5p; besides, the NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating the VEGFR-2 signaling pathway via SERPINE1.

Enhanced sensitivity of MoSe2 monolayer for gas adsorption induced by electric field.

According to recent studies, gas sensors based on MoSe2 have better detection performance than graphene-based sensors, especially for N-based gas molecules, but the reason for that is not fully understood at the microscopic level. Here, we investigate the adsorption of CO, CO2, NH3, NO and NO2 gas molecules on MoSe2 monolayer by the density functional theory calculations. Our results reveal that indeed MoSe2 monolayer is more sensitive to adsorption of N-containing gas molecules than C-containing, which can be attributed to the distinct charge transfer between the gas molecules and MoSe2. The conductance was further calculated using the nonequilibrium Green's function (NEGF) formalism. The reduced conductance was found for NH3 and NO2 adsorbed MoSe2, consistent with the high sensitivity of MoSe2 for NH3 and NO2 molecules in the recent experiments. In addition, the adsorption sensitivity can significantly be improved by an external electric field, which implies the controllable gas detection by MoSe2. The magnetic moments of adsorbed NO and NO2 molecules can also be effectively modulated by the field-sensitive charge transfer. Our results not only give microscopic explanations to the recent experiments, but also suggest using MoSe2 as a promising material for controlled gas sensing.

Total flavonoid aglycones extract in Radix Scutellariae induces cross-regulation between autophagy and apoptosis in pancreatic cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Scutellariae (RS), the dried root of Scutellariae baicalensis Georgi, known as a herbal medicine in several Asian countries including China, has been widely used to treat inflammation, hypertension, cardiovascular disease as well as cancer. The total flavonoid aglycone extracted (TFAE) was extracted by ethyl acetate and this extraction methodology was optimized and obtained the protection of Chinese patents. AIM OF THE STUDY: To investigate the underlying mechanism of the chemotherapeutic effects of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. MATERIALS AND METHODS: We performed CCK8 assays, AnnexinV-FITC/PI staining, flow cytometry assays, transmission electron microscopy, immunofluorescence analysis and Western blot to study the molecular mechanism of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo. RESULTS: In vitro, TFAE exhibits significant anti-tumor activity against pancreatic cancer cell lines, especially for BxPC3 (IC50 = 6.5 µg mL-1). Moreover, TFAE induces apoptosis and autophagy as evidenced by the increased apoptosis or autophagy-related protein level, the increased the fraction of apoptotic cells and the punctuate patterns of LC3 II. Furthermore, TFAE induce autophagy through PI3K/Akt/mTOR inhibition. Interestingly, pharmacological block autophagy by 3-MA enhanced TFAE-induced apoptosis, indicating that TFAE induced autophagy functions as a cytoprotective process against apoptosis. In vivo, 150 mg/kg TFAE inhibited the BxPC3 tumor growth in immune deficient mice with the inhibitory rate of 66.87% and induced both apoptosis and autophagy. CONCLUSION: TFAE have anti-tumor activity against pancreatic cancer and can induce apoptosis and autophagy through PI3K/Akt/mTOR signal pathway. TFAE might be a potential anticancer drug to be further developed for human pancreatic cancer therapy.

Robust monolithic polymer(resorcinol-formaldehyde) reinforced alumina aerogel composites with mutually interpenetrating networks.

Monolithic polymer(resorcinol-formaldehyde) reinforced alumina (RF/Al2O3) aerogel composites were prepared using a sol-gel method and supercritical fluid CO2 drying. The formation mechanism, chemical compositions, pore structures, morphologies, thermal and mechanical performances of RF/Al2O3 aerogel composites with different RF/Al molar ratios were investigated. The results show that the two networks of organic resorcinol-formaldehyde and inorganic alumina are completely independent of one another. The as-synthesized RF/Al2O3 aerogels consist of spherical organic carbon particles and fibrous alumina, which possess low bulk density (0.077-0.112 g cm-3), low shrinkage (1.55-2.76%), low thermal conductivity (0.024-0.028 W m-1 K-1), and high specific surface area (453.26-722.75 m2 g-1). Especially, the sample prepared with molar ratio RF/Al = 1 shows the best network structure with the higher compressive strength (1.83 MPa) and Young's modulus (122.57 MPa). The resulting robust RF/Al2O3 aerogel composites could be potentially used as thermal insulators, catalysts and adsorbents.

