Comparison of the value of adipose tissues in abdomen and lumbar vertebra for predicting disease activity in Crohn's disease: A preliminary study based on CSE-MRI.

BACKGROUND: To compare the value of adipose tissues in abdomen and lumbar vertebra for predicting Crohn's disease (CD) activity based on chemical shift encoded magnetic resonance imaging (CSE-MRI). METHODS: 84 CD patients were divided into remission, mild, and moderate-severely groups based on CD activity index (CDAI). Differences in different adipose parameters [subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), mesenteric fat index (MFI), and bone marrow fat fraction (BMFF)] and blood inflammatory indicators among three groups, as well as the correlation of above parameters and CDAI were analyzed. The areas under the receiver-operating characteristic curves (AUCs) for the parameters selected by multivariate logistic regression analysis for predicting active CD were calculated. RESULTS: There were no significant differences in VAT and MFI among three groups (both P > 0.05). The cross-sectional areas of SAT in moderate-severe group were significantly lower than those in remission group (P = 0.014). BMFF values of remission group were significantly higher than those in the mild and moderate-severe groups (both P < 0.001). BMFF was negatively correlated with CDAI (r = -0.595, P < 0.001). SAT exhibited no significant correlation with CDAI. Erythrocyte sedimentation rate (ESR) and BMFF were the independent predictors of CDAI. Both combined had a higher diagnostic efficacy for active CD with an AUC of 0.895. CONCLUSIONS: BMFF is the best marker for predicting CD activity in fat parameters of abdomen and lumbar vertebra based on CSE-MRI. The model based on BMFF and ESR has a high efficiency in predicting active CD. TRIAL REGISTRATION: No. 22 K164 (Registered 18-07-2022).

Experimental and Numerical Study on Hysteretic Behavior of Frictional Energy Dissipation Steel Truss.

In this study, the hysteretic behavior of a novel frictional energy dissipation steel truss (FED-ST) is examined. The proposed FED-ST incorporates a friction damper with brass as the friction material into the top chord of traditional truss to improve the seismic performance of the staggered truss framing systems. A FED-ST specimen with a scale of 1:2.5 was subjected to a hysteresis test. The hysteretic behavior, ductility, and energy dissipation capability were analyzed considering the test findings. It is demonstrated that the FED-ST specimen has favorable ductility and an energy dissipation capacity that is 7.3 times more than that of a conventional truss specimen. The test findings were then used to compare and validate a finite element (FE) model. The FE analysis results are in strong agreement with the test results, demonstrating the validity of the modeling approach. To further investigate the impact of the cover plate width on the behavior of the FED-ST, preliminary parametric research was also carried out.

The novel small molecule BH3 mimetic nobiletin synergizes with vorinostat to induce apoptosis and autophagy in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly lethal subtype of lung cancer with few therapeutic options; therefore, the identification of new targets and drugs with potent combination therapy is desirable. We previously screened BH3 mimetics from a natural product library, and in this study, we validated nobiletin as a BH3 mimetic. Specifically, we observed its combination potential and mechanism with vorinostat in SCLC in vitro and in vivo. The results showed that combination treatment with nobiletin and vorinostat reduced the proliferation of SCLC H82 cells and increased the levels of apoptotic proteins such as cleaved caspase-9 and cleaved PARP. The combination treatment increased LC3-II expression and induced autophagic cell death. In addition, this treatment significantly inhibited H82 cell xenograft SCLC tumor growth in nude mice. The combination treatment with nobiletin and vorinostat efficiently increased autophagy by inhibiting the PI3K-AKT-mTOR pathway and promoting dissociation of the BCL-2 and Beclin 1 complex, increasing the level of isolated Beclin 1 to stimulate autophagy. Molecular docking and surface plasmon resonance analysis showed that nobiletin stably bound to the BCL-2, BCL-XL and MCL-1 proteins with high affinity in a concentration-dependent manner. These results suggest that nobiletin is a BH3-only protein mimetic. Furthermore, the combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.

Discovery of phosphonate derivatives containing different substituted 1,2,3-triazole motif as promising tobacco mosaic virus (TMV) helicase inhibitors for controlling plant viral diseases.

