UGT1A1 genotype-guided irinotecan dosing during neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A prospective analysis of SN-38 concentration.

Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m2 ; UGT1A1*1*28: 65 mg/m2 ) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1-Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5-1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.

Unraveling Colorectal Cancer and Pan-cancer Immune Heterogeneity and Synthetic Therapy Response Using Cuproptosis and Hypoxia Regulators by Multi-omic Analysis and Experimental Validation.

Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA_COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs_classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy.

Dramatic improvement in the stability and mechanism of high-performance inverted polymer solar cells featuring a solution-processed buffer layer.

In this study, we demonstrate inverted PTB7:PC71BM polymer solar cells (PSCs) featuring a solution-processed s-MoO3 hole transport layer (HTL) that can, after thermal aging at 85 °C, retain their initial power conversion efficiency (PCE) for at least 2200 h. The T80 lifetimes of the PSCs incorporating the novel s-MoO3 HTL were up to ten times greater than those currently reported for PTB7- or low-band-gap polymer:PCBM PSCs, the result of the inhibition of burn-in losses and long-term degradation under various heat-equivalent testing conditions. We used X-ray photoelectron spectroscopy (XPS) to study devices containing thermally deposited t-MoO3 and s-MoO3 HTLs and obtain a mechanistic understanding of how the robust HTL is formed and how it prevented the PSCs from undergoing thermal degradation. Heat tests revealed that the mechanisms of thermal inter-diffusion and interaction of various elements within active layer/HTL/Ag electrodes controlled by the s-MoO3 HTL were dramatically different from those controlled by the t-MoO3 HTL. The new prevention mechanism revealed here can provide the conceptual strategy for designing the buffer layer in the future. The PCEs of PSCs featuring s-MoO3 HTLs, measured in damp-heat (65 °C/65% RH; 85 °C per air) and light soaking tests, confirmed their excellent stability. Such solution-processed MoO3 HTLs appear to have great potential as replacements for commonly used t-MoO3 HTLs.

Strain driven phase transition and mechanism for Fe/Ir(111) films.

By way of introducing heterogeneous interfaces, the stabilization of crystallographic phases is critical to a viable strategy for developing materials with novel characteristics, such as occurrence of new structure phase, anomalous enhancement in magnetic moment, enhancement of efficiency as nanoportals. Because of the different lattice structures at the interface, heterogeneous interfaces serve as a platform for controlling pseudomorphic growth, nanostructure evolution and formation of strained clusters. However, our knowledge related to the strain accumulation phenomenon in ultrathin Fe layers on face-centered cubic (fcc) substrates remains limited. For Fe deposited on Ir(111), here we found the existence of strain accumulation at the interface and demonstrate a strain driven phase transition in which fcc-Fe is transformed to a bcc phase. By substituting the bulk modulus and the shear modulus and the experimental results of lattice parameters in cubic geometry, we obtain the strain energy density for different Fe thicknesses. A limited distortion mechanism is proposed for correlating the increasing interfacial strain energy, the surface energy, and a critical thickness. The calculation shows that the strained layers undergo a phase transition to the bulk structure above the critical thickness. The results are well consistent with experimental measurements. The strain driven phase transition and mechanism presented herein provide a fundamental understanding of strain accumulation at the bcc/fcc interface.

Self-assembled magnetic heterostructure of Co/DLC films.

In order to adapt to the quick and large amount of necessity in data flow for 5G cloud generation, it is necessary to develop a technology of warm storage device in market which takes a great balance between the reading/writing performance and the price per storage capacity. The technologies of warm storage devices are assumed to adopt phase change memory (PCM), resistive random access memory or magnetoresistive random access memory which have the highest possibilities to 5G structures and magnetic properties of Co on non-hydrogenated diamond like carbon (DLC)/Si(100) films and Co/DLC interface are investigated. The self-assembled magnetic heterostructure is firstly reported in hexagonal close packing Co layers perpendicular magnetic anisotropy (PMA) on Co carbide layers (in-plane) during Co deposited on DLC/Si(100). A PMA/in-plane magnetic heterostructure is expected to have the highest switching current to the energy barrier ratio of near 4 in previous report, which has great potential for developing warm memory devices. Based on these unique characteristics, we provide a novel design called magnetic anisotropy-phase change memory (Mani-PCM) which can impact the developing blueprint of memory. The working process of Mani-PCM includes in set, reset and read states as a universal PCM. This brand new technology is highly promising as warm memory devices including high reading/writing performance and economical price per storage capacity.

