Clinical and molecular profiling of EGFR-mutant lung adenocarcinomas transformation to small cell lung cancer during TKI treatment

IntroductionSmall cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations.MethodsA total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases.ResultsThe median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1–84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7–10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort.DiscussionThe findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC

Effective Boundary Slip Induced by Surface Roughness and Their Coupled Effect on Convective Heat Transfer of Liquid Flow

As a significant interfacial property for micro/nano fluidic system, the effective boundary slip can be induced by the surface roughness. However, the effect of surface roughness on the effective slip is still not clear, both increased and decreased effective boundary slip were found with increased roughness. The present work develops a simplified model to study the effect of surface roughness on the effective boundary slip. In the created rough models, the reference position of the rough surfaces to determinate effective boundary slip was set based on ISO/ASME standard and the surface roughness parameters including Ra (arithmetical mean deviation of the assessed profile), Rsm (mean width of the assessed profile elements) and shape of the texture varied to form different surface roughness. Then, the effective boundary slip of fluid flow through the rough surface was analyzed by using COMSOL 5.3. The results show that the effective boundary slip induced by surface roughness of fully wetted rough surface keeps negative and further decreases with increasing Ra or decreasing Rsm. Different shape of roughness texture also results in different effective slip. A simplified corrected method for the measured effective boundary slip was developed and proved to be efficient when the Rsm is no larger than 200 nm. Another important finding in the present work is that the convective heat transfer firstly increases followed by an unobvious change with increasing Ra, while the effective boundary slip keeps decreasing. It is believed that the increasing Ra enlarges the area of solid-liquid interface for convective heat transfer, however, when Ra is large enough, the decreasing roughness-induced effective boundary slip counteracts the enhancement effect of roughness itself on the convective heat transfer

Cs⁺ Promoting the Diffusion of K⁺ and Inhibiting the Generation of Newberyite in Struvite-K Cements: Experiments and Molecular Dynamics Simulation Calculations

Struvite-K cements, also called magnesium potassium phosphate cements (MKPCs), are applicable for particular applications, especially the immobilization of radioactive Cs+ in the nuclear industry. This work focuses on how Cs+ affects the hydration mechanism of struvite-K cements because newberyite and brucite in the hydration products are deemed to be risky products that result in cracking. Experiments and molecular dynamics simulations showed that Cs+ promoted the diffusion of K+ to the surface of MgO, which greatly facilitates the formation of more K-struvite crystals, inhibiting the formation of newberyite and brucite. A total of 0.02 M Cs+ resulted in a 40.44%, 13.93%, 60.81%, and 32.18% reduction in the amount of newberyite and brucite, and the Cs immobilization rates were 99.07%, 99.84%, 99.87%, and 99.83% when the ratios of Mg/P were 1, 3, 5, and 7, respectively. This provides new evidence of stability for struvite-K cements on radioactive Cs+ immobilization. Surprisingly, another new crystal, [CsPO3·H2O]4, was found to be a dominating Cs-containing phase in Cs-immobilizing struvite-K cements, in addition to Cs-struvite

Effect of K⁺ Diffusion on Hydration of Magnesium Potassium Phosphate Cement with Different Mg/P Ratios: Experiments and Molecular Dynamics Simulation Calculations

Magnesium potassium phosphate cement (MKPC) is formed on the basis of acid–base reaction between dead burnt MgO and KH2PO4 in aqueous solution with K-struvite as the main cementitious phase. Due to the unique characteristics of these cements, they are suitable for special applications, especially the immobilization of radioactive metal cations and road repair projects at low temperature. However, there are few articles about the hydration mechanism of MKPC. In this study, the types, proportions and formation mechanism of MKPC crystalline phases under different magnesium to phosphorus (Mg/P) ratios were studied by means of AAS, ICP-OES, SEM, EDS and XRD refinement methods. Corresponding MD simulation works were used to explain the hydration mechanism. This study highlights the fact that crystalline phases distribution of MKPC could be adjusted and controlled by different Mg/P ratios for the design of the MKPC, and the key factor is the kinetic of K+

A Novel Tri-Layer Cellulose-Based Membrane for the Capture and Analysis of Mainstream Smoke of Tobacco

Efficient capture of particulate matter in the smoke mainstream using low-cost filter pads is important for cost-effective analysis of mainstream smoke. The Cambridge filter pad (CFP) is the standard material for the collection of particulate matter in the mainstream. In this work, we report a low-cost alternative to CFP, which is composed of a cellulose acetate fiber (CAF) interlayer and two cotton fiber (CF) layers on both sides. The CF/CAF/CF filter exhibited high affinity toward typical tobacco additives such as glycerol and glycerol triacetate. In addition, the CF/CAF/CF filter had a favorable porous structure for the trapping of particulate matter. Due to these beneficial features, the CF/CAF/CF filter exhibited improved particulate matter trapping performance. These results suggest that the as-developed CF/CAF/CF filter could be a low-cost alternative to CFP

Heat Triggered Release Behavior of Eugenol from Tobacco Leaf

Fragrance is a commonly used substance in a number of commercial products, and fine control over the release behavior of the fragrance is essential for its successful application. Understanding the release behavior of the fragrance is the key to realizing the control of its release. Herein, we use tobacco leaf as the model substrate and investigate the mechanism of eugenol release from tobacco leaf. Our results show that interaction between eugenol and tobacco leaf is weak physical adsorption, and the eugenol release from tobacco leaf substrate is a temperature-dependent process. Further analysis on the release behavior reveals that eugenol release is closely associated with the morphology change of tobacco leaves under heating conditions. Our results provide insight into the release mechanism of fragrance from polymer substrate and may be useful for the future design of fragrance release systems

