Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Identification of DDIT4 as a potential prognostic marker associated with chemotherapeutic and immunotherapeutic response in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogenous and aggressive subtype of breast cancer. Chemotherapy remains the standard treatment option for patients with TNBC owing to the unavailability of acceptable targets and biomarkers in clinical practice. Novel biomarkers and targets for patient stratification and treatment of TNBC are urgently needed. It has been reported that the overexpression of DNA damage-inducible transcript 4 gene (DDIT4) is associated with resistance to neoadjuvant chemotherapy and poor prognosis in patients with TNBC. In this study, we aimed to identify novel biomarkers and therapeutic targets using RNA sequencing (RNA-seq) and data mining using data from public databases. METHODS: RNA sequencing (RNA-Seq) was performed to detect the different gene expression patterns in the human TNBC cell line HS578T treated with docetaxel or doxorubicin. Sequencing data were further analyzed by the R package "edgeR" and "clusterProfiler" to identify the profile of differentially expressed genes (DEGs) and annotate gene functions. The prognostic and predictive value of DDIT4 expression in patients with TNBC was further validated by published online data resources, including TIMER, UALCAN, Kaplan-Meier plotter, and LinkedOmics, and GeneMANIA and GSCALite were used to investigate the functional networks and hub genes related to DDIT4, respectively. RESULTS: Through the integrative analyses of RNA-Seq data and public datasets, we observed the overexpression of DDIT4 in TNBC tissues and found that patients with DDIT4 overexpression showed poor survival outcomes. Notably, immune infiltration analysis showed that the levels of DDIT4 expression correlated negatively with the abundance of tumor-infiltrating immune cells and immune biomarker expression, but correlated positively with immune checkpoint molecules. Furthermore, DDIT4 and its hub genes (ADM, ENO1, PLOD1, and CEBPB) involved in the activation of apoptosis, cell cycle, and EMT pathways. Eventually, we found ADM, ENO1, PLOD1, and CEBPB showed poor overall survival in BC patients. CONCLUSION: In this study, we found that DDIT4 expression is associated with the progression, therapeutic efficacy, and immune microenvironment of patients with TNBC, and DDIT4 would be as a potential prognostic biomarker and therapeutic target. These findings will help to identify potential molecular targets and improve therapeutic strategies against TNBC.

Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity.

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer. METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS). RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p < 0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p = 0.035). CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.

Fibroblasts in breast cancer are activated and usually upregulated CAFs-related genes, including tenascin C (TNC) which participate in immunosuppression through the focal adhesion and PI3K-AKT signaling pathways.TNC expression in the CAFs and tumor cells, and was associated with most adverse clinicopathological features of breast cancer.High TNC expression in CAFs or tumor cells resulted in significantly worse MFS, and as an independent prognostic factor.

TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers.

Background: Membrane protein TMEM158 was initially reported as a Ras-induced gene during senescence and has been implicated as either an oncogenic factor or tumor suppressor, depending on tumor types. It is unknown if TMEM158 expression is altered in prostate cancers. Methods: Multiple public gene expression datasets from RNA-seq and cDNA microarray assays were utilized to analyze candidate gene expression profiles. TMEM158 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Comparisons of gene expression profiles were conducted using the bioinformatics software R package. Results: COX regression-based screening identified the membrane protein TMEM158 gene as negatively associated with disease-specific and progression-free survival in prostate cancer patients. Gene expression at the mRNA and protein levels revealed that TMEM158 expression was significantly reduced in malignant tissues compared to benign compartments. Meanwhile, TMEM158 downregulation was strongly correlated with advanced clinicopathological features, including late-stage diseases, lymph node invasion, higher PSA levels, residual tumors after surgery, and adverse Gleason scores. In castration-resistant prostate cancers, TMEM158 expression was negatively correlated with AR signaling activity but positively correlated with neuroendocrinal progression index. Consistently, in cell culture models, androgen treatment reduced TMEM158 expression, while androgen deprivation led to upregulation of TMEM158 expression. Correlation analysis showed a tight correlation of TMEM158 expression with the level of R-Ras gene expression, which was also significantly downregulated in prostate cancers. Tumor immune infiltration profiling analysis discovered a strong association of TMEM158 expression with NK cell and Mast cell enrichment. Conclusion: The membrane protein TMEM158 is significantly downregulated in prostate cancer and is tightly associated with disease progression, anti-tumor immune infiltration, and patient survival outcome.

