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Abstract: A femtosecond pulsed laser (pulse width: 120fs, wavelength: 800nm and repetition rate: 500Hz) was used for the pretreatment on the rake face of Al2O3/TiC ceramic cutting tools. The evolution of surface morphology of pretreated cutting tools irradiated with different pulse energies was measured by scanning electron microscope (SEM) and atomic force microscope (AFM). Dry cutting tests were carried out with these pretreated tools and conventional tools on hardened steel. The effect of pulse energy on the wear resistance of these pretreated tools was investigated. Results show that the cutting forces have no significant difference between laser pretreated tools and the conventional tool; the cutting temperatures of laser pretreated tools were slightly reduced compared with the conventional tool. Meanwhile, we found that the laser pretreated tools increased the adhesions of chips on the rake face, but they can significantly improve the wear resistance of the rake face; and laser pulse energy was found to have a profound effect on the wear resistance of the laser pretreated tools. [Copyright &y& Elsevier]

• Microbial community composition and function were related to SOM chemistry. • The relative abundance of AMF was lower in acidic soils. • Soil microbial biomass was positively related to microbial function and pH. • MAP and pH were important for overall microbial community composition. Despite the important roles of microorganisms in soil organic matter (SOM) decomposition and nutrient cycling, how their biomass, community composition and function are driven by a joint effect of edaphic and environmental factors at a large spatial scale remains unclear. Moreover, a mechanistic understanding of the associations among microbial communities and SOM chemistry as a key indicator of substrate availability over large spatial scales has been lacking until now. To fill this knowledge gap, we examined how soil microbial community abundance and composition (via phospholipid fatty acid (PLFA) analysis) and function (via enzyme activities and net N mineralization) were associated with the edaphic and environmental factors from six oriental oak (Quercus variabilis) forest sites arranged across a 11° latitudinal gradient in East China. We found strong relationships between SOM chemistry as indicated by 13C nuclear magnetic resonance (NMR) spectroscopy and microbial community composition and function along this gradient. For example, the ratio of fungi to bacteria (F/B) decreased with increasing carboxyl C percentage; the lower abundance of arbuscular mycorrhizal fungi (AMF) and decreased invertase activity in the southern sites were possibly related to higher ratio of alkyl to O alkyl (A/O); urease activity increased with carboxyl C percentage. Microbial biomass (total PLFAs) had positive relationships with urease activity, net N mineralization rate, and soil pH. Mean annual precipitation (MAP) and pH were important for overall microbial community composition. Overall, our results indicate that SOM chemistry is closely related to microbial community composition and function along the latitudinal gradient and should be considered in future studies. Our study contributes to a better prediction of microbial responses to possible substrate changes brought by future environmental changes, which is urgently needed under the context of accelerating global change. [ABSTRACT FROM AUTHOR]

Analysis of large-scale data-independent acquisition mass spectrometry (DIA-MS) metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS (DDA-MS), protein identification and quantification using DIA-MS, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-minute diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate (FDR) of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score = 0.67-0.90) in genus diversity and showed a high correlation (r Spearman = 0.73-0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia (DLP) patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Changes in microRNAs (miRNAs) are relevant to bariatric surgery and its comorbidities. The characteristics of changes in miRNAs of the early postoperative period following both bariatric procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), as well as the factors that related to the effectiveness of early weight loss remain unclear., Methods: We recruited 18 patients who performed SG and 15 patients who performed RYGB. Their preoperative and 1-month postoperative clinical data and fasting serum samples were collected, and the latter were analyzed by RNA-sequencing. Differential expression analysis of miRNAs was performed by the R-tool. Functional classification annotation and pathway enrichment analysis of targeted genes were analyzed by KOBAS software. The change profiles of miRNAs for both surgeries and their correlation with clinical characteristics and weight loss effectiveness were further analyzed., Results: A total of 85 differentially expressed miRNAs were identified before and after SG, while a total of 76 were found before and after RYGB. The target genes of these miRNAs were similar in the Gene Ontology enrichment analysis in SG and RYGB, and the enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes was mainly related to metabolic pathways. Hsa-miR-493-5p, hsa-miR-184, and hsa-miR-3199 exhibited similar changes in SG and RYGB, and the former two were correlated with clinical characteristics. Hsa-miR-6729-5p, hsa-miR-4659b-5p, and hsa-miR-2277-5p were correlated with the weight loss effectiveness of SG, while hsa-miR-4662a-5p was correlated with the weight loss effectiveness of RYGB., Conclusions: Short-term metabolic improvement and weight loss occurring after SG and RYGB surgery might be related to changes in miRNAs, which act on multiple biological pathways by regulating genes. In addition, some clinical characteristics and miRNAs were related to the effectiveness of early weight loss after SG and RYGB surgery., Clinical Trial Registration: ChiCTR2200058333., (© 2024. The Author(s).)

