Role of steroid receptor-associated and regulated protein in tumor progression and progesterone receptor signaling in endometrial cancer.

BACKGROUND: Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC. METHODS: Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection. RESULTS: Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A (WNT7A) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP-overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate. CONCLUSIONS: This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.

Iridium-Catalyzed Asymmetric Allylic Substitution Reaction of 4-Hydroxypyran-2-one.

Pyranones have raised great concerns owing to their considerable applications in a variety of sectors. However, the development of direct asymmetric allylation of 4-hydroxypyran-2-ones is still restricted. Herein, we present an effective iridium-catalyzed asymmetric functionalization technique for the synthesis of 4-hydroxypyran-2-one derivatives over direct and efficient catalytic asymmetric Friedel-Crafts-type allylation by using allyl alcohols. The allylation products could be obtained with good to high yields (up to 96%) and excellent enantioselectivities (>99% ee). Therefore, the disclosed technique provides a new asymmetric synthetic strategy to explore pyranone derivatives in depth, thus providing an interesting approach for global application and further utilization in organic synthesis and pharmaceutical chemistry.

Comparative analysis of whey proteins in yak milk from different breeds in China using a data-independent acquisition proteomics method.

Yak milk is rich in essential milk proteins of nutritional and therapeutic value. In this study, whey proteins of milk from 3 yak breeds (Gannan, GN; Huanhu, HH; Maiwa, MW) in China were comprehensively identified and compared using a data-independent acquisition quantitative proteomics approach. A total of 632 proteins were identified in yak milk whey samples, in which immune-related proteins were abundant. Compared with other milks, more proteins were involved in oxidation-reduction process and with ATP binding. In addition, we identified 96, 155, and 164 differentially expressed proteins (DEP) for GN versus HH, GN versus MW, and HH versus MW, respectively. "Phagosome" and "complement and coagulation cascades" were the most significant pathways for DEP of GN versus HH and GN or HH versus MW yak milk based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein-protein interaction network analysis showed that DEP for the 3 comparisons had significant biological interactions but were associated with different functions. The results provide useful information on yak milk from different breeds in China, and elucidate the biological functions of yak milk proteins.

Network toxicology prediction and molecular docking-based strategy to explore the potential toxicity mechanism of Metformin chlorination byproducts in drinking water.

BACKGROUND: Metformin (MET), a worldwide used drug for treating type 2 diabetes but not metabolized by humans, has been found with the largest amount in the aquatic environment. Two MET chlorination byproducts, including Y and C, were transformed into drinking water during chlorination. However, the potential toxicity of the byproducts in hepatotoxicity and reproduction toxicity remains unclear. METHODS: The TOPKAT database predicted the toxicological properties of metformin disinfection by-products. The targets of metformin disinfection by-products were mainly obtained from the PharmMapper database, and then the targets of hepatotoxicity and reproductive toxicity were screened from GeneCards. The overlapping targets of toxic component targets and the hepatotoxicity or reproduction toxicity targets were regarded as the key targets. Then, the STRING database analyzed the key target to construct a protein-protein interaction network (PPI) and GO, and KEGG analysis was performed by the DAVID platform. Meanwhile, the PPI network and compound-target network were constructed by Cytoscape 3.9.1. Finally, Discovery Studio 2019 software was used for molecular docking verification of the two toxic compounds and the core genes. RESULTS: Y and C exhibited hepatotoxicity, carcinogenicity, and mutagenicity evaluated by TOPKAT. There were 22 potential targets relating to compound Y and hepatotoxicity and reproduction toxicity and 14 potential targets relating to compound C and hepatotoxicity and reproduction toxicity. PPI network analysis showed that SRC, MAPK14, F2, PTPN1, IL2, MMP3, HRAS, and RARA might be the key targets; the KEGG analysis indicated that compounds Y and C caused hepatotoxicity through Hepatitis B, Pathways in cancer, Chemical carcinogenesis-reactive oxygen species, Epstein-Barr virus infection; compound Y and C caused reproduction toxicity through GnRH signaling pathway, Endocrine resistance, Prostate cancer, Progesterone-mediated oocyte maturation. Molecular docking results showed that 2 compounds could fit in the binding pocket of the 7 hub genes. CONCLUSION: This study preliminarily revealed the potential toxicity and possible toxicity mechanism of metformin disinfection by-products and provided a new idea for follow-up research.

