Organo-Photoredox Catalyzed gem-Difluoroallylation of Glycine and Glycine Residue in Peptides.

An organo-photoredox catalyzed gem-difluoroallylation of glycine with α-trifluoromethyl alkenes via direct C(sp3)-H functionalization of glycine and C-F bond activation of α-trifluoromethyl alkenes has been described. As a consequence, a broad range of gem-difluoroalkene-containing unnatural amino acids are afforded in moderate to excellent yields. This reaction exhibits multiple merits such as readily available starting materials, broad substrate scope, and mild reaction conditions. The feasibility of this reaction has been highlighted by the late-stage modification of several peptides as well as the improved in vitro antifungal activity of compound 3v toward Valsa mali compared to that with commercial azoxystrobin.

Enhancing Whole-Brain Magnetic Field Homogeneity for 3D-Magnetic Resonance Spectroscopic Imaging with a Novel Unified Coil: A Preliminary Study.

The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI's widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim-RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil. We also simulated a theoretical 3rd-, 4th-, and 5th-order SH shim as a benchmark to assess the UNIfied shim-RF coil (UNIC) improvements. In this preliminary study, the whole-brain coverage was simulated by using B0 field maps of twenty-four healthy human subjects (n = 24). Our results demonstrated that UNIC substantially improves brain field homogeneity, reducing whole-brain frequency standard deviations by 27% compared to the standard 2nd-order scanner shim and 17% compared to the iPRES shim. Moreover, UNIC enhances whole-brain coverage of 3D-MRSI by up to 34% compared to the standard 2nd-order scanner shim and up to 13% compared to the iPRES shim. UNIC markedly increases coverage in the prefrontal cortex by 147% and 47% and in the medial temporal lobe and temporal pole by 29% and 13%, respectively, at voxel resolutions of 1.4 cc and 0.09 cc for 3D-MRSI. Furthermore, UNIC effectively reduces variations in shim quality and brain coverage among different subjects compared to scanner shim and iPRES shim. Anticipated advancements in higher-order shimming (beyond 6th order) are expected via optimized designs using dimensionality reduction methods.

Mold-Free Manufacturing of Highly Sensitive and Fast-Response Pressure Sensors Through High-Resolution 3D Printing and Conformal Oxidative Chemical Vapor Deposition Polymers.

A new manufacturing paradigm is showcased to exclude conventional mold-dependent manufacturing of pressure sensors, which typically requires a series of complex and expensive patterning processes. This mold-free manufacturing leverages high-resolution 3D-printed multiscale microstructures as the substrate and a gas-phase conformal polymer coating technique to complete the mold-free sensing platform. The array of dome and spike structures with a controlled spike density of a 3D-printed substrate ensures a large contact surface with pressures applied and extended linearity in a wider pressure range. For uniform coating of sensing elements on the microstructured surface, oxidative chemical vapor deposition is employed to deposit a highly conformal and conductive sensing element, poly(3,4-ethylenedioxythiophene) at low temperatures (<60 °C). The fabricated pressure sensor reacts sensitively to various ranges of pressures (up to 185 kPa-1 ) depending on the density of the multiscale features and shows an ultrafast response time (≈36 µs). The mechanism investigations through the finite element analysis identify the effect of the multiscale structure on the figure-of-merit sensing performance. These unique findings are expected to be of significant relevance to technology that requires higher sensing capability, scalability, and facile adjustment of a sensor geometry in a cost-effective manufacturing manner.

Comprehensive evaluation of breast cancer immunotherapy and tumor microenvironment characterization based on interleukin genes-related risk model.

Breast cancer (BRCA) is the most prevalent malignancy and the leading cause of death in women. Interleukin (IL) genes are critical in tumor initiation and control. Nevertheless, the prognosis value of the IL in BRCA remains unclear. We collected data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and 94 IL genes were identified from GeneCard. Based on the random forest (RF), least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox regression analysis, we constructed an IL signature. GSE22219, GSE25065, and GSE21653 were derived as validation sets. The expression differences in the tumor microenvironment (TME), immunotherapy, and chemosensitivity of BRCA between the high- and low-risk groups were evaluated. Overall, 21 IL genes were selected to construct an IL risk model, of which IL18BP, IL17D, and IL23A were the first time identified as prognostic genes in BRCA. IL score could distinguish BRCA patients with inferior outcomes, and AUC of it was 0.70, 0.76, and 0.72 for 1-,3- and 5- years, respectively, which was also verified in GSE22219, GSE25065, and GSE21653 cohorts. Meanwhile, compared to luminal A and luminal B, HER2-positive and TNBC had significantly higher IL score. Besides, the high-risk group had a significantly higher prevalence of TP53 and TTN but a lower prevalence of PIK3CA, as well as higher tumor mutation burden (TMB) and neoantigen level. High- and low-risk groups exhibited notable differences in immunomodulators and tumor infiltrates immune cells (TIICs), and the high-risk group had significantly lower Tumor Immune Dysfunction and Exclusion (TIDE) score. Additionally, the high-risk group has more responders to immune or anti-HER2 combination therapy, whereas the low-risk group has higher sensitivity to docetaxel and paclitaxel. Consequently, we constructed a reliable risk model based on the IL genes, which can provide more information on both the risk stratification and personalizing management strategies for BRCA.