Background: Nursing students often make clinical errors due to their limited clinical experience and their orientation toward errors, revealing their attitude and behavioral tendencies regarding nursing errors. Understanding how self-efficacy, motivation, and a sense of security influence the error orientation of nursing students is important for developing strategies to enhance their error orientation., Objectives: This study aimed to explore the relationship between self-efficacy, motivation, and error orientation of nursing students during clinical internships., Method: This was a cross-sectional study. An electronic questionnaire was distributed to nursing students from 14 September 2023 to 30 September at a comprehensive tertiary A teaching hospital in Zhengzhou, Henan province. The instruments used in this study included the General Information Questionnaire, General Self-efficacy Scale, Achievement Motives Scale, Security Scale, and Error Orientation Scale. Statistical Product and Service Software Automatically (SPSSAU) was used to perform statistical description, mediation analysis, and moderated mediation analyses., Results: A total of 510 nursing students were included in this study. The motivation for success and failure-escaping fully mediated the relationships between self-efficacy and error orientation of nursing students, with a mediation effect of 0.101 (95% CI: 0.058-0.144). The security of nursing students moderated both the direct effect of this model and the indirect effect of motivation for failure-escaping. When security was high, the self-efficacy of nursing students was positively correlated with their error orientation, with an effect of 0.059 (95% CI: 0.003~0.116). When security was high, the moderation effect was significant, with an effect of -0.012 (95% CI: -0.026~-0.002). However, at low and median levels of security, the mediation effect was non-existent., Conclusion: The motivation for success and failure escaping play different roles in the paths between self-efficacy and error orientation. Clinical nursing teachers should take measures to enhance the motivation for success but reduce the failure-escaping motivation to improve the error orientation of nursing students. Additionally, it is crucial to pay attention to and improve the sense of security of students during clinical internships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Fan, Dong, Yang, Wang, Gao, Lv and Ma.)

Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as a novel therapeutic approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal in various physiological and pathological processes, their involvement in ferroptosis remains relatively unexplored. In this study, we constructed a ferroptosis-related lncRNA-mRNA correlation network in HCC using Pearson correlation analysis. Notably, the SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed a significant correlation between the expression levels of this pair and key clinical characteristics of HCC patients, including gender, pathology, Ishak scores and tumour size. And poor prognosis was associated with high expression of this pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to the 3'UTR region of SLC7A11 mRNA, enhanced its stability, thereby promoting HCC cell growth and resistance to erastin- induced ferroptosis. Additionally, in vivo studies confirmed that SLC7A11-AS1 knockdown potentiated the inhibitory effects of erastin on tumour growth. Overall, our findings suggest that targeting the SLC7A11-AS1/SLC7A11 pair holds promise as a potential therapeutic strategy for HCC patients., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Cardiac fibromas are benign tumours of the heart and are composed of fibroblasts and collagen. They are one of the most common cardiac tumours encountered in children and adolescents but are rare in adults., Case Report: The patient was a 57-year-old man who presented, complaining of a two-year history of chest tightness at rest. Transthoracic echocardiography revealed a severely calcified mass protruding from the anterior wall of the right ventricle near the apex. The patient was referred for tumour resection. Postoperative histopathological examination identified the calcified mass to be a cardiac fibroma. The patient's postoperative recovery was unremarkable and he was discharged eight days after surgery. During follow up, he has been free from any troublesome symptoms., Conclusions: Pre-operative diagnosis using various imaging modalities and early surgery are key to optimising the prognosis of patients with a cardiac fibroma.