Erratum: A cell-penetrating whole molecule antibody targeting intracellular HBx suppresses hepatitis B virus via TRIM21-dependent pathway: Erratum.

[This corrects the article DOI: 10.7150/thno.20047.].

Anti-Androgen Receptor Therapies in Prostate Cancer: A Brief Update and Perspective.

Prostate cancer is a major health issue in western countries and is the second leading cause of cancer death in American men. Prostate cancer depends on the androgen receptor (AR), a transcriptional factor critical for prostate cancer growth and progression. Castration by surgery or medical treatment reduces androgen levels, resulting in prostatic atrophy and prostate cancer regression. Thus, metastatic prostate cancers are initially managed with androgen deprivation therapy. Unfortunately, prostate cancers rapidly relapse after castration therapy and progress to a disease stage called castration-resistant prostate cancer (CRPC). Currently, clinical treatment for CRPCs is focused on suppressing AR activity with antagonists like Enzalutamide or by reducing androgen production with Abiraterone. In clinical practice, these treatments fail to yield a curative benefit in CRPC patients in part due to AR gene mutations or splicing variations, resulting in AR reactivation. It is conceivable that eliminating the AR protein in prostate cancer cells is a promising solution to provide a potential curative outcome. Multiple strategies have emerged, and several potent agents that reduce AR protein levels were reported to eliminate xenograft tumor growth in preclinical models via distinct mechanisms, including proteasome-mediated degradation, heat-shock protein inhibition, AR splicing suppression, blockage of AR nuclear localization, AR N-terminal suppression. A few small chemical compounds are undergoing clinical trials combined with existing AR antagonists. AR protein elimination by enhanced protein or mRNA degradation is a realistic solution for avoiding AR reactivation during androgen deprivation therapy in prostate cancers.

[Clinical and genetic analysis of a newborn with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION: The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.

One-Pot Synthesis of One-Dimensional Multijunction Semiconductor Nanochains from Cu1.94S, CdS, and ZnS for Photocatalytic Hydrogen Generation.

Chains of alternating semiconductor nanocrystals are complex nanostructures that can offer control over photogenerated charge carriers dynamics and quantized electronic states. We develop a simple one-pot colloidal synthesis of complex Cu1.94S-CdS and Cu1.94S-ZnS nanochains exploiting an equilibrium driving ion exchange mechanism. The chain length of the heterostructures can be tuned using a concentration dependent cation exchange mechanism controlled by the precursor concentrations, which enables the synthesis of monodisperse and uniform Cu1.94S-CdS-Cu1.94S nanochains featuring three epitaxial junctions. These seamless junctions enable efficient separation of photogenerated charge carriers, which can be harvested for photocatalytic applications. We demonstrate the superior photocatalytic activity of these noble metal free materials through solar hydrogen generation at a hydrogen evolution rate of 22.01 mmol g-1 h-1, which is 1.5-fold that of Pt/CdS heterostructure photocatalyst particles.

Dimethylimidazolium-Functionalized Polybenzimidazole and Its Organic-Inorganic Hybrid Membranes for Anion Exchange Membrane Fuel Cells.

A quaternized polybenzimidazole (PBI) membrane was synthesized by grafting a dimethylimidazolium end-capped side chain onto PBI. The organic-inorganic hybrid membrane of the quaternized PBI was prepared via a silane-induced crosslinking process with triethoxysilylpropyl dimethylimidazolium chloride. The chemical structure and membrane morphology were characterized using NMR, FTIR, TGA, SEM, EDX, AFM, SAXS, and XPS techniques. Compared with the pristine membrane of dimethylimidazolium-functionalized PBI, its hybrid membrane exhibited a lower swelling ratio, higher mechanical strength, and better oxidative stability. However, the morphology of hydrophilic/hydrophobic phase separation, which facilitates the ion transport along hydrophilic channels, only successfully developed in the pristine membrane. As a result, the hydroxide conductivity of the pristine membrane (5.02 × 10-2 S cm-1 at 80 °C) was measured higher than that of the hybrid membrane (2.22 × 10-2 S cm-1 at 80 °C). The hydroxide conductivity and tensile results suggested that both membranes had good alkaline stability in 2M KOH solution at 80 °C. Furthermore, the maximum power densities of the pristine and hybrid membranes of dimethylimidazolium-functionalized PBI reached 241 mW cm-2 and 152 mW cm-2 at 60 °C, respectively. The fuel cell performance result demonstrates that these two membranes are promising as AEMs for fuel cell applications.

Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma.