A practical method for fabricating superparamagnetic films and the mechanism involved.

Due to the widespread applications of biosensors, such as in magnetic resonance imaging, cancer detection and drug delivery, the use of superparamagnetic materials for preparing biosensors has increased greatly. We report herein on a strategy toward fabrication of a nanoscale biosensor composed of superparamagnetic films. On increasing the film thickness of magnetic layers, a phase transition typically occurs from either a low-Curie-temperature state or a superparamagnetic state to a ferromagnetic state. A new finding is demonstrated wherein a phase transition of such a superparamagnetic phase can be induced by controlling the thickness of ultrathin ferromagnetic layers with perpendicular magnetic anisotropy. Both the M-H curve with zero coercive force at 300 K and deviations of the normalized hysteresis loop at 2 K confirm the superparamagnetic state of Co/Ir(111) at room temperature. An overstrained film transforming into clusters (OFTC) model based on the new finding and our experimental evidence is proposed for modeling this phenomenon. From the energetic point of view of the OFTC model, we propose a limited distortion mechanism that can be useful in determining the critical thickness for the phase transition. This mechanism considers the balance between interfacial strain energy and surface free energy. A method for producing superparamagnetic films by taking advantage of the accumulation of strain and relaxation is reported.

Clinical value of circular RNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer.

BACKGROUND: Circular RNAs (circRNAs) are a special group of long-chain and non-coding RNAs characterized by a closed-loop structure without 3' and 5' polarity. In recent years, studies have demonstrated that circRNAs act as microRNA (miRNA) sponges to regulate the function of miRNAs. Increasing evidence indicates that circRNAs and targeted miRNAs are involved in the development, progression and metastasis of various cancers and drug resistance. A number of miRNAs are known to be associated with the pathogenesis, development and treatment of pancreatic cancer by regulating the autophagic activity. DATA SOURCES: A comprehensive literature search was executed in PubMed and EMBASE using the medical subject headings (MeSH) terms "Pancreatic Neoplasms", "autophagy", "RNA, circular" and "microRNA". We also used text terms such as "diagnosis", "prognosis" and "biomarker" to supplement the results. RESULTS: Autophagy-related miRNAs is closely related to pancreatic cancer. On basis of the retrieval results, we summarized the synthesis, features and functions of circRNAs and analyzed the association between autophagy-related miRNAs and pancreatic cancer. CONCLUSIONS: circRNAs act as the miRNA sponges and there is an association between miRNAs and autophagy, which provides a new concept to broaden the knowledge about the mechanisms underlying the development, progression and metastasis of pancreatic cancer. Additionally, clinical value of circRNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer would be further verified with in-depth researches.

Enhancing silicide formation in Ni/Si(111) by Ag-Si particles at the interface.

Compound formation at a metal/semiconductor interface plays crucial roles in the properties of many material systems. Applications of Ni silicides span numerous areas and have the potential to be used as new functionalities. However, the magnetic properties of ultrathin Ni layers on silicon surfaces and related chemical compositions at the interface are not fully understood and the influence of Ag additives on the reactivity of Ni/Si(111) remain unclear. We report herein on the fact that the dominant species produced at the interface is NiSi, which is produced by the spontaneous formation of strong bonds between Ni and Si atoms. Assuming that a Ni layer is formed over a NiSi layer with the total coverage as a constraint, we established a chemical shift-related concentration model that, in effect, represents a practical method for determining the amount of ultrathin Ni silicides that are produced at the buried interface. The formation of Ag-Si particles provide a viable strategy for enhancing silicide formation via a specific interaction transfer mechanism, even at room temperature. The mechanism is related to differences in the enthalpies of formation ΔHAg-Si, ΔHNi-Ag, and ΔHNi-Si, for these phases and provides insights into strategies for producing ultrathin silicides at a buried interface.