BACKGROUND: The discovery and identification of targets is of far-reaching significance for developing novel pesticide candidates and increasing the probability of success. To explore and identify highly effective tobacco mosaic virus (TMV) helicase-targeted lead structures, a series of novel phosphonate derivatives containing a 1,2,3-triazole motif were rationally engineered and their antiviral activity was assessed. RESULTS: Bioassay results showed that the optimized B17 exhibited more potent curative activity (EC50 = 271.5 µg mL-1 ) against TMV in vivo, which was superior to that of commercial Ribavirin (EC50 = 689.3 µg mL-1 ). B17 presented a stronger binding capacity through binding analysis with helicase, affording a corresponding value of 12.7 µM. Enzyme activity assay showed B17 exhibited excellent inhibitory activity on TMV helicase (39.2% at 300 µM). Furthermore, molecular docking simulations demonstrated that B17 displayed strong hydrogen-bond interactions (2.1, 2.1, 2.2, and 3.2 Å) with Ala-33, Gly-10, Gly-8, and Glu-217 of TMV helicase. Encouragingly, transmission electron microscopy analysis revealed that B17 could remarkably disrupt surface morphology and inhibit TMV proliferation. Additionally, these compounds also displayed potential anti-CMV (cucumber mosaic virus) and antipathogens (Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) by expanding their applications in agriculture. CONCLUSION: Current research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry.

A new NASH model in aged mice with rapid progression of steatohepatitis and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, with a significant proportion of patients progressing into non-alcoholic steatohepatitis (NASH) and further into cirrhosis and hepatocellular carcinoma (HCC). Most of the current animal models of NASH have limitations, such as incompatibility with human pathogenesis characteristics or long induction periods, which severely limit the development of new drugs and preclinical studies for NASH. We investigated the progression of NASH and fibrosis, as well as metabolic indicators, at different time points in aged mice induced by the Gubra Amylin NASH (GAN) diet, a high-fat, high-sugar, high-cholesterol diet, and attempted to establish a rapid and useful mouse model of NASH. Young and aged C57BL/6 mice were induced on a normal chow or GAN diet for 12 and 21 weeks, respectively. After 12 weeks of induction, aged mice developed NASH, including hepatic steatosis, lobular inflammation and hepatic ballooning, and the phenotype was more severe compared with young mice. After 21 weeks of induction, aged mice developed hepatic fibrosis, which greatly shortened the induction time compared with young mice. Furthermore, analysis of immune cell infiltration in the liver by flow cytometry elucidated the changes of multiple immune cells during the pathogenesis of NASH. These findings suggest that aged mice may develop NASH and fibrosis more rapidly under GAN diet induction, which may significantly shorten the period for preclinical studies of NASH.

Novel cinnamic acid derivatives as a versatile tool for developing agrochemicals for controlling plant virus and bacterial diseases by enhancing plant defense responses.

BACKGROUND: Plant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity. RESULTS: The bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A5 (median effective concentration [EC50 ] = 287.7 µg mL-1 ), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC50  = 622.0 µg mL-1 ). In addition, compound A17 had a protective efficiency of 84.3% at 200 µg mL-1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion. CONCLUSION: This research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry.

Resistance-driven innovations in the discovery of bactericides: novel triclosan derivatives decorating isopropanolamine moiety as promising anti-biofilm agents against destructive plant bacterial diseases.

BACKGROUND: Controlling bacterial infections in plants is a major challenge owing to the appearance of resistant strains. As a physical barrier, the bacterial biofilm helps bacterial infections acquire drug resistance by enabling bacteria to accommodate complex and volatile environmental conditions and avoid bactericidal effects. Thus, developing new antibacterial agents with antibiofilm potency is imperative. RESULTS: A series of simple triclosan derivatives containing isopropanolamine moiety were elaborately designed and assessed for their antibacterial behavior. Bioassay results showed that some title compounds had excellent bioactivity against three destructive bacteria Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Notably, compound C8 displayed high bioactivities toward Xoo and Xac, with EC50 values were 0.34 and 2.11 µg mL-1 , respectively. In vivo trials revealed that compound C8 exhibited excellent protective activities against rice bacterial blight and citrus bacterial canker at 200 µg mL-1 , with control effectivenesses of 49.57% and 85.60%, respectively. Compound A4 had remarkably inhibitory activity toward Psa, with an EC50 value of 2.63 µg mL-1 , and demonstrated outstanding protective activity with a value of 77.23% against Psa in vivo. Antibacterial mechanisms indicated that compound C8 dose-dependently prevented biofilm formation and extracellular polysaccharide production. C8 also significantly weakened the motility and pathogenicity of Xoo. CONCLUSION: This study contributes to the development and excavation of novel bactericidal candidates with broad-spectrum antibacterial activity by targeting bacterial biofilm to control refractory plant bacterial diseases. © 2023 Society of Chemical Industry.

