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Abstract Quantitative structure–property relationships have been extensively studied in the field of predicting retention times in liquid chromatography (LC). However, making transferable predictions is inherently complex because retention times are influenced by both the structure of the molecule and the chromatographic method used. Despite decades of development and numerous published machine learning models, the practical application of predicting small molecule retention time remains limited. The resulting models are typically limited to specific chromatographic conditions and the molecules used in their training and evaluation. Here, we have developed a comprehensive dataset comprising over 10,000 experimental retention times. These times were derived from 30 different reversed-phase liquid chromatography methods and pertain to a collection of 343 small molecules representing a wide range of chemical structures. These chromatographic methods encompass common LC setups for studying the retention behavior of small molecules. They offer a wide range of examples for modeling retention time with different LC setups.

In this study, the effects of surface treatment namely electro-pulsing followed by laser shock peening (EP-LSP) on wear resistance properties of Ti–6Al–4V alloy are investigated. It was compared with samples treated solely with laser shock peening (LSP) and electro-pulsing treatment (EP) to investigate the effects of different processes on the friction and wear properties of Ti–6Al–4V alloy. In addition, the friction coefficient, wear rate, wear morphology were also investigated. Finally, the wear mechanism was described in detail. The results demonstrated a significant reduction in grain size for the samples after EP-1-LSP treatments. Furthermore, compared with the as-received samples, the maximum hardness of EP-1, LSP and EP-1-LSP treated samples increased by 6.5%, 5.9%, and 19.6%, respectively, and the compressive residual stress on the surface increased by 2.4%, 15.0%, and 37.2%, respectively. Under the same friction conditions, the depth of wear scar of the samples after EP-1, LSP, and EP-1-LSP treatments decreased by 7.2%, 10.6%, and 18.5% than that of the as-received sample. The as-received samples mainly exhibited severe oxidative and adhesive wear, and the LSP and EP-1 treated samples showed slight adhesive and oxidative wear. The EP-1-LSP treated samples predominantly showed signs of abrasive wear.

Abstract Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS–based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post–projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 35 external calibrants to eliminate the impact of LC setups on projection accuracy. Results showed that post–projection calibration consistently achieved a median projection error below 3.2% of the elution time. The ranking results of putative candidates reached similar levels among different CMs. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.

The high-temperature wear resistance plays an important role for Ti–6Al–4V alloy components working in extreme environments, especially vital for avoiding unexpected failure. However, the reasonable method of surface modification should meet the requirement of improving in wear resistance and less decreasing in mechanical properties simultaneously, which brings a great challenge. In the present research, the laser shock peening (LSP) technique was applied to optimize the superficial layer of Ti–6Al–4V alloy by different processing. The microstructure, elastic modulus, nano-hardness and high-temperature tribology properties of the LSP processed Ti–6Al–4V were investigated to reveal the improving effect. The results demonstrate the LSP processing transforms the dual-size grain structure to relative homogeneous grain structure and forms the gradient nano-structure in superficial layer. With the increasing of LSP processing numbers, the density of geometrically necessary dislocation (GND) decreases obviously, but the density of statistically stored dislocation (SSD) rises significantly, which promotes the increase of total dislocation density compared with the as-received (AR) alloy. Due to the crystal evolution, the Ti–6Al–4V alloy with three-times LSP processing has the lowest wear rate which is less than half of the as-received state. The observations on worn surface and adjacent cross-sectional microstructure reveal the severe scratching and many inner microcracks in the AR sample but the slight scraping and few inner microcracks in the three-times LSP processed sample. Considering the elevated nano-hardness and elastic modulus, the improved tribological properties should be mainly attributed to the optimized microstructure and dislocation state by LSP processing. The present research provides a more reasonable method to improve the high-temperature wear properties of Ti–6Al–4V alloy.

In recent decades, substantial advancements in epigenetics have unveiled a profound understanding of its mechanisms in tumorigenesis and have offered promising strategies for epigenetic therapy in cancer patients. In our study, through bioinformatics analysis, we discovered a significant downregulation and hypermethylation of FOXI2 in clear cell renal cell carcinoma (ccRCC), while the expression in chromophobe cell carcinoma (chRCC) exhibited the opposite trend. Moreover, we established a strong correlation between FOXI2 expression levels and the prognosis of ccRCC. Gene enrichment analysis and cell function experiments unequivocally demonstrate that FOXI2 possesses the capability to induce cell cycle arrest and inhibit cell proliferation.Our research findings demonstrate that the expression of FOXI2 in ccRCC is under the regulation of promoter hypermethylation. Furthermore, in vitro experiments have conclusively shown that the overexpression of FOXI2 induces cell cycle arrest and inhibits cell proliferation.

