Search

Chromothripsis is a complex genomic rearrangement event in which localized regions of one or several chromosomes fragment in response to stress (ionizing radiation, chemical stimulation, infection, etc.) and then assembles in random order. In recent years, through whole genome sequencing, single nucleotide polymorphism array, comparative genome hybridization and other technologies, it has been found that such highly complex genomic aberration events are common in all types of tumors, and they occur more frequently in sarcoma and nervous system tumors. The mechanism of chromothripsis is not clear, and there are two main mechanisms of chromothripsis formation: ① Formation of micronuclei and fragmentation of chromosomes in micronuclei; ② Generation of breakage-fusion-bridge cycles. Chromothripsis is catastrophic for the vast majority of cells, but some cells still survive this process. The fragmented chromosome fragments in cells are randomly combined to cause genome rearrangement through non-homologous end-joining, alternative end joining and microhomology-mediated break-induced replication. Oncogene amplification, tumor suppressor gene deletion or fusion gene formation may occur in the rearranged genome, which endowing cells with significant selective growth advantages and promoting the occurrence and development of tumors. Some criteria have been proposed to infer whether chromothripsis occurs in the genome. Recent clinical cohort studies have shown that the clinical prognosis of cancer patients is also related to the frequency of chromothripsis. The higher the frequency of chromothripsis, the worse the prognosis. The prevalence and poor prognosis of chromothripsis in tumors suggest that detection of chromothripsis may be a way to evaluate the survival and prognosis of cancer patients. It has been found that chromothripsis plays an important role in the occurrence and development of tumors, however, the causes of chromothripsis, the mechanism of tumorigenesis, the diagnosis and treatment of chromothripsis remain to be further studied. With the answers to the related questions of chromothripsis, it will be helpful to better understand the role of chromothripsis in tumor progression, and provide a new theoretical basis for the prevention and treatment of cancer. This article reviewed the research progress of chromothripsis and tumorigenesis.

Quantum dot sensitized solar cells (QDSCs) represent a promising third‐generation photovoltaic technology, boasting a high theoretical efficiency of 44% and cost efficiency. However, their practical efficiency is constrained by reduced photovoltage (Voc) and fill factor (FF). One primary reason is the inefficient charge transfer and elevated recombination rates at the counter electrode (CE). In this work, a novel CE composed of a titanium mesh loaded with Co,N─C@MoS2 is introduced for the assembly of QDSCs. The incorporation of nanosized MoS2 enhances the density of catalytic sites, while the Co,N─C component ensures high conductivity and provides a substantial active surface area. Additionally, the titanium mesh's 3D structure serves as an effective electrical conduit, facilitating rapid electron transfer from the external circuit to the composite. These improvements in catalytic activity, charge transfer rate, and stability of the CE significantly enhance the photovoltaic performance of QDSCs. The optimized cells achieve a groundbreaking power conversion efficiency (PCE) of 16.39%, accompanied by a short‐circuit current density (Jsc) of 27.26 mA cm−2, Voc of 0.818 V, and FF of 0.735. These results not only offer a new strategy for designing electrodes with high catalytic activity but also underscore the promising application of the Co,N─C@MoS2 composite in enhancing QDSC technology. [ABSTRACT FROM AUTHOR]

Objectives: Calcaneus defect remains challenging with limited strategies for reconstruction. Current methods, including graft transplantation, substitution, and distraction osteogenesis, showed limited advantages with certain shortcomings. Current calcaneus lengthening for partial calcaneus loss reconstruction requires bone loss of less than 35%. We introduced our combination of tarsal bone fusion and gradual lengthening method in treating massive calcaneus loss. Methods: From January 2015 to December 2021, tarsal bone fusion and calcaneus gradual lengthening were performed in six patients with unilateral massive traumatic loss of the calcaneal tuberosity. A retrospective study was held to evaluate the outcomes of this novel technique. Clinical outcomes were assessed based on the American Orthopedic Foot and Ankle Score (AOFAS). Radiological data were assessed, which included tibio‐calcaneal angle (TCA), calcaneal interface angle (CIA), metatarsal declination angle (MDA), angle of longitudinal arch (ALA), and the amount of calcaneus axial lengthening (CAL). Results: The mean calcaneal axial lengthening was 43.8 ± 3.1 mm (range, 39–49.5 mm), and the mean proportion of the lengthened calcaneus was 47.8% ± 3.7% (range, 42.8–55.3%). The mean external fixation time was 104.8 ± 67.5 days (range, 69 to 242 days), and the mean external fixation index was 2.4 ± 1.6 days/cm. All patients stuck to the postoperative follow‐up plan with an average follow‐up time (FT) of 35.0 ± 6.7 months (range, 26–40 months). Deformities of the injured limbs were all corrected according to radiography. Based on the AOFAS, three excellent and three good results were achieved. Conclusion: The Ilizarov technique remains an option for calcaneus reconstruction with a great amount of loss once combined with tarsal bone fusion. The function of the injured foot and ankle can be satisfactorily restored using these techniques in our study. Apart from calcaneus elongation, tarsal bone fusion is somehow necessary to reinforce the proximal segment of the distracted calcaneus for creating a larger distraction callus, correcting concomitant foot deformities, and enhancing hindfoot stability. It is necessary to choose flexibly when tarsal bones should be fused. [ABSTRACT FROM AUTHOR]

By combining transformation optics and van der Waals layered materials, an invisibility concentrator with a thin layer of α-MoO3 wrapping around a cylinder is proposed. It inherits the effects of invisibility and energy concentration at Fabry–Pérot resonance frequencies, with tiny scattering. Due to the natural in-plane hyperbolicity in α-MoO3, the challenges of experimental complexity and infinite dielectric constant can be resolved perfectly. Through analytical calculation and numerical simulations, the relevant functionalities including invisibility, energy concentration and illusion effect of the designed device are confirmed, which provides guidelines for the subsequent experimental verification in future.

Background: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. Methods: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. Results: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. Conclusion: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. Translational potential statement: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.