The efficacy and safety of pyrotinib in treating HER2-positive breast cancer patients with brain metastasis: A multicenter study.

PURPOSE: To investigate the efficacy and safety of pyrotinib in treating patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancers with brain metastasis. PATIENTS AND METHODS: This is a multicenter retrospective study, and the HER2-positive breast cancer patients with brain metastasis were studied. The enrolled patients were given pyrotinib 400 mg orally once per day for 21 days as one cycle, and evaluated every two cycles. All relevant data were detected for final assessments including medical history, clinical examination, histopathology, immunohistochemistry, radiographic imaging, treatment outcome, and adverse events. RESULTS: Forty-two female patients in total were enrolled in this study. The objective response rate (ORR) and disease control rate (DCR) of central nervous system (CNS), were found in 20 of 42 (47.6%) and in 39 of 42 (92.8%), respectively, while for extra-CNS, the respective ORR and DCR were in 9 of 38 (23.6%) and in 36 of 38 (94.7%), respectively. The compounded ORR and DCR were seen in 17 of 42 (40.4%) and in 39 of 42 (92.8%), respectively. The improvement rate of craniocerebral symptoms after treatment was (19/19) 100% and the median duration was 15 months. The median effective time of brain metastases and other metastases was 43 and 50 days. The median follow-up time was 22 months (interquartile range, 16.0-24.3 months). The median time for progression in brain metastasis was 16.6 months. The median time to progress for our group patients was 11.1 months. Sixteen patients (36%) with adverse reactions were recorded in the study. CONCLUSION: Pyrotinib combined with chemotherapy/radiotherapy or alone showed significantly greater local control rates and progression free survival (PFS), with manageable toxicity for patients with HER2-positive breast cancer with brain metastases, and further follow-up will provide an overall survival (OS) data.

Mechanisms of Coreopsis tinctoria Nutt in the treatment of diabetic nephropathy based on network pharmacyology analysis of its active ingredients / Mecanismos de Coreopsis tinctoria Nutt. En el tratamiento de la nefropatía diabética basado en el análisis farmacológico de red de sus principios activos

SUMMARY: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) can protect diabetic kidneys, but the mechanisms are unclear. This work is to investigate the potential mechanisms of C. tinctoria Nutt. in the treatment of diabetic nephropathy based on network pharmacology analysis of its active ingredients. Twelve small molecular compounds of C. tinctoria Nutt. and targets related to diabetic nephropathy were docked by Discovery Studio 3.0. DAVID database was used for GO enrichment and KEGG pathway analysis. Cytoscape 3.6.1 was used to construct active ingredient-target network. Cell viability was detected with MTT. Glucose consumption was analyzed with glucose oxidase method. Protein expression was measured with Western blot and immunofluorescence. Electron microscopy observed autophagosomes. The core active ingredients of C. tinctoria Nutt. included heriguard, flavanomarein, maritimein, and marein. Twenty-one core targets of the 43 potential targets were PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK, and ABL2. These 21 core targets were significantly enriched in 50 signaling pathways. Thirty- four signaling pathways were closely related to diabetic nephropathy, of which the top pathways were PI3K/AKT, insulin, and mTOR, and insulin resistance. The enriched GO terms included biological processes of protein phosphorylation, and the positive regulation of PI3K signaling and cytokine secretion; cellular components of cytosol, extracellular region, and extracellular space; and molecular function of protein kinase activity, ATP binding, and non-membrane spanning protein tyrosine kinase activity. In vitro experiments found that marein increased the expression of phosphorylated AKT/AKT in human renal glomerular endothelial cells of an insulin resistance model induced by high glucose, as well as increased and decreased, respectively, the levels of the microtubule-associated proteins, LC3 and P62. C. tinctoria Nutt. has many active ingredients, with main ingredients of heriguard, flavanomarein, maritimein, and marein, and may exert anti-diabetic nephropathy effect through various signaling pathways and targets.

