A highly selective and sensitive method for Cd(II) detection was developed based on aptamer and gold nanoparticles (AuNPs) combined with a colorimetric smartphone readout. The experimental conditions such as reaction time of polydiene dimethyl ammonium chloride (PDDA) and AuNPs, PDDA dose, time of aptamer and PDDA incubation, and aptamer concentration were optimized. Under the optimized conditions, the color and red(R) value of the solution was concentration-dependent on Cd(II). The proposed method exhibited a linear range of 1-400 ng/mL (r2 = 0.9794) with a limit of detection (LOD) of 1 ng/mL. This method had been successfully applied to test and quantify Cd(II) in water and rice samples, and the results were in full agreement with those from the atomic absorption spectrometer. Therefore, low-cost colorimetry demonstrated its potential for practical application in visual or quantitative detection with a smartphone. This approach can be readily applied to other analytes.

Uridine diphosphate glycosyltransferases (UGTs) are multifunctional detoxification enzymes, which are involved in metabolizing various chemicals and contribute to the development of insecticide resistance. However, the possible roles of UGTs in chlorantraniliprole resistance in Chilo suppressalis have rarely been studied in detail. Based on genome data, 24 UGT genes in C. suppressalis belonging to 11 families were identified, which were designated by the UGT nomenclature committee. Synergism assay data suggested that UGTs are potentially involved in chlorantraniliprole resistance in C. suppressalis. CsUGT40AL1 and CsUGT33AG3 were significantly overexpressed in the chlorantraniliprole resistant strain (12.36- and 5.34-fold, respectively). The two UGTs were highly expressed in the larval Malpighian tubules, fat body, and midgut; however, expression was lowest in the head. Injection of individual dsRNAs reduced the expression of the two target genes (by 69.34% and 48.74%, respectively) and caused significant higher larval mortality (81.33% and 54.67%, respectively). Overexpression of CsUGT40AL1 and CsUGT33AG3 was potentially involved in chlorantraniliprole resistance in C. suppressalis, as confirmed by the RNAi assay. Our findings suggest that overexpression of UGTs may contribute to chlorantraniliprole resistance in C. suppressalis.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.

This study aimed to investigate the effect of NPTX1 on the prognosis of gastric cancer (GC), as well as the metastatic process in GC.

NLRC5, a protein belonging to the NOD-like receptor protein family (NLRs), is highly expressed in immune tissues and cells. NLRC5 plays an important role in the immune response of humans, where its regulatory mechanism has been elucidated. However, the function and regulation of NLRC5 in chickens remains unclear. In this study, temporal expression characteristics of NLRC5 and associated genes in the STAT1 pathway in chickens following infection with Salmonella pullorum were investigated using quantitative real-time polymerase chain reaction and hierarchical cluster analyses. The role of transcription factor STAT1 in NLRC5 promoter activity was studied via point mutation of the STAT1-binding cis-element and dual-luciferase assays. Our results showed a strong correlation between NLRC5 and NF-κB. In addition, STAT1 played a crucial role in NLRC5 promoter activity, and may be activated via the interferon pathway. There was also a close relationship between CD80 and NF-κB, and CD80 may up-regulate NF-κB expression and enhance its protein activity in chickens. These findings reveal the temporal characteristics of chicken NLRC5 and STAT1 genes during S. pullorum infection, and highlight the role of STAT1 in NLRC5 promoter activity. This information aids our understanding of the regulatory mechanisms of NLRC5 and associated genes, and will help elucidate their function in the immune response of chickens.

To evaluate the accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer patients with axillary lymph node (ALN) metastasis.

Patient-specific cranial implants are important and necessary in the surgery of cranial defect restoration. However, traditional methods of manual design of cranial implants are complicated and time-consuming. Our purpose is to develop a novel software named EasyCrania to design the cranial implants conveniently and efficiently. The process can be divided into five steps, which are mirroring model, clipping surface, surface fitting, the generation of the initial implant and the generation of the final implant. The main concept of our method is to use the geometry information of the mirrored model as the base to generate the final implant. The comparative studies demonstrated that the EasyCrania can improve the efficiency of cranial implant design significantly. And, the intra- and inter-rater reliability of the software were stable, which were 87.07 ± 1.6% and 87.73 ± 1.4% respectively.