Background: Detection of SHOX2 methylation has been used to assist in the early diagnosis of lung cancer in many hospitals as SHOX2 may be important in the tumorigenesis of lung cancer. However, there are few studies on the mRNA expression, methylation, and molecular mechanism of SHOX2 in lung cancer. We aimed to explore the role of SHOX2 in lung adenocarcinoma (LUAD). Methods: First, we examined the differential expression of SHOX2 mRNA and methylation in cancerous and normal tissues using databases. Second, we analyzed the relationship between SHOX2 expression and common clinical parameters in LUAD patients. Third, we further explored the methylated level and its specific location of SHOX2 and the mainly factors of SHOX2 gene expression. Finally, we screened the correlatively expressed genes to analyze the pathways from the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes using DAVID. Results: We found that the mRNA expression of SHOX2 was higher in multiple cancers, including LUAD and lung squamous cell carcinoma (LUSC), than in normal tissues. Among LUAD patients, SHOX2 expression was higher in patients of middle-young age, with smoking history, in advanced stages, and with nodal distant metastasis. In addition, our results showed that patients with high expression of SHOX2 are prone to recurrence, poor differentiation, and poor prognosis. Thus, we identified that SHOX2 might be an oncogene for LUAD progression. The main factor influencing the high expression of SHOX2 mRNA may be DNA methylation, followed by copy number variation (CNV), but not by gene mutations in LUAD. Unexpectedly, we found that SHOX2 undergoes hypomethylation in the gene body instead of hypermethylation in the promoter. Additionally, SHOX2 has cross talk in the PI3K-Akt signaling pathway and ECM-receptor interaction. Conclusion: SHOX2 is highly expressed in most cancers. SHOX2 gene expression might be mainly regulated by methylation of its gene body in LUAD, and its high expression or hypomethylation indicates poor differentiation and poor prognosis. SHOX2 could be involved in PI3K-Akt and other important cancer-related signaling pathways to promote tumorigenesis.

Clinical report of a neonate carrying a large deletion in the 10p15.3p13 region and review of the literature.

BACKGROUND: Terminal deletion of chromosome 10p is a rare chromosomal abnormality. We report a neonatal case with a large deletion of 10p15.3p13 diagnosed early because of severe clinical manifestations. CASE PRESENTATION: Our patient presented with specific facial features, hypoparathyroidism, sen sorineural deafness, renal abnormalities, and developmental retardation, and carried a 12.6 Mb deletion in the 10p15.3 p13 region. The terminal 10p deletion involved in our patient is the second largest reported terminal deletion reported to date, and includes the ZMYND11 and GATA3 genes and a partial critical region of the DiGeorge syndrome 2 gene (DGS2). CONCLUSION: On the basis of a literature review, this terminal 10p deletion in the present case is responsible for a specific contiguous gene syndrome. This rare case may help the understanding of the genotype-phenotype spectrum of terminal deletion of chromosome 10p.

MOF-derived core/shell C-TiO2/CoTiO3 type II heterojunction for efficient photocatalytic removal of antibiotics.

A novel core/shell C-TiO2/CoTiO3 type II heterojunction was successfully synthesized via a direct calcination method by using MIL-125/Co core-shell nanocakes as a sacrificial template and precursor. In the calcination process, the organic ligand in MIL-125 acts as an in-situ carbon doping source to form a carbon-doped TiO2 core (C-TiO2). At the same time, CoTiO3 nanoparticles are formed on the surface of C-TiO2 by an in-situ solid-state reaction between the C-TiO2 and Co2+ shell of MIL-125/Co. Due to such delicate core/shell structural features, carbon doping and type II heterojunctions, C-TiO2/CoTiO3 core/shell composites can effectively harvest visible light, facilitate the interfacial separation and suppress the recombination of photogenerated electron-hole pairs, leading to the remarkable photocatalytic activity for removal of ciprofloxacin (CIP). In particular, C-TiO2/CoTiO3-3 exhibits the best photocatalytic degradation activity of CIP with a degradation efficiency of 99.6% and a total carbon content removal percentage of 76% under visible-light illumination for 120 min. In addition, the proposed photocatalytic mechanism study illustrated that the main radical species in the photocatalytic degradation of CIP using C-TiO2/CoTiO3 as the photocatalyst is •OH. This work provides a new approach and insight for synthesizing core/shell heterojunction-based photocatalysts for various applications.

Novel 2D/2D BiOBr/UMOFNs direct Z-scheme photocatalyst for efficient phenol degradation.

