Four glycosyltransferase genes are responsible for synthesis and accumulation of different flavonol glycosides in apple tissues.

Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP-dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3-O-galactosyltransferase (UGT78T6), flavonol 3-O-glucosyltransferase (UGT78S1), flavonol 3-O-xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3-O-rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3-O-glycosyltransferases of other plant species.

Infection with a human-derived enteroinvasive Escherichia coli strain altered intestinal barrier function in guinea pigs.

BACKGROUND/AIMS: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. MATERIALS AND METHODS: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. RESULTS: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. CONCLUSIONS: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.

The role of 99mTc-MIBI SPECT/CT in patients with secondary hyperparathyroidism: comparison with 99mTc-MIBI planar scintigraphy and ultrasonography.

BACKGROUND: This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. METHODS: In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. RESULTS: The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P < 0.001). The average LBR, maximum diameter and volume of lesions in MDG and NMDG were 3.42 ± 1.28, 9.32 ± 2.69 mm, 208.51 ± 163.22 mm3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. CONCLUSIONS: 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

Extramedullary Blast Crisis in a Patient with T315I BCR-ABL Mutated Chronic Myeloid Leukemia.

BACKGROUND: Extramedullary blast crisis (EBC) of T315I BCR-ABL mutated chronic myelogenous leukemia (CML) is extremely rare. METHODS: We report an unusual case characterized by fever, right shoulder swelling, pleural effusion, and multiple bone destruction as the first signs of EBC of T315I BCR-ABL mutated CML. RESULTS: The patient did not respond to chemotherapy consisting of anthracyclines, cytarabine and etoposide. His condition improved after the treatment with ponatinib combined with allogenic stem cell transplantation (alloHCT), but soon worsened after ponatinib withdrawal. He got slight relief after he continued ponatinib. CONCLUSIONS: Ponatinib is an important treatment to control EBC even after allo-HCT.

Solution Cathode Glow Discharge Based on Charge Coupled Device Detector.

In 21st century, many countries pay much attention to lithium because lithium is an ideal material for green energy and light alloys as well as an important kind of strategic resources. The main source of lithium is from salt lake brine. China has rich resources of salt lake brine, but these brine resources are mainly distributed in the remote western region, which are in urgent need of portable analytical instrument for on-site exploration and exploitation. However, the available experimental techniques at present can not achieve the target of on-site analysis. Over the past decade, based on atmospheric pressure solution cathode glow discharge-atomic emission spectrometry (SCGD-AES) has been paid attention to analytical researchers because it runs without common air conditions such as fuel gas, carrier gas and vacuum environment. On the basis of previous studies of other researchers, we have developed a portable SCGD based on a charge coupled device (CCD) detector by ourselves, which is short for Li-K analyzer. The length, width, height and weight of the portable Li-K analyzer is 35 cm, 19 cm, 27 cm and 10 kg, respectively, which is very conducive to carry. This work selected the wavelength of 670.78 nm as the characteristic spectral line of Li and has established a rapid analytical method for Li in salt lake brine based on two different types of brines from Tibet. Under the optimum operating conditions, the detection limit of Li was 4 ng·mL-1 and the measured precision (RSD) was better than 2%. The analytical results of Li were much different from those obtained by inductively coupled plasma-mass spectrometry (ICP-MS) with different dilution ratios by standard curve method, which may be related to the matrix effect of solution. However, the analytical results of Li agreed well with the results obtained by ICP-MS using standard addition method, which showed that standard addition method can effectively reduce the matrix effect and improve the analytical accuracies. A great deal of experimental results showed that standard addition method could obtain accurate results of Li using only two points and can greatly reduce the workloads. This work laid a methodological foundation for on-site determination of Li in salt lake brine by the portable Li-K analyzer.

[On-Site Analysis of Heavy Metals in Water with Handheld X-Ray Fluorescence and Pre-Concentration Device without External Power Supply].

