Missing WD40 Repeats in ATG16L1 Delays Canonical Autophagy and Inhibits Noncanonical Autophagy.

Canonical autophagy is an evolutionarily conserved process that forms double-membrane structures and mediates the degradation of long-lived proteins (LLPs). Noncanonical autophagy (NCA) is an important alternative pathway involving the formation of microtubule-associated protein 1 light chain 3 (LC3)-positive structures that are independent of partial core autophagy proteins. NCA has been defined by the conjugation of ATG8s to single membranes (CASM). During canonical autophagy and NCA/CASM, LC3 undergoes a lipidation modification, and ATG16L1 is a crucial protein in this process. Previous studies have reported that the WDR domain of ATG16L1 is not necessary for canonical autophagy. However, our study found that WDR domain deficiency significantly impaired LLP degradation in basal conditions and slowed down LC3-II accumulation in canonical autophagy. We further demonstrated that the observed effect was due to a reduced interaction between ATG16L1 and FIP200/WIPI2, without affecting lysosome function or fusion. Furthermore, we also found that the WDR domain of ATG16L1 is crucial for chemical-induced NCA/CASM. The results showed that removing the WDR domain or introducing the K490A mutation in ATG16L1 significantly inhibited the NCA/CASM, which interrupted the V-ATPase-ATG16L1 axis. In conclusion, this study highlights the significance of the WDR domain of ATG16L1 for both canonical autophagy and NCA functions, improving our understanding of its role in autophagy.

Glyoxalase 1 inhibitor BBGC suppresses the progression of chronic lymphocytic leukemia and promotes the efficacy of Palbociclib.

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Despite recent tremen-dous progress in managing CLL, the disease remains incurable with clinical therapies, and relapse is inevitable. To overcome this, new diagnostic and prognostic markers need to be investigated. We thus screened through the public database for genes with diagnostic, prognostic, and therapeutic implications in CLL. We further performed RT-qPCR and Western blot analysis to measure the candidate gene and protein expression levels, respectively, in peripheral blood mononuclear cells. Our results indicated that Glyoxalase 1 (GLO1) expression was significantly higher in patients with CLL than in healthy controls. Furthermore, cell proliferation, apoptosis, and cell cycle assay results together indicated that S-p-bromobenzylglutathione cyclopentyl diester (BBGC), an effective inhibitor of GLO1, suppresses the progression of CLL. Bioinformatics analysis revealed that GLO1 expression is closely associated with CDK4 expression in a wide variety of cancer types, and inhibition of CDK4 through silencing of genes or inhibitors can downregulate GLO1 expression. Subsequent validation experiments demonstrated that GLO1 protein levels were downregulated in MEC-1 and Jurkat cell lines after palbociclib exposure, and combination treatment of palbociclib with GLO1 inhibitor BBGC effectively delayed the growth of tumor cell lines.

MiR-181c-5p ameliorates learning and memory in sleep-deprived mice via HMGB1/TLR4/NF-κB pathway.

Sleep deprivation (SD) can lead to cognitive impairment caused by neuroinflammation. MiR-181c-5p/HMGB1 axis plays a part in anti-inflammation effects. However, the mechanism that miR-181c-5p facilitates learning and memory in SD mice remains unclear. So we investigated the role of miR-181c-5p in learning and memory impairment induced by SD. We overexpressed miR-181c-5p in the mice hippocampus by injecting lentivirus vector-miR-181c-5p (LV-miR-181c-5p) particles. Mice were divided into four groups: control (Ctrl), SD, SD + miR-181c-5p and SD + vector. We found that mice in the third group showed ameliorated learning and memory compared with the fourth group. The content of ionized calcium binding adaptor molecule 1 (IBA-1) in the third group was decreased compared with the fourth group. Moreover, the expression levels of HMGB1, TLR4 and p-NF-κB in the hippocampus of overexpressed miR-181c-5p mice were reduced. In total, miR-181c-5p ameliorated learning and memory in SD mice via the HMGB1/TLR4/NF-κB pathway.