Welding processing is an important method to connect precision component, but the internal stress and crystal anisotropy reduce its performance, which are difficult to solve due to the specific demand on regional post-treatment. In the present research, the asynchronized laser shock peening (ALSP) and synchronized laser shock peening (SLSP) processing technologies were applied to treat the laser joined Ti–6Al–4V thin plates. The microstructure and mechanical properties of the as-welded joint, ALSP and SLSP processed joint were investigated. The results revealed that the as-welded joint presents obvious anisotropic characteristics, and high strain level exists on the prior β grain boundary, which causes stress concentration. The ultimate tensile strength (UTS) and elongation (EL) values of as-welded joint just reach the 92.18% and 72.33% of as-received plate, respectively. ALSP processing could result in the deformation with the depth more than ten microns and introduce compress stress in the top layer, but has little effect on decreasing the anisotropy. The grain boundary becomes obscure and the strain distribution is relatively uniform, accompanying with some dynamic recrystallized laths exist along the grain boundary. Its values of UTS and EL are 5.23% and 5.59% higher than as-welded joint, respectively. With the SLSP processing, the deformation depth exceeds twenty microns, and the crystal isotropy could be greatly promoted. Moreover, higher compressive stress is introduced from top layer to center area of joint. The grain boundary becomes obviously obscure, which is completely replaced by recrystallized lath structures. The residual strain in the top layer is partly eliminated, and the stress concentration phenomenon along grain boundary is dramatically decreased. The UTS and EL values are 6.16% and 20.58% higher than as-welded joint, and reach 97.86% and 87.22% of as-received plate, respectively.

Oligosaccharide is a new type of functional glycogen and widely used in the food field. β-glucooligosaccharides are kinds of oligosaccharides composed of 2~20 glucoses connected by β-glycosidic bonds, which are mainly prepared by the degradation from β-glucans with different methods. β-glucooligosaccharides possess characteristics of low molecular weight, good water solubility, unique structure and high absorption efficiency, resulting in many biological activities such as regulating intestinal flora, enhancing immunity and anti-tumor, etc. Therefore, they have a broad application prospect in food, health products, medicine and other fields. In order to promote the research and development of β-glucooligosaccharides, this paper reviews the recent studies on the degradation preparation, separation and purification, structural characterization and biological activity of β-glucooligosaccharides, which is expected to provide references for the further research and utilization of β-glucooligosaccharides.

BackgroundPrevious studies have shown that estrogen, kidney function, and homocysteine (Hcy) or hyperhomocysteinemia (HHcy) are related to each other. However, the underlying biological mechanisms still remain unclear. We aimed to explore the association between estradiol (E2) and HHcy in the female population, and to further evaluate the mediating role of renal function indicators.MethodsThis unmatched case–control study consisted of 1,044 female participants who were 60.60 ± 12.46 years old. Data on general demographic characteristics, such as age, smoking and drinking status, menopause and so on were collected in a personal interview, and laboratory examinations were performed by well-trained personnel. The mediating effect model was applied to analyze the direct and indirect effects of E2 on Hcy.ResultsThe average levels of Hcy and E2 of the participants were 12.6 μmol/L and 14.95 pg/ml. There were statistical differences in renal indexes blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), glomerular filtration rate (GFR) and E2 between HHcy group and non-HHcy group. The logistic regression models showed that UA was risk factor for HHcy (P

Abstract Background RNA‐binding motif protein 24 (RBM24) functions as a splicing regulator, which is critical for organ development and is dysregulated in human cancers. Here, we aim to uncover the biological function of RBM24 in colorectal tumourigenesis. Methods Xenograft tumour model, Rbm24 knockout and Apcmin/+ mouse models were utilised. Colorectal cancer cells overexpressing or silencing RBM24 were established. RNA immunoprecipitation (RIP) assay was conducted to detect protein‐RNA associations. Gene expression was measured by immunohistochemistry, western blotting, or quantitative PCR (qPCR). Results Rbm24‐knockout mice developed spontaneous colorectal adenomas with lower expression of phosphatase and tensin homolog (PTEN). Immunohistochemical staining for the proliferation markers Ki‐67 and pHH3 and BrdU assay showed intestinal hyperplasia in Rbm24‐knockout mice compared to wild‐type mice. RBM24 expression in colorectal adenoma tissues of Apcmin/+ mouse was downregulated compared with adjacent normal samples and was positively correlated with PTEN expression. In vitro, RBM24 overexpression suppressed cell proliferation, migration, invasion and increased sensitivity to 5‐FU or cisplatin in CRC cells. Mechanistically, RBM24 maintained PTEN mRNA stability by directly binding to the GT‐rich region at positions 8101–8251 in the 3′‐UTR of PTEN mRNA, prolonging the half‐life of PTEN mRNA, thereby increasing PTEN expression. Hence, low expression of RBM24 downregulated PTEN mRNA, causing the activation of PI3K‐Akt signalling in CRC cells. Furthermore, RBM24 expression in CRC tissues was lower than adjacent normal samples. RBM24 expression was positively correlated with PTEN expression and negatively correlated with Ki‐67 level. CRC patients with high RBM24 expression had a favourable outcome. Conclusions Taken together, RBM24 expression is markedly lower in colorectal tumours than in para‐carcinoma tissues. Rbm24‐knockout mice develop spontaneous colorectal adenomas. RBM24 directly binds and stabilises PTEN mRNA, which could cause the suppression of CRC cell proliferation, migration and invasion, thereby repressing colorectal tumourigenesis. These findings support the tumour‐suppressive role of RBM24. Targeting RBM24 holds strong promise for the diagnosis and treatment of CRC.

