Genome-Wide Identification and Interaction Analysis of Turbot Heat Shock Protein 40 and 70 Families Suggest the Mechanism of Chaperone Proteins Involved in Immune Response after Bacterial Infection.

Hsp40-Hsp70 typically function in concert as molecular chaperones, and their roles in post-infection immune responses are increasingly recognized. However, in the economically important fish species Scophthalmus maximus (turbot), there is still a lack in the systematic identification, interaction models, and binding site analysis of these proteins. Herein, 62 Hsp40 genes and 16 Hsp70 genes were identified in the turbot at a genome-wide level and were unevenly distributed on 22 chromosomes through chromosomal distribution analysis. Phylogenetic and syntenic analysis provided strong evidence in supporting the orthologies and paralogies of these HSPs. Protein-protein interaction and expression analysis was conducted to predict the expression profile after challenging with Aeromonas salmonicida. dnajb1b and hspa1a were found to have a co-expression trend under infection stresses. Molecular docking was performed using Auto-Dock Tool and PyMOL for this pair of chaperone proteins. It was discovered that in addition to the interaction sites in the J domain, the carboxyl-terminal domain of Hsp40 also plays a crucial role in its interaction with Hsp70. This is important for the mechanistic understanding of the Hsp40-Hsp70 chaperone system, providing a theoretical basis for turbot disease resistance breeding, and effective value for the prevention of certain diseases in turbot.

The mediating role of nutritional care literacy on the relationship between self-directed learning ability and nursing competence.

BACKGROUND: Nurses' nursing competence and nutritional care literacy directly affect patients' health and safety. Self-directed learning ability was pervasive throughout the entire work process of nursing work and was the basis for improving both. However, there are few studies has explored the mechanism from the perspective of nutritional care literacy. The purpose of this study was to analyze the relationship between self-directed learning ability and nursing competence, and to explore the mediating role of nutritional care literacy between self-directed learning and nursing competence among clinical nurses in China. METHODS: A cross-sectional survey was conducted among 805 clinical nurses recruited from seven general hospitals in Hunan Province, China, between January 25 and March 6, 2022. The self-directed learning ability, nutritional care literacy and nursing competence of nurses were evaluated through investigation. A total of 799 questionnaires were received, resulting in an response rate of 99.25%.We performed an intermediary modeling to examine the mediating roles of nutritional care literacy on the relationship between self-directed learning ability and nursing competence in clinical nurses. RESULTS: Self-directed learning ability was positively correlated with nutritional care  literacy (r=0.792, P<0.001) and nursing competence (r=0.696, P<0.001). Nutritional care literacy was positively correlated with nursing competence (r=0.658, P<0.001). Nutritional care literacy mediated the relationship between self-directed learning ability and nursing competence. The mediating effect accounted for 32.48% of the total effect and 48.10% of the direct effect . CONCLUSIONS: This study confirmed the positive correlation between self-directed learning ability, nutritional care literacy, and nursing competence. Nutritional care  literacy played a mediating role in the relationship between self-directed learning ability and nursing competence. The findings not only provide a novel strategy for cultivating nursing professionals and improving nurse disease care abilities, but also offer a new perspective for nursing educators and managers.

A pathway activity-based proteomic classifier stratifies prostate tumors into two subtypes.

Prostate cancer (PCa) is the second most common cancer in males worldwide. The risk stratification of PCa is mainly based on morphological examination. Here we analyzed the proteome of 667 tumor samples from 487 Chinese PCa patients and characterized 9576 protein groups by PulseDIA mass spectrometry. Then we developed a pathway activity-based classifier concerning 13 proteins from seven pathways, and dichotomized the PCa patients into two subtypes, namely PPS1 and PPS2. PPS1 is featured with enhanced innate immunity, while PPS2 with suppressed innate immunity. This classifier exhibited a correlation with PCa progression in our cohort and was further validated by two published transcriptome datasets. Notably, PPS2 was significantly correlated with poor biochemical recurrence (BCR)/metastasis-free survival (log-rank P-value < 0.05). The PPS2 was also featured with cell proliferation activation. Together, our study presents a novel pathway activity-based stratification scheme for PCa.