Prevalence and genotype distribution of HPV and cervical pathological results in Sichuan Province, China: a three years surveys prior to mass HPV vaccination.

BACKGROUND: HPV persistent infection is a strong carcinogenic factor that can induce cervical cancer. Investigation of HPV epidemiology and genotype distribution is of great meaning for the development of cervical cancer prevention and control strategies. METHODS: By using PCR-based hybridization gene chip assay, HPV genotype was detected from 14,185 women that came from HEC (Health Examination Center) or OGOC (Obstetrics and Gynecology Outpatient Clinics) between 2015 and 2017 in Sichuan area. The epidemiology and genotype distribution as well as the relationship between HPV infection and histology/cytology abnormalities were analyzed. RESULTS: The positivity rate of HPV was 23.84%. The HPV-positive rate of OGOC group (37.62%) was significantly higher than that of HEC group (15.29%), p < 0.05. The prevalence of HPV reached peak at age 41-50 (5.86%) in HEC group, but at age 21-30 (14.74%) in OGOC group. Of all the HPV positive women, single genotype infection was the most common form in both HEC and OGOC group (62.06% in total screening population, 74.36% in HEC group and 54.01% in OGOC group). Three most prevalent HPV types were HPV-52 (5.02%), 58 (3.61%), and 16 (3.24%) in total screening population. Of all the HPV positive women, the top three types were HPV-52 (20.93%), CP8304 (15.32%), and 58 (14.42%) in HEC group, while were HPV-52 (21.14%), 16 (16.34%), and 58 (15.61%) in OGOC group. HPV 52/16/58 accounted for 41.84% of cytology and 56.52% of histological abnormalities. CONCLUSIONS: Women in Sichuan area were facing the great threat of HPV infection, especially the women aged between 21 ~ 30 or 41-50 years old. The priority HPV types were HPV 52, 58, and 16 in OGOC group, while were HPV 52, CP8304, and 58 in HEC group. HPV 52/16/58 accounted for the majority of cytology and histological abnormalities. Our analysis was found to be valuable for providing a scientific basis for the prevention and control strategies of cervical cancer in Sichuan area.

Prevalence and Genotype Distribution of Human Papillomavirus From 9,182 Individuals Participated Health Examination.

BACKGROUND: Human papillomavirus (HPV) is the cause of nearly all cervical cancers and the primary cause of anal cancers. Prevalence of HPV varies largely among countries and regions, and population-based data are largely insufficient. The aim of this study is to determine the prevalence and genotype distribution of HPV infection among the women received a general health check. METHODS: In the years 2015, 2016, and 2017, a total of 553,654 individuals received a general health check in the Sichuan Provincial People's Hospital. Among them, 9,182 unselected and asymptomatic individuals received the HPV screening test. Samples of exfoliated endocervical cells were collected and DNA isolation was performed with a Cell Lysis Kit. Fragments of HPV DNA were amplified by PCR. Twenty-one different HPV genotypes, including HPV 6, 11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 56, 58, 59, 66, 68, and CP8304, were detected from PCR products using a GenoArray Diagnostic Hybridization Kit. HPV genotype was read on the colored position on the array. RESULTS: A total of 1,207 individuals were positive for at least one HPV genotype, giving a crude prevalence of 13.2% (95% CI: 12.5 - 13.9%). The prevalence did not differ much among age groups. HPV-positive individuals were 291, 389, and 527 in 2015, 2016, and 2017, respectively. The majority of the HPV-positive participants (960/1,207 = 80%) had one type of virus. Approximately 15% had two genotypes of HPV. One individual had HPV of 6 different genotypes, including 16, 18, 52, 53, 56, and CP8304. The most frequent genotype was 52, followed by CP8304, 58, and 53. The oncogenic types 16 and 18 were found in 112 and 52 participants, corresponding to a prevalence of 0.9% (CI: 0.8 - 1.1%) and 0.4% (CI: 0.3 - 0.6%), respectively, for the 9,182 individuals included in this study. CONCLUSIONS: The prevalence of 13.2% for HPV among unselected and asymptomatic individuals who received a general health check is high in the Sichuan area. Identification of high-risk HPV types is essential for preventing or early detection of cervical cancers and consequently save life.

