Toxicological safety assessment of a water extract of Lithocarpus litseifolius by a 90-day repeated oral toxicity study in rats.

Lithocarpus litseifolius although known as "Sweet Tea" (ST), has been traditionally accepted as a daily beverage and used as a folk medicine in southern China with little understanding of its potential toxicity. This study evaluated the safety of a water extract of ST by a subchronic toxicity study in Sprague-Dawley rats. A total of 80 rats were randomized divided into 4 groups with 10 males and 10 females in each group, treated with 2000, 1,000, 500 and 0 mg/kg body weight of ST extract by gavage for 90 days, respectively. The results of the study showed that ST extract did not induce treatment-related changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine indices, and histopathology in rats. The NOAEL of ST extract was observed to be 2000 mg/kg/day for rats of both sexes. These results indicated that ST extract was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer.

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer types. Despite extensive efforts, the absence of a druggable active site for small molecules has rendered these mutants therapeutically non-actionable. Here we develop a selective and effective proteolysis-targeting chimera (PROTAC) for p53-R175H, a common hotspot mutant with dominant-negative and oncogenic activity. Using a novel iterative molecular docking-guided post-SELEX (systematic evolution of ligands by exponential enrichment) approach, we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for p53-R175H. Leveraging this resulting aptamer as a binder for PROTACs, we successfully developed a selective p53-R175H degrader, named dp53m. dp53m induces the ubiquitin-proteasome-dependent degradation of p53-R175H while sparing wildtype p53. Importantly, dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo, without toxicity. Moreover, dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin, a commonly used chemotherapy drug. These findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

Case report: Novel NUS1 variant in a Chinese patient with tremors and intellectual disability.

Introduction: Nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) gene variants are associated with a range of phenotypes, including epilepsy, intellectual disability, cerebellar ataxia, Parkinson's disease, dystonia, and congenital disorders of glycosylation. Additionally, cases describing genotypes and clinical features are rare. Case Presentation: Herein, we report the case of a 23-year-old Chinese female patient who presented with tremors, intellectual disability, and epilepsy. A history of carbon monoxide exposure, brain trauma, or encephalitis was not present in this case. Trio whole-exome sequencing analysis revealed a de novo pathogenic variant of c.750del in exon 4, leading to p.Leu251* amino acid substitution. Genetic analysis failed to identify the identical mutations in the remaining family members who underwent screening. The patient was diagnosed with a rare congenital disease, "congenital glycosylation disorder, type 1aa, autosomal dominant, type 55, with seizures (MRD-55)." Conclusion: We provide further evidence for the role of variants in NUS1 in the development of tremors, epilepsy, and intellectual disabilities. These findings expand our understanding of the clinical phenotypes of NUS1 variants.

Correlation between blood inflammatory indices and carotid intima-media thickness in the middle-aged and elderly adults.

OBJECTIVES: This study aimed to investigate the correlations between carotid intima-media thickness (IMT) and systemic immune inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte (NLR) ratio. MATERIALS AND METHODS: This was a cross-sectional study enrolling a total of 582 middle-aged and elderly patients. The correlations between SII, PLR, and NLR with IMT were assessed using logistic regression models, which were subsequently incorporated into the underlying models with traditional risk factors and their predictive values for IMT. RESULTS: NLR exhibited a significant correlation with IMT in the simple regression analysis (ß = 0.01, 95 %CI= 0.00-0.02, p < 0.05). After controlling for potential confounding variables in the multivariate analysis, the association between NLR and both Maximum IMT [ß = 0.04, 95 %CI = 0.02-0.07, p = 0.0006] and Mean IMT [ß = 0.05, 95 %CI = 0.02-0.07, p = 0.0001] remained statistically significant. Additionally, PLR was found to be a significant independent predictor of Maximum IMT [ß = 0.04, 95 % CI =0.00-0.07, p = 0.0242] and Mean IMT [ß = 0.04, 95 % CI = 0.01-0.07, p = 0.0061]. Similarly, SII was identified as an independent predictor of Maximum IMT [ß = 1.87, 95 % CI =1.24, p = 0.0003]. The study found a significant positive correlation between Maximum IMT and the levels NLR, PLR, and SII. Specifically, in the Maximum IMT group, higher quartiles of NLR, PLR, and SII were associated with increased odds ratios (OR) for elevated IMT levels, with statistically significant results for NLR (Q4vsQ1: OR 3.87, 95 % CI 1.81-8.29), PLR (Q4vsQ1: OR 2.84, 95 % CI 1.36-5.95), and SII (Q4vsQ1: OR 2.64, 95 % CI 1.30-5.37). Finally, the inclusion of NLR, PLR, and NLR+PLR+SII in the initial model with traditional risk factors resulted in a marginal improvement in the predictive ability for Maximum IMT, as evidenced by the net reclassification index (p < 0.05). CONCLUSIONS: This study discovered a positive correlation between SII, PLR, NLR, and IMT, which are likely to emerge as new predictors for IMT thickening. These findings lay a theoretical reference for future predictive research and pathophysiological research on carotid intima-media thickening.

