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Enzyme kinetic parameters (kcat, Km, and kcat/Km) are fundamental for quantifying catalytic efficiency and substrate specificity in biochemistry and drug discovery. However, experimental determination is resource intensive, and accurate prediction remains a persistent challenge due to the complex spatial nature of catalysis. In this paper, we present UniKineG, a novel deep learning framework that redefines kinetic prediction by modeling the explicit spatial state of enzyme–substrate complexes. Unlike conventional methods that treat proteins and ligands as isolated modalities, UniKineG employs molecular docking to embed both entities into a unified 3D coordinate system. Within this shared geometric context, we utilize a heterogeneous graph neural network integrated with geometric vector perceptrons (GVPs) to capture intricate vector-based interactions, such as directional hydrogen bonds, hydrophobic contacts, and electrostatic complementarity. This structure-based approach confers exceptional robustness: UniKineG effectively overcomes the dependency on high-sequence homology, demonstrating superior generalization on out-of-distribution (OOD) datasets encompassing both unseen enzyme sequences and diverse substrate scaffolds. Consistently outperforming state-of-the-art predictors, UniKineG achieves high-precision predictions. This work establishes a solid foundation for understanding enzyme–small molecule interactions in 3D space and offers a transformative tool for computational enzymology.

Background/ObjectivesThe results linking body iron stores to the risk of gestational diabetes mellitus (GDM) are conflicting. We aimed to measure the serum ferritin level of women in early pregnancy and evaluate the risk of GDM in a Chinese urban population.Subjects/MethodsIn total, 851 pregnant women between 10 and 20 weeks of gestation took part in the prospective, observational study conducted. The women were divided into four groups by quartiles of serum ferritin levels (Q1–4). Their blood samples were collected and assayed for several biochemical variables at the beginning of the study, and the women were followed up with a 75-g oral glucose tolerance test at 24–28 weeks of gestation.ResultsThe participants had an average serum ferritin concentration of 65.67 μg/L. GDM prevalence within each serum ferritin quartile was 9.4%, 14.6%, 18.8% and 19.3%, respectively, (P = 0.016). The odds ratio for GDM in the ferritin Q2–4 was 1.64 (CI: 0.90–2.99), 2.23 (CI: 1.26–3.96) and 2.31 (CI: 1.30–4.10), compared with Q1, respectively. This association persisted after adjusting for potential confounders factors. In addition, in Q4, pregnant women with a pre-pregnancy body mass index ≥24 kg/m2, maternal age ≤35 years old or haemoglobin≥ 110 g/L did have an increased risk of developing GDM.ConclusionsElevated serum ferritin concentrations in early gestation are associated with an increased risk of GDM, especially in pregnant women who have a high baseline iron storage status with no anaemia or who are overweight/obese. Individual iron supplementation should be considered to minimize the risk of GDM.

Skeletal muscle provides inspiration on how to achieve reversible, macroscopic, anisotropic motion in soft materials. Here we report on the bottom-up design of macroscopic tubes that exhibit anisotropic actuation driven by a thermal stimulus. The tube is built from a hydrogel in which extremely long supramolecular nanofibers are aligned using weak shear forces, followed by radial growth of thermoresponsive polymers from their surfaces. The hierarchically ordered tube exhibits reversible anisotropic actuation with changes in temperature, with much greater contraction perpendicular to the direction of nanofiber alignment. We identify two critical factors for the anisotropic actuation, macroscopic alignment of the supramolecular scaffold and its covalent bonding to polymer chains. Using finite element analysis and molecular calculations, we conclude polymer chain confinement and mechanical reinforcement by rigid supramolecular nanofibers are responsible for the anisotropic actuation. The work reported suggests strategies to create soft active matter with molecularly encoded capacity to perform complex tasks. Skeletal muscles are impressive as they can achieve reversible, macroscopic, anisotropic motion in soft materials. Here the authors show a bottom-up design of macroscopic hydrogel tubes containing supramolecular nanofibers that can undergo anisotropic actuation by thermal stimuli.