Association between lncRNA H19 rs217727 polymorphism and the risk of cancer: an updated meta-analysis.

BACKGROUND: We have performed this study to evaluate the association between H19 rs217727 polymorphism and the risk of cancer. METHODS: An odds ratio (OR) with a 95% confidence interval (CI) was applied to determine a potential association. RESULTS: A total of 17 case-control publications were selected. This meta-analysis showed that H19 rs217727 has a significant increased association with cancer risk in allelic, homozygous, heterozygote, dominant and recessive models (T vs C: OR = 1.16, 95% CI = 1.06-1.27, I2 = 75.7; TT vs CC: OR = 1.29, 95% CI = 1.06-1.56, I2 = 71.6; CT vs CC: OR = 1.15, 95% CI = 1.01-1.31, I2 = 75.4; CT + TT vs CC: OR = 1.20, 95% CI = 1.05-1.36, I2 = 76.5; TT vs CT + CC: OR = 1.22, 95% CI = 1.02-1.45, I2 = 70.6;). In the subgroup analysis of smoking status, both smokers and nonsmokers showed an increase in cancer risk in allelic, homozygous, dominant and heterozygote models. CONCLUSION: This meta-analysis revealed H19 rs217727 may influence cancer susceptibility.

Atroposelective Phosphoric Acid Catalyzed Three-Component Cascade Reaction: Enantioselective Synthesis of Axially Chiral N-Arylindoles.

An efficient organocatalytic atroposelective three-component cascade reaction of 2,3-diketoesters, aromatic amines, and 1,3-cyclohexanediones has been developed for the highly enantioselective synthesis of axially chiral N-arylindoles. The success of this method derives from the use of a newly developed second-generation chiral spirocyclic phosphoric acid as the catalyst. In addition, this protocol was extended to the synthesis of an axially chiral monophosphorus ligand.

Retraction: Enantioselective synthesis of α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines via chiral phosphoric acid catalysis.

[This retracts the article DOI: 10.1039/D2RA03750E.].

Enantioselective synthesis of α-tetrasubstituted (1-indolizinyl) (diaryl)-methanamines via chiral phosphoric acid catalysis.

An enantioselective Friedel-Crafts reaction of cyclic α-diaryl N-acyl imines with indolizines catalyzed by a chiral spirocyclic phosphoric acid has been developed. The asymmetric transformation proceeds smoothly to afford α-tetrasubstituted (1-indolizinyl) (diaryl)methanamines in good yields with up to 98% ee under mild conditions.

The effect of miR­155­5p on long­term memory of sleep­deprived mice through the BDNF/NF­κB pathway.

Sleep deprivation (SD) is a prevalent sleep issue in modern society that significantly impairs neurological function and quality of life in affected individuals. This study seeks to investigate the involvement of the miR­155­5p/BDNF axis in SD mice, aiming to establish a theoretical foundation for potential treatment strategies. Male C57BL/6 mice were utilized in the construction of a SD model using the flower pot technique. HT22 cells were selected for cellular experiments. The Morris water maze was employed to assess the learning and memory capabilities of the mice. HE staining was utilized to observe pathological changes in hippocampal tissue. Levels of IL­1ß, IL­6, and TNF­α were analyzed using ELISA. The expression level of miR­155­5p was quantified via RT­qPCR. The binding between miR­155­5p and brain­derived neurotrophic factor (BDNF) was confirmed through a dual­luciferase reporter assay. Apoptosis of hippocampal neurons was assessed using TUNEL. Western blot analysis was conducted to evaluate the expression levels of BDNF, p65, and p­p65. The Morris water maze test revealed that the mice exhibited prolonged escape latency, decreased swimming velocity, and reduced time spent in the target platform quadrant, which are indicative of a successful construction of the SD model. The observed cognitive deficits in the mice were associated with SD­induced damage to the hippocampal tissue, leading to increased levels of miR­155­5p and decreased levels of BDNF. miR­155­5p was found to directly bind to BDNF, thereby suppressing its mRNA and protein expression. The upregulation of BDNF effectively mitigated hippocampal damage by attenuating cell apoptosis and reducing inflammation levels in SD mice. Additionally, the BDNF/NF­κB pathway was found to be suppressed in SD mice through the downregulation of miR­155­5p. Therefore, the silencing of miR­155­5p inhibited the activation of the NF­κB pathway by upregulating BDNF, which improved long­term memory and reduced neuronal damage in SD mice.