A novel 2D/2D BiOBr/ultrathin metal-organic framework nanosheets (UMOFNs) direct Z-scheme photocatalyst was successfully synthesized by using a simple deposition-precipitation method. The photocatalytic performance was evaluated under light irradiation, which revealed that the 2D/2D BiOBr/UMOFNs Z-scheme photocatalyst exhibits higher photocatalytic degradation of phenol compared to pristine BiOBr and UMOFNs. A BiOBr/UMOFNs-40% (mass ratio for BiOBr and UMOFNs of 1:0.4) photocatalyst was found to show the best photocatalytic degradation efficiency and stability, reaching 99% phenol degradation under light irradiation of 270 min and maintaining 97% degradation after 5 recycling runs. Results obtained from a trapping experiment and electron paramagnetic resonance suggest that reactive ·OH and O2 ·- play a major role in phenol degradation. Photoluminescence and photocurrent results reveal that the excellent photocatalytic activity of the 2D/2D BiOBr/UMOFNs photocatalyst can be ascribed to the efficient separation of photogenerated electron-hole pairs through a direct Z-scheme system. This article provides a possible reference for designing Z-scheme photocatalysts by using MOFs and semiconductors for practical organic pollutant treatment.

Antibacterial polypeptide/heparin composite hydrogels carrying growth factor for wound healing.

We report an efficient growth factor delivering system based on polypeptide/heparin composite hydrogels for wound healing application. Linear and star-shaped poly(l-lysine) (l-PLL and s-PLL) were chosen due to not only their cationic characteristics, facilitating the efficient complexation of negatively charged heparin, but also the ease to tune the physical and mechanical properties of as-prepared hydrogels simply by varying polypeptide topology and chain length. The results showed that polymer topology can be an additional parameter to tune hydrogel properties. Our experimental data showed that these composite hydrogels exhibited low hemolytic activity and good cell compatibility as well as excellent antibacterial activity, making them ideal as wound dressing materials. Unlike other heparin-based hydrogels, these composite hydrogels with heparin densely deposited on the surface can increase the stabilization and concentration of growth factor, which can facilitate the healing process as confirmed by our in vivo animal model. We believe that these PLL/heparin composite hydrogels are promising wound dressing materials and may have potential applications in other biomedical fields.

AQ-4, a deuterium-containing molecule, acts as a microtubule-targeting agent for cancer treatment.

The important physiological function of microtubules makes them an indispensable and clinically effective target of anti-tumor agents. Herein, we sought to design, synthesize, and evaluate a novel 4-anilinoquinazoline derivative and identify its anti-tumor activity in vitro and in vivo. The novel compound, N-(4-methoxyphenyl)-N-methyl-2-(methyl-d3)quinazolin-4-amine (AQ-4), was identified as a representative scaffold and potent microtubule-targeting agent. As a promising antimitotic agent, AQ-4 displayed remarkable anti-tumor activity with an average IC50 value of 19 nM across a panel of 14 human cancer cell lines. AQ-4 also exhibited nearly identical potent activities against drug-resistant cells, with no evidence of toxicity towards normal cells. A further target verification study revealed that AQ-4 targets the tubulin-microtubule system by significantly inhibiting tubulin polymerization and disrupting the intracellular microtubule spindle dynamics. According to the results of mechanism study, AQ-4 induced cell cycle arrest in the G2/M phase, promoting evident apoptosis and a collapses of mitochondrial membrane potential. The superior anti-tumor effect of AQ-4 in vivo suggests that it should be further investigated to validate its use for cancer therapy.

Inhibition of bleomycin-induced pulmonary fibrosis in mice by the novel peptide EZY-1 purified from Eucheuma.

For the first time, a new 16-amino-acid peptide was isolated from Eucheuma, an edible seaweed, and named EZY-1. EZY-1 was used to interfere with bleomycin-induced mice pulmonary fibrosis. The target proteins of EZY-1 were screened by an in vitro pull-down method combined with LC-MS/MS. The results showed that EZY-1 can inhibit the idiopathic pulmonary fibrosis (IPF) induced by bleomycin. The potency and safety of EZY-1 are superior to those of the drug used for clinical treatment, pirfenidone. The results showed that EZY-1 suppresses the TGF-ß/Smad, PI3K-Akt-mTOR, Rac1-PAK2-cAb1 and MAPK signal transduction pathways. Proteins such as ERK, Akt, PDGF receptor ß, vitronectin, raptor and SHP2 exhibited binding to EZY-1 in an in vitro pull-down assay combined with LC-MS/MS analysis. EZY-1 was confirmed to be an effective component of Eucheuma in the inhibition of IPF. The signalling pathways and target proteins of EZY-1 were preliminarily predicted. This study lays the foundation for the development of new drugs from Eucheuma for the treatment of IPF.