Synthetic Self-adjuvanted Lipopeptide Vaccines Conferred Protection Against Helicobacter pylori Infection.

Helicobacter pylori colonize the stomach epithelium of half the world's population and are responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against Helicobacter pylori infection depends primarily on the specific mucosal and T cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern recognition receptors such as TLR, NLR and RLR, and but also stimulate BMDCs to secret cytokines that have the potential to modulate T cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicited robust epitope-specific T cell responses in mice, only Hp10 confers protection against Helicobacter pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against Helicobacter pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T cell and mucosal antibody responses. Our results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against Helicobacter pylori infection. This article is protected by copyright. All rights reserved.

Laser Electrochemical Deposition Hybrid Preparation of an Oil-Water Separation Mesh with Controllable Pore Diameter Based on a BP Neural Network.

With the increasing problem of water pollution, oil-water separation technology has attracted widespread attention worldwide. In this study, we proposed laser electrochemical deposition hybrid preparation of an oil-water separation mesh and introduced a back-propagation (BP) neural network model to realize the regulation of metal filter mesh. Among them, the coating coverage and electrochemical deposition quality were improved by laser electrochemical deposition composite processing. Based on the BP neural network model, the pore size after electrochemical deposition could be obtained only by inputting the processing parameters into the model, enabling the prediction and control of the pore size of the processed stainless-steel mesh (SSM), and the maximum residual difference between the predicted value and the experimental value was 1.5%. According to the oil-water separation theory and practical requirements, the corresponding electrochemical deposition potential and electrochemical deposition time were determined by the BP neural network model, which reduced the cost and time loss. In addition, the prepared SSM was found to achieve efficient separation of oil and water mixtures, reaching 99.9% separation efficiency in a combination with oil-water separation, along with other performance tests without chemical modification. The prepared SSM showed good mechanical durability and the separation efficiency exceeded 95% after sandpaper abrasion, thus, still maintaining the separation ability of oil-water mixture. Compared to other similar preparation methods, the method proposed in this study has the advantages of controllable pore size, simplicity, convenience, environmental friendliness, and durable wear resistance, offering important application potential in the treatment of oily wastewater.

Combined Transcriptome and Metabolome Analysis Reveals Adaptive Defense Responses to DON Induction in Potato.

Phytophthora infestans poses a serious threat to potato production, storage, and processing. Understanding plant immunity triggered by fungal elicitors is important for the effective control of plant diseases. However, the role of the potato stress response to Fusarium toxin deoxynivalenol (DON)-induced stress is still not fully understood. In this study, the metabolites of DON-treated potato tubers were studied for four time intervals using UPLC-MS/MS. We identified 676 metabolites, and differential accumulation metabolite analysis showed that alkaloids, phenolic acids, and flavonoids were the major differential metabolites that directly determined defense response. Transcriptome data showed that differentially expressed genes (DEGs) were significantly enriched in phenylpropane and flavonoid metabolic pathways. Weighted gene co-expression network analysis (WGCNA) identified many hub genes, some of which modulate plant immune responses. This study is important for understanding the metabolic changes, transcriptional regulation, and physiological responses of active and signaling substances during DON induction, and it will help to design defense strategies against Phytophthora infestans in potato.

Parallel genome-wide CRISPR screens to identify state-dependent self-renewal regulators of mouse embryonic stem cells.

The pluripotency of embryonic stem cells (ESCs) is more accurately viewed as a continuous developmental process rather than a fixed state. However, the factors that play general or state-specific roles in regulating self-renewal in different pluripotency states remain poorly defined. In this study, parallel genome-wide CRISPR/Cas9 knockout (KO) screens were applied in ESCs cultured in the serum plus LIF (SL) and in the 2i plus LIF (2iL) conditions. The candidate genes were classified into seven groups based on their positive or negative effects on self-renewal, and whether this effect was general or state-specific for ESCs under SL and 2iL culture conditions. We characterized the expression and function of genes in these seven groups. The loss of function of novel pluripotent candidate genes Usp28, Zfp598, and Zfp296 was further evaluated in mouse ESCs. Consistent with our screen, the knockout of Usp28 promotes the proliferation of SL-ESCs and 2iL-ESCs, whereas Zfp598 is indispensable for the self-renewal of ESCs under both culture conditions. The cell phenotypes of Zfp296 KO ESCs under SL and 2iL culture conditions were different. Our work provided a valuable resource for dissecting the molecular regulation of ESC self-renewal in different pluripotency states.