Organic solar cells (OSCs) represent one of the most important emerging photovoltaic technologies that can implement solar energy conversion efficiently. The chemical structure of organic semiconductors deployed in the active layer of OSCs plays a critical role in the photovoltaic performance and chemical/physical stability of relevant devices. With the structure innovation of organic semiconductors, especially nonfullerene acceptors (NFAs), the performance of OSCs have been promoted rapidly in recent years, with state-of-the-art power conversion efficiencies (PCEs) exceeding 19.5%. Compared with other photovoltaics like perovskite, the shortcoming of OSCs mainly lies in the high nonradiative recombination loss. However, the photocurrent density is superior in OSCs owing to the easy modulation of the NFA band gap toward the near-infrared region. In these regards, the effort to further boost the PCE of OSCs to achieve a milestone >21% should be devoted to reducing the nonradiative loss while further broadening the absorption band. Developing organic semiconductors with biaxially extended conjugated structures has provided a potential solution to achieve these goals. Herein, we summarize the design rules and performance progress of biaxially extended conjugated materials for OSCs. The descriptions are divided into two major categories, i.e., polymers and NFAs. For p-type polymers, we focus on the biaxial conjugation on some representative building blocks, e.g., polythiophene, triphenylamine, and quinoxaline. Whereas for n-type polymers, some structures with large conjugated planes in the normal direction are presented. We also elaborate on the biaxial conjugation strategies in NFAs with modification site at either the π-core or side-group. The general structure-property relationships are further retrieved within these materials, with focus on the short-wavelength absorption and nonradiative energy loss. Finally, we provide an outlook for the further structure modification strategies of biaxially conjugated materials toward highly efficient, stable, and industry-compatible OSCs.

Mass spectrometry-based proteomics plays a critical role in current biological and clinical research. Technical issues like data integration, missing value imputation, batch effect correction and the exploration of inter-connections amongst these technical issues, can produce errors but are not well studied. Although proteomic technologies have improved significantly in recent years, this alone cannot resolve these issues. What is needed are better algorithms and data processing knowledge. But to obtain these, we need appropriate proteomics datasets for exploration, investigation, and benchmarking. To meet this need, we developed MultiPro (Multi-purpose Proteome Resource), a resource comprising four comprehensive large-scale proteomics datasets with deliberate batch effects using the latest parallel accumulation-serial fragmentation in both Data-Dependent Acquisition (DDA) and Data Independent Acquisition (DIA) modes. Each dataset contains a balanced two-class design based on well-characterized and widely studied cell lines (A549 vs K562 or HCC1806 vs HS578T) with 48 or 36 biological and technical replicates altogether, allowing for investigation of a multitude of technical issues. These datasets allow for investigation of inter-connections between class and batch factors, or to develop approaches to compare and integrate data from DDA and DIA platforms., (© 2023. The Author(s).)