Impact factors for the outcome of the first 131I radiotherapy in patients with papillary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: To investigate the impact factors of the outcome of the first 131I treatment in patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. METHODS: Three hundred and fifty-three patients [256 females, 97 males, average age (43.58 ± 12.33 years)] with PTC after total thyroidectomy who underwent 131I treatment from July 2014 to August 2017 were retrospectively analyzed. Curative efficacy of 131I treatment was assessed 6 months afterward. Therapeutic outcome was determined according to thyrotropin (TSH)-stimulated thyroglobulin (sTg) level, 131I diagnostic whole-body scan (Dx-WBS) after 131I treatment and other imaging modalities. Twelve possible factors affecting the therapeutic outcome of 131I treatment including patients' gender, age, interval between surgery and 131I treatment, primary tumor size and extrathyroidal extension (ETE), number and range of primary tumor lesions, result of 99mTcO4- thyroid scan, number of metastatic lymph nodes (LN), pre-treatment laboratory measurements [TSH, sTg and Tg antibody (TgAb)], therapeutic dose of 131I and result of 131I post-treatment whole-body scan (Rx-WBS) were analyzed using univariate and multivariate logistic regression. The receiver operator characteristic (ROC) curve and diagnostic cutoff value were analyzed to evaluate the predictive value of the significant quantitative impact factors for the outcome of 131I treatment. RESULTS: The curative rate of the first 131I treatment in patients with PTC after total thyroidectomy was 62.32% (220/353). Univariate analysis indicated that gender, age, number and range of primary tumor lesions, number of metastatic LN, pre-treatment sTg and TgAb, therapeutic dose of 131I and result of 131I Rx-WBS (all P < 0.05) were significant factors affecting the outcome of 131I treatment. Multivariate analysis revealed that the numbers of metastatic LN (regression coefficient = 1.170) and sTg (regression coefficient = 0.280) were significant impact factors (all P < 0.001). The regression equation was: Logit P = - 3.997 + 1.170 × number of metastatic LN + 0.280 × sTg (χ2 = 210.68, P < 0.001). Taking sTg as a predictive factor for the outcome of the first 131I treatment, the area under the curve (AUC) of ROC for sTg was 0.917 (95% CI 0.890-0.944). The cutoff value of sTg was 2.69 ng/mL with a sensitivity of 92.48% (123/133) and specificity of 74.09% (163/220). CONCLUSION: Patients with PTC after total thyroidectomy with low pre-treatment sTg level and few lymph node metastases are more likely to be cured by the first 131I treatment.

MicroRNA­223 promotes hepatocellular carcinoma cell resistance to sorafenib by targeting FBW7.

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy associated with a poor patient prognosis. We investigated the relationship between microRNA­223 (miR­223) expression and the sensitivity of HCC cells to sorafenib treatment. miR­223 expression was determined in HCC cell lines with differential sorafenib sensitivity using reverse transcription­quantitative PCR. miR­223 inhibitor, miR­223 mimic, and F­box and WD repeat domain­containing 7 (FBW7) short interfering RNAs (siRNAs) were transfected into the HCC cells to regulate the expression levels of miR­223 and FBW7. Cell proliferation was evaluated using an ethynyl deoxyuridine (EdU) incorporation assay and Cell Counting Kit­8. FBW7 protein expression levels were observed using western blotting. miR­223 expression was increased in the HCC cells with sorafenib resistance. HCC cells with miR­223 knockdown had significantly increased sorafenib sensitivity, but the miR­223 mimic had the opposite effect. The TargetScan web server predicted that FBW7 is a target of miR­223, which was confirmed by western blotting. Furthermore, FBW7 siRNA transfection increased HCC cell resistance to sorafenib in an obvious manner, and entirely eliminated the effect of the miR­223 inhibitor on enhancing sorafenib sensitivity. To conclude, miR­223 expression is upregulated in sorafenib­resistant HCC cells, and miR­223 knockdown significantly enhances HCC cell sensitivity to sorafenib by increasing expression of the target gene, FBW7, suggesting that miR­223 may be a new therapeutic target for overcoming sorafenib resistance.