Engineering cyanobacteria as a new platform for producing taxol precursors directly from carbon dioxide.

Taxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.

Identification and validation of an H2AZ1-based index model: a novel prognostic tool for hepatocellular carcinoma.

The H2A.Z variant histone 1 (H2AZ1) is aberrantly expressed in various tumors, correlating with an unfavorable prognosis. However, its role in hepatocellular carcinoma (HCC) remains unclear. We aimed to elucidate the pathways affected by H2AZ1 and identify promising therapeutic targets for HCC. Following bioinformatic analysis of gene expression and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus database, we found 6,344 dysregulated genes related to H2AZ1 overexpression in HCC tissues (P < 0.05). We performed weighted gene co-expression network analysis to identify the gene module most related to H2AZ1. The H2AZ1-based index was further developed using Cox regression analysis, which revealed that the poor prognosis in the high H2AZ1-based index group could be attributed to elevated tumor stemness (P < 0.05). Moreover, the clinical model showed good prognostic potential (AUC > 0.7). We found that H2AZ1 knockdown led to reduced superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) levels, and increased apoptosis rate in tumor cells (P < 0.001). Thus, we developed an H2AZ1-based index model with the potential to predict the prognosis of patients with HCC. Our findings provide initial evidence that H2AZ1 overexpression plays a pivotal role in HCC initiation and progression.

Small Cajal Body-Specific RNA12 Promotes Carcinogenesis through Modulating Extracellular Matrix Signaling in Bladder Cancer.

Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes in gene expression patterns and functional pathways in BLCA patients with different expressions of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle, and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays, and in vivo nude mice xenograft models, respectively. Finally, a chromatin isolation by RNA purification (ChIRP) experiment was further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, and CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase and promoted apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. A ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate the transcription program and then affect BLCA progression. Conclusions: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

CCDC134 is down-regulated in gastric cancer and its silencing promotes cell migration and invasion of GES-1 and AGS cells via the MAPK pathway.

CCDC134 (coiled coil domain containing 134), a novel secretory protein, acts as an inhibitor of Erk1/2 and JNK/SAPK pathways. However, the role of CCDC134 in cancer development is still lacking. In this study, we found that CCDC134 expression significantly reduced in gastric cancer tissues compared with normal tissues (P < 0.001) and lesion tissues (P < 0.001). But no statistically significant difference was observed between normal and lesion tissues (P = 0.842). In vitro transient transfection of CCDC134-specific siRNA significantly promoted the migration and invasion of both the normal gastric epithelial cell line GES-1 and gastric cancer cell line AGS cells. Further analysis revealed that the attenuated expression of CCDC134 promoted the activation of Erk1/2 and JNK/SAPK, but had no effect on p38. The activation of Erk1/2 and JNK/SAPK was required for CCDC134-mediated migration and invasion. Besides, CCDC134-RNAi could induce the expression of MMP-2 and MMP-9, which are key molecules involved in regulating cell migration and invasion. Therefore, CCDC134 may be a candidate biomarker for malignant transformation. It plays a role in regulation of cell migration and invasion, and could be a therapeutic target of gastric cancer.

Repeated neonatal isoflurane exposure facilitated stress-related fear extinction impairment in male mice and was associated with ΔFosB accumulation in the basolateral amygdala and the hippocampal dentate gyrus.

