Depletion of L-Methionine in Foods with an Engineered Thermophilic Methionine γ-lyase Efficiently Inhibits Tumor Growth.

Dietary restriction of l-methionine, an essential amino acid, exerts potent antitumor effects on l-methionine-dependent cancers. However, dietary restriction of l-methionine has not been practical for human therapy because of the problem with the administration of l-methionine concentration in foods. Here, a thermophilic methionine γ-lyase (MGL), that catalyzes the cleavage of the C-S bond in l-methionine to produce α-ketobutyric acid, methanethiol, and ammonia was engineered from human cystathionine γ-lyase and almost completely depleted l-methionine at 65 °C, a temperature that accelerates the volatilization of methanethiol and its oxidation products. The high efficiency of l-methionine lysis may be attributed to the cooperative fluctuation and moderate the structural rigidity of 4 monomers in the thermophilic MGL, which facilitates l-methionine access to the entrance of the active site. Experimental diets treated with thermophilic MGL markedly inhibited prostate tumor growth in mice, and in parallel, the in vivo concentrations of l-methionine, its transformation product l-cysteine, and the oxidative stress indicator malondialdehyde significantly decreased. These findings provide a technology for the depletion of l-methionine in foods with an engineered thermophilic MGL, which efficiently inhibits tumor growth in mice.

CBX2 Expression in Colorectal Mucosa-adenoma-adenocarcinoma Sequence.

OBJECTIVE: To investigate the expression of chromobox 2 (CBX2) in colorectal adenoma (CRA) and colorectal cancer (CRC), and analyse its correlation with various clinicopathological parameters. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Pathology Department, Huashan Hospital, Fudan University, from December 2019 to December 2020. METHODOLOGY: The mRNA level of CBX2 in colorectal mucosa, CRA and CRC was evaluated in gene expression profiling interactive analysis (GEPIA) and gene expression omnibus (GEO) dataset, then verified by quantitative real-time PCR (qRT-PCR). CBX2 expression by immunohistochemistry was determined in 122 samples, then its correlation was analysed with various clinicopathological parameters. Diagnostic value of CBX2 was estimated by the receiver operating characteristic curve (ROC). Prognostic value of CBX2 mRNA expression was evaluated via the Kaplan-Meier method in GEPIA. RESULTS: CBX2 expression rate in CRC (89.8%) was greater than adenoma (37.74%) and mucosa (20%). CBX2 protein levels were highest in adenocarcinoma and lowest in mucosa with intermediate level in adenoma. The area under curve (AUC) of CBX2 was 0.810 and 0.734, respectively, in distinguishing CRA from mucosa and CRC from CRA. CBX2 hyperexpression was not significantly correlated with clinicopathological variables, either in CRA or CRC. Kaplan-Meier survival analysis revealed that CBX2 mRNA hyperexpression was not associated with overall survival (OS) of CRC. Although the disease-free survival (DFS) of high CBX2 patients was shorter than those with low expression, but no obvious significance was found in colon adenocarcinoma (COAD, p=0.052) and rectal adenocarcinoma (READ, p=0.097). CONCLUSION: CBX2 expression progressively increased in the sequence of mucosa-adenoma-carcinoma, which may be used as a diagnostic biomarker and therapeutic target for CRA and CRC. Key Words: CBX2, Colorectal adenoma, Colorectal cancer, Biomarker.

Distinguishing colorectal adenoma from hyperplastic polyp by WNT2 expression.

BACKGROUND: Colorectal adenoma (CRA) is a classical premalignant lesion, with high incidence and mainly coexisting with hyperplastic polyp (HPP). Hence, this study aimed to distinguish CRA from HPP by molecular expression profiling and advance the prevention of CRA and its malignance. METHODS: CRA and paired HPP biopsies were collected by endoscopy. Through RNA-sequencing (RNA-seq), the differentially expressed genes (DEGs) were obtained. Functional enrichment analysis was performed based on the DEGs. The STRING database and Cytoscape were used to construct the protein-protein interaction (PPI) network and perform module analysis. Hub genes were validated by real-time quantitative PCR (RT-qPCR) and immunohistochemistry. The ROC curve was drawn to establish the specificity of the hub genes. RESULTS: 485 significant DEGs were identified including 133 up-regulated and 352 down-regulated. The top 10 up-regulated genes were DLX5, MMP10, TAC1, ACAN, TAS2R38, WNT2, PHYHIPL, DKK4, DUSP27, and ABCA12. The top 10 down-regulated genes were SFRP2, CHRDL1, KBTBD12, RERGL, DPP10, CLCA4, GREM2, TMIGD1, FEV, and OTOP3. Wnt signaling pathway and extracellular matrix (ECM) were up-regulated in CRA. Three hub genes including WNT2, WNT5A, and SFRP1 were filtered out via Cytoscape. Further RT-qPCR and immunohistochemistry confirmed that WNT2 was highly expressed in CRA. The area under the ROC curve (AUC) at 0.98 indicated the expression level of WNT2 as a candidate to differ CRA from HPP. CONCLUSION: Our study suggests Wnt signaling pathway and ECM are enriched in CRA, and WNT2 may be used as a novel biomarker for distinguishing CRA from HPP and preventing the malignance of CRA.