Spatial difference on nitrogen removal in the water based on different resolutions for Sanhuanpao wetland, Northeast China.

The research on the deviations caused by different resolutions is relevant to the study of spatial scale effects. In 2018, spatial interpolations were performed using the removal ratios of the TN, NH4-N, and NO3-N of the layers of different resolutions, respectively. Based on the mean and the standard deviation, the area, shape, and position were obtained for four levels related to the removal ratios of the three nitrogen forms. The linear and 6th function fitting methods were used to reveal the differences in nitrogen removal in wetland water at different spatial resolutions. The results showed that a resolution of 25 times the original was the key scale of the spatial effects. Due to the fact that 52 of the 72 functions did not reach a significant level (P < 0.05), the spatial scale effect of the nitrogen removal was mainly characterized by disorderly fluctuations. The results have a certain extrapolation value for the analysis of spatial scale effects. PRACTITIONER POINTS: The resolution difference was not sufficient to change the spatial pattern of the geographic phenomena. The resolution of 25 times the original was the important scale for determining spatial effects. When studying the spatial scale effects caused by differences in resolution, it was necessary to comprehensively consider various resolutions.

Evaluation of cardiac index and right ventricular hypertrophy index in rats under a chronic hypoxic environment at high altitude.

High-altitude areas are characterized by low pressure and hypoxia, which have a significant impact on various body systems. This study aimed to investigate the alterations in cardiac index and right ventricular hypertrophy index(RVHI) in rats at different altitudes.Twenty-one male Sprague-Dawley (SD) rats aged 4 weeks were randomly divided into three groups based on altitude. The rats were raised for 28 weeks and then transferred to Qinghai University Plateau Medicine Laboratory. Body weight was measured, heart organs were isolated and weighed, and cardiac index and right ventricular hypertrophy index were determined. Statistical analysis was performed on the data from the three groups. Compared with the plain group, the body weight of the middle-altitude group was significantly decreased (P < 0.05), and cardiac index, RVHI-1, RVHI-2 increased significantly ((P < 0.05). The body weight, whole heart mass, right ventricular mass were significantly decreased in high-altitude group (P < 0.05), RVHI-1 and RVHI-2 were significantly increased (P < 0.05). Compared with the middle-altitude group, the body weight, whole heart mass and right ventricular mass of the high-altitude group were significantly decreased (P < 0.05), and RVHI-1 and RVHI-2 were significantly increased (P < 0.05). Increasing altitude led to a decrease in body weight, whole heart mass, and right ventricular mass in rats, indicating structural changes in the right heart. Additionally, the proportion of right heart to body weight and whole heart increased with altitude.

Molecular basis of SAP05-mediated ubiquitin-independent proteasomal degradation of transcription factors.

SAP05, a secreted effector by the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to the 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, we report the crystal structures of SAP05 in complex with SPL5, GATA18 and RPN10, which provide detailed insights into the protein-protein interactions involving SAP05. SAP05 employs two opposing lobes with an acidic path and a hydrophobic path to contact TFs and RPN10, respectively. Our crystal structures, in conjunction with mutagenesis and degradation assays, reveal that SAP05 targets plant GATAs but not animal GATAs dependent on their direct salt-bridged electrostatic interactions. Additionally, SAP05 hijacks plant RPN10 but not animal RPN10 due to structural steric hindrance and the key hydrophobic interactions. This study provides valuable molecular-level information into the modulation of host proteins to prevent insect-borne diseases.