To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.

Anti-PD-1 therapy has been approved for cancer treatment. However, the response rate is unsatisfactory. The expression of PD-L1 in tumor tissues is unreliable to predict the treatment response. Recent studies have suggested that exosomal PD-L1 not only exerts immunosuppressive effects but also plays a significant role in the development of tumor microenvironment. Thus, the present study aims to investigate exosomal PD-L1 in improving its predictive value and efficacy. A total of 44 patients of advanced tumors of several types, treated with anti-PD-1 therapy, were enrolled. Exosomes were collected and purified from plasma. The exosomal PD-L1 was detected with ELISA. The cytokines were measured with the MILLIPLEX magnetic bead assay. Compared to the responders, exosomal PD-L1 of the non-responders was significantly higher than that of the responders (P = 0.010) before the treatment. Concurrently, exosomal PD-L1 and tumor burden decreased when the therapy was effective. And, the baseline expression of CD28 was higher in the responders than that in the non-responders (P = 0.005). Univariate and multivariate analyses validated with 1,000 times bootstrapping suggested that high exosomal PD-L1 and low CD28 expressions were negative factors for progression-free survival (PFS) of the patients who underwent anti-PD-1 treatment. The combination of exosomal PD-L1 and CD28 obtained more area under the curve (AUC) of receiver operating characteristic (ROC) (AUC 0.850 vs. 0.784 vs. 0.678) and showed a higher probability of no progression via nomograph. These findings suggested that the expression of exosomal PD-L1 and CD28 could serve as the predictive biomarkers for clinical responses to anti-PD-1 treatment.

Survivin and XIAP are two important members of the inhibitor of apoptosis protein family and have been considered as potential targets for cancer treatment due to their overexpression in large variety of cancers including colorectal cancer. It has been reported that survivin and XIAP can synergistically inhibit apoptosis by forming survivin-XIAP complex. In this study, we aimed to design a peptide that targets the survivin-XIAP complex and elucidate its anticancer mechanisms in colorectal cancer cells.

Vanin1 (VNN1) is a pantetheinase that can catalyze the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies showed that VNN1 is specifically expressed in chicken liver. In this study, we aimed to investigate the roles of peroxisome proliferators activated receptor α (PPARα) and miRNA-181a-5p in regulating VNN1 gene expression in chicken liver.

The mutational profile of oncogenic driver genes play an important role in non-small-cell lung cancer (NSCLC). The need of a testing panel capable of comprehensively determining patient genotypes in limited amounts of material has increased since the recent association of nine core oncogenic driver genes as tumor predictive biomarkers.

Background: The major limitation of targeted cancer therapy is development of acquired resistance. Intratumoral heterogeneity and coexist of multiple resistance mechanisms make combination therapies targeting one specific mechanism inefficient. Methods: Transcriptional signature obtained from GEO was used to reposition FDA-approved drugs to treat lung and breast cancers as well as overcome acquired resistance to EGFR TKIs in lung cancer and to tamoxifen in breast cancer via CMap. In vitro and in vivo models were used to examine candidate drugs for their anti-cancer and anti-resistance efficacy and underlying mechanisms. Results: We found that aspirin, the most commonly used drug, not only inhibited proliferation and promoted apoptosis of cancer cells, but also delayed and overcame acquired resistance to targeted therapy using in vitro and in vivo models. The underlying mechanism could be attributed to enhanced cancer stemness and activated NF-κB signaling in acquired resistant tumors, both of which were suppressed by aspirin and rendered resistant tumors more sensitive to aspirin. Conclusions: Our data identify aspirin as a potential candidate for combination therapy for lung and breast cancers.

Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance.

Recently, the relationships between uncoupling protein-2 (UCP2) -866G/A (rs659366) and Ala55Val (rs660339) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have been explored considerably, but the results are greatly inconsistent. This meta-analysis was performed to further identify the association of UCP2 rs659366 and rs660339 with the risk of T2DM.