MXene and black phosphorus based 2D nanomaterials in bioimaging and biosensing: progress and perspectives.

Bioimaging and biosensing have garnered interest in early cancer diagnosis due to the ability of gaining in-depth insights into cellular functions and providing a wide range of diagnostic parameters. Emerging 2D materials of multielement MXenes and monoelement black phosphorous nanosheets (BPNSs) with unique intrinsic physicochemical properties such as a tunable bandgap and layer-dependent fluorescence, high carrier mobility and transport anisotropy, efficient fluorescence quenching capability, desirable light absorption and thermoelastic properties, and excellent biocompatibility and biosafety properties provide promising nano-platforms for bioimaging and biosensing applications. In view of the growing attention on the rising stars of the post-graphene age in the progress of bioimaging and biosensing, and their common feature characteristics as well as complementarity for constructing complexes, the main objective of this review is to reveal the recent advances in the design of MXene or BPNS based nanoplatforms in the field of bioimaging and biosensing. The preparation and surface functionalization methods, biosafety, and other important aspects of bioimaging and biosensing applications of MXenes and BPNSs have been assessed systematically, along with highlighting the main challenges in further biomedical application. The review not only focuses on the advancements in 2D materials for use in bioimaging and biosensing but also assesses the possibility of their future potential in bioapplications.

Solo Smart Fluorogenic Probe for Potential Cancer Diagnosis and Tracking in Vivo Tumorous Lymphatic Systems via Distinct Emission Signals.

A versatile twisted-intramolecular-charge-transfer (TICT)-based near-infrared (NIR) fluorescent probe (L) has been judiciously designed and synthesized that could be utilized for potential cancer diagnosis and to track lymph node(s) in mice through distinct emission signals. Essentially, the probe rendered the capability to preferentially recognize the cancer cells over the noncancer cells by polarity-guided lipid droplet specific differential bioimaging (in green emission channel) studies. The probe also exhibited selective turn-on fluorescence response toward HSA/BSA in physiological media (aqueous PBS buffer; pH 7.4) at far-red/NIR regions, because of the 1:1 chelation between the probe and HSA/BSA. Therefore, the fluorescent probe was then maneuvered to track the draining lymphatic system and sentinel lymph node in tumor mice model by fluorescence imaging (NIR/deep-red channel), wherein the accumulated albumin protein in the draining tumor lymphatic system facilitated the in situ formation of the fluorescent albumin-L complex.

The Structure and Performance of Short Glass Fiber/High-Density Polyethylene/Polypropylene Composite Pipes Extruded Using a Shearing⁻Drawing Compound Stress Field.

Glass fiber reinforced polyolefin composite materials have many advantages regarding their performance and have been widely used in many fields. However, there are few reports on the simultaneously bidirectional self-enhancement of glass fiber reinforced polyethylene/polypropylene composite pipe. To self-reinforce the pipe's circular and axial properties simultaneously, short glass fiber reinforced high-density polyethylene/polypropylene (SGF/HDPE/PP) pipes were extruded using a shearing-drawing two-dimensional compound stress field pipe-extrusion device. The effects of the rotating speed of the rotating shear sleeve on the orientation, heat behavior, microstructure, and tensile strength of the pipe were investigated in this paper. The microstructure was observed using scanning electron microscopy (SEM), and the crystal diffraction was analyzed using a polycrystalline X-ray diffractometer (WAXD), the heat behavior was measured using a differential scanning calorimeter (DSC), and the tensile strength was tested using a universal electronic tensile testing machine. The results showed that the shear induction effect induced by the shear rotating promoted the formation of the oriented structure of the crystal plate and SGFs along the circular and axial directions of the pipe simultaneously. Furthermore, it increased the crystallinity of the system, and self-improved the pipe's circular and axial tensile strength at the same time.

EMC3 coordinates surfactant protein and lipid homeostasis required for respiration.

Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.