Secondary Metabolites Produced by Coculture of Pleurotus ostreatus SY10 and Pleurotus eryngii SY302.

A new isovaleryl-monoterpene, pleurotusin A (1), and a new cyclopentenone derivative, pleurotusin B (7), together with five related known terpenoids (2-6), were isolated from the coculture broth of two edible fungi, Pleurotus ostreatus SY10 and Pleurotus eryngii SY302. The absolute configurations of 1 and 7 were elucidated by comprehensively using the density functional theory calculation of NMR and ECD data, DP4+ probability analysis, Mo2 (OAc)4 -based CD experiment and optical rotation. The antimicrobial activities of these compounds except for the unstable compound 7, were evaluated against two types of human-pathogenic fungi, Candida albicans and Cryptococcus neoformans, and three types of human-pathogenic bacteria, Staphylococcus aureus, Escherichia coli, and Shigella sp. Compound 1 displayed moderate activity against S. aureus with an MIC50 value of 90.3 µM. In addition, the antioxidant activities of high-yielding 2-6 were tested using DPPH, and compound 4 showed moderate activity with an EC50 value of 573 µM.

Near Miss Research in the Healthcare System: A Scoping Review.

OBJECTIVES: The aim of this study was to depict a comprehensive description of near miss research and clarify research gaps. BACKGROUND: Learning from near miss can provide early warnings and is critical for proactive and prospective risk management. Because of the lack of structured reviews, there is little knowledge about how near miss management has been managed in the past. METHODS: This review was conducted following the Arksey and O'Malley's methodology and reported by the PRISMA Extension for Scoping Reviews. RESULTS: Sixty-seven research articles were included. The results revealed that the most investigated fields include near miss reporting, near miss characteristics, and good catch project. Poor theoretical investigation, underreporting, and inconsistent outcome indicators are major problems. CONCLUSIONS: Solely understanding causes of near misses cannot guarantee effective learning; we also need to apply appropriate learning theories. Advanced technologies should be applied to solve long-standing underreporting issues. Accurate and consistent indicators should be applied in near miss research and management.

Near-miss organizational learning in nursing within a tertiary hospital: a mixed methods study.

BACKGROUND: Near-miss organizational learning is important for perspective and proactive risk management. Although nursing organizations are the largest component of the healthcare system and act as the final safety barrier, there is little research about the current status of near-miss organizational learning. Thus, we conducted this study to explore near-miss organizational learning in a Chinese nursing organization and offer suggestions for future improvement. METHODS: This was a mixed methods study with an explanatory sequence. It was conducted in a Chinese nursing organization of a tertiary hospital under the guidance of the 4I Framework of Organizational Learning. The quantitative study surveyed 600 nurses by simple random sampling. Then, we applied purposive sampling to recruit 16 nurses across managerial levels from low-, middle- and high-scored nursing units and conducted semi-structured interviews. Descriptive statistics, structured equation modelling and content analysis were applied in the data analysis. The Good Reporting of A Mixed Methods Study (GRAMMS) checklist was used to report this study. RESULTS: Only 33% of participants correctly recognized near-misses, and 4% of participants always reported near-misses. The 4I Framework of Organizational Learning was verified in the surveyed nursing organization (χ2 = 0.775, p = 0.379, RMSEA < 0.01). The current organizational learning behaviour was not conducive to near-miss organizational learning due to poor group-level learning (ßGG = 0.284) and poor learning absorption (ßMisalignment= -0.339). In addition, the researchers developed 13 codes, 9 categories and 5 themes to depict near-miss organizational learning, which were characterized by nurses' unfamiliarity with near-misses, preferences and the dominance of first-order problem-solving behaviour, the suspension of near-miss learning at the group level and poor learning absorption. CONCLUSION: The performance of near-miss organizational learning is unsatisfactory across all levels in surveyed nursing organization, especially with regard to group-level learning and poor learning absorption. Our research findings offer a scientific and comprehensive description of near-miss organizational learning and shed light on how to measure and improve near-miss organizational learning in the future.