The molecular basis of circadian rhythm, driven by core clock genes such as Per1/2, has been investigated on the transcriptome level, but not comprehensively on the proteome level. Here we quantified over 11,000 proteins expressed in eight types of tissues over 46 h with an interval of 2 h, using WT and Per1/Per2 double knockout mouse models. The multitissue circadian proteome landscape of WT mice shows tissue-specific patterns and reflects circadian anticipatory phenomena, which are less obvious on the transcript level. In most peripheral tissues of double knockout mice, reduced protein cyclers are identified when compared with those in WT mice. In addition, PER1/2 contributes to controlling the anticipation of the circadian rhythm, modulating tissue-specific cyclers as well as key pathways including nucleotide excision repair. Severe intertissue temporal dissonance of circadian proteome has been observed in the absence of Per1 and Per2. The γ-aminobutyric acid might modulate some of these temporally correlated cyclers in WT mice. Our study deepens our understanding of rhythmic proteins across multiple tissues and provides valuable insights into chronochemotherapy. The data are accessible at https://prot-rhythm.prottalks.com/., Competing Interests: Conflict of interest T. G. and Y. Z. are shareholders of Westlake Omics Inc; Y. L. W. G. and Q. Z. are employees of Westlake Omics Inc. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The plant actin cytoskeleton is characterized by the basic properties of dynamic array, which plays a central role in numerous conserved processes that are required for diverse cellular functions. Here, we focus on how actins and actin-related proteins (ARPs), which represent two classical branches of a greatly diverse superfamily of ATPases, are involved in fundamental functions underlying signal regulation of plant growth and development. Moreover, we review the structure, assembly dynamics, and biological functions of filamentous actin (F-actin) from a molecular perspective. The various accessory proteins known as actin-binding proteins (ABPs) partner with F-actin to finely tune actin dynamics, often in response to various cell signaling pathways. Our understanding of the significance of the actin cytoskeleton in vital cellular activities has been furthered by comparison of conserved functions of actin filaments across different species combined with advanced microscopic techniques and experimental methods. We discuss the current model of the plant actin cytoskeleton, followed by examples of the signaling mechanisms under the supervision of F-actin related to cell morphogenesis, polar growth, and cytoplasmic streaming. Determination of the theoretical basis of how the cytoskeleton works is important in itself and is beneficial to future applications aimed at improving crop biomass and production efficiency.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning., (©The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.)

Backgruound: MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed., Methods: We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared., Results: Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM., Conclusion: We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

Background: Promoting rapid wound healing with functional recovery of all skin appendages is the main goal of regenerative medicine. So far current methodologies, including the commonly used back excisional wound model (BEWM) and paw skin scald wound model, are focused on assessing the regeneration of either hair follicles (HFs) or sweat glands (SwGs). How to achieve de novo appendage regeneration by synchronized evaluation of HFs, SwGs and sebaceous glands (SeGs) is still challenging. Here, we developed a volar skin excisional wound model (VEWM) that is suitable for examining cutaneous wound healing with multiple-appendage restoration, as well as innervation, providing a new research paradigm for the perfect regeneration of skin wounds., Methods: Macroscopic observation, iodine-starch test, morphological staining and qRT-PCR analysis were used to detect the existence of HFs, SwGs, SeGs and distribution of nerve fibres in the volar skin. Wound healing process monitoring, HE/Masson staining, fractal analysis and behavioral response assessment were performed to verify that VEWM could mimic the pathological process and outcomes of human scar formation and sensory function impairment., Results: HFs are limited to the inter-footpads. SwGs are densely distributed in the footpads, scattered in the IFPs. The volar skin is richly innervated. The wound area of the VEWM at 1, 3, 7 and 10 days after the operation is respectively 89.17% ± 2.52%, 71.72% ± 3.79%, 55.09 % ± 4.94% and 35.74% ± 4.05%, and the final scar area accounts for 47.80% ± 6.22% of the initial wound. While the wound area of BEWM at 1, 3, 7 and 10 days after the operation are respectively 61.94% ± 5.34%, 51.26% ± 4.89%, 12.63% ± 2.86% and 6.14% ± 2.84%, and the final scar area accounts for 4.33% ± 2.67% of the initial wound. Fractal analysis of the post-traumatic repair site for VEWM vs human was performed: lacunarity values, 0.040 ± 0.012 vs 0.038 ± 0.014; fractal dimension values, 1.870 ± 0.237 vs 1.903 ± 0.163. Sensory nerve function of normal skin vs post-traumatic repair site was assessed: mechanical threshold, 1.05 ± 0.52 vs 4.90 g ± 0.80; response rate to pinprick, 100% vs 71.67% ± 19.92%, and temperature threshold, 50.34°C ± 3.11°C vs 52.13°C ± 3.54°C., Conclusions: VEWM closely reflects the pathological features of human wound healing and can be applied for skin multiple-appendages regeneration and innervation evaluation., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To screen for Jk(a-b-) phenotype among blood donors from Jining area and explore its molecular basis to enrich the rare blood group bank for the region., Methods: The population who donated blood gratuitously at Jining Blood Center from July 2019 to January 2021 were selected as the study subjects. The Jk(a-b-) phenotype was screened with the 2 mol/L urea lysis method, and the result was confirmed by using classical serological methods. Exons 3 to 10 of the SLC14A1 gene and its flanking regions were subjected to Sanger sequencing., Results: Among 95 500 donors, urea hemolysis test has identified three without hemolysis, which was verified by serological method as the Jk(a-b-) phenotype and demonstrated no anti-Jk3 antibody. The frequency of the Jk(a-b-) phenotype in Jining area is therefore 0.0031%. Gene sequencing and haplotype analysis showed that the genotypes of the three samples were JK*02N.01/JK*02N.01, JK*02N.01/JK-02-230A and JK*02N.20/JK-02-230A, respectively., Conclusion: The splicing variant of c.342-1G>A in intron 4, missense variants of c.230G>A in exon 4, and c.647_ 648delAC in exon 6 probably underlay the Jk(a-b-) phenotype in the local population, which is different from other regions in China. The c.230G>A variant was unreported previously.