Si-Disordering in MgAl2O4-Spinel under High P-T Conditions, with Implications for Si-Mg Disorder in Mg2SiO4-Ringwoodite

A series of Si-bearing MgAl2O4-spinels were synthesized at 1500–1650 °C and 3–6 GPa. These spinels had SiO2 contents of up to ~1.03 wt % and showed a substitution mechanism of Si4+ + Mg2+ = 2Al3+. Unpolarized Raman spectra were collected from polished single grains, and displayed a set of well-defined Raman peaks at ~610, 823, 856 and 968 cm−1 that had not been observed before. Aided by the Raman features of natural Si-free MgAl2O4-spinel, synthetic Si-free MgAl2O4-spinel, natural low quartz, synthetic coesite, synthetic stishovite and synthetic forsterite, we infer that these Raman peaks should belong to the SiO4 groups. The relations between the Raman intensities and SiO2 contents of the Si-bearing MgAl2O4-spinels suggest that under some P-T conditions, some Si must adopt the M-site. Unlike the SiO4 groups with very intense Raman signals, the SiO6 groups are largely Raman-inactive. We further found that the Si cations primarily appear on the T-site at P-T conditions ≤~3–4 GPa and 1500 °C, but attain a random distribution between the T-site and M-site at P-T conditions ≥~5–6 GPa and 1630–1650 °C. This Si-disordering process observed for the Si-bearing MgAl2O4-spinels suggests that similar Si-disordering might happen to the (Mg,Fe)2SiO4-spinels (ringwoodite), the major phase in the lower part of the mantle transition zone of the Earth and the benchmark mineral for the very strong shock stage experienced by extraterrestrial materials. The likely consequences have been explored

Polymer carriers for controlled fragrance release

Fragrance is a class of material commonly used in many consumer products such as food and tobacco. Since most of the fragrance is highly volatile, the successful use of fragrance in practical application requires effective preservation of fragrance with appropriate substrate material. As a low cost and versatile material, polymer holds great promise as a fragrance carrier. In this review, we summarize representative polymer carriers developed recently for sustained and controlled release of fragrance, which include natural polymers and novel synthetic polymers. The results summarized in this mini-review would shed light on the future design of advanced fragrance carrier for various applications

Unveiling the impact of glycerol phosphate (DOP) in the dinoflagellate Peridinium bipes by physiological and transcriptomic analysis

Background The ability to use dissolved organic phosphorus (DOP) is important for survival and competition when phytoplankton are faced with scarcity of dissolved inorganic phosphorus (DIP). However, phosphorus availability to the freshwater dinoflagellate Peridinium bipes has received relatively little attention, the efficiency of glycerol phosphate use by phytoplankton has rarely been investigated, and the regulatory molecular mechanisms remain unclear. Result In the present study, cultures of the freshwater dinoflagellate Peridinium bipes were set up in 119 medium (+DIP), DIP-depleted 119 medium (P-free), and beta-glycerol phosphate-replacing-DIP medium (+DOP). Gene expression was analyzed using transcriptomic sequencing. The growth rate of cells in DOP treatment group was similar to that in DIP group, but chlorophyll a fluorescence parameters RC/CS0, ABS/CS0, TR0/CS0, ET0/CS0 and RE0/CS0 markedly decreased in the DOP group. Transcriptomic analysis revealed that genes involved in photosynthesis, including psbA, psbB, psbC, psbD, psaA and psaB, were downregulated in the DOP group relative to the DIP group. Glycerol-3-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, rather than alkaline phosphatase, were responsible for beta-glycerol phosphate use. Intercellular gluconeogenesis metabolism was markedly changed in the DOP group. In addition, genes involved in ATP synthases, the TCA cycle, oxidative phosphorylation, fatty acid metabolism and amino acid metabolism in P. bipes were significantly upregulated in the DOP group compared with the DIP treatment. Conclusions These findings suggested that beta-glycerol phosphate could influence the photosynthesis and metabolism of P. bipes, which provided a comprehensive understanding of the phosphorus physiology of P. bipes. The mechanisms underlying the use of beta-glycerol phosphate and other DOPs are different in different species of dinoflagellates and other phytoplankton. DIP reduction may be more effective in controlling the bloom of P. bipes than DOP reduction

PtNi Alloy Coated in Porous Nitrogen-Doped Carbon as Highly Efficient Catalysts for Hydrogen Evolution Reactions

The development of low platinum loading hydrogen evolution reaction (HER) catalysts with high activity and stability is of great significance to the practical application of hydrogen energy. This paper reports a simple method to synthesize a highly efficient HER catalyst through coating a highly dispersed PtNi alloy on porous nitrogen-doped carbon (MNC) derived from the zeolite imidazolate skeleton. The catalyst is characterized and analyzed by physical characterization methods, such as XRD, SEM, TEM, BET, XPS, and LSV, EIS, it, v-t, etc. The optimized sample exhibits an overpotential of only 26 mV at a current density of 10 mA cm−2, outperforming commercial 20 wt% Pt/C (33 mV). The synthesized catalyst shows a relatively fast HER kinetics as evidenced by the small Tafel slope of 21.5 mV dec−1 due to the small charge transfer resistance, the alloying effect between Pt and Ni, and the interaction between PtNi alloy and carrier