Critical cultural competence of clinical nurses in China: A cross-sectional survey.

AIM: To determine the level of critical cultural competence (CCC) among Chinese clinical nurses and explore its influencing factors. BACKGROUND: Previous research has only focused on the theoretical model of CCC and the development of assessment tools; however, no large-scale study has been conducted on the level of clinical nurses' CCC and its influencing factors. METHOD: Clinical nurses in 14 Level A tertiary hospitals (n = 3858) were surveyed using Almutairi's critical cultural competence scale (CCCS). Descriptive, univariate and multivariate analyses were performed. RESULTS: The mean score of CCC was 4.44 (SD = 0.33). Critical empowerment (M = 4.85, SD = 0.58) and critical awareness (M = 3.57, SD = 0.99) had the highest and lowest scores, respectively. Female nurses, nurses in the nursing department and nurses with higher positions had higher CCC. CONCLUSION: The CCC of clinical nurses can be strengthened through targeted training, especially considering the fact that male and low-ranking nurses who had the lower level of CCC work in different departments. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators should pay attention to the importance of culture and cultural differences among different countries or ethnic groups. Creating an equal and fair nursing environment and encouraging nurses to provide critical cultural nursing is important.

The SR Splicing Factors: Providing Perspectives on Their Evolution, Expression, Alternative Splicing, and Function in Populus trichocarpa.

Serine/arginine-rich (SR) proteins are important splicing factors in plant development and abiotic/hormone-related stresses. However, evidence that SR proteins contribute to the process in woody plants has been lacking. Using phylogenetics, gene synteny, transgenic experiments, and RNA-seq analysis, we identified 24 PtSR genes and explored their evolution, expression, and function in Popolus trichocarpa. The PtSR genes were divided into six subfamilies, generated by at least two events of genome triplication and duplication. Notably, they were constitutively expressed in roots, stems, and leaves, demonstrating their fundamental role in P. trichocarpa. Additionally, most PtSR genes (~83%) responded to at least one stress (cold, drought, salt, SA, MeJA, or ABA), and, especially, cold stress induced a dramatic perturbation in the expression and/or alternative splicing (AS) of 18 PtSR genes (~75%). Evidentially, the overexpression of PtSCL30 in Arabidopsis decreased freezing tolerance, which probably resulted from AS changes of the genes (e.g., ICE2 and COR15A) critical for cold tolerance. Moreover, the transgenic plants were salt-hypersensitive at the germination stage. These indicate that PtSCL30 may act as a negative regulator under cold and salt stress. Altogether, this study sheds light on the evolution, expression, and AS of PtSR genes, and the functional mechanisms of PtSCL30 in woody plants.

Nurses' Grief Counseling for Bereaved Family Members of COVID-19 Patients in Wuhan, China: A Cross-Sectional Survey.

This is the first study to assess nurses' attitudes and skills regarding grief counseling for bereaved family members of patients who died from coronavirus disease 2019 (COVID-19) in Wuhan, China. Using a cross-sectional design, 412 nurses selected through convenience sampling completed a demographic characteristics survey, Attitudes of Grief Counseling Scale, (AGCS) and Skills of Grief Counseling Scale (SGCS). Average AGCS score was 32.89 (SD = 9.46), with an overall percentage rate score of 65.6%. Factors influencing attitudes toward grief counseling included other grief counseling skills, educational level, communication skills, and training related to grief counseling (p < 0.05). Average SGCS score was 18.81 (SD = 4.25), with an overall percentage rate score of 58.7%. Factors influencing skills of grief counseling included responsibilities and roles, frequency of contact with the bereaved, and positive view of grief counseling (p < 0.05). Nurses' attitudes and skills regarding grief counseling were low, indicating an urgent need to improve grief counseling. [Journal of Psychosocial Nursing and Mental Health Services, 59(11), 18-24.].

Inflammatory indexes are not associated with sarcopenia in Chinese community-dwelling older people: a cross-sectional study.