Currently, increasing importance has been attached to heavy metal pollution of water environment. In order to help geologist and environmentalist to obtain on-site experimental data, there is an urgent need to develop portable analysis techniques of water quality, which can be used to give an timely and accurate assessment of water quality of the contaminated area with low cost and to monitor water environment conveniently in daily preventing and controlling work of water pollution. Based on adsorption with Purolite S930 chelating resin at pH 4 and thin-film sample preparation technique, a rapid and simple on-site-oriented analysis method of heavy metal ions, namely Mn, Fe, Ni, Cu, Zn and Pb in aqueous solutions, was developed utilizing a handheld energy-dispersive X-ray fluorescence in this paper. The correlation coefficients of the calibration curves were greater than 0.992 for all six metal ions, the lower limits of detection were between 5.8 and 18.6 µg·L-1. Precision tests carried out on multi-element mixed solutions showed that the relative standard deviations (RSD, n=10) were better than 15%. The method has been used on-site to analysis 21 water samples collected from different river or well sites near a mining area northeast China. Out of the five underground water samples one was found contaminated by Cu and Zn (Class Ⅲ), one by Zn and Fe (Class Ⅱ), and one by Fe(in between Class Ⅱ to Ⅲ). Surface water samples showed better qualities. But two out of the sixteen were found to be contaminated by Mn heavily (Class Ⅳ). Laboratory ICPMS was used to analyze the same samples. The results for Cu, Ni and Pb were coincident with the on-site data in general. But for Zn and Mn with higher concentrations, on-site data were lower than that by ICPMS. The reason for that might be the inclusion of the fine suspending particles in the samples by ICPMS. We conclude that the on-site data were effective. With the described method, an overall data acquisition time, including sampling, processing and measuring, can be within 12 hours for a batch of 10 samples. The pre-concentration device and the XRF instrument are both small, light, portable and can operate without external power supply. So, the method is suitable for on-site water sample analysis, especially in remote areas.

An approach for detecting five typical vegetation types on the Chinese Loess Plateau using Landsat TM data.

Remote sensing can provide large-scale spatial data for the detection of vegetation types. In this study, two shortwave infrared spectral bands (TM5 and TM7) and one visible spectral band (TM3) of Landsat 5 TM data were used to detect five typical vegetation types (communities dominated by Bothriochloa ischaemum, Artemisia gmelinii, Hippophae rhamnoides, Robinia pseudoacacia, and Quercus liaotungensis) using 270 field survey data in the Yanhe watershed on the Loess Plateau. The relationships between 200 field data points and their corresponding radiance reflectance were analyzed, and the equation termed the vegetation type index (VTI) was generated. The VTI values of five vegetation types were calculated, and the accuracy was tested using the remaining 70 field data points. The applicability of VTI was also tested by the distribution of vegetation type of two small watersheds in the Yanhe watershed and field sample data collected from other regions (Ziwuling Region, Huangling County, and Luochuan County) on the Loess Plateau. The results showed that the VTI can effectively detect the five vegetation types with an average accuracy exceeding 80 % and a representativeness above 85 %. As a new approach for monitoring vegetation types using remote sensing at a larger regional scale, VTI can play an important role in the assessment of vegetation restoration and in the investigation of the spatial distribution and community diversity of vegetation on the Loess Plateau.

Berberine chloride suppresses pancreatic adenocarcinoma proliferation and growth by targeting inflammation-related genes: an in silico analysis with in vitro and vivo validation.

PURPOSE: Targeting inflammatory crosstalk between tumors and their microenvironment has emerged as a crucial method for suppressing pancreatic adenocarcinoma (PAAD) progression. Berberine (BBR) is a natural pentacyclic isoquinoline alkaloid known for its anti-inflammatory and antitumor pharmacological effects; however, the mechanism underlying PAAD suppression remains unclear. We aim to investigate the effects of BBR on PAAD progression and their underlying mechanisms. METHODS: The prognostic value of inflammation-related genes in PAAD was assessed using bioinformatics analyses, then the pharmacological effects and potential mechanisms of BBR on PAAD will be investigated in silico, in vitro, and in vivo. RESULTS: Fifty-eight prognostic inflammation-related genes were identified in PAAD, which were shown to have good sensitivity and specificity using a novel inflammation-related gene risk-prognosis prediction model. Among these, four candidate genes (CAPS3, PTGS2, ICAM1, and CXCR4) were predicted as targets of BBR in PAAD in silico. Molecular docking simulations showed that the four key targets docked well with BBR. Further BBR treatment suppressed cell proliferation, colony formation, and induced cell cycle arrest in vitro. Moreover, BBR exhibited a significant tumor-suppressive effect in murine subcutaneous xenografts without macroscopic hepatic and renal toxicities. In addition, BBR downregulated CAPS3, PTGS2, ICAM1, and CXCR4 protein expression. CONCLUSION: This study not only elucidated the prognostic value of inflammation-related genes in PAAD but also demonstrated the potential of BBR to inhibit PAAD by targeting these genes.

Tumor metabolism derived from 18F-FDG PET/CT in predicting the macrotrabecular-massive subtype of hepatocellular carcinoma.