Aim: To develop a Head Nurse Research Leadership Scale and evaluate its reliability and validity., Design: A psychometric instrument validation study was conducted in two phases., Methods: The item tool was generated based on a literature review, semi-structured interview and brainstorming. Twenty experts validated the content of the initial version for two rounds. Thirty-nine clinical nurses conducted the HNRLS-v3 to test the readability of the items in pilot study I. Items were screened based on the critical ratio, correlation coefficient analysis, Cronbach's α coefficient and factor analysis using the data collected from 265 nurses in pilot study II. A cross-sectional survey was conducted in six hospitals to evaluate the reliability and validity between 4 January 2022 and 15 January 2022. Three hundred and sixteen nurses participated in this survey, and 60 completed the questionnaire to validate the test-retest reliability between 1 February and 6 February., Results: A 15-item Head Nurse Research Leadership Scale based on 5 dimensions was developed, and the content validity was satisfied. The 15 items accounted for 77.9% of the variance. Confirmatory factor analysis showed acceptable convergent validity and discriminant validity. The Cronbach's α coefficient, split-half reliability and test-retest reliability of the scale were 0.966, 0.9633 and 0.927, respectively., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

High-throughput lysis and proteolytic digestion of biopsy-level tissue specimens is a major bottleneck for clinical proteomics. Here we describe a detailed protocol of pressure cycling technology (PCT)-assisted sample preparation for proteomic analysis of biopsy tissues. A piece of fresh frozen or formalin-fixed paraffin-embedded tissue weighing ~0.1-2 mg is placed in a 150 μL pressure-resistant tube called a PCT-MicroTube with proper lysis buffer. After closing with a PCT-MicroPestle, a batch of 16 PCT-MicroTubes are placed in a Barocycler, which imposes oscillating pressure to the samples from one atmosphere to up to ~3,000 times atmospheric pressure. The pressure cycling schemes are optimized for tissue lysis and protein digestion, and can be programmed in the Barocycler to allow reproducible, robust and efficient protein extraction and proteolysis digestion for mass spectrometry-based proteomics. This method allows effective preparation of not only fresh frozen and formalin-fixed paraffin-embedded tissue, but also cells, feces and tear strips. It takes ~3 h to process 16 samples in one batch. The resulting peptides can be analyzed by various mass spectrometry-based proteomics methods. We demonstrate the applications of this protocol with mouse kidney tissue and eight types of human tumors., (© 2022. Springer Nature Limited.)

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods., (© 2022. The Author(s).)

Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction., (© 2022. The Author(s).)