RESUMEN: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) puede proteger riñones diabéticos, sin embargo los mecanismos son desconocidos. Este trabajo se realizó para investigar los potenciales mecanismos de C. tinctoria Nutt. en el tratamiento de la nefropatía diabética basado en el análisis de farmacología en red de sus principios activos. Doce compuestos moleculares pequeños de C. tinctoria Nutt. y los objetivos relacionados con la nefropatía diabética fueron acoplados por Discovery Studio 3.0. La base de datos DAVID se utilizó para el enriquecimiento GO y el análisis de la vía KEGG. Se usó Cytoscape 3.6.1 para construir una red de ingrediente-objetivo activa. La viabili- dad celular se detectó mediante MTT. El consumo de glucosa se analizó con el método de glucosa oxidasa. La expresión proteica fue determinada mediante Western blot e inmunofluorescencia. En la microscopía electrónica se observó autofagosomas. Los principales ingredientes activos de C. tinctoria Nutt. incluyeron heriguard, flavanomarein, maritimin y marein. Veintiún de los 43 objetivos potenciales fueron PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK y ABL2. Estos 21 objetivos principales se enriquecieron significativamente en 50 vías de señalización. Treinta y cuatro vías de señalización estuvieron estrechamente relacionadas con la nefropatía diabética, de las cuales las principales vías fueron PI3K/ AKT, insulina y mTOR, y resistencia a la insulina. Los términos GO enriquecidos incluyeron procesos biológicos de fosforilación proteica, la regulación positiva de la señalización de PI3K y la secreción de citoquinas; componentes celulares del citosol, región extracelular y espacio extracelular; y la función molecular de la actividad de la proteína quinasa, la unión de ATP y la actividad de la proteína tirosina quinasa que no se extiende por la membrana. Los experimentos in vitro encontraron que la mareína aumentaba la expresión de AKT/AKT fosforilada en células endoteliales glomerulares renales humanas en un modelo de resistencia a la insulina inducida por niveles elevados de glucosa, así como aumentaron y disminuyeron respectivamente, los niveles de las proteínas asociadas a los microtúbulos, LC3 y P62. C. tinctoria Nutt. tiene muchos principios activos, con ingredientes principales de heriguard, flavanomarein, maritimain y marein, y puede ejercer un efecto de nefropatía antidiabética a través de distintass vías de señalización y objetivos.

Reactivation of the tumor suppressor PTEN by mRNA nanoparticles enhances antitumor immunity in preclinical models.

Increasing clinical evidence has demonstrated that the deletion or mutation of tumor suppressor genes such as the gene-encoding phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in cancer cells may correlate with an immunosuppressive tumor microenvironment (TME) and poor response or resistance to immune checkpoint blockade (ICB) therapy. It is largely unknown whether the restoration of functional PTEN may modulate the TME and improve the tumor's sensitivity to ICB therapy. Here, we demonstrate that mRNA delivery by polymeric nanoparticles can effectively induce expression of PTEN in Pten-mutated melanoma cells and Pten-null prostate cancer cells, which in turn induces autophagy and triggers cell death-associated immune activation via release of damage-associated molecular patterns. In vivo results illustrated that PTEN mRNA nanoparticles can reverse the immunosuppressive TME by promoting CD8+ T cell infiltration of the tumor tissue, enhancing the expression of proinflammatory cytokines, such as interleukin-12, tumor necrosis factor-α, and interferon-γ, and reducing regulatory T cells and myeloid-derived suppressor cells. The combination of PTEN mRNA nanoparticles with an immune checkpoint inhibitor, anti-programmed death-1 antibody, results in a highly potent antitumor effect in a subcutaneous model of Pten-mutated melanoma and an orthotopic model of Pten-null prostate cancer. Moreover, the combinatorial treatment elicits immunological memory in the Pten-null prostate cancer model.

Limited Lymph Node Resection Does Not Decrease Postoperative Mortality After Esophagectomy in Octogenarians With Thoracic Esophageal Cancer.