Gastric juice non-coding RNAs as potential biomarkers for gastric cancer.

Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.

Photostable Cascade Activatable Peptide Self-assembly on a Cancer Cell Membrane for High-Performance Identification of Human Bladder Cancer.

Missed or residual tumor burden results in high risk for bladder cancer relapse. However, existing fluorescent probes cannot meet the clinical needs because of inevitable photobleaching properties. Performance could be improved by maintaining intensive and sustained fluorescence signals via resistance to intraoperative saline flushing and intrinsic fluorescent decay, providing surgeons with sufficiently clear and high-contrast surgical fields, avoiding residual tumors or missed diagnosis. This study designs and synthesizes a photostable cascade-activatable peptide, a target reaction-induced aggregation peptide (TRAP) system, which can construct polypeptide-based nanofibers in situ on the cell membrane to achieve long-term and stable imaging of bladder cancer. The probe has two parts: a target peptide (TP) targets CD44v6 to recognize bladder cancer cells, and a reaction-induced aggregation peptide (RAP) was introduced and effectively reacted with TP via a click reaction to enhance the hydrophobicity of the whole molecule, assembling into nanofibers and further nanonetworks. Accordingly, probe retention on the cell membrane was prolonged, and photostability was significantly improved. Finally, the TRAP system is successfully employed in the high-performance identification of human bladder cancer in ex vivo bladder tumor tissues. This cascade-activatable peptide molecular probe based on the TRAP system enables efficient and stable imaging of bladder cancer. This article is protected by copyright. All rights reserved.

Promoted Skin Wound Healing by Tail-Amputated Eisenia foetida Proteins via the Ras/Raf/MEK/ERK Signaling Pathway.

Skin wound healing is an important fundamental problem in biological and medical fields. This study aimed to investigate wound healing promotion of protein extract from tail-amputated Eisenia foetida (E. foetida) and reveal the mechanism correlated with the Ras/Raf/MEK/ERK signaling pathway. Proteins extracted from tail-amputated E. foetida were applied on rats' full-thickness excisional wounds to evaluate their regenerative efficacy. Rat skin tissues around surgical defects were analyzed by immunofluorescence staining and Western blot methods. The Ras/Raf/MEK/ERK signaling pathway was further investigated in vitro using the NIH3T3 cell line. A tail-amputated protein extract (ES2) from E. foetida significantly accelerated rat wound healing ability via higher re-epithelialization and ECM deposition in the tissue section compared to the blank control and un-amputated earthworm extract groups. Furthermore, ES2 treatment dramatically accumulated the expressions of platelet-derived growth factor (PDGF), transforming growth factor-ß (TGF-ß), and hydroxyproline (HYP) in wound areas on day 7 without their accumulation on day 21 post-wounding, diminishing excessive scar formation. Accelerated wound healing ability with the ES2 was proved to correlate with the up-regulation of the Ras/Raf/MEK/ERK signaling pathway. The mRNA expression of this pathway increased significantly in NIH3T3 cells after being treated with the ES2 at an appropriate concentration. The tail-amputated E. foetida proteins (ES2) can significantly promote skin wound healing better than the un-amputated earthworm tissue extract without excessive scar tissue formation. This effect was related to the up-regulation of the Ras/Raf/MEK/ERK signaling pathway.

High-level and reusable preparation of sulforaphane by yeast cells expressing myrosinase.