Type I collagen promotes tumor progression of integrin ß1 positive gastric cancer through a BCL9L/ß-catenin signaling pathway.

The mechanism of extracellular matrix induced tumor progression is poorly understood. Based on the TCGA database and clinical tumor tissues analysis, we observed abundant type I collagen expression in tumor tissues and poor overall survival in gastric patients with high integrin ß1 (ITGB1) expression. In vitro, our study found that 3D collagen culture promoted the capability of colony formation and growth in ITGB1 positive gastric cancer, whereas limited colony growth was observed in ITGB1 negative gastric cancer, suggesting the role of ITGB1 in type I collagen associated tumor progression. Mechanistically, we demonstrated that type I collagen was capable of promoting the activation of BCL9L/ß-catenin signaling pathway through ITGB1, thereby contributing to the gastric cancer development. Subsequently, ß-catenin signals further up-regulated the expression anti-apoptosis protein BCL2, leading to the chemo-resistance in gastric cancer cells. Blockade of ß-catenin signals efficiently improved the anticancer effects of chemotherapy, providing an innovative sight for clinical gastric cancer therapy.

The Prognostic Value of Baseline Distant Metastasis in Icotinib-Treated Patients with EGFR-Mutated Stage IV Non-Small Cell Lung Cancer.

PURPOSE: Several studies have revealed the prognostic value distant metastasis in non-small-cell lung cancer (NSCLC) patients receiving first-line epidermal growth factor receptor (EGFR) inhibitors. However, the question of whether the specific metastatic site could predict survival outcomes remain elusive. This study evaluated the prognostic value of specific metastatic site at diagnosis in first-line icotinib-treated patients with EGFR-mutated advanced NSCLC. METHODS: A total of 216 patients with EGFR-mutated stage IV NSCLC who received first-line icotinib treatment were retrospectively enrolled. The associations between the presence of distant metastasis to certain organs at diagnosis and survival outcomes were analyzed. PATIENTS AND METHODS: The presence of distant metastases was not associated with progression-free survival. Patients with liver metastasis showed a significantly shorter OS than those without liver metastasis (14.6m vs 33.0m, p=0.024). Patients with brain metastasis showed a marginally shorter OS than those without brain metastasis (26.5m vs 33.8m, p=0.051). Patients with lung metastasis showed a significantly longer OS than those without lung metastasis (36.0m vs 28.6m, p=0.038). Multivariable Cox regression analysis showed the presence of liver metastasis (HR [hazard ratio]: 2.265, 95% CI [confidence interval]: 1.239-4.139, p=0.008) and brain metastasis (HR: 1.493, 95% CI: 1.012-2.202, p=0.043) were independent predictors for unfavorable OS, while lung metastasis (HR: 0.669, 95% CI: 0.460-0.971, p=0.034) was an independent predictor for favorable OS. CONCLUSION: The presence of liver and brain metastasis predicted unfavorable OS, while the presence of lung metastasis predicted favorable OS in first-line icotinib-treated patients with EGFR-mutated stage IV NSCLC.

TiO2 anchored on MoS2 nanosheets based on molybdenite exfoliation as an efficient cathode for enhanced Cr (VI) reduction in microbial fuel cell.

MoS2 nanosheet-decorated TiO2 nanocomposites were prepared via facile liquid-phase exfoliation of natural molybdenite combined with in situ hydrolysis route. These materials were used as a photocathode for the first time in microbial fuel cell (MFC) to reduce hexavalent chromium (Cr (VI)). Results showed the maximum power density of 1 wt% MoS2/TiO2-based MFC was 3.7 and 1.9 times higher than that of blank graphite and TiO2-based MFC, respectively. This MFC achieved 99.57% removal of Cr (VI) with a concentration of 20 mg L-1 within 8 h under visible light illumination at pH 2 and high degradation rate of 2.49 g m-3 h-1. The introduction of MoS2 nanosheets as a cocatalyst can expand the absorption of visible light, thereby leading to increased electronic participation in Cr (VI) reduction. Moreover, the appropriate amounts of MoS2 nanosheets also contribute to electrons migration and additional active site. The enhanced power output and Cr (VI) reduction efficiency of MFC can be attributed to the synergistic coupling between bioanode and MoS2/TiO2 photocathode. On the basis of its facile and scalable synthetic strategy as well as its stable and outstanding photoelectrocatalytic performance for MFC, this MoS2/TiO2 nanocomposite showed potential in the efficient treatment of wastewater.