Volatile anesthetics elicit neurodevelopmental toxicity in rodents and primates and lead to more exaggerated anxiety-like behavior in response to future stress. Anxiety and fear are closely correlated and maladaptive fear-associated learning is regarded as the core mechanism underlying anxiety-related disorders. However, little is known about the interaction between early-life anesthetic exposure and future stress and the accompanying effect on fear-associated learning. In the present study, we evaluated the alterations in fear-associated learning (fear acquisition and extinction) occurring in mice receiving repeated neonatal isoflurane exposure and chronic variable stress (CVS) successively through a series of fear conditioning, fear reinforcing, and fear extinction paradigms. The corticosterone (CORT) response during CVS and the immunohistochemical levels of ΔFosB and c-Fos expression in the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG) after the extinction retrieval test were also investigated. The results showed that neonatal isoflurane exposure could increase CORT levels following the first diurnal CVS procedure, but not after completion of the whole CVS paradigm. Neonatal isoflurane exposure exerted a repressive effect on fear acquisition, in contrast to that seen with CVS. Neonatal isoflurane exposure and CVS both exerted suppressive effects on fear extinction and there was a significant synergy between them. Furthermore, neonatal isoflurane exposure facilitated CVS-mediated ΔFosB accumulation in the BLA and the hippocampal DG, which may have been responsible for c-Fos expression deficits and fear extinction impairment. Collectively, these findings contribute to the understanding of the interaction between early-life anesthetic exposure and future stress, as well as the accompanying behavioral alterations.

Single-cell RNA sequencing reveals cell subpopulations in the tumor microenvironment contributing to hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is among the deadliest cancers worldwide, and advanced HCC is difficult to treat. Identifying specific cell subpopulations in the tumor microenvironment and exploring interactions between the cells and their environment are crucial for understanding the development, prognosis, and treatment of tumors. Methods: In this study, we constructed a tumor ecological landscape of 14 patients with HCC from 43 tumor tissue samples and 14 adjacent control samples. We used bioinformatics analysis to reveal cell subpopulations with potentially specific functions in the tumor microenvironment and to explore the interactions between tumor cells and the tumor microenvironment. Results: Immune cell infiltration was evident in the tumor tissues, and BTG1 + RGS1 + central memory T cells (Tcms) interact with tumor cells through CCL5-SDC4/1 axis. HSPA1B may be associated with remodeling of the tumor ecological niche in HCC. Cancer-associated fibroblasts (CAFs) and macrophages (TAMs) were closely associated with tumor cells. APOC1 + SPP1 + TAM secretes SPP1, which binds to ITGF1 secreted by CAFs to remodel the tumor microenvironment. More interestingly, FAP + CAF interacts with naïve T cells via the CXCL12-CXCR4 axis, which may lead to resistance to immune checkpoint inhibitor therapy. Conclusion: Our study suggests the presence of tumor cells with drug-resistant potential in the HCC microenvironment. Among non-tumor cells, high NDUFA4L2 expression in fibroblasts may promote tumor progression, while high HSPA1B expression in central memory T cells may exert anti-tumor effects. In addition, the CCL5-SDC4/1 interaction between BTG1 + RGS1 + Tcms and tumor cells may promote tumor progression. Focusing on the roles of CAFs and TAMs, which are closely related to tumor cells, in tumors would be beneficial to the progress of systemic therapy research.

Imaging signs and the qualitative diagnosis of solitary rib lesions using 99mtechnetium-methylene diphosphonate whole-body bone imaging in patients with a malignant tumor.

Background: The aim of this study was to summarize the valuable information for qualitative diagnosis by investigating the imaging signs from the whole-body bone imaging of solitary rib lesions. Methods: A retrospective analysis was conducted of the data from 313 patients with malignant tumors and solitary rib lesions identified using whole-body bone imaging in Department of Nuclear Medicine of Central South University Xiangya School Affiliated Haikou Hospital between January 2015 and December 2017. Based on the final comprehensive diagnosis of the rib lesions, the patients were divided into a bone metastasis group, fracture group, other benign lesions group, and an uncertain group, and the characteristic imaging changes in rib lesions in each group were explored. Results: (I) Significant differences were identified among the 4 groups (P<0.001) in the distribution of lesions in the anterior, posterior, and lateral ribs and proximal costal cartilage. The fracture group had the highest proportion of lesions in the anterior ribs (99/121, 81.8%) and proximal costal cartilage (74.4%, 90/121). (II) Significant differences were detected in morphology, concentration, boundaries, and radioactivity distribution among the 4 groups of patients (P<0.001). The bone metastasis group had the highest proportion of lesions appearing as stripes (35/67, 52.2%), and the fracture group had the highest proportion of lesions appearing as spots (94.2%, 114/121) and the lowest proportion appearing as stripes (3/121, 2.5%). (III) Significant differences were found in the longitudinal diameter, transverse diameter, aspect ratio, and tumor-to-normal tissue ratio between the 4 groups (P<0.001). The longitudinal diameter (27.8±16.0 mm) and aspect ratio (1.9±1.0) of the bone metastasis group were the highest, whereas the longitudinal diameter (15.2±3.9 mm) and aspect ratio (1.0±0.2) of the fracture group were the smallest. Conclusions: This study revealed that different types of solitary rib lesions had relatively characteristic imaging signs in whole-body bone imaging.

Enantioselective synthesis of α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines via chiral phosphoric acid catalysis.

An enantioselective Friedel-Crafts reaction of cyclic α-diaryl N-acyl imines with indolizines catalyzed by a chiral spirocyclic phosphoric acid has been developed. The asymmetric transformation proceeds smoothly to afford α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines in good yields with up to 98% ee under mild conditions.

Adsorption and desorption mechanisms on graphene oxide nanosheets: Kinetics and tuning.

A knowledge of the adsorption and desorption behavior of sorbates on surface adsorptive site (SAS) is the key to optimizing the chemical reactivity of catalysts. However, direct identification of the chemical reactivity of SASs is still a challenge due to the limitations of characterization techniques. Here, we present a new pathway to determine the kinetics of adsorption/desorption on SASs of graphene oxide (GO) based on total internal reflectance fluorescence microscopy. The switching on and off of the fluorescent signal of SAS lit by carbon dots (CDs) was used to trace the adsorption process and desorption process. We find that sodium pyrophosphate (PPi) could increase the adsorption equilibrium of CDs thermodynamically and promote the substrate-assisted desorption pathway kinetically. At the single turnover level, it was disclosed that the species that can promote desorption may also be an adsorption promoter. Such discovery provides significant guidance for improving the chemical reactivity of the heterogeneous catalyst.

Proteomic profiling of proteins associated with lymph node metastasis in colorectal cancer.

Lymph node metastasis (LNM) is associated with poor prognosis in colorectal cancer (CRC). The presence or absence of lymph node metastases is a strong independent prognostic factor for CRC survival. Investigation of proteins associated with the process of lymph node metastasis (LNM) is crucial for understanding of the molecular mechanisms underlying the LNM process and for predicting the CRC prognosis. In the present study, proteins from CRC tissues and adjacent normal mucosa (NMC) were examined using two-dimensional gel electrophoresis coupled with MALDI-TOF-MS. The expression levels of Ferritin Heavy Chain (FHC) were decreased in LNM CRC as compared to those in non-LNM CRC, while the expression of Cathepsin D and Ubiquitin C-terminal hydrolase-L1 (UCH-L1) were increased in LNM CRC. The results were confirmed by Western blotting and immunohistochemical staining. Furthermore, in vitro cell invasion assay showed that the overexpression of UCH-L1 through gene transfection increased the invasive ability of HCT8 cells, suggesting that UCH-L1 is not only a biomarker for LNM in CRC, but also a functional protein that may play a significant role in cell migration. The proteins identified in the present study should further our understanding of the LNM process of CRC and may become useful markers for diagnosis and targets for therapeutic interventions.