Intracranial aneurysm (IA) is a cerebrovascular disorder in which abnormal dilation of a blood vessel results from weakening of the blood vessel wall. The aneurysm may rupture, leading to subarachnoid hemorrhage with severe outcomes. This study was conducted to identify the genetic factors involved in the etiology of IA. Whole-exome sequencing was performed in three IA-aggregate families to identify candidate variants. Further association studies of candidate variants were performed among sporadic cases and controls. Bioinformatic analysis was used to predict the functions of candidate genes and variants. Twenty variants were identified after whole-exome sequencing, among which eight were selected for replicative association studies. ANK3 c.4403G>A (p.R1468H) was significantly associated with IA (odds ratio 4.77; 95% confidence interval 1.94-11.67; p-value = 0.00019). Amino acid R1468 in ANK3 was predicted to be located in the spectrin-binding domain of ankyrin-G and may regulate the migration of vascular endothelial cells and affect cell-cell junctions. Therefore, the variation p.R1468H may cause weakening of the artery walls, thereby accelerating the formation of IA. Thus, ANK3 is a candidate gene highly related to IA.

Background: The major limitation of EGFR TKIs in EGFR-mutant lung cancer therapy is the development of acquired resistance. The underlying mechanisms remain unknown in about 30% of cases. NF-κB activation was encountered in the acquired resistance to EGFR TKIs. Unfortunately, none of NF-κB inhibitors has been clinically approved. The most commonly used antidiabetic drug metformin has demonstrated antitumor effects associated with NF-κB inhibition. Therefore, in this study, metformin was examined for its antitumor and antiresistance effects and underlying mechanisms. Methods: In vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to EGFR TKIs were used. Results: We found that NF-κB was activated in EGFR-mutant lung cancer cells with acquired resistance to EGFR TKIs. Metformin inhibited proliferation and promoted apoptosis of lung cancer cells, especially those with acquired EGFR TKI resistance. Moreover, metformin reversed and delayed acquired resistance to EGFR TKIs as well as suppressed cancer stemness in EGFR-mutant lung cancer. Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-κB signaling. Conclusions: Our data provided novel and further molecular rationale and preclinical data to support combination of metformin with EGFR TKIs to treat EGFR-mutant lung cancer patients, especially those with acquired resistance.

Immune checkpoints, as pivotal regulators of immune escape in cancer, can motivate the emergence of immune checkpoint inhibitors (ICIs). The aim of this study is to identify the expression of the immune checkpoint genes (ICGs) in colorectal cancer (CRC) and to relate their individual as well as combined expression to prognosis and therapeutic effectiveness in CRC.

Although immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies.

Macrophage polarization is a process by which macrophages acquire a distinct phenotypic and functional profile in response to microenvironmental signals. The classically and alternatively activated (M1 and M2, respectively) macrophage phenotypes are defined by the specific molecular characteristics induced in response to prototypic pro- and anti-inflammatory cues. In this study, we used LPS/IFN-γ and IL-4 to stimulate porcine alveolar macrophages (PAMs) in vitro and investigated the expression changes of several novel markers during macrophage polarization. Notably, we found that LPS/IFN-γ-stimulated PAMs express prototypical M1 molecules, whereas IL-4-stimulated PAMs express M2 molecules. We also demonstrated that replication of the highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) strain HuN4 was effectively suppressed in LPS/IFN-γ-stimulated M1 PAMs (M1 type), but not IL-4 stimulated M2 PAMs. However, this was not observed with the classic, less pathogenic CH-1a strain. Moreover, we found that M2 marker expression gradually increased after PAM infection with PRRSV, whereas no significant changes were found with M1 marker expression, suggesting that PRRSV infection may skew macrophage polarization towards an M2 phenotype. Finally, we found that anti-viral cytokine expression was significantly higher in M1 macrophages than in M2 macrophages or nonpolarized controls. In summary, our results show that PRRSV replication was significantly impaired in M1 PAMs, which may serve as a foundation for further understanding of the dynamic phenotypic changes during macrophage polarization and their effects on viral infection.