Background: Large pulmonary valve perforation, which is rarely seen with infective endocarditis, general atrophy, or congenital fenestration, often leads to potentially fatal outcomes, including heart failure., Case Presentation: Transthoracic and transesophageal echocardiographic evaluation of a 69-year-old woman revealed a severely eccentric pulmonary regurgitation with concomitant pulmonary valve stenosis, patent ductus arteriosus, patent foramen ovale, and pulmonary artery aneurysm. In the operation, a large perforation was found in the pulmonary valve leaflet. She underwent complicated surgery that involved closure of the congenital heart defects and replacement of a pulmonary valve with successful results. But the cause of her pulmonary valve perforation remained undetermined., Conclusion: This case highlights two important points: the need for timely management of congenital heart disease and being aware of the possibility of pulmonary valve perforation, which in this case was indicated by an eccentric pulmonary regurgitant jet seen on echocardiography., (© 2022. The Author(s).)

Only a few work have been done for peptides from non-venom gland tissues of venomous animals. Here, with the help of the whole body transcriptomic and the hemolymph proteomic data of the Chinese scorpion Buthus martensii Karsch, we identified the first Ascaris-type peptide BmHDP from scorpion hemolymph. The precursor of BmHDP has 80 residues, including a 16 residue signal peptide and a 64 residue mature peptide. The mature peptide has 10 conserved cysteines and adopts a conserved Ascaris-type fold. Using combined inclusion body refolding and biochemical identification strategies, recombinant BmHDP was obtained successfully. Protease inhibitory assays showed that BmHDP inhibited chymotrypsin apparently at a concentration of 8 nM. Patch-clamp experiments showed that BmHDP inhibited the Kv1.3 potassium channel apparently at a concentration of 1000 nM. Coagulation experiment assays showed that BmHDP inhibited intrinsic coagulation pathway apparently at a concentration of 500 nM. To the best of our knowledge, BmHDP is the first Ascaris-type peptide from scorpion hemolymph. Our work highlighted a functional link between scorpion non-venom gland peptides and venom gland toxin peptides, and suggested that scorpion hemolymph might be a new source of bioactive peptides., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Here we describe a proteomic data resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry. We developed the DIA-expert software to curate and visualize the SWATH data, leading to reproducible detection of over 3,100 SwissProt proteotypic proteins and systematic quantification of pathway activities. Stoichiometric relationships of interacting proteins for DNA replication, repair, the chromatin remodeling NuRD complex, β-catenin, RNA metabolism, and prefoldins are more evident than that at the mRNA level. The data are available in CellMiner (discover.nci.nih.gov/cellminercdb and discover.nci.nih.gov/cellminer), allowing casual users to test hypotheses and perform integrative, cross-database analyses of multi-omic drug response correlations for over 20,000 drugs. We demonstrate the value of proteome data in predicting drug response for over 240 clinically relevant chemotherapeutic and targeted therapies. In summary, we present a novel proteome resource for the NCI-60, together with relevant software tools, and demonstrate the benefit of proteome analyses., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

A two-dimensional liquid chromatography (2D LC) system was developed to separate proteins from rice leaves, which was extracted by phenol method, followed by the analysis with linear trap quadrupole orbitrap mass spectrometry (LTQ/Orbitrap MS). After proteins were extracted with phenol method, the enzymolytic peptides were separated by offline two-dimensional RP-RP system and detected by LTQ/Orbitrap MS, yielding 2712 proteins. Liquid chromatography separation system (1D LC and 2D LC) and protein extraction methods (phenol method, sodium dodecyl sulfate method (SDS method) and trichloroacetic acid/acetone method (TCA/acetone method)) were compared. Proteins identified by 2D LC were 2712, 2415 and 1914 with the above three extraction methods, respectively. The proteins were 2.7-fold, 2.5-fold and 1.9-fold the number of proteins identified by 1D LC respectively. And in terms of 2D LC, the proteins identified by phenol method were 297 and 798 more than SDS method and TCA/acetone method, respectively. Some proteins with extreme properties, such as very acidic or basic protein and high relative molecular mass proteins, were only identified in phenol method. Furthermore, proteins, which were extracted by different extraction methods and separated by 2D LC, were classified according to biological functions. It was found that protein functions by the three extraction methods were complementary. However, phenol method had the most variety of functions. The method provides technological support for rice proteomics and reference for research techniques of other crop proteomics.