BACKGROUND: Octogenarians with esophageal cancer typically have a poor physical condition, reduced physiological reserves, and high postoperative mortality (POM). Extensive lymph node dissection increases surgical trauma and postoperative complications. The purpose of this study was to examine the associations between the number of dissected lymph nodes and short-term and long-term postoperative outcomes in octogenarians with thoracic esophageal cancer. METHODS: We examined the data of patients from the Surveillance, Epidemiology, and End Results database. We divided the patients into two groups in accordance with the number of lymph nodes dissected: patients with <15 examined lymph nodes (eLNs) and patients with ≥15 eLNs. Mortality was quantified at 30, 60, and 90 d after surgery. Univariable and multivariable logistic regression analyses were performed to identify predictors of 90-day mortality. Kaplan-Meier analysis and the log-rank test were used to analyze the overall survival and cause-specific survival of the patients. RESULTS: A total of 208 octogenarians with thoracic esophageal cancer were included in the analysis. The 30-day POM rates were 10.3% and 6.9%, the 60-day POM rates were 16.9% and 13.9%, and the 90-day POM rates were 21.3% and 19.4% for patients with <15 eLNs and ≥15 eLNs, respectively. However, the differences in POM between the two groups were statistically nonsignificant (all P > 0.05). In accordance with the multivariable logistic regression analysis, age and marital status were significantly associated with 90-day POM. Furthermore, no significant difference was found between the groups in terms of long-term survival. The 5-year overall survival rates were 29% and 26.8% (P = 0.719) and the 5-year cause-specific survival rates were 43.2% and 34.1% (P = 0.446) in patients with <15 eLNs and ≥15 eLNs, respectively. CONCLUSIONS: We have demonstrated that octogenarians undergoing esophagectomy are associated with an unacceptably high POM, and less extensive lymph node resection does not decrease POM. Octogenarians may not benefit from esophagectomy with lymphadenectomy. Additional studies need to be conducted to further guide clinicians performing highly selective esophagectomy.

LINC00476 Suppresses the Progression of Non-Small Cell Lung Cancer by Inducing the Ubiquitination of SETDB1.

Long non-coding RNAs are involved in the tumorigenesis of non-small cell lung cancer (NSCLC). Here we investigated whether LINC00476 affects the proliferation, invasion and migration of NSCLC cells via the SETDB1-activated Wnt/ß-catenin pathway. The expression of LINC00476, SETDB1, Wnt1 and ß-catenin were determined in NSCLC tumor tissues and the paired adjacent tissues, as well as in NSCLC cell lines and bronchial epithelioid cell lines. Cell proliferation, invasion and migration were determined using cell counting kit-8 assay and transwell assay. The relationship between LINC00476 and SETDB1 was elucidated using RNA pull-down, RNA immunoprecipitation and ubiquitination assays. LINC00476 was found to be significantly downregulated, while SETDB1, Wnt1 and ß-catenin were upregulated in NSCLC tumor tissues and cell lines compared to the normal ones. Overexpression of LINC00476 promoted the proliferation, invasion and migration of NSCLC cells, and suppressed tumor growth in the mouse xenograft. Meanwhile, overexpression of LINC00476 induced the degradation of SETDB1 by promoting its ubiquitination. The simultaneous overexpression of LINC00476 and SETDB1 negated the inhibition of LINC00476 overexpression on the proliferation, invasion and migration of NSCLC cells. In conclusion, these findings indicate that LINC00476 acts as a tumor suppressor in NSCLC by downregulating SETDB1, which provides a novel target in the treatment of NSCLC.

Clinical Analysis of Congenital Deficient Tracheal Cartilage Rings: Six Case Reports and a Literature Review.

Congenital deficiency of tracheal rings is a rare tracheal malformation that can cause central airway obstruction. Herein we reported the clinical data of six patients with symptomatic congenital deficient tracheal rings. There were five cases, with isolated short-segment absent cartilage ring located on the distal trachea (three cases), cervical trachea (one case), and distal trachea combined with bilateral bronchi (one case). Among them, four (4/5) received surgical tracheal resection, three fully recovered, and one died of severe infection. Besides that, one patient, who could not be weaned off the mechanical ventilation, died after rejecting surgery. One case had episodes of recurrent dyspnea and extubation failure due to long-segment tracheomalacia after repair of esophageal atresia and tracheoesophageal fistula. For this patient, deficient cartilage rings were suspected and confirmed at the age of 26 months. Moreover, the clinical characteristics of 12 cases with congenital deficient tracheal cartilage rings reported in previous literature were reviewed. The different characteristics between short- and long-segment deficient cartilage rings were discussed.