TiO2-modified two-dimensional composite of nitrogen-doped molybdenum trioxide nanosheets as a high-performance anode for lithium-ion batteries.

Nitrogen-doped molybdenum trioxide (MoO3/NC) has drawbacks such as volume expansion during long-term charging and discharging cycles, which severely limit its further application. This work proposes the addition of titanium dioxide nanoparticles (TiO2 NPs) for performance improvement of MoO3/NC. TiO2 NPs embedded on the surface of a MoO3/NC nanosheet can alleviate its volume expansion and the accumulation of lithiated products and improve the conductivity of the electrode material. The results show that the MoO3/NC nanosheet decorated with TiO2 NPs (TiO2@MoO3/NC), when used as an electrode material, exhibited a discharge specific capacity of 419 mA h g-1 at a current density of 0.05 A g-1 and retained a discharge specific capacity of 517 mA h g-1 after 600 cycles at a current density of 1 A g-1.

MLLT11 siRNA Inhibits the Migration and Promotes the Apoptosis of MDA-MB-231 Breast Cancer Cells.

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.

Prostate zones and tumor morphological parameters on magnetic resonance imaging for predicting the tumor-stage diagnosis of prostate cancer.

PURPOSE: To determine whether the morphological parameters of prostate zones and tumors on magnetic resonance imaging (MRI) can predict the tumor-stage (T-stage) of prostate cancer (PCa) and establish an optimal T-stage diagnosis protocol based on three-dimensional reconstruction and quantization after image segmentation. METHODS: A dataset of the prostate MRI scans and clinical data of 175 patients who underwent biopsy and had pathologically proven PCa from January 2018 to November 2020 was retrospectively analyzed. The authors manually segmented and measured the volume, major axis, and cross-sectional area of the peripheral zone (PZ), transition zone, central zone (CZ), anterior fibromuscular stroma, and tumor. The differences were evaluated by the One-Way analysis of variance, Pearson's chi-squared test, or independent samples t-test. Spearman's correlation coefficient and receiver operating characteristic curve analyses were also performed. The cut-off values of the T-stage diagnosis were generated using Youden's J index. RESULTS: The prostate volume (PV), PZ volume (PZV), CZ volume, tumor's major axis (TA), tumor volume (TV), and volume ratio of the TV and PV were significantly different among stages T1 to T4. The cut-off values of the PV, PZV, CZV, TA, TV, and the ratio of TV/PV for the discrimination of the T1 and T2 stages were 53.63 cm3, 11.60 cm3, 1.97 cm3, 2.30 mm, 0.90 cm3, and 0.03 [area under the curves (AUCs): 0.628, 0.658, 0.610, 0.689, 0.724, and 0.764], respectively. The cut-off values of the TA, TV, and the ratio of TV/PV for the discrimination of the T2 and T3 stages were 2.80 mm, 8.29 cm3, and 0.12 (AUCs: 0.769, 0.702, and 0.688), respectively. The cut-off values of the TA, TV, and the ratio of TV/PV for the discrimination of the T3 and T4 stages were 4.17 mm, 18.71 cm3, and 0.22 (AUCs: 0.674, 0.709, and 0.729), respectively. CONCLUSION: The morphological parameters of the prostate zones and tumors on the MRIs are simple and valuable diagnostic factors for predicting the T-stage of patients with PCa, which can help make accurate diagnoses and lateral treatment decisions.

Evaluation of Myocardial Microcirculation in Rats under a High-Altitude Hypoxic Environment by Computed Tomography Myocardial Perfusion Imaging.

This study aims to examine the changes in myocardial microcirculation in rats in a high-altitude hypoxic environment via computed tomography (CT) myocardial perfusion imaging technology. Rats in two groups were raised in different environments from 4 weeks of age for a period of 24 weeks. At 28 weeks of age, both groups underwent CT myocardial perfusion scanning, and the following myocardial perfusion parameters were measured: time to peak (TTP), mean transit time (MTT), blood flow (BF), and blood volume (BV). Following the scan, the rats were sacrificed, the cardiac index and right ventricular hypertrophy index were obtained, and hematoxylin-eosin (HE) staining was utilized to observe the pathological changes in the myocardium. In the group of rats that are subject to a high-altitude hypoxic environment for 24 weeks (the high-altitude group), the TTP and MTT values were increased (P < 0.05), the BF and BV values were lower (P < 0.05), the right heart mass was higher (P < 0.05) than that in the low-altitude group. As shown by the pathological results of HE staining, the gap between cardiomyocytes in the high-altitude group was widened, the arrangement of cardiomyocytes was irregular, and the cells were filled with a few fat vacuoles. The myocardial microcirculation is altered in a high-altitude hypoxic environment. In particular, the myocardium is in a state of inadequate perfusion, the BF in the myocardium slows down, and the right heart displays compensatory hypertrophy.