A method was developed for the determination of pyriminobac-methyl and bispyribac-sodium residues in rice by liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with modified QuEChERS. The samples were extracted with acidified acetonitrile, and then purified by octadecylsilane bonded silica (C 18 ) adsorbents. The analytes were separated on a ZORBAX SB C 18 column through a gradient elution using 0.1% (v/v) aqueous formic acid aqueous containing 5 mmol/L ammonium acetate and acetonitrile as mobile phases. Positive electrospray ionization (ESI + ) was used. Qualitative work was performed using selected dynamic multiple reaction monitoring (dynamic MRM) mode. Quantization was performed using external standard method. The results showed good linearities of pyriminobac-methyl and bispyribac-sodium with correlation coefficients ( r 2 ) not less than 0.996. The limits of detection (LODs) of the method were 0.8 μ g/kg for pyriminobac-methyl, and 3 μ g/kg for bispyribac-sodium. The mean spiked recoveries of pyriminobac-methyl and bispyribac-sodium at three spiked levels were 76.6%-85.6% and 73.0%-86.7%, respectively, and the relative standard deviations (RSDs) of pyriminobac-methyl and bispyribac-sodium were 0.9%-3.4% and 1.2%-5.5%, respectively. This method is simple, rapid, sensitive, and suitable for the simultaneous determination of pyriminobac-methyl and bispyribac-sodium in rice.

Objective: To explore the serological characteristics and molecular basis for an individual with para-Bombay phenotype., Methods: Blood type of the proband was determined with routine serological methods. Exons 6 and 7 of the ABO gene and coding regions of the FUT1 and FUT2 genes were amplified by PCR and sequenced., Results: The para-Bombay phenotype was confirmed to be of Ah-secretion type. The genotype of the individual was determined as A102/O01. Position 328 of the FUT1 gene was mutated from A to G, resulting in replacement of Alanine (Ala) at position 110 by Threonine (Thr)., Conclusion: The G to A mutation of nt328 of the FUT1 gene probably underlies the para-Bombay phenotype in this individual.

Aneurysms of the coronary sinus and superior vena cava are rare and their aetiologies remain controversial. Some studies have shown that these acquired venous aneurysms are caused by an increase in right atrial pressure, which may be related to right heart failure. However, few reports have provided direct evidence to support this hypothesis. We present a rare case of combined giant aneurysms of the coronary sinus and vena cava, diagnosed using multiple imaging modalities. This case strongly supports the hypothesis that right heart diastolic failure may be an important mechanism underlying the pathogenesis of combined giant aneurysms.

Purpose: To compare the merits and limitations of hematoxylin-eosin (HE) and methyl violet staining for displaying ghost cells from vitreous or aqueous humor., Methods: A specimen containing ghost cells was adjusted to five different concentrations: (12 x 10(4), 10 x 10(4), 8 x 10(4), 6 x 10(4) and 4 x 10(4) cells/ml) and subjected to smearing and methyl violet and HE staining. The staining results were observed by light microscopy., Results: The ghost cells were readily observed at a cell density of > 8 x 10(4) cells/ml with methyl violet staining, but only a few cells were occasionally seen at lower cell densities. In contrast, ghost cells were seen at all cell densities with HE staining., Conclusion: Methyl violet staining is more rapid and simpler for the identification of ghost cells, but its staining color more readily fades, the slides cannot be stored, and it is only effective at a cell density of > 8 x 10(4) cells/ml. In contrast, HE staining is more time-consuming but it can display cell morphology and distinguish cell components more explicitly and slides can be permanently stored. HE staining has advantages over methyl violet staining in detecting the ghost cells when the concentration is < 8 x 10(4) cells/ml.

A bisabolane sesquiterpene, rel-(1S,4R,5S,6R)-4,5-diacetoxy-6- [(R)-5-hydroxy-1,5-dimethylhex-3-enyl]- 3-methylcyclohex-2-enyl (Z)-2-methylbut-2 -enoate, which was newly isolated from the roots of Leontopodium longifolium, presented specific anticancer activity against human leukemia HL-60 cells, but did not inhibit proliferation of human hepatoma SMMC-7721 cells and human normal hepatocytes L02 cells. Nitroblue tetrazolium (NBT) reduction, phagocytosis of latex beads, and cell electrophoresis all demonstrated that this bisabolane sesquiterpene presented its anticancer activity against human leukemia HL-60 cells in vitro via inducing cell differentiation. Our results may have implications for treatment of human leukemia with the sesquiterpene.