Self-renewal of embryonic stem cells (ESCs) is orchestrated by a vast number of genes at the transcriptional and translational levels. However, the molecular mechanisms of post-translational regulatory factors in ESC self-renewal remain unclear. Histidine phosphorylation, also known as hidden phosphorylation, cannot be detected by conventional experimental methods. A recent study defined phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) as a histidine phosphatase, which regulates various biological behaviors in cells via histidine dephosphorylation. In this study, the doxycycline (DOX)-induced hLHPP-overexpressing mouse ESCs and mouse LHPP silenced mESCs were constructed. Quantitative polymerase chain reaction (qPCR), western blotting analysis, immunofluorescence, Flow cytometry, colony formation assays, alkaline phosphatase (AP) and bromodeoxyuridine (Brdu) staining were performed. We found that the histidine phosphorylation level was strikingly reduced following LHPP overexpression. Besides, the expression of Oct4 and Lefty1, indispensable genes in the process of ESCs self-renewal, was significantly down-regulated, while markers related to the differentiation were markedly elevated. Moreover, LHPP-mediated histidine dephosphorylation induced G0/G1 phase arrest in mESCs, suggesting LHPP was implicated in cell proliferation and cell cycle. Conversely, silencing of Lhpp promoted the self-renewal of mESCs and reversed the RA induced increased expression of genes associated with differentiation. Mechanistically, our findings suggested that the enzymatic active site of LHPP was the cysteine residue at position 226, not 53. LHPP-mediated histidine dephosphorylation lowered the expression levels of β-catenin and the cell cycle-related genes CDK4 and CyclinD1, while it up-regulated the cell cycle suppressor genes P21 and P27. Taken together, our findings reveal that LHPP-mediated histidine dephosphorylation plays a role in the self-renewal of ESCs. LHPP-mediated histidine dephosphorylation inhibited the self-renewal of ESCs by negatively regulating the Wnt/β-catenin pathway and downstream cell cycle-related genes, providing a new perspective and regulatory target for ESCs self-renewal.

ObjectiveThe aim of this study was to detect the key changes during sit-to-stand (STS) movement cycle in hemiparetic stroke survivors using a five-phase kinematic and kinetic analysis.MethodsTwenty-five subacute stroke survivors and 17 age-matched healthy adults participated in this study. The kinematic and kinetic parameters during STS cycle were measured using three-dimensional motion analysis system with force plates. The five standard phases of STS cycle were identified by six timing transitional points.ResultsLonger total time as well as larger changes were observed at the initial phase (phase I, 0.76 ± 0.62 VS 0.43 ± 0.09 s; p = 0.049) and at the end of hip and knee extension phase (phase IV, 0.93 ± 0.41 VS 0.63 ± 0.14 s; p = 0.008) in the stroke group than healthy group. Time to maximal knee joint moment was significantly delayed in the stroke group than in the control group (1.14 ± 1.06 VS 0.60 ± 0.09 s, p

Studies have demonstrated that STAT3 is essential in maintaining self-renewal of embryonic stem cells (ESCs) and modulates ESC differentiation. However, there is still lack of direct evidence on STAT3 functions in ESCs and embryogenesis because constitutive STAT3 knockout (KO) mouse is embryonic lethal at E6.5–E7.5, prior to potential functional role in early development can be assessed. Therefore, in this study, two inducible STAT3 ESC lines were established, including the STAT3 knockout (InSTAT3 KO) and pSTAT3 overexpressed (InSTAT3 CA) using Tet-on inducible system in which STAT3 expression can be strictly controlled by doxycycline (Dox) stimulation. Through genotyping, deletion of STAT3 alleles was detected in InSTAT3 KO ESCs following 24 hours Dox stimulation. Western blot also showed that pSTAT3 and STAT3 protein levels were significantly reduced in InSTAT3 KO ESCs while dominantly elevated in InSTAT3 CA ECSs upon Dox stimulation. Likewise, it was found that STAT3-null ESCs would affect the differentiation of ESCs into mesoderm and cardiac lineage. Taken together, the findings of this study indicated that InSTAT3 KO and InSTAT3 CA ESCs could provide a new tool to clarify the direct targets of STAT3 and its role in ESC maintenance, which will facilitate the elaboration of the mechanisms whereby STAT3 maintains ESC pluripotency and regulates ESC differentiation during mammalian embryogenesis.