The Role of Remnant Cholesterol Beyond Low-Density Lipoprotein Cholesterol in Arterial Stiffness: A Cross-Sectional Study.

Background: Previous evidence has demonstrated that elevated low-density lipoprotein cholesterol (LDL-C) was associated with atherosclerosis. However, there is scarce population-based evidence for the role of remnant cholesterol (remnant-C) in arterial stiffness, an imaging marker for subclinical atherosclerosis. Herein, we aimed to evaluate the correlation of remnant-C with arterial stiffness beyond LDL-C in a check-up population. Methods: The study included consecutive subjects who visited the Murakami Memorial Hospital for health check-ups between 2004 and 2012. The calculation of remnant-C occurred as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) minus LDL-C. The brachial-ankle pulse wave velocity (baPWV) >1400 cm/sec was defined as arterial stiffness or baPWV abnormality. The independent correlation of remnant-C level to arterial stiffness was evaluated using adjusted regression models. Results: A total of 909 participants were included (mean age 51.1 ± 9.6 years, male sex 64.9%). In multivariate linear regression analyses, remnant-C remained an independent predictor of the baPWV predictor [ß: 94.76, 95% confidence interval (CI) 42.19-147.33, P < 0.001] after adjusting for confounders. After multivariable adjustment, including LDL-C, the highest remnant-C quartile odd ratio (OR) (95% CI) was 2.79 (1.27-6.09) for baPWV abnormality compared to the lowest quartile. Furthermore, each 10-mg/dL increase in remnant-C correlated with a 28% increased risk for baPWV abnormality (OR: 1.28, 95% CI: 1.04-1.57). Moreover, the correlation between remnant-C and baPWV abnormality was still significant in the participant subgroup with optimal levels of LDL-C. Conclusions: Our findings demonstrated that remnant-C levels correlated to arterial stiffness with the dependence of LDL-C and other cardiovascular risk factors in a check-up population.

Facile synthesis of Bi2Se3/nitrogen-doped carbon dot nanoplates for aqueous zinc ion battery cathodes.

Bi2Se3 is a promising cathode material for aqueous zinc ion batteries (AZIBs), but its limited capacity and poor cycling stability deter its further use in the development of AZIBs. To solve this issue, Bi2Se3/NCD composites have been synthesized via a simple two-step solvothermal method. The introduction of nitrogen-doped carbon dots (NCDs) provides more active sites and makes the composite surface rich in functional groups, which facilitates contact with aqueous electrolytes. The results showed that Bi2Se3/NCDs improved the zinc storage properties of Bi2Se3 as a cathode material. The discharge specific capacity is 318 mA h g-1 at 0.1 A g-1. The cycling performance of Bi2Se3/NCDs was also relatively excellent compared to that of Bi2Se3. This work offers a productive and feasible strategy for metal chalcogenides (MCs) as cathode materials for AZIBs to improve the zinc storage capacity.

Association of remnant cholesterol with intracranial atherosclerosis in community-based population: The ARIC study.

