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In cancer biology, the aberrant overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) has been correlative with an ominous prognosis, thereby underscoring its pivotal role in fostering metastatic progression. Consequently, EIF5A2 has garnered significant attention as a compelling prognostic biomarker for various malignancies. Our research endeavors were thus aimed at elucidating the utility and significance of EIF5A2 as a robust indicator of cancer outcome prediction.

Background and purpose: The plasma used for routine coagulation test (CCT) can only reflect a single component at a certain coagulation time point/segment, while thromboelastography (TEG) can depict the overall dynamic process curve of coagulation and fibrinolysis, which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing. This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy, and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy, so as to provide reference for clinical monitoring of hypercoagulable state. Methods: A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group, and 80 healthy subjects were selected as the control group. Then the experimental group was divided into a group without thrombosis (82 cases) and a group with thrombosis (78 cases) according to whether they had thrombosis or not. The determinations of thromboelastography (TEG) [coagulation reaction time (R), coagulation formation time (K), blood clot formation rate (α-Angle), maximum amplitude (MA) and coagulation index (CI)], conventional coagulation tests (CCT) [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fib), D-dimer (DD), fibrinogen degradation products (FDP)] and platelet count (PLT) were studied among three groups. With or without thrombosis as the criterion of hypercoagulable state, statistically significant indicators were selected to be included in the binary logistic regression analysis, and the receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy. Basic information, tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer. Logistic regression analysis was performed to explore the risk factors of thrombosis. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (number: 050432-4-2108*). Results: Compared with the control group, the R, TT and PLT of the group with thrombosis were decreased (P

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442–454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology .

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P

Zn–Al–Mg coating galvanized steel in resistance spot welded (RSW) in different configurations of DC51D was investigated to illustrate the nugget evolution process and mechanical properties of the joints. Results show that the microstructure of welded joints can be divided into nugget zone (FZ), heat-affected zone (HAZ), and base metal zone (BM). FZ was composed of lath martensite. The average hardness value of the weld joint was 110 HV0.2 while the FZ was up to 300 HV0.2 due to the formation of lath martensite. The failure modes can be divided into interface fracture (IF) and pull-out fracture occurred (PF) under different welding parameters, in which shear dimples showed had a typical plastic fracture morphology. The best range for welding parameters was found to be 12–18 cycles in which the nugget diameter reached 5.5 mm. The process of nugget evolution in HAZ and FZ was discussed.

Skeletal muscle stem cells are actively maintained in quiescence, but can activate quickly upon extrinsic stimulation. Here the authors show that CPEB1 promotes muscle stem cell activation by reprogramming the translational landscape.

Abstract Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Abstract Background Pancreatic cancer is one of the most common malignant tumors of the digestive tract, and it has a poor prognosis. Traditional methods are not effective to accurately assess the prognosis of patients with pancreatic cancer. Immunotherapy is a new promising approach for the treatment of pancreatic cancer; however, some patients do not respond well to immunotherapy, which may be related to tumor microenvironment regulation. In this study, we use gene expression database to mine important immune genes and establish a prognostic prediction model for pancreatic cancer patients. We hope to provide a feasible method to evaluate the prognosis of pancreatic cancer and provide valuable targets for pancreatic cancer immunotherapy. Results We used univariate COX proportional hazard regression analysis, the least absolute shrinkage and selection operator, and multivariate COX regression analysis to screen 8 genes related to prognosis from the 314 immune-related genes, and used them to construct a new clinical prediction model in the TCGA pancreatic cancer cohort. Subsequently, we evaluated the prognostic value of the model. The Kaplan–Meier cumulative curve showed that patients with low risk scores survived significantly longer than patients with high risk scores. The area under the ROC curve (AUC value) of the risk score was 0.755. The univariate COX analysis showed that the risk score was significantly related to overall survival (HR 1.406, 95% CI 1.237–1.598, P

Objectives In order to improve the quality of sinusoidal waveform output by the ship's high-frequency inverter charging device and reduce the CPU occupancy rate, an asymmetric regular sampling sinusoidal pulse width modulation (SPWM) method based on tangent approximation is proposed.Methods According to the basic principle and calculation method of the asymmetric regular sampling SPWM method based on tangent approximation, a Matlab/Simulink simulation model is built, and then the software algorithm flow that can be used in the high-frequency inverter charging device is designed together with the actual output of the tangent approximation method. The effects are then compared and verified by experiments.Results The simulation results show that under pure resistive load and resistive inductive load, the total harmonic distortion (THD) of the load-end waveform based on tangent approximation method is 2.12% and 2.08%, respectively, and its waveform quality is better than symmetric regular sampling. The experimental results show that the THD of load-end waveform based on the tangent approximation method is significantly lower than the symmetric regular sampling method. When the effective value of the input line voltage is 580 V (the modulation ratio is 0.8), the quality of the output waveform is relatively optimal.Conclusions The asymmetric regular sampling SPWM method based on tangent approximation overcomes the shortcomings of the traditional symmetric regular sampling method, such as the low quality of the output waveform and the traditional asymmetric regular sampling method's high sampling frequency and high CPU occupancy rate. The research results can provide reference for the design of ship's high frequency inverter charging devices.