Background NAD (P) H: quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues. However, high-level expression of NQO1 has been correlated with numerous human malignancies, suggesting a role in carcinogenesis and tumor progression. This study aimed to explore the clinicopathological significance of NQO1 and as a prognostic determinant in breast cancer. Methods A total of 176 breast cancer patients with strict follow-up, 45 ductal carcinoma in situ (DCIS), 22 hyperplasia and 52 adjacent non-tumor breast tissues were selected for immunohistochemical staining of NQO1 protein. Immunofluorescence staining was also performed to detect the subcellular localization of NQO1 protein in MCF-7 breast cancer cells. Eight fresh breast cancers paired with adjacent non-tumor tissues were quantified using real time RT-PCR (qRT-PCR) and western blot. The correlations between NQO1 overexpression and the clinical features of breast cancer were evaluated using chi-square test and Fisher’s exact tests. The survival rate was calculated using the Kaplan–Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazards models. Results NQO1 protein showed a mainly cytoplasmic staining pattern in breast cancer. The strongly positive rate of NQO1 protein was 61.9% (109/176) in breast cancer, and was significantly higher than in DCIS (31.1%, 14/45), hyperplasia tissues (13.6%, 3/22) and adjacent non-tumor tissues (13.5%, 7/52). High-level expression of NQO1 protein was correlated with late clinical stage, poor differentiation, lymph node metastasis, Her2 expression and disease-free and 10-year overall survival rates in breast cancer. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer. Conclusions High-level expression of NQO1 appears to be associated with breast cancer progression, and may be a potential biomarker for poor prognostic evaluation of breast cancers.

Valproic acid (VPA) constitutes a branched-chain, short-chain fatty acid that serves as an antiepileptic medication. It has been increasingly recognized that VPA has presented potential anti-tumor properties, including breast cancer. However, the exploration of novel breast cancer treatment methods necessitates a more comprehensive and in-depth understanding of the novel mechanism of VPA inhibition of breast cancer. It has been proven that farnesyl-diphosphate farnesyltransferase 1 (FDFT1) participate in oncogenesis and development of cancers. However, the effect of FDFT1 on breast cancer is still obscure. Thus, it is important to investigate the potential of VPA to trigger ferroptosis in breast cancer cells via targeting FDFT1. In this study, the underlying mechanisms of VPA on ferroptosis in breast cancer cells were explored in vitro and vivo. Initially, the effects of VPA on the proliferation of breast cancer cells were assessed utilizing the Cell Counting Kit-8, cell counting, and colony formation assays. Subsequently, the ferroptosis in breast cancer cells treated with VPA were determined through the use of the Lipid Peroxidation malondialdehyde Assay Kit, reduced glutathione and oxidized glutathione disulfide Assay Kit, flow cytometry, transmission electron microscopy, and western bloting. To explore the impact of VPA in combination with ferrostatin-1, Erastin or RSL3, on MDA-MB-231 cell proliferation and ferroptosis, respective CCK-8, colony formation and WB assays were conducted. Thereafter, we assessed whether VPA facilitated ferroptosis in MDA-MB-231 cells by modulating the expression of FDFT1. Finally, the anti-breast cancer effects of VPA in vivo were validated through a xenograft mouse model, and histological examination via hematoxylin-eosin staining and immunohistochemistry staining were employed to delve into the underlying mechanisms of VPA's inhibitory effects on breast cancer cells in vivo. The assay outcomes indicated that VPA impedes the proliferation of breast cancer cells. The findings from the ferroptosis index demonstrated that MDA-MB-231 cells are more sensitive to VPA induced ferroptosis than MCF-7 cells. Subsequent to the introduction of ferrostatin-1 (Fer-1), Erastin or RSL3, it was observed that Fer-1 reversed the ferroptosis facilitated by VPA, whereas Erastin or RSL3, in conjunction with VPA, respectively, induced ferroptosis in MDA-MB-231 cells. We revealed that the downregulation of FDFT1 enhanced proliferation and inhibited ferroptosis of MDA-MB-231 cells. Additionally, we discovered that VPA may facilitate ferroptosis in MDA-MB-231 cells by negatively modulating the levels of the solute carrier family 7 member 11 (SLC7A11) protein through the upregulation of FDFT1 expression. In conclusion, this study elucidated that VPA induced the ferroptosis of MDA-MB-231 cells via targeting FDFT1, representing a novel mechanism underlying its efficacy in potentially inhibiting breast cancer.

Different microorganisms can produce different proteases, which can adapt to different industrial requirements such as pH, temperature, and pressure. Salt-tolerant proteases (STPs) from microorganisms exhibit higher salt tolerance, wider adaptability, and more efficient catalytic ability under extreme conditions compared to conventional proteases. These unique enzymes hold great promise for applications in various industries including food, medicine, environmental protection, agriculture, detergents, dyes, and others. Scientific studies on microbial-derived STPs have been widely reported, but there has been little systematic review of microbial-derived STPs and their application in high-salt conventional soybean fermentable foods. This review presents the STP-producing microbial species and their selection methods, and summarizes and analyzes the salt tolerance mechanisms of the microorganisms. It also outlines various techniques for the isolation and purification of STPs from microorganisms and discusses the salt tolerance mechanisms of STPs. Furthermore, this review demonstrates the contribution of modern biotechnology in the screening of novel microbial-derived STPs and their improvement in salt tolerance. It highlights the potential applications and commercial value of salt-tolerant microorganisms and STPs in high-salt traditional soy fermented foods. The review ends with concluding remarks on the challenges and future directions for microbial-derived STPs. This review provides valuable insights into the separation, purification, performance enhancement, and application of microbial-derived STPs in traditional fermented foods.