OBJECTIVE: To evaluate the association between remnant cholesterol (remnant-C) and intracranial atherosclerotic disease (ICAD) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: We studied 1,564 participants with data on lipid profiles and high-resolution vessel wall MRI (VWMRI) from the ARIC-NCS. Remnant-C was computed as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C). The primary outcomes were the presence of intracranial plaques and luminal stenosis. Contributors were separated into four different groups based on remnant-C (22 mg/dL) and LDL-C (100 mg/dL) levels to investigate the function of remnant-C vs. LDL-C on ICAD. Multivariable logistic regression models were utilized to estimate the correlation among the discordant/concordant remnant-C and LDL-C, and ICAD. RESULTS: A total of 1,564 participants were included (age 76.2 ± 5.3). After multivariable adjustment, log remnant-C was correlated with greater ICAD risk [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.01 to 1.83]. The lower remnant-C/higher LDL-C group and the higher remnant-C/lower LDL-C group manifested a 1.53-fold (95% CI 1.06 to 2.20) and 1.52-fold (95% CI 1.08 to 2.14) greater risk of ICAD, relative to those having lower remnant-C/low LDL-C. Additionally, remnant-C ≥ 22 mg/dL distinguished participants at a greater risk of the presence of any stenosis compared to those at lower levels, even in participants with optimal levels of LDL-C. CONCLUSIONS: Elevated levels of remnant-C were connected to ICAD independent of LDL-C and traditional risk factors. The mechanisms of remnant-C association with ICAD probably offer insight into preventive risk-factor of ischemic stroke.

Clinical development of mRNA therapies against solid tumors.

The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to cancer, which needs to be summarized to provide data supports for industries and research institutions. Based on the Trialtrove database, a total of 108 clinical trials from 1999 to 2021 were retrospectively analyzed. We have demonstrated that the clinical development of mRNA therapies against solid tumors is still at an early stage. There are evolutions in delivery systems from the dendritic cell to the lipid-based platform and in encoding strategies from the fixed tumor antigens to the personalized neoantigens. The adjuvant or maintenance therapy and the combination treatment with checkpoint inhibitors are becoming the major clinical development orientation.

Could tumour volume and major and minor axis based on CTA statistical anatomy improve the pre-operative T-stage in oesophageal cancer?

OBJECTIVES: To statistically study the 3D shape of oesophageal cancer (EC) and its spatial relationships based on computed tomography angiography (CTA) 3D reconstruction, to determine its relationship with T-stages, and to create an optimal T-stage diagnosis protocol based on CTA calculation. METHODS: Pre-operative CTA images of 155 patients with EC were retrospectively collected and divided into four groups: T1-T4. We used Amira software to segment and 3D reconstruct the EC, oesophagus, aorta, pericardium and peripheral lymph nodes and measured their surface area, volume, major axis, minor axis, longitudinal length, roughness and relationship to the aorta of the EC. One-way ANOVA, independent sample t-test, ROC, etc., were performed and critical values between different T-stages were calculated. We also invited two radiologists to evaluate the measurements. RESULTS: There were no significant differences in EC longitudinal length, roughness score and relationship with the aorta between the different T-stages of EC. There were significant differences in EC surface area, EC volume and mean major and minor axis among the different T-stages. The volumes of the T1-T4 tumours were 12,934.36 ± 7739.25, 23,095.27 ± 14,975.67, 37,577.98 ± 36,085.64 and 58,579.25 ± 41,073.96 mm3 separately (p < 0.05), and the T1-T4 volume cut-off values were 11,712.00, 19,809.00 and 44,103.50 mm3 separately. For comparison with radiologists, the AUC value of our measurements was 0.704, which was higher than the radiologists of AUC = 0.630. CONCLUSIONS: EC volume, major and minor axis can be used as important factors for surgeons in the T-stage diagnosis of EC, which helps to improve prognosis and treatment decisions after CTA.

Enrichment of Isaria felina Culture with Selenium Enhances its in vivo Antitumor Effects on H22 Hepatoma via Decreasing the Expression of VEGF.

BACKGROUND: The polysaccharide extract of C. sinensis, Isaria felina (IF), has antitumor effects. Selenium (Se) can improve disease prevention and reduce the toxicity of toxic elements, but the effect of Se-enriched IF on hepatoma remains unknown. OBJECTIVE: To determine the organic transformation of Se and compare the antitumor effects between Se-enriched IF (IF-Se) and IF on xenograft H22 hepatoma-bearing mice. METHODS: Se was added to the solid-state culture medium, and the organic Se content was detected by HPLC-ICP-MS. Forty-two Kunming mice were randomly divided into seven groups to test the antitumor effects of low- (300 mg/kg) and high- (600 mg/kg) doses of IF-Se and IF through xenograft. Huai'er granules were administered as the positive control. In addition, interleukin (IL)-2 and vascular endothelial growth factor (VEGF) expressions were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method. RESULTS: The conversion rate in the IF-Se70, IF-Se140, and IF-Se280 groups were 91.5%, 93.4%, and 89.3%, respectively. Therefore, IF-Se140 was used to carry out the subsequent experiments. The tumor inhibition rates of IF-Se were significantly higher compared with IF (P < 0.05). Moreover, the spleen coefficient, IL-2, and VEGF expression levels significantly decreased (all Ps < 0.05), and the thymus coefficient significantly increased (P < 0.05) in the high-dose IF-Se group compared with the model control group. CONCLUSION: The inhibitory effects of IF on H22 hepatoma-bearing mice were enhanced after Se enrichment. Therefore, Se-enriched IF might be a new strategy for treating hepatoma.

