LncRNA SH3PXD2A-AS1 facilitates cisplatin resistance in non-small cell lung cancer by regulating FOXM1 succinylation

Abstract Background Long noncoding RNAs (lncRNAs) play vital regulatory functions in non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance has significantly decreased the effectiveness of DDP-based chemotherapy in NSCLC patients. This study aimed to investigate the effects of SH3PXD2A antisense RNA 1 (SH3PXD2A-AS1) on DDP resistance in NSCLC. Methods Proliferation and apoptosis of DDP-resistant NSCLC cells were detected using cell counting kit-8 and flow cytometry assays. The interaction between SH3PXD2A-AS1 and sirtuin 7 (SIRT7) was assessed using co-immunoprecipitation (Co-IP), RNA pull-down, RNA immunoprecipitation (RIP), RNA fluorescence in situ hybridization, and immunofluorescence assays, while succinylation (SUCC) of Forkhead Box M1 (FOXM1) was analyzed by IP and Western blot assays. The role of SH3PXD2A-AS1 in vivo was explored using a xenografted tumor model. Results Expression of SH3PXD2A-AS1 was found elevated in DDP-resistant NSCLC cells, while it’s knocking down translated into suppression of cell viability and promotion of apoptosis. Moreover, silencing of SH3PXD2A-AS1 resulted in decreased FOXM1 protein level and enhanced FOXM1-SUCC protein level. The SIRT7 was found to interact with FOXM1, translating into inhibition of FOXM1 SUCC at the K259 site in human embryonic kidney (HEK)-293T cells. Overexpressing of SIRT7 reversed the increase of FOXM1-SUCC protein level and apoptosis, and the decrease of cell viability induced by silencing of SH3PXD2A-AS1. In tumor-bearing mice, SH3PXD2A-AS1 inhibition suppressed tumor growth and the protein levels of Ki67, SIRT7, and FOXM1. Conclusion SH3PXD2A-AS1 promoted DDP resistance in NSCLC cells by regulating FOXM1 SUCC via SIRT7, offering a promising therapeutic approach for NSCLC

A brief overview of single-port laparoscopic appendectomy as an optimal surgical procedure for patients with acute appendicitis: still a long way to go

Single-port laparoscopic appendectomy (SPLA) has become a good alternative to the traditional surgical treatment of acute appendicitis, due to its advantages of small incision, mild postoperative pain, short hospital stay, and good cosmetic effect. However, the further application of SPLA has been restricted by its relatively long operating time, high level of operating difficulty, and increased equipment and technical requirements. Clinical teams worldwide have attempted to improve and optimize SPLA technical protocols and equipment to maintain stable intraoperative pneumoperitoneal pressure, improve the ‘triangle relationship’ of operating angles, and develop new surgical procedures with less trauma and higher cost-effectiveness. Here, new SPLA techniques reported over the past decade are reviewed and compared, with the aim of providing new insights into technical improvements, equipment upgrades and clinical studies in the coming years

Effect of subsoil tillage depth on nutrient accumulation, root distribution, and grain yield in spring maize

A four-year field experiment was conducted to investigate the effect of subsoiling depth on root morphology, nitrogen (N), phosphorus (P), and potassium (K) uptake, and grain yield of spring maize. The results indicated that subsoil tillage promoted root development, increased nutrient accumulation, and increased yield. Compared with conventional soil management (CK), root length, root surface area, and root dry weight at 0–80 cm soil depth under subsoil tillage to 30 cm (T1) and subsoil tillage to 50 cm (T2) were significantly increased, especially the proportions of roots in deeper soil. Root length, surface area, and dry weight differed significantly among three treatments in the order of T2 > T1 > CK at the 12-leaf and early filling stages. The range of variation of root diameter in different soil layers in T2 treatment was the smallest, suggesting that roots were more likely to grow downwards with deeper subsoil tillage in soil. The accumulation of N, P, and K in subsoil tillage treatment was significantly increased, but the proportions of kernel and straw were different. In a comparison of T1 with T2, the grain accumulated more N and P, while K accumulation in kernel and straw varied in different years. Grain yield and biomass were increased by 12.8% and 14.6% on average in subsoil tillage treatments compared to conventional soil treatment. Although no significant differences between different subsoil tillage depths were observed for nutrient accumulation and grain yield, lodging resistance of plants was significantly improved in subsoil tillage to 50 cm, a characteristic that favors a high and stable yield under extreme environments

Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors

Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is a newly identified member of Family Coronaviridae. Coronavirus envelope spike protein S is a class I viral fusion protein which is characterized by the existence of two heptad repeat regions (HR1 and HR2) (forming a complex called fusion core). Here we report that by using in vitro bio-engineering techniques, SARS-CoV HR1 and HR2 bind to each other and form a typical 6-helix bundle. The HR2, either as a synthetic peptide or as a GST-fusion polypeptide, is a potent inhibitor of virus entry. The results do show that SARS-CoV follows the general fusion mechanism of class I viruses and this lays the ground for identification of virus fusion/entry inhibitors for this devastating emerging virus

Morphological and Compositional Features of Chronic Internal Carotid Artery Occlusion in MR Vessel Wall Imaging Predict Successful Endovascular Recanalization

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization

Characterization of the heptad repeat regions, HR1 and HR2, and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome (SARS) coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emergent virus responsible for a worldwide epidemic in 2003. The coronavirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaviruses is predicted to be considerably longer than that in other type I virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronavirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency virus (HIV), for the treatment of SARS infection