BACKGROUND: Inflammatory indexes (platelet-to-lymphocyte ratio [PLR], neutrophil-to-lymphocyte ratio [NLR], and lymphocyte-to-monocyte ratio [LMR]) are recently supposed to be the biomarkers of sarcopenia. We aimed to validate the association between these inflammatory indexes and sarcopenia in Chinese community-dwelling older people. METHODS: We consecutively recruited community-dwelling older adults aged 60 years or older. The neutrophil, lymphocyte, monocyte, and platelet counts, and C-reactive protein (CRP) were tested using standard methods. Sarcopenia was defined according to different criteria: the Asian Working Group for Sarcopenia (AWGS), the updated version of AWGS (AWGS 2019), the European Working Group on Sarcopenia in Older People (EWGSOP), the updated version of EWGSOP (EWGSOP2), the International Working Group on Sarcopenia (IWGS), and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). Multiple logistic regression analysis was performed. RESULTS: We included 384 participants. A total of 61 participants (15.9%) were diagnosed with sarcopenia according to the AWGS criteria. There was no significant difference in PLR, NLR, LMR, and CRP between the sarcopenia group and the non-sarcopenia group regardless of the diagnostic criteria. No significant association between PLR, NLR, LMR, and AWGS-defined sarcopenia was found (PLR per 1- standard deviation [SD]: adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.82 to 1.45; NLR per 1-SD: adjusted OR 0.96, 95% CI 0.71 to 1.30; LMR per 1-SD: adjusted OR 1.01, 95% CI 0.74 to 1.38). Similar results were found when sarcopenia was defined by different criteria and when PLR, NLR, LMR were treated as categorical variables. CONCLUSIONS: Our study did not support the utility of the inflammatory indexes (NLR, PLR, and LMR) as the biomarkers of sarcopenia in Chinese community-dwelling older people. However, considering the inflammatory indexes can be simply calculated from a routine blood test, further studies in different populations remain warranted.

Unusual and Highly Bioactive Sesterterpenes Synthesized by Pleurotus ostreatus during Coculture with Trametes robiniophila Murr.

Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 µg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis.IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.

Metabolic engineering of Methylobacterium extorquens AM1 for the production of butadiene precursor.

BACKGROUND: Butadiene is a platform chemical used as an industrial feedstock for the manufacture of automobile tires, synthetic resins, latex and engineering plastics. Currently, butadiene is predominantly synthesized as a byproduct of ethylene production from non-renewable petroleum resources. Although the idea of biological synthesis of butadiene from sugars has been discussed in the literature, success for that goal has so far not been reported. As a model system for methanol assimilation, Methylobacterium extorquens AM1 can produce several unique metabolic intermediates for the production of value-added chemicals, including crotonyl-CoA as a potential precursor for butadiene synthesis. RESULTS: In this work, we focused on constructing a metabolic pathway to convert crotonyl-CoA into crotyl diphosphate, a direct precursor of butadiene. The engineered pathway consists of three identified enzymes, a hydroxyethylthiazole kinase (THK) from Escherichia coli, an isopentenyl phosphate kinase (IPK) from Methanothermobacter thermautotrophicus and an aldehyde/alcohol dehydrogenase (ADHE2) from Clostridium acetobutylicum. The Km and kcat of THK, IPK and ADHE2 were determined as 8.35 mM and 1.24 s-1, 1.28 mM and 153.14 s-1, and 2.34 mM and 1.15 s-1 towards crotonol, crotyl monophosphate and crotonyl-CoA, respectively. Then, the activity of one of rate-limiting enzymes, THK, was optimized by random mutagenesis coupled with a developed high-throughput screening colorimetric assay. The resulting variant (THKM82V) isolated from over 3000 colonies showed 8.6-fold higher activity than wild-type, which helped increase the titer of crotyl diphosphate to 0.76 mM, corresponding to a 7.6% conversion from crotonol in the one-pot in vitro reaction. Overexpression of native ADHE2, IPK with THKM82V under a strong promoter mxaF in M. extorquens AM1 did not produce crotyl diphosphate from crotonyl-CoA, but the engineered strain did generate 0.60 µg/mL of intracellular crotyl diphosphate from exogenously supplied crotonol at mid-exponential phase. CONCLUSIONS: These results represent the first step in producing a butadiene precursor in recombinant M. extorquens AM1. It not only demonstrates the feasibility of converting crotonol to key intermediates for butadiene biosynthesis, it also suggests future directions for improving catalytic efficiency of aldehyde/alcohol dehydrogenase to produce butadiene precursor from methanol.