A high-resolution gridded grazing dataset of grassland ecosystem on the Qinghai-Tibet Plateau in 1982-2015.

Grazing intensity, characterized by high spatial heterogeneity, is a vital parameter to accurately depict human disturbance and its effects on grassland ecosystems. Grazing census data provide useful county-scale information; however, they do not accurately delineate spatial heterogeneity within counties, and a high-resolution dataset is urgently needed. Therefore, we built a methodological framework combining the cross-scale feature extraction method and a random forest model to spatialize census data after fully considering four features affecting grazing, and produced a high-resolution gridded grazing dataset on the Qinghai-Tibet Plateau in 1982-2015. The proposed method (R2 = 0.80) exhibited 35.59% higher accuracy than the traditional method. Our dataset were highly consistent with census data (R2 of spatial accuracy = 0.96, NSE of temporal accuracy = 0.96) and field data (R2 of spatial accuracy = 0.77). Compared with public datasets, our dataset featured a higher temporal resolution (1982-2015) and spatial resolution (over two times higher). Thus, it has the potential to elucidate the spatiotemporal variation in human activities and guide the sustainable management of grassland ecosystem.

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling.

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

[Correlation analysis of serum CTRP3 and PGC-1α expression with traumatic fracture healing].

OBJECTIVE: To investigate the relationship between serum C1q/tumor necrosis factor-related protein-3(CTRP3) and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) on predictive value of expression level on fracture healing. METHODS: From January 2019 to January 2020, 80 patients with traumatic tibial plateau fractures were treated by internal fixation with support plates through the posterior approach of the knee joint. The patients were followed up for 12 months. According to the criteria for delayed fracture healing, the patients were divided into two groups:54 patients in fracture healing group included 24 males and 30 females, aged 29 to 75 years old with an average of (52.36±13.17) years;In the delayed healing group, there were 26 cases, 13 males and 13 females, aged from 29 to 75 with an average od (53.82±13.52) years. The serum levels of CTRP3, PGC-1αand 25 hydroxyvitamin D3[25(OH)D3] in patients with traumatic fracture were detected by enzyme-linked immunosorbent assay(ELISA);Blood phosphorus and calcium levels were measured by automatic biochemical analyzer, and the product of calcium and phosphorus was calculated;Pearson's method was used to analyze the correlation between serum CTRP3, PGC-1αand bone biochemical indexes in patients with delayed union one week after operation;The predictive value of serum levels of CTRP3 and PGC-1αon traumatic fracture healing was analyzed by receiver operating characteristic curve(ROC curve). RESULTS: PGC-1α, calcium phosphorus product and 25(OH)D3 in the fracture healing group were higher than those in the delayed healing group at 1 and 4 weeks after operation(P<0.05). Serum CTRP3 was positively correlated with PGC-1α(r=0.637, P<0.05) and positively correlated with calcium phosphorus product and 25(OH)D3(P<0.05). The areas under the curve(AUC) of serum ctrp3 and PGC-1α levels in predicting traumatic fracture healing were 0.845 and 0.855, respectively. The cutoff values were 188.678 pg/ml and 2.697 ng/ml, respectively. The specificity was 96.2% and 80.8%, and the sensitivity was 53.7% and 77.8%;The predicted AUC was 0.904, the specificity was 88.5%, and the sensitivity was 81.5%. CONCLUSION: The serum levels of CTRP3 and PGC-1 in patients with delayed union of traumatic fracture at 1 and 4 weeks after operation α The expression level is of certain reference value to predict the fracture healing status of patients.