Background There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. Methods The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Participants’ demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. Results In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. Conclusions In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

Hyperlipidemia is a chronic disorder that is difficult to cure and usually treated with long-term lipid-reducing drugs. Recent trends have led to the use of diet therapies or food-derived strategies in the treatment of such long-term diseases. The Chinese rice wine (huangjiu) contains a wide range of bioactive peptides that are produced during the multi-species fermentation process. To clarify the regulation effects of lipid metabolism and gut microbiota by huangjiu bioactive peptides, three huangjiu peptides were isolated, purified and characterized by hyper-filtration, macroporous resin, gel filtration separation and structural identification. Meanwhile, a mouse model of high-fat diet-induced hyperlipidemia was established to study the effects of huangjiu peptides on serum biomarker, hepatic metabolism and gut microbiota dysbiosis. Experimental results showed that huangjiu peptides T1 and T2 (HpT1, HpT2) treatment alleviated the increase in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol levels and aberrant hepatic lipid accumulation in the high-fat diet-induced hyperlipidemia mice. Furthermore, HpT2 and HpT1 restored the α -diversity and structure of gut microbial community after hyperlipidemia-induced microbiota disturbance compared with simvastatin and HpT3. The administration of HpT2 and HpT1 regulated the microbiota-mediated gut ecology through alterations of characteristic taxa including Lactobacillus , Ileibacterium , Faecalibaculum and Alloprevotella by linear discriminant analysis effect size analysis. Collectively, our results offer new insights into the abilities of food-derived peptides on alleviation of high-fat diet-induced hyperlipidemia, hepatic steatosis and gut dysbiosis in mice.

Huangjiu is rich in low-molecular-weight peptides and has an umami taste. In order for its umami peptides to be discovered, huangjiu was subjected to ultrafiltration, ethanol precipitation, and macroporous resin purification processes. The target fractions were gathered according to sensory evaluation. Subsequently, we used peptidomics to identify the sum of 4158 peptides in most umami fractions. Finally, six novel umami peptides (DTYNPR, TYNPR, SYNPR, RFRQGD, NFHHGD, and FHHGD) and five umami-enhancing peptides (TYNPR, SYNPR, NFHHGD, FHHGD, and TVDGPSH) were filtered via virtual screening, molecular docking, and sensory verification. Moreover, the structure–activity relationship was discussed using computational approaches. Docking analysis showed that all umami peptides tend to bind with T1R1 through hydrogen bonds and hydrophobic forces, which involve key residues HIS71, ASP147, ARG151, TYR220, SER276, and ALA302. The active site calculation revealed that the positions of the key umami residues D and R in the terminal may cause taste differences in identified peptides.

Background Fetal growth restriction (FGR) is a major determinant of perinatal morbidity and mortality. Our study aimed to develop a prediction model for the risk of FGR developing adverse perinatal outcome (APO) and evaluate its performance. Methods This was a prospective observational cohort study of consecutive singleton gestations meeting the ACOG-endorsed criteria for FGR from January 2022 to June 2023 at Obstetrics and Gynecology Hospital of Fudan University. Clinical information, ultrasound indicators and serum biomarkers were collected. The primary composite APO comprised one or more of: perinatal death, intrauterine demise, intraventricular hemorrhage, periventricular leukomalacia, seizures, necrotizing enterocolitis, neonatal respiratory distress syndrome, sepsis and the length of stay in the neonatal intensive care unit  >  7 days. Least absolute shrinkage and selection operator regression was used to screen variables for nomogram model construction. The discrimination, calibration and clinical effectiveness of the nomogram were evaluated using receiver operating characteristic curve, calibration plots and decision curve analysis in training and validation cohorts. Results A total of 122 pregnancies were enrolled in the final statistical analysis. Five variables were identified to establish a nomogram, including gestational weeks at diagnosis, abnormal umbilical artery Doppler, abnormal uterine artery Doppler, and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The area under the receiver-operating-characteristics curve of 0.87 (95% CI, 0.75–0.99) and 0.86 (95% CI, 0.74–0.98) in the training and validation cohort respectively, indicated satisfactory discriminative ability of the nomogram. The calibration plots showed favorable consistency between the nomogram’s predictions and actual observations. Decision curve analysis supported its practical value in a clinical setting. Conclusions A nomogram was developed and validated to possess the promising capacity of predicting APO in FGR-afflicted neonates, and may prove useful in counseling and management of pregnancies complicated by FGR.