Expression, purification and guanine nucleotide binding characterization of Arabidopsis RabE1d13-185 GTPase.

Arabidopsis RabE1d subclass plays important plant-specific functions in plant growth and development, response to ethylene and defence to plant pathogen, besides their basic cellular role in membrane trafficking. In this study, we present the expression, purification, and characterization of the recombinant core domain of AtRabE1d13-185. AtRabE1d13-185 was successfully expressed in Escherichia coli and purified via two-step nickel affinity chromatography followed by gel filtration, and identified single band in SDS-PAGE. The resultant protein was functionally active, as determined by interaction with guanine nucleotide by a fluorescence-based assay. The intrinsic tryptophan of AtRabE1d13-185 showed fluorescence resonance energy transfer (FRET) effect upon forming complex with fluorescent methylanthraniloyl (mant)-GDP, but quenched when binding with non-labelled guanine nucleotide. The association rate of mantGDP with AtRabE1d13-185 was determined to be 3.48 × 10(7) s(-1) M(-1). The dissociation rates of GDP and mantGDP from the complex with AtRabE1d13-185 were similar. The koff values were determined to be 4.02 × 10(-4) s(-1) based on the FRET effect for the AtRabE1d13-185:GDP and 5.41 × 10(-4) s(-1) for mantGDP excited directly.

Multi-target anti-diabetic styrylpyrones from Phellinus igniarius: Inhibition of α-glucosidase, protein glycation, and oxidative stress.

Bioactivity screening revealed that the EtOAc extract from the culture broth of Phellinus igniarius SY489 exhibited remarkable α-glucosidase inhibitory activity, with an IC50 value of 1.92 µg/mL. Activity- and ultraviolet (UV) profile-guided isolation led to the discovery of four anti-diabetic styrylpyrones (1-4), including two novel compounds, phelignidins A (1) and B (2). Compounds 1 and 2 represent a rare structural type of styrylpyrone dimer, in which one of the pyrone moieties exists in an open-ring state. The absolute configurations of the new compounds 1 and 2, as well as the previously unresolved compound 3, were established. Compounds 1-4 were effective in α-glucosidase inhibition, anti-glycation, and antioxidant assays, surpassing or being comparable to the positive control drugs, with minimal cytotoxicity. Furthermore, studies on α-glucosidase inhibition mechanisms suggested that these compounds interact with α-glucosidase at a single binding site, causing secondary structure unfolding and exerting inhibitory activity via a mixed-type mechanism. These results provide an important basis for developing novel, low-toxicity, multi-target anti-diabetic drugs from edible and medicinal fungi.

Multi-scale microstructural construction in ultralight graphene aerogels enables super elasticity and unprecedented durability for impact protection materials.

Ultralight graphene aerogels have gained extensive recognition in the impact protection field. However, attaining both elasticity and durability at low material density is challenging due to their intrinsic conflicts. Inspired by the mantis ootheca, we present a simultaneous improvement in the elasticity, durability, and density restrictions of ultralight graphene aerogels via constructing a multiscale honeycomb microstructure (MHM) within the graphene skeleton. This approach enables resulting graphene aerogel to achieve a strength per unit volume of 284.6 cm3 mg-1, the ability to recover its shape within 10 ms after an impact at 3.569 m/s, and maintain 97.2 % of its sample height after 20,000 cycles at 90 % strain. The operand analyses and calculation results reveal that the MHM structure facilitates this aerogel's dual-stage stress transfer pathway. Initially, the macroscale honeycomb structure (millimeter-scale) of the graphene aerogels bear and transmit stress to the surrounding regions, followed by the microscale honeycomb structure (micron-scale) deformation to convert stress kinetic energy into elastic potential energy. This two-stage stress transition mechanism of the MHM structure can effectively mitigate excessive local stress and suppress strain localization, thus providing remarkable elasticity and durability. Ultimately, the obtained graphene aerogel demonstrates promising applications as a fall height detection device and impact protective material.