Direct Exfoliation of Natural SiO2-Containing Molybdenite in Isopropanol: A Cost Efficient Solution for Large-Scale Production of MoS2 Nanosheetes.

The cost-effective exfoliation of layered materials such as transition metal dichalcogenides into mono- or few- layers is of significant interest for various applications. This paper reports the preparation of few-layered MoS2 from natural SiO2-containing molybdenite by exfoliation in isopropanol (IPA) under mild ultrasonic conditions. One- to six-layer MoS2 nanosheets with dimensions in the range of 50-200 nm are obtained. By contrast, MoS2 quantum dots along with nanosheets are produced using N-methyl-pyrrolidone (NMP) and an aqueous solution of poly (ethylene glycol)-block-poly (propylene glycol)-block-poly (ethylene glycol) (P123) as exfoliation solutions. Compared with molybdenite, commercial bulk MoS2 cannot be exfoliated to nanosheets under the same experimental conditions. In the exfoliation process of the mineral, SiO2 associated in molybdenite plays the role of similar superfine ball milling, which significantly enhances the exfoliation efficiency. This work demonstrates that isopropanol can be used to exfoliate natural molybdenite under mild conditions to produce nanosheets, which facilitates the preparation of highly concentrated MoS2 dispersions or MoS2 in powder form due to the volatility of the solvent. Such exfoliated MoS2 nanosheets exhibit excellent photoconductivity under visible light. Hence, the direct mild exfoliation method of unrefined natural molybdenite provides a solution for low-cost and convenient production of few-layered MoS2 which is appealing for industrial applications.

Degradation of streptomycin in aquatic environment: kinetics, pathway, and antibacterial activity analysis.

Streptomycin used in human and veterinary medicine is released into the environment mainly through excretions. As such, its elimination in water should be investigated to control pollution. In this study, the degradation of streptomycin in water was studied, and the influence of variables, including light exposure, solution pH, temperature, ionic strength, dissolved organic matter (DOM), and coexisting surfactants, on degradation was investigated. Streptomycin degradation was consistent with the first-order model in aquatic environments. Its degradation rate under light exposure was 2.6-fold faster than that in the dark. Streptomycin was stable under neutral conditions, but it was easily decomposed in acidic and basic environments. Streptomycin degradation was enhanced by high temperature, and its half-life decreased from 103.4 days at 15 °C to 30.9 days at 40 °C. This process was also accelerated by the presence of Ca2+ and slightly improved by the addition of HA. Streptomycin degradation was suppressed by high levels of the cationic surfactant cetyltri- methylammonium bromide (CTAB), but was promoted by the anionic surfactant sodium dodecyl benzene sulfonate (SDBS). The main degradation intermediates/products were identified through liquid chromatography-mass spectrometry, and the possible degradation pathway was proposed. The antibacterial activity of streptomycin solution was also determined during degradation. Results showed that STR degradation generated intermediates/products with weaker antibacterial activity than the parent compound.

The promoter of the Chinese hamster ovary dihydrofolate reductase gene regulates the activity of the local origin and helps define its boundaries.

The dihydrofolate reductase (DHFR) and 2BE2121 genes in the Chinese hamster are convergently transcribed in late G1 and ea ly S phase, and bracket an early-firing origin of replication that consists of a 55-kb zone of potential initiation sites. To test whether transcription through the DHFR gene is required to activate this origin in early S phase, we examined the two-dimension (2D) gel patterns of replication intermediates from several variants in which parts or all of the DHFR promote had been deleted. In those variants in which transcription was undetectable, initiation in the intergenic space was markedly suppressed (but not eliminated) in early S phase. Further more, replication of the locus required virtually the entire S period, as opposed to the usual 3-4 h. However, restoration of transcription with either the wild-type Chinese hamster promote or a Drosophila-based construct restored origin activity to the wild-type pattern. Surprisingly, 2D gel analysis of promote less variants revealed that initiation occurs at a low level in ea ly S phase not only in the intergenic region, but also in the body of the DHFR gene. The latter phenomenon has never been observed in the wild-type locus. These studies suggest that transcription through the gene normally increases the efficiency of origin firing in early S phase, but also suppresses initiation in the body of the gene, thus helping to define the boundaries of the downstream origin.