A cell-penetrating whole molecule antibody targeting intracellular HBx suppresses hepatitis B virus via TRIM21-dependent pathway.

Rationale: Monoclonal antibodies (mAbs) mostly targeting extracellular or cell surface molecules have been widely used in the treatment of various diseases. However, mAbs cannot pass through the cell membrane as efficiently as small compounds, thus limiting their use against intracellular targets. Methods to shuttle antibodies into living cells may largely expand research and application in areas based on mAbs. Hepatitis B virus X protein (HBx) is an important intracellular multi-functional viral protein in the life cycle of hepatitis B virus (HBV). HBx plays essential roles in virus infection and replication and is strongly associated with HBV-related carcinogenesis. Methods: In this study, we developed a cell-penetrating whole molecule antibody targeting HBx (9D11-Tat) by the fusion of a cell penetrating peptide (CPP) on the C-terminus of the heavy chain of a potent mAb specific to HBx (9D11). The anti-HBV effect and mechanism of 9D11-Tat were investigated in cell and mouse models mimicking chronic HBV infection. Results: Our results demonstrated that the recombinant 9D11-Tat antibody could efficiently internalize into living cells and significantly suppress viral transcription, replication, and protein production both in vitro and in vivo. Further analyses suggested the internalized 9D11-Tat antibody could greatly reduce intracellular HBx via Fc binding receptor TRIM21-mediated protein degradation. This process simultaneously stimulated the activations of NF-κB, AP-1, and IFN-ß, which promoted an antiviral state of the host cell. Conclusion: In summary, our study offers a new approach to target intracellular pathogenesis-related protein by engineered cell-penetrating mAb expanding their potential for therapeutic applications. Moreover, the 9D11-Tat antibody may provide a novel therapeutic agent against human chronic HBV infection.

Galangin suppresses hepatocellular carcinoma cell proliferation by reversing the Warburg effect.

Hepatocellular carcinoma (HCC) is the sixth most common cancer. The Warburg effect is an important way by which HCC adapts to a hypoxic environment. The aim of the present study was to determine whether and how galangin reverses the Warburg effect in HCC cells. We treated three HCC cell lines, HepG2, Hep3B and PLC/PRF/5 with galangin for 24h, respectively. Cell proliferation was measured with MTT assay. Glucose uptake, lactate production and the oxygen consumption were measured. Pyruvate kinase activities were detected by measuring the consumption of NADH, and glycolytic pathway-related proteins were measured by Western blotting. The results showed that galangin suppressed proliferation of HCC cells, decreased glucose absorption and lactate production of HCC. In addition, galangin also gave rise to increased oxygen consumption in all three HCC cell lines. After treatment with galangin, the activity of pyruvate kinase was up-regulated and the expression levels of glycolytic pathway-related proteins were changed. These results suggest that galangin suppresses the Warburg effect in HCC cells, indicating that galangin might be a potential therapeutic agent for HCC.

Tolerance of Ricinus communis L. to Cd and screening of high Cd accumulation varieties for remediation of Cd contaminated soils.

Response of castor (Ricinus communis L.) to cadmium (Cd) was assessed by a seed-suspending seedbed approach. Length of total radicle was the most sensitive indicator of Cd tolerance among the tested germination and growth characters. The ED50 value for Cd was 11.87 mg L(-1), indicating high Cd tolerance in castor. A pot experiment was conducted by growing 46 varieties of castor under CK (without Cd) and Cd1 (10 mg kg(-1) of Cd) and Cd2 (50 mg kg(-1) of Cd) treatments to investigate genotype variations in growth response and Cd accumulation of castor under different Cd exposures. Castor possessed high Cd accumulation ability; average shoot and root Cd concentrations of the 46 tested varieties were 21.83 and 185.43 mg kg(-1), and 174.99 and 1181.96 mg kg(-1) under Cd1 and Cd2, respectively. Great variation in Cd accumulation was observed among varieties, and Cd concentration of castor was genotype dependent. The correlation between biomass and Cd accumulation was significantly positive, while no significant correlation was observed between Cd concentration and Cd accumulation, which indicated that biomass performance is the dominant factor in determining Cd accumulation ability.