Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics

Characterization of a cuproptosis-related signature to evaluate immune features and predict prognosis in colorectal cancer

PurposeCuproptosis is a newly discovered type of cell death. Little is known about the roles that cuproptosis related genes (CRGs) play in colorectal cancer (CRC). The aim of this study is to evaluate the prognostic value of CRGs and their relationship with tumor immune microenvironment.MethodsTCGA-COAD dataset was used as the training cohort. Pearson correlation was employed to identify CRGs and paired tumor-normal samples were used to identify those CRGs with differential expression pattern. A risk score signature was constructed using LASSO regression and multivariate Cox stepwise regression methods. Two GEO datasets were used as validation cohorts for confirming predictive power and clinical significance of this model. Expression patterns of seven CRGs were evaluated in COAD tissues. In vitro experiments were conducted to validate the expression of the CRGs during cuproptosis.ResultsA total of 771 differentially expressed CRGs were identified in the training cohort. A predictive model termed riskScore was constructed consisting of 7 CRGs and two clinical parameters (age and stage). Survival analysis suggested that patients with higher riskScore showed shorter OS than those with lower (P<0.0001). ROC analysis revealed that AUC values of cases in the training cohort for 1-, 2-, and 3-year survival were 0.82, 0.80, 0.86 respectively, indicating its good predictive efficacy. Correlations with clinical features showed that higher riskScore was significantly associated with advanced TNM stages, which were further confirmed in two validation cohorts. Single sample gene set enrichment analysis (ssGSEA) showed that high-risk group presented with an immune-cold phenotype. Consistently, ESTIMATE algorithm analysis showed lower immune scores in riskScore-high group. Expressions of key molecules in riskScore model are strongly associated with TME infiltrating cells and immune checkpoint molecules. Patients with a lower riskScore exhibited a higher complete remission rate in CRCs. Finally, seven CRGs involved in riskScore were significantly altered between cancerous and paracancerous normal tissues. Elesclomol, a potent copper ionophore, significantly altered expressions of seven CRGs in CRCs, indicating their relationship with cuproptosis.ConclusionsThe cuproptosis-related gene signature could serve as a potential prognostic predictor for colorectal cancer patients and may offer novel insights into clinical cancer therapeutics

Mn-Mediated Electrochemical Trifluoromethylation/C(sp^2)–H Functionalization Cascade for the Synthesis of Azaheterocycles

A general electrohemical strategy for the combined trifluoromethylation/C(sp^2)–H functionalization using Langlois’ reagent as the CF_3 source under oxidant-free conditions was developed. Using Mn salts as the redox mediator, this method provides an efficient and sustainable means to access a variety of functionalized heterocycles bearing a CF_3 moiety. Detailed mechanistic studies are consistent with the formation of CF_3-bound high oxidation state Mn species, suggesting a transition-metal-mediated CF_3 transfer mechanism for this trifluoromethylation/C(sp^2)–H functionalization process

Transition-Metal-Free Borylation of Alkyl Iodides via a Radical Mechanism

We describe an operationally simple transition-metal-free borylation of alkyl iodides. This method uses commercially available diboron reagents as the boron source and exhibits excellent functional group compatibility. Furthermore, a diverse range of primary and secondary alkyl iodides could be effectively transformed to the corresponding alkylboronates in excellent yield. Mechanistic investigations suggest that this borylation reaction proceeds through a single-electron transfer mechanism featuring the generation of an alkyl radical intermediate

A Bond-Wire Drift Offset Minimized Capacitance-to-Digital Interface for MEMS Accelerometer with Gain-Enhanced VCO-Based Quantization and Nested Digital Chopping Feedback Loops

This paper presents an output offset minimized capacitance-to-digital interface for a MEMS accelerometer. With a gain-enhanced voltage-controlled oscillator (VCO)-based quantization loop, the interface is able to output a digital signal with improved dynamic range. For optimizing the output offset caused by nonideal factors (e.g., the bond-wire drift), a nested digital chopping feedback loop is embedded in the VCO-based quantization loop. It enables the interface to minimize the output offset without digital filtering and digital-to-analog conversion. The proposed architecture is well suited for dynamic range and offset improvements with low cost. Fabricated with a 0.18 μm Global Foundry (GF) CMOS process, the interface offers a 78 dB dynamic range with 0.4% nonlinearity from a single 2 V supply. With the input referred offset up to 1.3 pF, the offset cancellation loop keeps the DC output offset within 40 mV. The power dissipation is 6.5 mW with a bandwidth of 4 kHz

A Bond-Wire Drift Offset Minimized Capacitance-to-Digital Interface for MEMS Accelerometer with Gain-Enhanced VCO-Based Quantization and Nested Digital Chopping Feedback Loops

This paper presents an output offset minimized capacitance-to-digital interface for a MEMS accelerometer. With a gain-enhanced voltage-controlled oscillator (VCO)-based quantization loop, the interface is able to output a digital signal with improved dynamic range. For optimizing the output offset caused by nonideal factors (e.g., the bond-wire drift), a nested digital chopping feedback loop is embedded in the VCO-based quantization loop. It enables the interface to minimize the output offset without digital filtering and digital-to-analog conversion. The proposed architecture is well suited for dynamic range and offset improvements with low cost. Fabricated with a 0.18 μm Global Foundry (GF) CMOS process, the interface offers a 78 dB dynamic range with 0.4% nonlinearity from a single 2 V supply. With the input referred offset up to 1.3 pF, the offset cancellation loop keeps the DC output offset within 40 mV. The power dissipation is 6.5 mW with a bandwidth of 4 kHz