The long QT syndrome gene human ether-a-go-go related gene (HERG) encodes a K(+) channel critical to cardiac repolarization. It peculiarly overexpresses in cancer cells of different histogenesis and promotes tumorigenesis. To decipher the molecular mechanisms for HERG overexpression, we identified and characterized the promoter region of the HERG gene, which contains cis-elements for multiple oncoproteins and tumor suppressors. Oncoprotein Sp1 was found to be essential to driving the HERG promoter thereby transcription. Another oncoprotein NF-kappaB transactivated, while tumor suppressor Nkx3.1 repressed HERG promoter activity and endogenous HERG transcription. Loss-of-function mutations in the corresponding cis-elements rendered a loss of the ability of the oncoproteins Sp1 and NF-kappaB to transactivate, and of the tumor repressor Nkx3.1 to repress, HERG transcription. Either activation of Sp1 and NF-kappaB or silencing of Nkx3.1 promoted tumor cell growth, and the effects were abrogated by HERG inhibition or knockdown, but facilitated by overexpression of HERG, indicating that HERG mediates the cell growth signals generated by activation of oncoproteins or inactivation of tumor suppressors. Binding of Sp1, NF-kappaB, and Nkx3.1 to their respective cis-elements in the HERG promoter in vitro and their presence on the HERG promoter in vivo were confirmed. Therefore, the HERG promoter region is characterized by multiple Sp1 binding sites that are responsible for transcription initiation of the HERG gene and by binding sites for multiple other oncogenes and tumor suppressor genes being important for regulating HERG expression. The HERG K(+) channel is likely a mediator of growth-promoting processes induced by oncoproteins and/or by silencing of tumor suppressors.

Congestive heart failure (CHF) is associated with susceptibility to lethal arrhythmias and typically increases levels of tumor necrosis factor-alpha (TNF-alpha) and its receptor, TNFR1. CHF down-regulates rapid delayed-rectifier K(+) current (I(Kr)) and delays cardiac repolarization. We studied the effects of TNF-alpha on cloned HERG K(+) channel (human ether-a-go-go-related gene) in HEK293 cells and native I(Kr) in canine cardiomyocytes with whole-cell patch clamp techniques. TNF-alpha consistently and reversibly decreased HERG current (I(HERG)). Effects of TNF-alpha were concentration-dependent, increased with longer incubation period, and occurred at clinically relevant concentrations. TNF-alpha had similar inhibitory effects on I(Kr) and markedly prolonged action potential duration (APD) in canine cardiomyocytes. Immunoblotting analysis demonstrated that HERG protein level was slightly higher in canine hearts with tachypacing-induced CHF than in healthy hearts, and TNF-alpha slightly increased HERG protein level in CHF but not in healthy hearts. In cells pretreated with the inhibitory anti-TNFR1 antibody, TNF-alpha lost its ability to suppress I(HERG), indicating a requirement of TNFR1 activation for HERG suppression. Vitamin E or MnTBAP (Mn(III) tetrakis(4-benzoic acid) porphyrin chloride), a superoxide dismutase mimic) prevented, whereas the superoxide anion generating system xanthine/xanthine oxidase mimicked, TNF-alpha-induced I(HERG) depression. TNF-alpha caused robust increases in intracellular reactive oxygen species, and vitamin E and MnTBAP abolished the increases, in both HEK293 cells and canine ventricular myocytes. We conclude that the TNF-alpha/TNFR1 system impairs HERG/I(Kr) function mainly by stimulating reactive oxygen species, particularly superoxide anion, but not by altering HERG expression; the effect may contribute to APD prolongation by TNF-alpha and may be a novel mechanism for electrophysiological abnormalities and sudden death in CHF.