Myrosinase is a key tool for the fast and efficient preparation of sulforaphane which is one of the prominent natural ingredients found in brassicaceous vegetables. Here, the glucoraphanin-hydrolyzing activity of a Yarrowia lipolytica 20-8 harboring myrosinase reached 73.28 U/g dry cell weight, indicating that it had a potential application in sulforaphane preparation from glucoraphanin. An efficient and reusable process for sulforaphane preparation via myrosinase produced by Y. lipolytica 20-8 was constructed. In detail, as high as 10.32 mg sulforaphane could be produced from 1 g broccoli seed under the reaction of 40 U yeast whole-cell catalyst within 15 min with the conversion efficiency of 99.86%. Moreover, when the yeast whole-cell catalyst was reused 7 and 10 times, as high as 92.53% and 87.56% of sulforaphene yield of the initial level could be retained, respectively. Therefore, this yeast whole-cell is a potent biocatalyst for the efficient and reusable preparation of sulforaphane.

Echocardiography E/A Abnormality is Associated with the Development of Primary Left Ventricle Remodeling in Middle-Aged and Elderly Women: A Longitudinal Study.

Background: Impaired left ventricular (LV) relaxation is indicative of grade I diastolic dysfunction, which is mainly assessed by late diastolic transmitral flow velocity (E/A ratio). Although the E/A ratio has important diagnostic and prognostic implications with cardiac outcomes, the causal link between abnormal E/A ratio and left ventricle remodeling (LV remodeling) remains unclear. Methods: A longitudinal analysis of 869 eligible women aged ≥45 years, who had received echocardiography scans as well as 5-year follow-up assessments between 2015 and 2020. Women with pre-existing cardiac abnormalities including grade II/III diastolic dysfunction as diagnosed by echocardiography, or structural heart disease were excluded. E/A abnormality was defined as baseline E/A ratio <0.8. The classification of LV remodeling was based on the measurements of left ventricular mass index (LVMI) and relative wall thickness (RWT). Logistic and linear regression models were used. Results: Among the 869 women (60.71±10.01 years), 164 (18.9%) had developed LV remodeling after the 5-year follow-up. The proportion of women with E/A abnormality versus non-abnormality was also significantly different (27.13% vs 16.59%, P=0.007). Multivariable-adjusted regression models showed that E/A abnormality (OR: 4.14, 95%Cl:1.80-9.20, P=0.009) was significantly associated with higher risk of concentric hypertrophy (CH) after follow-up. No such association was found in either concentric remodeling (CR) or eccentric hypertrophy (EH). Higher baseline E/A ratio was correlated with lower ΔRWT during the 5-year follow-up (ß=-0.006 m/s, 95% CI: -0.012 to -0.002, P=0.025), which was independent of demographics and biological factors. Conclusion: E/A abnormality is associated with a higher risk of CH. Higher baseline E/A ratio may be associated with decreased relative changes in RWT.

Context-dependent responses of terrestrial invertebrates to anthropogenic nitrogen enrichment: A meta-analysis.

Anthropogenic increases in nitrogen (N) concentrations in the environment are affecting plant diversity and ecosystems worldwide, but relatively little is known about N impacts on terrestrial invertebrate communities. Here, we performed an exploratory meta-analysis of 4365 observations from 126 publications reporting on the richness (number of taxa) or abundance (number of individuals per taxon) of terrestrial arthropods or nematodes in relation to N addition. We found that the response of invertebrates to N enrichment is highly dependent on both species' traits and local climate. The abundance of arthropods with incomplete metamorphosis, including agricultural pest species, increased in response to N enrichment. In contrast, arthropods exhibiting complete or no metamorphosis, including pollinators and detritivores, showed a declining abundance trend with increasing N enrichment, particularly in warmer climates. These contrasting and context-dependent responses may explain why we detected no overall response of arthropod richness. For nematodes, the abundance response to N enrichment was dependent on mean annual precipitation and varied between feeding guilds. We found a declining trend in abundance with N enrichment in dry areas and an increasing trend in wet areas, with slopes differing between feeding guilds. For example, at mean levels of precipitation, bacterivore abundance showed a positive trend in response to N addition while fungivore abundance declined. We further observed an overall decline in nematode richness with N addition. These N-induced changes in invertebrate communities could have negative consequences for various ecosystem functions and services, including those contributing to human food production.

