Frontier knowledge and future directions of programmed cell death in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies of the urinary system. Patient outcomes are relatively poor due to the lack of early diagnostic markers and resistance to existing treatment options. Programmed cell death, also known as apoptosis, is a highly regulated and orchestrated form of cell death that occurs ubiquitously throughout various physiological processes. It plays a crucial role in maintaining homeostasis and the balance of cellular activities. The combination of immune checkpoint inhibitors plus targeted therapies is the first-line therapy to advanced RCC. Immune checkpoint inhibitors(ICIs) targeted CTLA-4 and PD-1 have been demonstrated to prompt tumor cell death by immunogenic cell death. Literatures on the rationale of VEGFR inhibitors and mTOR inhibitors to suppress RCC also implicate autophagic, apoptosis and ferroptosis. Accordingly, investigations of cell death modes have important implications for the improvement of existing treatment modalities and the proposal of new therapies for RCC. At present, the novel modes of cell death in renal cancer include ferroptosis, immunogenic cell death, apoptosis, pyroptosis, necroptosis, parthanatos, netotic cell death, cuproptosis, lysosomal-dependent cell death, autophagy-dependent cell death and mpt-driven necrosis, all of which belong to programmed cell death. In this review, we briefly describe the classification of cell death, and discuss the interactions and development between ccRCC and these novel forms of cell death, with a focus on ferroptosis, immunogenic cell death, and apoptosis, in an effort to present the theoretical underpinnings and research possibilities for the diagnosis and targeted treatment of ccRCC.

Genome-wide identification, evolution and expression profiles analysis of bHLH gene family in Castanea mollissima.

The basic helix-loop-helix (bHLH) transcription factors (TFs) gene family is an important gene family in plants, and participates in regulation of plant apical meristem growth, metabolic regulation and stress resistance. However, its characteristics and potential functions have not been studied in chestnut (Castanea mollissima), an important nut with high ecological and economic value. In the present study, 94 CmbHLHs were identified in chestnut genome, of which 88 were unevenly distributed on chromosomes, and other six were located on five unanchored scaffolds. Almost all CmbHLH proteins were predicted in the nucleus, and subcellular localization demonstrated the correctness of the above predictions. Based on the phylogenetic analysis, all of the CmbHLH genes were divided into 19 subgroups with distinct features. Abundant cis-acting regulatory elements related to endosperm expression, meristem expression, and responses to gibberellin (GA) and auxin were identified in the upstream sequences of CmbHLH genes. This indicates that these genes may have potential functions in the morphogenesis of chestnut. Comparative genome analysis showed that dispersed duplication was the main driving force for the expansion of the CmbHLH gene family inferred to have evolved through purifying selection. Transcriptome analysis and qRT-PCR experiments showed that the expression patterns of CmbHLHs were different in different chestnut tissues, and revealed some members may have potential functions in chestnut buds, nuts, fertile/abortive ovules development. The results from this study will be helpful to understand the characteristics and potential functions of the bHLH gene family in chestnut.

Genome-wide identification, evolution and transcriptome analysis of GRAS gene family in Chinese chestnut (Castanea mollissima).

GRAS transcription factors play an important role in regulating various biological processes in plant growth and development. However, their characterization and potential function are still vague in Chinese chestnut (Castanea mollissima), an important nut with rich nutrition and high economic value. In this study, 48 CmGRAS genes were identified in Chinese chestnut genome and phylogenetic analysis divided CmGRAS genes into nine subfamilies, and each of them has distinct conserved structure domain and features. Genomic organization revealed that CmGRAS tend to have a representative GRAS domain and fewer introns. Tandem duplication had the greatest contribution for the CmGRAS expansion based on the comparative genome analysis, and CmGRAS genes experienced strong purifying selection pressure based on the Ka/Ks. Gene expression analysis revealed some CmGRAS members with potential functions in bud development and ovule fertility. CmGRAS genes with more homologous relationships with reference species had more cis-acting elements and higher expression levels. Notably, the lack of DELLA domain in members of the DELLA subfamily may cause de functionalization, and the differences between the three-dimensional structures of them were exhibited. This comprehensive study provides theoretical and practical basis for future research on the evolution and function of GRAS gene family.

Cranioplasty of large cranial defect at an early stage after decompressive craniectomy performed for severe head trauma.

Large cranial defects resulting from decompressive craniectomy performed for refractory intracranial hypertension after head trauma is one of the indications for cranioplasty, and this procedure is commonly performed 3 months after craniectomy. However, the large cranial defect would lead to the kinds of complications early during the phase of these patients' recovery, which would go against rehabilitation. This study retrospectively reviewed 23 patients undergoing early cranioplasty (5-8 weeks after craniectomy) in the last 4 years with a detailed choice of patients, outcome of complications after head trauma and large craniectomy, as well as assessment of prognosis. The early outcome (1 month later) revealed most of the patients who had conscious disturbance before the cranioplasty recovered their consciousness and presented an improved neurologic function. The long-dated prognosis (18 months later) revealed that 17 patients were good (independent patients) in this series (74%), whereas four patients survived with a severe disability (17%) and two remained in a vegetative state (9%). No dead patients or intracranial infection after the procedure were found in this study. Most patients' complications were relieved after the cranioplasty with improvements of symptoms or image of computed tomography scan. In conclusion, we consider that with the appropriate choice of patients and materials, early cranioplasty for large cranial defects after decompressive craniectomy would be safe and helpful for the improvement of patients' neurologic function and prognosis. To our knowledge, this series may be the first detailed report in English about early cranioplasty after decompressive craniectomy. We are going to perform prospective and retrospective contrastive studies to further confirm the effects of this procedure on the patients with large cranial defects after decompressive craniectomy.