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Abstract Background Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.

The main purpose of this article is to use some identities of the classical Gauss sums, the properties of character sums, and Dedekind sums (modulo an odd prime) to study the computational problem of one-kind mean values related to Dedekind sums and give some interesting identities for them.

Abstract Background Skin cutaneous melanoma (SKCM) is an extremely malignant tumor that is associated with a poor prognosis. LSM2 has been found to be related to different types of tumors; however, its role in SKCM is poorly defined. We aimed to determine the value of LSM2 as a prognostic biomarker for SKCM. Methods The expression profile of LSM2 mRNA was compared between tumor and normal tissues in public databases, such as TCGA, GEO, and BioGPS. LSM2 protein expression was explored using immunohistochemistry (IHC) on a tissue microarray containing 44 SKCM tissues and 8 normal samples collected at our center. Kaplan-Meier analysis was performed to assess the prognostic value of LSM2 expression in patients with SKCM. SKCM cell lines with LSM2 knockdown were used to determine the effects of LSM2. Cell counting kit-8 (CCK8) and colony formation assays were conducted to assess cell proliferation, whereas wound healing and transwell assays were carried out to assess the migration and invasion abilities of SKCM cells. Results LSM2 was more highly expressed at the mRNA and protein levels in SKCM than that in normal skin. Moreover, elevated expression of LSM2 was associated with shorter survival time and early recurrence in patients with SKCM. The in vitro results revealed that the silencing of LSM2 in SKCM cells significantly inhibited cell proliferation, migration, and invasion. Conclusion Overall, LSM2 contributes to malignant status and poor prognosis in patients with SKCM and may be identified as a novel prognostic biomarker and therapeutic target.

Abstract Background WRINKLED1 (WRI1) encodes a transcription factor, belonging to the APETALA2 (AP2) family, and plays a key role in regulating plant oil biosynthesis. As a newly woody oil crop, tree peony (Paeonia rockii) was notable for the abundant unsaturated fatty acids in its seed oil. However, the role of WRI1 during the accumulation of P. rockii seeds oil remains largely unknown. Results In this study, a new member of the WRI1 family was isolated from P. rockii and was named PrWRI1. The ORF of PrWRI1 consisted of 1269 nucleotides, encoding a putative protein of 422 amino acids, and was highly expressed in immature seeds. Subcellular localization analysis in onion inner epidermal cells showed that PrWRI1 was located at the nucleolus. Ectopic overexpression of PrWRI1 could significantly increase the total fatty acid content in Nicotiana benthamiana leaf tissue and even PUFAs in transgenic Arabidopsis thaliana seeds. Furthermore, the transcript levels of most genes related to fatty acids (FA) synthesis and triacylglycerol (TAG) assembly were also up-regulated in transgenic Arabidopsis seeds. Conclusions Together, PrWRI1 could push carbon flow to FA biosynthesis and further enhance the TAG amount in seeds with a high proportion of PUFAs.

Objective: To investigate the CT manifestations of primary intestinal lymphoma (PIL) so as to improve the diagnosis and differential diagnosis. Methods: 21 patients with PIL confirmed pathologically in our hospital from March 2013 to February 2022 were enrolled in this study, their CT phenotypes and features were analyzed. Results: All 21 cases of PIL were non-Hodgkin's lymphoma (NHL), 12 cases were diffuse large B-cell lymphoma (DLBCL), 3 cases were follicular lymphoma, 2 cases were NK/T-cell lymphoma, 2 cases were T-cell lymphoma, mucosa-associated lymphoid tissue lymphoma (MALT) and mantle cell lymphoma (MCL) were identified 1 case each. The lesions were located in the colon in 7 cases, ileum in 5 cases, small intestine mesentery in 4 cases, ileocecum in 2 cases, jejunum in 1 case, rectum in 1 case, and both right hemicolon and ileocecum in 1 case. CT findings showed intestinal wall infiltration in 3 cases, intestinal wall thickening in 3cases, mass in 4 cases, aneurysmal dilation in 7 cases and mesenteric multiple nodules in 4 cases. CT enhancement mostly showed homogeneous mild/moderate enhancement. Among the 21 patients, 2 case was complicated by by intestinal perforation, and 2 cases were complicated by intestinal obstruction. Conclusion: The characteristic imaging features of CT in PIL include multifocal involvement of the intestines, marked mural thickening in a focal or diffuse manner, aneurysmal dilatation of lumen, eccentric intestinal mass of uniform density and mesenteric "sandwich sign". Recognition of these signs is of diagnostic value for primary intestinal lymphoma.

It can be seen that the corrosion failure of transmission and transformation equipment has increasingly restricted the safe operation of the Zhejiang power grid bottleneck problem. If effective anticorrosion measures are not taken promptly, transmission and transformation equipment serving in various sophisticated atmospheric environments will suffer serious corrosion damage in a relatively short period, which endangers the safe usage of transmission and transformation equipment and the security of grid operation. In this article, through the establishment of transmission and transformation steel components corrosion fracture mechanics model, a standard corrosion spectrum grading software based on DeepLabV3+ image segmentation technology is developed to determine the quantitative assessment method of corrosion damage and assess the corrosion status with safety degree of transmission and transformation equipment. According to the assessment results, the operation and maintenance units are guided to adopt differentiated corrosion maintenance and replacement strategies, so as to reduce corrosion safety hazards and reduce safety accidents and economic losses caused by corrosion, which is of great significance for the safe operation of power grids.

Abstract Background Integrative medicine is commonly used in China. Researchers prefer to report efficacy outcomes rather than safety outcomes in clinical trials; thus, evidence regarding safety in integrative medicine is unclear. Developing a core outcome set (COS) for safety outcomes is necessary. In this study, a representative example of the methodology for developing COS to assess safety outcomes of cardiovascular diseases in clinical trials investigating integrated medicine will be developed. Methods and analysis Safety information will be extracted from package inserts and through systematic reviews of treatments for cardiovascular diseases (including angina pectoris, myocardial infarction, heart failure, arrhythmia, and hypertension) to develop an extensive list of safety outcomes, which will then be categorized according to whether subjective or objective outcomes. Questionnaires for clinician-reported safety outcomes and patient-reported safety outcomes will be developed. Two rounds of the Delphi survey will then be conducted for different stakeholders (traditional Chinese medicine clinicians and researchers in cardiovascular diseases, Western medicine clinicians and researchers in cardiovascular diseases, integrated medicine clinicians and researchers of cardiovascular diseases, pharmacologists, methodologists of evidence-based medicine, and patients). After round 2 of the Delphi analysis, a face-to-face consensus meeting will be held to determine the final COS for assessing safety outcomes in cardiovascular diseases. Discussion A COS for safety outcomes in cardiovascular diseases may improve the consistency of reporting results and will help identify potential bias of selective reporting in the future. Trial registration This study was registered in the Core Outcome Measures in Effectiveness Trials database as study 1564 .

In this article, we use the elementary methods and the estimate for character sums to study a problem related to quadratic residues and the Pythagorean triples, and prove the following result. Let $ p $ be an odd prime large enough. Then for any positive number $ 0 < \epsilon < 1 $, there must exist three quadratic residues $ x, \ y $ and $ z $ modulo $ p $ with $ 1\leq x, \ y, \ z\leq p^{1+\epsilon} $ such that the equation $ x^2+y^2 = z^2 $.

The location of the grounding grid conductors is critical for performing corrosion diagnosis and maintenance work. An improved magnetic field differential method to locate the unknown grounding grid based on truncation errors and the round-off errors analysis is presented in this paper. It was proven that a different order of the magnetic field derivative can be used to determine the position of the grounding conductor according to the peak value of the derivative. Due to the accumulative error of higher differentiation, the truncation error and rounding error were used to analyze to accumulative error and to determine the optimal step size to measure and calculate the higher differentiation. The possible range and probability distribution of the two kinds of errors at each order are described, and the index of peak position error was derived, which can be used to locate the grounding conductor in the power substation.

Modern crowdsourcing offers the potential to produce solutions for increasingly complex tasks requiring teamwork and collective labor. However, the vast scale of the crowd makes forming project teams an intractable problem to coordinate manually. To date, most crowdsourcing collaborative platforms rely on algorithms to automate team formation based on worker profiling data and task objectives. As a top-down strategy, algorithmic crowd team formation tends to alienate workers causing poor collaboration, interpersonal clashes, and dissatisfaction. In this paper, we investigate different ways that crowd teams can be formed through three team formation models namely bottom-up, top-down, and hybrid. By simulating an open collaboration scenario such as a hackathon, we observe that the bottom-up model forms the most competitive teams with the highest teamwork quality. Furthermore, we note that bottom-up approaches are particularly suitable for populations with high-risk appetites (most workers being lenient toward exploring new team configurations) and high degrees of homophily (most workers preferring to work with similar teammates). Our study highlights the importance of integrating worker agency in algorithm-mediated team formation systems, especially in collaborative/competitive settings, and bears practical implications for large-scale crowdsourcing platforms.

In many higher plants, seed oil accumulation is governed by complex multilevel regulatory networks including transcriptional regulation, which primarily affects fatty acid biosynthesis. Tree peony (Paeonia rockii), a perennial deciduous shrub endemic to China is notable for its seed oil that is abundant in unsaturated fatty acids. We discovered that a tree peony trihelix transcription factor, PrASIL1, localized in the nucleus, is expressed predominantly in developing seeds during maturation. Ectopic overexpression of PrASIL1 in Nicotiana benthamiana leaf tissue and Arabidopsis thaliana seeds significantly reduced total fatty acids and altered the fatty acid composition. These changes were in turn associated with the decreased expression of multitudinous genes involved in plastidial fatty acid synthesis and oil accumulation. Thus, we inferred that PrASIL1 is a critical transcription factor that represses oil accumulation by down-regulating numerous key genes during seed oil biosynthesis. In contrary, up-regulation of oil biosynthesis genes and a significant increase in total lipids and several major fatty acids were observed in PrASIL1-silenced tree peony leaves. Together, these results provide insights into the role of trihelix transcription factor PrASIL1 in controlling seed oil accumulation. PrASIL1 can be targeted potentially for oil enhancement in tree peony and other crops through gene manipulation.