Linc01014 regulates gefitinib resistance in oesophagus cancer via EGFR-PI3K-AKT-mTOR signalling pathway.

This study aimed to explore the underlying mechanism of linc01014 in oesophagus cancer gefitinib resistance. Gefitinib-resistant oesophagus squamous cell carcinoma (ESCC gefitinibR) cell lines were constructed by using different gefitinib treatment in FLO-1, KYAE-1, TE-8 and TE-5 cell lines and confirmed by MTS50 and proliferation assays. Expression of linc01014 was overexpressed/silenced in FLO-1 cells followed by gefitinib treatment, and then, the apoptosis-associated markers Bax and Bcl-2, and PI3KCA in PI3K signalling pathway were determined using Western blotting. MST50 and morphology analyses showed that ESCC gefitinibR cell lines presented obvious gefitinib resistance than their parental ESCC cell lines. ESCC gefitinibR cell lines showed significantly higher proliferation abilities than their parental ESCC cell lines after treating with gefitinib. Overexpression of linc01014 significantly inhibited the apoptosis of FLO-1 cells induced by gefitinib and silencing linc01014 obviously promoted the apoptosis of FLO-1 cells induced by gefitinib. Silencing linc01014 could significantly increase the gefitinib chemotherapy sensitivity of oesophagus cancer via PI3K-AKT-mTOR signalling pathway.

Redox-Responsive Nanoparticle-Mediated Systemic RNAi for Effective Cancer Therapy.

Biodegradable polymeric nanoparticles (NPs) have demonstrated significant potential to improve the systemic delivery of RNA interference (RNAi) therapeutics, such as small interfering RNA (siRNA), for cancer therapy. However, the slow and inefficient siRNA release inside tumor cells generally observed for most biodegradable polymeric NPs may result in compromised gene silencing efficacy. Herein, a biodegradable and redox-responsive NP platform, composed of a solid poly(disulfide amide) (PDSA)/cationic lipid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery to tumor cells, is developed. This newly generated NP platform can efficiently encapsulate siRNA under extracellular environments and can respond to the highly concentrated glutathione (GSH) in the cytoplasm to induce fast intracellular siRNA release. By screening a library of PDSA polymers with different structures and chain lengths, the optimized NP platform shows the unique features of i) long blood circulation, ii) high tumor accumulation, iii) fast GSH-triggered intracellular siRNA release, and iv) exceptionally effective gene silencing. Together with the facile polymer synthesis technique and robust NP formulation enabling scale-up, this new redox-responsive NP platform may become an effective tool for RNAi-based cancer therapy.

Fully-covered metallic stenting in an infant with tracheoesophageal fistula due to button battery ingestion.

Previously, the main treatment options for tracheoesophageal fistula included surgery and conservative treatment. Herein, we report a child suffering from severe tracheoesophageal fistula due to button battery ingestion. The child relapsed soon after a repair surgery. Then, he was endotracheally implanted with a fully-covered metallic stent combined with a jejunal tube feeding. He recovered soon and the stent was removed five months later. The fistula was healed with no relapse during a 25-month follow-up. Therefore, endotracheal implantation of fully-covered metallic stent is an alternative treatment for tracheoesophageal fistula due to button battery ingestion, especially in cases with severe respiratory disorders.

[Early predictors of necrotizing pneumonia in children].