Abstract Background Grain shape is a critical agronomic trait affecting grain yield and quality. Exploration and functional characterization of grain shape-related genes will facilitate rice breeding for higher quality and yield. Results Here, we characterized a recessive mutant named Oat-like rice for its unique grain shape which highly resembles oat grains. The Oat-like rice displayed abnormal floral organs, an open hull formed by remarkably elongated leafy lemmas and paleae, occasionally formed conjugated twin brown rice, an aberrant grain shape and a low seed setting rate. By map-based cloning, we discovered that Oat-like rice harbors a novel allele of OsMADS1 gene (OsMADS1 Olr), which has a spontaneous point mutation that causes the substitution of an amino acid that is highly conserved in the MADS-box domain of the MADS-box family. Further linkage analysis indicated that the point mutation in the OsMADS1 Olr is associated with Oat-like rice phenotype, and expression analysis of the OsMADS1 by qRT-PCR and GUS staining also indicated that it is highly expressed in flower organs as well as in the early stages of grain development. Furthermore, OsMADS1 Olr-overexpressing plants showed similar phenotypes of Oat-like rice in grain shape, possibly due to the dominant negative effect. And OsMADS1-RNAi plants also displayed grain phenotypes like Oat-like rice. These results suggested that OsMADS1 Olr is responsible for the Oat-like rice phenotype including aberrant grain shape. Moreover, the expression levels of representative genes related to grain shape regulation were apparently altered in Oat-like rice, OsMADS1 Olr-overexpressing and OsMADS1-RNAi transgenic plants. Finally, compared with Oat-like rice, OsMADS1 Olr-overexpressing and OsMADS1-RNAi plants, mild phenotype of seed-specific OsMADS1-RNAi transgenic plants indicated that OsMADS1 may has has a direct regulation role in grain development and the grain phenotypes of Oat-like rice, OsMADS1 Olr-overexpressing and OsMADS1-RNAi plants are majorly caused by the abnormal lemma and palea development. Conclusions Altogether, our results showed that grain shape and a low seed setting rate of the notable ‘Oat-like rice’ are caused by a spontaneous point mutation in the novel allele OsMADS1 Olr. Furthermore, our findings suggested that OsMADS1 mediates grain shape possibly by affecting the expression of representative genes related to grain shape regulation. Thus, this study not only revealed that OsMADS1 plays a vital role in regulating grain shape of rice but also highlighted the importance and value of OsMADS1 to improve the quality and yield of rice by molecular breeding.

Wide gamut and angle-insensitive structural colors are highly desirable for many applications. Herein, a new type of lithography-free, planar bilayer nanostructures for generating structural colors is presented, which is basically composed of a deep-subwavelength, highly absorbing dielectric layer on an opaque metallic substrate. Experimental results show that a galaxy of brilliant structural colors can be generated by our structures, and which can cover ∼50% of the standard red–green–blue color space by adjusting the nanostructure dimensions. The color appearances are robust with respect to the angle of vision. Theoretical partial reflected wave analyses reveal that the structural color effect is attributed to the strong optical asymmetric Fabry–Perot-type (F–P-type) thin-film resonance interference. The versatility of the structural color properties as well as the simplicity of their fabrication processes make this bilayer structures very promising for various applications, such as security marking, information encryption, and color display, etc.

Background: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study. Methods: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986). Findings: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA). Interpretation: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

Summary: Quiescent muscle stem cells, also called satellite cells (SCs), are essential for muscle regeneration. However, quiescent SCs are quickly activated during fluorescence-activated cell sorting (FACS) isolation. Here, we present an optimized protocol to isolate quiescent muscle stem cells from fixative-perfused mice and generate high-quality cDNA libraries for RNA-sequencing analysis. Fixation preserves the signatures of quiescent muscle stem cells in vivo. Isolated SCs can be used for downstream analysis such as immunofluorescence, RNA sequencing, and mass spectrometry.For complete information on the use and execution of this protocol, please refer to Yue et al. (2020).

Advanced glycation end products (AGEs) are glycosylated metabolic products generated in vivo and are associated with aging-related diseases. They are also formed during heat treatment in food processing. In this work, we investigated the contribution of linoleic acid (LA) to AGE formation using a protein/glucose model. An electronic tongue, denaturing polyacrylamide gel electrophoresis, electron spin resonance spectroscopy, circular dichroism, and ultraperformance liquid chromatography-tandem mass spectrometry were used to analyse reaction intermediates and reactive radical formation. The results show that LA is the key factor responsible for the change in flavour including the rapid triggering of glycation reactions. The amount of lipid-induced reactive radicals was significantly higher than in the non-fat system, radical generation in the non-fat system was gradually quenched after a robust radical-yielding reaction in the first 25 minutes. Subsequent unsaturated lipid oxidation, and AGE accumulation surpass Maillard reaction-only outcomes. Initial LA-induced changes in protein structure are followed by glycation and are enhanced by hydrophobic interactions and increased carbonyl levels resulting from lipid oxidation. These findings implicate lipids and lipid oxidation as the main factors responsible for AGE formation during the processing of fat-rich unsaturated fatty acid-containing foods.