El aumento de las concentraciones de nitrógeno en el medio ambiente de forma antropogénica está afectando a la diversidad vegetal y a los ecosistemas de todo el mundo, pero aún se sabe relativamente poco sobre su impacto en comunidades de invertebrados terrestres. En este trabajo realizamos modelos meta-analíticos para explorar el efecto del enriquecimiento de nitrógeno en comunidades de invertebrados terrestres a escala global. Para ello, utilizamos una base de datos proveniente de 4.365 observaciones pareadas correspondientes a 126 publicaciones que estudiaron el efecto del enriquecimiento de nitrógeno en la riqueza (número de taxones) y/o abundancia (número de individuos por taxón) de artrópodos y/o nematodos. Encontramos que la respuesta de los invertebrados al enriquecimiento de nitrógeno depende en gran medida tanto de los rasgos de las especies como del clima local. La abundancia de artrópodos con metamorfosis incompleta, incluyendo especies que pueden crear plagas agrícolas, aumentó en respuesta al enriquecimiento de nitrógeno. Por el contrario, los artrópodos con metamorfosis completa o nula, incluidos polinizadores y detritívoros, mostraron una tendencia negativa de su abundancia con respecto al aumento de nitrógeno, especialmente en climas más cálidos. Además, no detectamos una respuesta general de la riqueza de artrópodos posiblemente por la variabilidad en respuestas observadas, tanto negativas como positivas. En el caso de los nematodos, la respuesta de sus abundancias al enriquecimiento de nitrógeno fue dependiente de la precipitación media anual y de su grupo trófico. En general, observamos una respuesta negativa de la abundancia de nematodos al enriquecimiento de nitrógeno en zonas secas y una tendencia positiva en zonas más húmedas, pero además los diferentes grupos tróficos estudiados presentaron diferentes respuestas. Por ejemplo, la abundancia de bacterívoros mostró una tendencia positiva en respuesta al enriquecimiento de nitrógeno bajo niveles medios de precipitación, mientras que la abundancia de fungívoros disminuyó. Además, observamos un descenso general de la riqueza de nematodos con más enriquecimiento de nitrógeno. Estos cambios inducidos por el nitrógeno en las comunidades de invertebrados podrían tener consecuencias negativas para diversas funciones y servicios de los ecosistemas, incluyendo aquellos que contribuyen a la producción de alimentos.

Influence of resective extent of epileptogenic tuber on seizure outcome in patients with tuberous sclerosis complex-related epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to identify whether tuberectomy and tuberectomy plus are associated with different postoperative seizure outcomes in patients with tuberous sclerosis complex (TSC) -related epilepsy. METHODS: Electronic databases (PubMed, Embase, Cochrane, Proquest, Web of Science, Scopus, Biosis Previews) were searched without date restriction. Retrospective cohort studies of participants with TSC-associated epilepsy undergoing resective surgery that reported demographics, presurgical evaluation, extent of resection and postoperative seizure outcomes were included. Title, abstract and the full text were checked independently and in duplicate by two reviewers. Disagreements were resolved through discussion. One author extracted data which was verified by a second author using identified common standard in advance, including using a risk of bias tool we agreed on to evaluate study quality. RESULTS: Five studies, with a total of 327 participants, were included. One hundred and sixty patients received tuberectomy, and 93 of them (58.1%) achieved postoperative seizure freedom, while the other 167 patients underwent tuberectomy plus, and 128 of them (76.6%) achieved seizure freedom after adequate follow-ups (RR=0.72, 95% CI [0.60, 0.87], P<0.05). Subgroup analysis found that 40 of 63 (63.5%) patients after tuberectomy and 66 of 78 (84.6%) patients after tuberectomy plus of a single tuber achieved seizure freedom (RR = 0.71, 95% CI [0.56,0.91], P<0.05). In the multituber subrgroup, 16 of 42 (38.1%) and 21 of 31 (67.7%) patients achieved seizure freedom, after tuberectomy and tuberectomy plus, respectively (RR = 0.57, 95% CI [0.32,1.03], P = 0.06). CONCLUSIONS: Tuberectomy plus is a more effective treatment than tuberectomy for patients with TSC-related intractable epilepsy.

Construction of a prognostic model of acute myeloid leukemia associated with immunogenic cell death.

