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With the widespread use of alectinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), its cardiotoxicity has gradually emerged, including new-onset sinus bradycardia (SB). However, the incidence, timing, severity, and risk factors of alectinib-induced bradycardia remain unknown.From January 2020 to June 2022, 93 patients with ALK-positive NSCLC treated with alectinib were enrolled in this retrospective analysis. These patients had heart rate (HR) recorded before and after alectinib administration. By reviewing electronic medical records and follow-up, the HR changes of patients during medication were recorded. The potential risk factors associated with alectinib-induced SB were explored.According to an HR cut-off of 60 beats per minute (bpm), 47 patients (50.54%) experienced at least one recorded bradycardia. The mean HR of total participants before alectinib administration was 78.32 (standard deviation [SD], 9.48) and after was 64.88 (SD, 12.21). The median maximum change in HR (range) for all patients was 11 (-55, +4) bpm. For the bradycardia subgroup, the HR of most patients (76.60%) hovered around 50-60 bpm, and 61.70% of SB occurred within 3 months after alectinib administration. Multivariate analysis indicated that baseline HR (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.79-0.93, p 0.001) and history of hypertension (OR 13.71, 95% CI 2.49-76.38, p = 0.003) were independent risk factors for alectinib-related bradycardia.Alectinib-induced bradycardia had a high incidence, appeared relatively early, and was reversible by dose reduction or withdrawal.

Background: Lung adenocarcinoma (LUAD) is the prevalent non-small cell lung cancer (NSCLC) histological subtype, with rising morbidity and mortality. This study was conducted with the motive to develop a prognostic model by examining the relation between immune-related gene (IRGs) profiles.Methods: We combined immune-related gene (IRG) expression profiles and progression-free intervals (PFIs) in 594 LUAD patients by using TCGA dataset. The COX regression analysis and computational difference technique were used to predict survival-associated and differentially expressed IRGs in LUAD patients. Computational biology was also used to investigate the characteristics and molecular mechanisms of these LUAD-specific IRGs. Using multivariable COX analysis, a novel prognostic index based on immune-related genes was established.Results: There was a strong correlation between the clinical outcome of LUAD patients and 58 differentially expressed immune-related genes. These genes were found to be actively involved in a KEGG pathway involving cytokines and cytokine receptors, as demonstrated by functional enrichment analysis. A prognostic signature comprised of IRGs (CRABP1, S100A16, FGF2, RBP2, FURIN, SLC11A1, ANGPTL4, VIPR1, BDNF, IL11, INHA, SEMA4B, TNFRSF11A) performed relatively well in prognostic prediction and was associated with tumour stage, tumour burden, age, number of lesions, and metastasis. Surprisingly, the IRG-based prognostic index effectively predicted immune cell infiltration.Conclusions: Our findings collectively identified multiple clinically relevant IRGs, identified regulators of the immunological repertoire, as well as established the critical role of a tailored, surveillance, IRG-based immune signature in the diagnosis, and prognosis of LUAD.

Background: The 14-3-3ζ protein, which acts as a putative oncoprotein, has been found to promote the proliferation, metastasis, and chemoresistance of cancer cells in several cancers including lung adenocarcinoma (LUAD); however, its significance in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance remains unknown. Methods: The Cancer Genome Atlas (TCGA) database was used to determine 14-3-3ζ expression in pancancer and LUAD. 14-3-3ζ and ID1 expression was then examined in clinical LUAD samples by immunohistochemistry (IHC). Lentiviral transfection with 14-3-3ζ-specific small hairpin RNA (shRNA) was used to establish stable 14-3-3ζ knockdown gefitinib-resistant PC9 (PC9/GR) and H1975 cell lines. The effect of 14-3-3ζ knockdown on reversing EGFR-TKI resistance was determined in vitro by Cell Counting Kit-8 (CCK-8), wound healing, Transwell assays, and flow cytometry. A xenograft tumor model was established to evaluate the role of 14-3-3ζ in EGFR-TKI resistance. Microarray analysis results showed multiple pathways regulated by 14-3-3ζ-shRNA. Results: In the present study, we demonstrated that based on the TCGA, pancancer and LUAD 14-3-3ζ expression was elevated and predicted unfavorable prognosis. In addition, high 14-3-3ζ expression was associated with advanced T stage, TNM stage, presence of lymph node metastasis and, importantly, poor treatment response to EGFR-TKIs in LUAD patients with EGFR-activating mutations. 14-3-3ζ shRNA sensitized EGFR-TKI-resistant human LUAD cells to gefitinib and reversed epithelial-to-mesenchymal transition (EMT). After 14-3-3ζ depletion, bone morphogenetic protein (BMP) signaling activation was decreased in EGFR-TKI-resistant cells in microarray analysis, which was further validated by Western blot analysis. Furthermore, the expression of 14-3-3ζ positively correlates with ID1 expression in human EGFR-mutant LUAD patient samples. In vivo, there was a reduction in the tumor burden in mice treated with 14-3-3ζ shRNA and gefitinib compared to mice treated with gefitinib alone. Conclusion: Our work uncovers a hitherto unappreciated role of 14-3-3ζ in EGFR-TKI resistance. This study might provide a potential therapeutic approach for treating LUAD patients harboring EGFR mutations.

Deeper soil horizons might provide an opportunity to enhance C sequestration because soil organic matter (SOM) at depth is assumed to be stable. However, it is unknown whether the stable composition of organic carbon in subsoils changes with the length of cropping time and the type of soil. The objectives of this study were to determine the effects on the chemical structures of SOM of cropping time after conversion from grassland to arable land under a Phaeozem and Chernozem in northeast China. Near‐quantitative multiple cross‐polarization (multiCP) ¹³C nuclear magnetic resonance (NMR) spectroscopy was applied, and 11 types of carbon (C) functional groups were identified. Principal component analysis of these functional groups showed that the chemical composition of SOM was differentiated by soil type and depth. The Phaeozem and Chernozem profiles differed mainly in their relative proportions of aromatic C–C and (CH₂)ₙ groups: the Phaeozem contained relatively more aromatic C–C, whereas the Chernozem contained relatively more (CH₂)ₙ groups. The fused‐ring aromatic C–C carbon was probably derived from char‐like organic matter generated by burning of plant litter or from SOM humification, whereas the (CH₂)ₙ groups were likely to be from plant‐ or microbially‐derived residues. The main differences between top‐ and sub‐soils were the occurrence of more protonated C in the topsoils and more non‐protonated C in the subsoils. With increasing length of cropping time, aromatic C–C and C–O groups and COO/N–C=O groups increased, but (CH₂)ₙ groups decreased in the Phaeozem subsoils and increased in the Chernozem subsoils. Our findings suggested that leaching and soil moisture might influence the origin, redistribution and transformation of the recalcitrant components of SOM in the soil profile, resulting in changes in SOM composition under different climates and soil types. HIGHLIGHTS: Characterization of chemical structures of soil organic matter (SOM) in soil profiles by solid‐state ¹³C NMR SOM composition varied between a Phaeozem and Chernozem and to a larger extent in the subsoils Fused‐ring aromatics and (CH₂)ₙ groups accumulated in subsoils of the Phaeozem and Chernozem, respectively SOM composition of subsoil changed probably with precipitation‐controlled translocation or transformation

Background: 14-3-3ζ protein which acts as a putative oncoprotein has been found to promote proliferation, metastasis and chemoresistance of cancer cells in several cancers including lung adenocarcinoma (LUAD), however, its significance in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance remains unknown. Methods: The Cancer Genome Atlas (TCGA) database was used to determine 14-3-3ζ expression in pan-cancer and LUAD. 14-3-3ζ and ID1 expression was then examined in clinical LUAD samples by immunohistochemistry (IHC). Lentiviral transfection with 14-3-3ζ-specific shRNA was used to establish stable 14-3-3ζ knockdown gefitinib resistant PC9 (PC9/GR) and H1975 cell lines. The effect of 14-3-3ζ knockdown on reversing EGFR-TKI resistance was determined in vitro by CCK-8, wound healing, transwell assays and flow cytometry. A xenograft tumor model was established to evaluate the role of 14-3-3ζ in EGFR-TKI resistance. Microarray analysis results showed the multiple pathways regulated by 14-3-3ζ-shRNA. Results: In the present study, we firstly demonstrated that 14-3-3ζ expression was elevated and predicted unfavourable prognosis in pan-cancer including LUAD based on TCGA. In addition, high 14-3-3ζ expression was significantly associated with advanced T stage, TNM stage, present of lymph node metastasis and, importantly, poor treatment response to EGFR-TKI in LUAD patients with EGFR-activating mutations. 14-3-3ζ shRNA significantly sensitized EGFR-TKI-resistant human LUAD cells to gefitinib and, notably, reversed epithelial-to-mesenchymal transition (EMT). BMP signaling activation was decreased in EGFR-TKI resistant cells followed by 14-3-3ζ depletion in microarray analysis, which was further validated by Western blot analysis. Furthermore, the expression of 14-3-3ζ positively correlates with ID1 expression in human EGFR-mutant LUAD patient samples. In vivo , 14-3-3ζ shRNA and gefitinib treatment resulted in a significant reduction in the tumor burden compared to that treated with gefitinib alone. Conclusion: Our work uncovers a hitherto unappreciated role of 14-3-3ζ in EGFR-TKI resistance. This study might provide a potential therapeutic approach for treating LUAD patients harboring EGFR mutations.

Two ordering states, antiferromagnetism and nematicity, have been observed in most iron-based superconductors (SCs). In contrast to those SCs, the newly discovered SC $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ exhibits an antiferromagnetic (AFM) state, called hedgehog spin-vortex crystal (SVC) structure, without nematic order, providing the opportunity for the investigation into the relationship between spin fluctuations and SC without any effects of nematic fluctuations. Our $^{75}\mathrm{As}$ nuclear magnetic resonance studies on $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ ($0\ensuremath{\le}x\ensuremath{\le}0.049$) revealed that ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ is located close to a hidden hedgehog SVC AFM quantum-critical point (QCP). The magnetic QCP without nematicity in $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ highlights the close connection of spin fluctuations and superconductivity in iron-based SCs. The advantage of stoichiometric composition also makes ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ an ideal platform for further detailed investigation of the relationship between magnetic QCP and superconductivity in iron-based SCs without disorder effects.

Multiphase materials attract attention due to possible combination of various properties attributed to each phase. The phase diagram of Mg–Si system shows that solidification of a melt containing about 45 and 55 at.% of Mg and Si should result in formation of Mg2Si and Si. Two alloys, Mg45Si55 and Mg46Si54 + 0.5 wt.% Cu have been synthesized and studied using XRD, SEM, and 29Si NMR at 300 K, and the Seebeck effect, electrical resistivity, and thermal conductivity in the temperature range of 300–750 K have been measured. 29Si NMR detects two distinct signals, at −177 and −80 ppm, in both materials, which are assigned to Mg2Si and Si phases, respectively. Both phases are slightly nonstoichiometric and doped with Mg. Two phases also are found by XRD and electron microscopy. 29Si NMR spin-lattice relaxation measurements in Mg2Si and Si phases show at least two components, short and long, which can be attributed to different local carrier concentrations, high and low, respectively, reflecting a local electronic inhomogeneity in each phase. The carrier concentrations range between 0.6 × 1019 and 9 × 1019 cm−3. The Seebeck coefficient in both alloys is mostly determined by the Si phase, while the thermal conductivity is limited by the Mg2Si phase with a lower value than that of the Si phase. By utilizing all characterization tools, we show how various experimental methods can be used as complementary methods to better understand the individual and combined properties of multiphase alloys.

The ability of solid-state 13C NMR to detect and quantify small amounts of sp2-hybridized carbon on the surface of ~5 nm diameter nanodiamond particles is demonstrated. The C=C carbon fraction is only 1.1 ± 0.4% in pristine purified detonation nanodiamond, while a full single-layer graphitic or “bucky diamond” shell would contain ca. 25% of all C in a 5 nm diameter particle. Instead of large aromatic patches repeatedly proposed in the recent literature, sp3-hybridized CH and COH carbons cover most of the nanodiamond particle surface, accounting for ~5% each. C=O and COO groups also seen in X-ray absorption near-edge structure spectroscopy (XANES) but not detected in previous NMR studies make up ca. 1.5% of all C. They are removed by heat treatment at 800 °C, which increases the aromatic fraction. 13C{1H} NMR demonstrates that the various sp2-hybridized carbons are mostly not protonated, but cross-polarization shows that they are separated from 1H by only a few bond lengths, which proves that they are near the protonated surface. Together, the observed C–H, C–OH, C=O, and C=C groups account for 12–14% of all C, which matches the surface fraction expected for bulk-terminated 5 nm diameter diamond particles.

We have carried out $^{125}\mathrm{Te}$ nuclear magnetic resonance (NMR) in a wide temperature range of 1.5--300 K to investigate the electronic properties of ${\mathrm{Ge}}_{50}{\mathrm{Te}}_{50},\phantom{\rule{0.16em}{0ex}}{\mathrm{Ag}}_{2}{\mathrm{Ge}}_{48}{\mathrm{Te}}_{50}$, and ${\mathrm{Sb}}_{2}{\mathrm{Ge}}_{48}{\mathrm{Te}}_{50}$ from a microscopic point of view. From the temperature dependence of the NMR shift $(K)$ and nuclear spin lattice relaxation rate $(1/{T}_{1})$, we found that two bands contribute to the physical properties of the materials. One band overlaps the Fermi level providing the metallic state where no strong electron correlations are revealed by Korringa analysis. The other band is separated from the Fermi level by an energy gap of ${E}_{\mathrm{g}}/{k}_{\mathrm{B}}\ensuremath{\sim}67$ K, which gives rise to semiconductorlike properties. First-principles calculation reveals that the metallic band originates from the Ge vacancy while the semiconductorlike band is related to the fine structure of the density of states near the Fermi level. Low-temperature $^{125}\mathrm{Te}$ NMR data for the materials studied here clearly show that Ag substitution increases hole concentration while Sb substitution decreases it.

125Te NMR spectra and spin-lattice relaxation times, T1, have been measured for several GeTe-based materials with Te excess. The spectra show inhomogeneous broadening by several thousand ppm and a systematic variation in T1 relaxation time with resonance frequency. The quadratic dependence of the spin-lattice relaxation rate, 1/T1, on the Knight shift in the Korringa relation is found to be valid over a wide range of Knight shifts. This result confirms that T1 relaxation in GeTe-based materials is mostly dominated by hyperfine interaction between nuclei and free charge carriers. In GeTe with 2.5% excess of Te, about 15% of the material exhibits a Knight shift of ≥4500 ppm and a T1 of only 0.3 ms, indicating a high hole concentration that could correspond to close to 50% vacancies on the Ge sublattice in this component. Our findings provide a basis for determining the charge carrier concentration and its distribution in complex thermoelectric and phase-change tellurides, which should lead to a better understanding of electronic and thermal transport properties as well as chemical bonding in these materials.

ZnO is an important wide bandgap compound semiconducting material and exhibits a wide range of novel structures that can be grown by tuning the growth rates along its fast growth directions. Highly ordered macroporous materials by using colloidal crystal template method are of great interest in many fields including photonic crystals and catalysts. In this study, ZnO with highly ordered porous structure was deposited by different electrochemical method. Nanomeshes, inverse opal structures, and spherical/ellipsoidal particles with pore arrays are fabricated by the colloidal crystals with different functional groups. The template effects on the morphology of the macroporous structures for different surface groups are studied. All the nanomeshes grows along the {111} plane family by colloidal crystals without functional groups. Disordered arrangements of the nanomeshes are induced by colloidal crystals with hydroxyl groups. The inverse opal structures fabricated by template with carboxyl groups are smoother in surface.

Algal samples were fractionated into lipid (LP), lipid free (LF), alkaline nonhydrolyzable carbon (ANHC), and acid nonhydrolyzable carbon (NHC) fractions, and were characterized by the quantitative (13)C multiCP NMR technique. The biosorption isotherms for nonylphenol (NP) were established and compared with previously published data for phenanthrene (Phen). The log KOC values are significantly higher for the field-collected plankton samples than for the commercial algae and cultured algae samples, correlating with their lipid contents and aliphatic carbon structure. As the NHC fraction contains more poly(methylene) carbon, it exhibits a higher biosorption capacity. The sorption capacities are negatively related to the polarity index, COO/N-C=O, polar C and O-alkyl C concentrations, but are positively related to the H/O atomic ratios and poly(methylene) carbon. The higher sorption capacities observed for NP than for Phen on the investigated samples are explained by specific interactions such as hydrogen bonding and π-π interaction.

MnBi has attracted much attention in recent years due to its potential as a rare-earth-free permanent magnet material. It is unique because its coercivity increases with increasing temperature, which makes it a good hard phase material for exchange coupling nanocomposite magnets. MnBi phase is difficult to obtain, partly because the reaction between Mn and Bi is peritectic, and partly because Mn reacts readily with oxygen. MnO formation is irreversible and harmful to magnet performance. In this paper, we report our efforts toward developing MnBi permanent magnets. To date, high purity MnBi (>90%) can be routinely produced in large quantities. The produced powder exhibits 74.6 emu g(-1) saturation magnetization at room temperature with 9 T applied field. After proper alignment, the maximum energy product (BH)max of the powder reached 11.9 MGOe, and that of the sintered bulk magnet reached 7.8 MGOe at room temperature. A comprehensive study of thermal stability shows that MnBi powder is stable up to 473 K in air.