OBJECTIVE: To investigate the early predictors of necrotizing pneumonia in children. METHODS: The clinical data of 43 children with necrotizing pneumonia and 83 children with lobar pneumonia were retrospectively analyzed. Sex, age, the number of days with fever, laboratory examination results, and bronchoscopic findings were compared between the two groups. The multiple logistic regression analysis was used to identify the early predictors of necrotizing pneumonia. RESULTS: The necrotizing pneumonia group had a higher percentage of girls than the lobar pneumonia group (P<0.05). Compared with the lobar pneumonia group, the necrotizing pneumonia group had a larger number of days with fever, a higher peripheral blood white blood cell count (WBC), a higher percentage of neutrophils (NE%), and higher serum levels of high-sensitivity C-reactive protein (hs-CRP), albumin (Alb), and lactate dehydrogenase (LDH) (P<0.05). The necrotizing pneumonia group also had higher percentages of children with a large amount of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps and children with rice-water-like bronchoalveolar lavage fluid (P<0.05). The multiple logistic regression analysis showed that being a female, the presence of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps, the number of days with fever, WBC, hs-CRP, and LDH were independent predictors of necrotizing pneumonia. The receiver operating characteristic curve analysis showed that the cut-off values of the latter 4 predictors were 18.5 d, 15.1×10(9)/L, 121.5 mg/L, and 353.5 U/L, respectively. CONCLUSIONS: Increased WBC (≥15.1×10(9)/L), increased hs-CRP (≥121.5 mg/L), increased serum LDH (≥353.5 U/L), and the presence of sputum bolt under a bronchoscope which needs to be removed with biopsy forceps and rice-water-like bronchoalveolar lavage fluid may be the early predictors of necrotizing pneumonia in children.

Sacro-anterior haemangiopericytoma: a case report.

Haemangiopericytoma (HPC) is a rare vascular tumor with borderline malignancy, considerable histological variability, and unpredictable clinical and biological behavior. HPC can present a diagnostic challenge because of its indeterminate clinical, radiological, and pathological features. HPC generally presents in adulthood and is equally frequent in both sexes. HPC can arise in any site in the body as a slowly growing and painless mass. The precise cell type origin of HPC is uncertain. One third of HPCs occur in the head and neck areas. Exceptional cases of hemangioblastoma arising outside the head and neck areas have been reported, but little is known about their clinicopathologic and immunohistochemical features. This study reports on a case of a large sacro-anterior HPC in a 65-year-old male.

Adsorption of soluble oil from water to graphene.

The toxicity of soluble oil to the aquatic environment has started to attract wide attention in recent years. In the present work, we prepare graphene according to oxidation and thermal reduction methods for the removal of soluble oil from the solution. Characterization of the as-prepared graphene are performed by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman spectra, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, and contact angle analysis. The adsorption behavior of soluble oil on graphene is examined, and the obtained adsorption data are modeled using conventional theoretical models. Adsorption experiments reveal that the adsorption rate of soluble oil on graphene is notably fast, especially for the soluble diesel oil, which could reach equilibrium within 30 min, and the kinetics of adsorption is perfectly consistent with a pseudo-second-order model. Furthermore, it is determined that the adsorption isotherm of soluble diesel oil with graphene fit the Freundlich model best, and graphene has a very strong adsorption capacity for soluble diesel oil in the solution. These results demonstrate that graphene is the material that provided both good adsorptive capacity and good kinetics, implying that it could be used as a promising sorbent for soluble oil removal from wastewater.

cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression.

The Raf kinase inhibitory protein (RKIP) is down-regulated in multiple types of human cancers. Decreased RKIP transcription activity may be one of the major mechanisms responsible for the downregulation of RKIP expression in human diseases. To test this hypothesis, we need to gain basic knowledge of the transcriptional regulation of RKIP. To achieve this objective, we made a systematic effort to identify cis-acting elements and trans-acting factors that control RKIP promoter activity. We found that full RKIP promoter activity requires the region -56 to +261 relative to the transcription start site. Within the full promoter region, there are two motifs rich in G/C that responded to transcription factor Sp1, one cAMP-responsive element that responded to the transcription factor CREB, and one docking site for the histone acetylase p300. In human melanoma A375 cells and human cervical cancer HeLa cells, mutation or deletion of each of these cis-acting elements decreased promoter activity. In A375 cells, knockdown of the corresponding transcription factors Sp1, CREB, or p300 decreased RKIP promoter activity, whereas overexpression of CREB and p300 increased RKIP promoter activity. The results obtained with HeLa cells also supported the idea that Sp1 and CREB play positive roles in the regulation of RKIP transcription. These findings suggest that regulators of the expression or activity of Sp1, CREB, and p300 are involved in regulating RKIP transcription.