Discovery of New Antimicrobial Metabolites in the Coculture of Medicinal Mushrooms.

Bioactivity screening revealed that the antifungal activities of EtOAc extracts from coculture broths of Trametes versicolor SY630 with either Vanderbylia robiniophila SY341 or Ganoderma gibbosum SY1001 were significantly improved compared to that of monocultures. Activity-guided isolation led to the discovery of five aromatic compounds (1-5) from the coculture broth of T. versicolor SY630 and V. robiniophila SY341 and two sphingolipids (6 and 7) from the coculture broth of T. versicolor SY630 and G. gibbosum SY1001. Tramevandins A-C (1-3) and 17-ene-1-deoxyPS (6) are new compounds, while 1-deoxyPS (7) is a new natural product. Notably, compound 2 represents a novel scaffold, wherein the highly modified p-terphenyl bears a benzyl substituent. The absolute configurations of those new compounds were elucidated by X-ray diffraction, ECD calculations, and analysis of physicochemical constants. Compounds 1, 2, and 5-7 exhibited different degrees of antimicrobial activity, and the antifungal activities of compounds 6 and 7 against Candida albicans and Cryptococcus neoformans are comparable to those of fluconazole, nystatin, and sphingosine, respectively. Transcriptome analysis, propidium iodide staining, ergosterol quantification, and feeding assays showed that the isolated sphingolipids can extensively downregulate the late biosynthetic pathway of ergosterol in C. albicans, representing a promising mechanism to combat antibiotic-resistant fungi.

Deciphering the role of female reproductive tract microbiome in reproductive health: a review.

Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

An individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma.

Pediatric papillary thyroid carcinomas (PPTCs) exhibit high inter-tumor heterogeneity and currently lack widely adopted recurrence risk stratification criteria. Hence, we propose a machine learning-based objective method to individually predict their recurrence risk. We retrospectively collect and evaluate the clinical factors and proteomes of 83 pediatric benign (PB), 85 pediatric malignant (PM) and 66 adult malignant (AM) nodules, and quantify 10,426 proteins by mass spectrometry. We find 243 and 121 significantly dysregulated proteins from PM vs. PB and PM vs. AM, respectively. Function and pathway analyses show the enhanced activation of the inflammatory and immune system in PM patients compared with the others. Nineteen proteins are selected to predict recurrence using a machine learning model with an accuracy of 88.24%. Our study generates a protein-based personalized prognostic prediction model that can stratify PPTC patients into high- or low-recurrence risk groups, providing a reference for clinical decision-making and individualized treatment.

Forager-farmer transition at the crossroads of East and Southeast Asia 4900 years ago.

The southward expansion of East Asian farmers profoundly influenced the social evolution of Southeast Asia by introducing cereal agriculture. However, the timing and routes of cereal expansion in key regions are unclear due to limited empirical evidence. Here we report macrofossil, microfossil, multiple isotopic (C/N/Sr/O) and paleoproteomic data directly from radiocarbon-dated human samples, which were unearthed from a site in Xingyi in central Yunnan and which date between 7000 and 3300 a BP. Dietary isotopes reveal the earliest arrival of millet ca. 4900 a BP, and greater reliance on plant and animal agriculture was indicated between 3800 and 3300 a BP. The dietary differences between hunter-gatherer and agricultural groups are also evident in the metabolic and immune system proteins analysed from their skeletal remains. The results of paleoproteomic analysis indicate that humans had divergent biological adaptations, with and without farming. The combined application of isotopes, archaeobotanical data and proteomics provides a new approach to documenting dietary and health changes across major subsistence transitions.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.