BACKGROUND: Immunogenic cell death (ICD)is a kind of regulatory cell death, which causes a series of antigen-specific adaptive immune responses by generating and emitting some danger signals or damage-associated molecular patterns (DAMPs). At present, little is known about the prognostic value of ICD and its related processes in acute myeloid leukemia (AML). The aim of the study was to explore the relationship between ICD and tumor immune microenvironment changes in AML. RESEARCH DESIGN & METHODS: In the study, AML samples were divided into two groups by consensus clustering analysis, and then gene enrichment analysis and GSEA analysis were performed on the ICD high expression group. Furthermore, CIBERSORT was used to analyze the tumor microenvironment and immune characteristics of AML. Finally, a prognostic model related to ICD was constructed by using univariate and multivariate regression analysis. RESULTS: ICD was divided into two groups according to the level of ICD gene expression. The ICD high expression group was associated with good clinical results and high levels of immune cell infiltration. CONCLUSIONS: The study constructed and verified the prognostic characteristics of AML related to ICD, which has important value in predicting the overall survival time of AML patients.

Effects and impacts of technical processing units on the nutrients and functional components of fruit and vegetable juice.

Fruit and vegetable juice (FVJ) has become a favorite beverage for all age groups because of its excellent sensory and nutritional qualities. FVJ has a series of health benefits such as antioxidant, anti-obesity, anti-inflammatory, anti-microbial and anti-cancer. Except for raw materials selection, processing technology and packaging and storage also play a vital role in the nutrition and functional components of FVJ. This review systematically reviews the important research results on the relationship between FVJ processing and its nutrition and function in the past 10 years. Based on the brief elucidation of the nutrition and health benefits of FVJ and the unit operation involved in the production process, the influence of a series of key technology units, including pretreatment, clarification, homogenization, concentration, sterilization, drying, fermentation and packaging and storage, on the nutritional function of FVJ was systematically expounded. This contribution provides an update on the impacts of technical processing units on the nutrients and functional components of FVJ and new perspectives for future studies.

Quantification of Free Short-Chain Fatty Acids in Raw Cow Milk by Gas Chromatography-Mass Spectrometry.

Free short-chain fatty acids (FSCFAs) are a momentous contributor to the flavor of the raw cow milk. Hence, the purpose of this research was to build an approach for the quantification of 10 FSCFAs in raw cow milk. Raw cow milk samples are acidified by hydrochloric acid ethanol (0.5%) solution pretreatment and then processed on the gas chromatography-mass spectrometry. With the exception of iso C5:0 and anteiso C5:0 co-flux, the remaining eight FSCFAs were effectively separated by chromatography. The methodological validation data revealed that the linear relationship satisfied the assay requirements (coefficient of determination >0.999), the limits of quantification were 0.167 to 1.250 µg mL-1, the recoveries ranged from 85.62% to 126.42%, the coefficients of variation were 1.40~12.15%, and no SCFAs in the triglyceride form were potential degradation, and the precision ranging from 0.56% to 9.09%. Our easy, fast, and robust method successfully determined three FSCFAs in raw cow milk without derivatization. Some characteristic features of FSCFAs have been discovered in raw cow milk such as its higher percentages of C4:0 and C6:0. Our research has provided a very valuable method for the future quality and safety control of raw milk and nutritional studies.

Enhancement Mechanism of Pt/Pd-Based Catalysts for Oxygen Reduction Reaction.

The oxygen reduction reaction (ORR) is one of the key catalytic reactions for hydrogen fuel cells, biofuel cells and metal-air cells. However, due to the complex four-electron catalytic process, the kinetics of the oxygen reduction reaction are sluggish. Platinum group metal (PGM) catalysts represented by platinum and palladium are considered to be the most active ORR catalysts. However, the price and reserves of Pt/Pd are major concerns and issues for their commercial application. Improving the catalytic performance of PGM catalysts can effectively reduce their loading and material cost in a catalytic system, and they will be more economical and practical. In this review, we introduce the kinetics and mechanisms of Pt/Pd-based catalysts for the ORR, summarize the main factors affecting the catalytic performance of PGMs, and discuss the recent progress of Pt/Pd-based catalysts. In addition, the remaining challenges and future prospects in the design and improvement of Pt/Pd-based catalysts of the ORR are also discussed.

Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells.

Prostate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies.