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Surface shot peening and annealing heat treatment were applied to the Fe-30Mn-3Al-3Si TWIP steel to achieve toughening. The effects of shot peening and shot peening combined with annealing on the microstructure of TWIP steel were analyzed by means of metallurgical microscopy, X-ray diffraction and transmission. The hardness distribution, mechanical properties and work-hardening behaviors of the original samples, shot peened and shot peened + annealed samples were analyzed by using the micro-Vickers hardness tester and universal material testing machine. Results showed that the strong plastic deformation on the surface of TWIP steels was induced by shot peening, which resulted in the formation of highly deformed layer containing dislocation clusters of 60～100 nm size and transition layer containing micro and nanoscale deformation twin structures. This nano-micron scale grain size gradient structure could significantly increase the hardness of the highly deformed layer on the surface of TWIP steels to 366 HV0.1. Under the combined action of residual compressive stress, the yield strength of the sample increased to 485 MPa, which was much higher than the corresponding value of the initial sample. However, its fracture elongation was only 41.8% due to the surface roughness induced by shot peening and the nanocrystals with low plasticity in the highly deformed layer. After the annealing treatment, the deformed microstructure in the shot peened sample underwent recovery and recrystallization, with recrystallized grain sizes ranging from 1 to 3 μm in the strongly deformed layer position, and the hardness also decreased to 215 HV0.1. The yield strength of the formed micron-micron scale grain size gradient structure specimen declined to 261 MPa, but the elongation was improved to 65.3%. Besides, the grain size gradient structure was promotable to enhance the yield and tensile strength of TWIP steel, but was not favorable for the improvement of elongation.

Poly ADP-ribose polymerase (PARP) inhibitor monotherapies are selectively effective in patients with pancreatic, breast, prostate, and ovarian cancers with BRCA1 mutations. Cancer patients with more frequent wild-type BRCA show poor responses to PARP inhibitors. Moreover, patients who are initially sensitive to these inhibitors eventually respond poorly to drugs. In the present study, we discover that abrogation of Kruppel-like factor 5 (KLF5) significantly inhibits homologous recombination, which is the main mechanism for DNA double-stranded repair. Furthermore, the downregulation of KLF5 expression promotes the DNA damage induced by olaparib and significantly reduces the IC50 of the RARP inhibitor in pancreatic cancer cells. Overexpression of BRCA1 reverses the above effects caused by silencing of KLF5. Olaparib combined with a KLF5 inhibitor has an enhanced cytotoxic effect. Mechanistically, we identify BRCA1 as a KLF5 target gene. BRCA1 is positively correlated with KLF5 in PDAC tissue. Our results indicate that inhibition of KLF5 may induce BRCAness in a larger pancreatic cancer subset with proficient BRCA. The combination of KLF5 inhibitors and PARP inhibitors provides a novel treatment strategy to enhance the sensitivity of BRCA1-proficient pancreatic cancer to PARP inhibitors.

Immunotherapies targeting immune checkpoints have undergone rapid evolution, and have been preliminary explored in treatment of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) in recent years. However, their potential to deliver tangible clinical benefits remains uncertain. In this article, we systematically reviewed the current status and efficacy of clinical trials, which evaluated immune checkpoint inhibitor (ICI) as monotherapy or in dual-ICI therapy for GEP-NEN. Despite lacking substantial breakthroughs in GEP-NEN treatment, ICI demonstrated some antitumor activity and safety in treating recurrent or metastatic GEP-NEN, albeit with a generally low objective response rate (ORR). The ORR of ICI in GEP-NEN treatment exhibited a negative correlation with tumor differentiation, suggesting that poorly diffe-rentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) might achieve better clinical responses. Disease control rate of dual-ICI therapy was higher than that of monotherapy. However, dual-ICI also got more severe side effects. Given the rarity of mismatch repair gene defects and high microsatellite instability (dMMR/MSI-H) in GEP-NEN, patients with high tumor mutational burden (TMB-H≥10 muts/Mb) could get potentially benefit from ICI therapy. In the future, it is expected to further explore the synergistic combined application of ICI with chemotherapy, radiotherapy, and antiangiogenic drugs in GEP-NEN, which may enhance its antitumor efficacy. Clinically, the benefit groups of ICI immunotherapy should be evaluated comprehensively according to pathological grading, immune markers, disease progression, and patient's physical condition.

Combining atomic force microscopy (AFM) with other optical microscopic techniques is pivotal in nanoscale investigations, particularly leveraging the surface-sensitive properties of total internal reflection fluorescence microscopy (TIRF). A novel design that integrates AFM with a multi-wavelength TIRF is displayed, providing simultaneous fluorescence imaging and spectral acquisition capabilities. We elaborate on the considerations in the instrument design process and demonstrate the performance and potential applications of the instrument through fluorescence imaging and spectroscopy testing of individual nanoparticles. This AFM and TIRF correlated system (AFM–TIRF) emerges as a promising option for single-molecule fluorescence studies, enabling simultaneous manipulation and detection of fluorescence from individual molecules. [ABSTRACT FROM AUTHOR]

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation. [ABSTRACT FROM AUTHOR]