Background: The recently described pathological subtype of hepatocellular carcinoma (HCC), named macrotrabecular massive (MTM), is associated with an unfavorable prognosis. This study aimed to evaluate the potential for tumor metabolism obtained by ß-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) to be used as a preoperative imaging indicator for predicting MTM-HCCs. Methods: This study was designed to be cross-sectional. Patients who underwent preoperative 18F-FDG PET/CT and who had surgically-diagnosed HCC between June 2015 and June 2021 were retrospectively included. Tumor metabolism was determined by the tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor as shown on 18F-FDG PET/CT. Clinical, pathological, and PET/CT characteristics were compared between non-MTM-HCCs and MTM-HCCs. Univariate analyses were used to screen the predictive factors of MTM-HCCs, then multivariate binary logistic regression analyses were performed. A regression-based diagnostic model was then established. Substantial necrosis was assessed to compare the predictive performance between traditional imaging and TLR measured on 18F-FDG PET/CT. The receiver operating characteristic (ROC) curve analyses and the DeLong test were used to assess the predictive performance. Results: A total of 93 patients (mean age, 52.6±11.3 years; 81 male) with 36 MTM-HCCs were included. Multivariate binary logistic regression analyses identified higher platelet count [PLT; ≥118.5×103/µL; odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13-12.87; P=0.035], higher aspartate transaminase (AST; ≥52 IU/L; OR, 4.15; 95% CI: 1.34-14.33; P=0.017), and larger TLR (≥2.2; OR, 5.55; 95% CI: 1.90-17.56; P=0.002) as independent predictors of MTM-HCCs. A TLR ≥2.2 helped to identify 72.2% of the MTM-HCCs with a specificity of 75.4%. The AUC of the regression-based diagnostic model for predicting MTM-HCCs was 0.835 (95% CI: 0.746-0.923), with a sensitivity of 80.6% and a specificity of 78.9%. Substantial necrosis enabled the identification of MTM-HCCs with 52.8% sensitivity and 87.7% specificity, with an AUC of 0.702 (95% CI: 0.588-0.817). There was no statistical difference between TLR and substantial necrosis in predicting MTM-HCCs using the DeLong test (P>0.05). Conclusions: Tumor metabolism determined by TLR on 18F-FDG PET/CT is a valuable imaging indicator for MTM-HCCs. Noninvasive prediction of this subtype can achieve good sensitivity and excellent predictive performance based on the regression model of AST, PLT, and TLR.

18F-FDG PET/CT-based radiomics nomogram for preoperative prediction of macrotrabecular-massive hepatocellular carcinoma: a two-center study.

PURPOSE: To explore the potential of ß-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) and to apply radiomics approach to build a radiomics nomogram for predicting MTM-HCC. METHODS: This study included 140 (training cohort:101; validation cohort:39) HCC patients who underwent preoperative 18F-FDG PET/CT at two institutions. The clinical features and tumor FDG metabolism measured by the tumor-to-liver ratio (TLR) via 18F-FDG PET/CT were retrospectively collected. Radiomics features were extracted from 18F-FDG PET/CT images and a radiomics score (Rad-score) was calculated. A radiomics nomogram was then constructed by combining Rad-score and independent clinical features and was assessed with a calibration curve. The performance of the radiomics nomogram, Rad-score and TLR was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: A total of six top weighted radiomics features were selected from PET/CT images by the least absolute shrinkage and selection operator (LASSO) regression algorithm and were used to construct a Rad-score. Multivariate analysis identified Rad-score (OR = 2.183, P = 0.004), age ≤ 50 years (OR = 3.136, P = 0.036), AST > 40U/L (OR = 0.270, P = 0.017) and TLR (OR = 1.641, P = 0.049) as independent predictors of MTM-HCC. The radiomics nomogram had a higher area under the curves (AUCs) than the Rad-score and TLR for predicting MTM-HCC in both training (0.849 [95% CI 0.774-0.924] vs. 0.764 [95% CI 0.669-0.843], 0.763 [95% CI 0.668-0.842]) and validation (0.749 [95% CI 0.584-0.873] vs. 0.690 [95% CI 0.522-0.828], 0.541 [95% CI 0.374-0.701]) cohorts. DCA showed the radiomics nomogram to be more clinically useful than Rad-score and TLR. CONCLUSIONS: Tumor FDG metabolism is significantly associated with MTM-HCC. A 18F-FDG PET/CT-based radiomics nomogram may be useful for preoperatively predicting the MTM subtype in primary HCC patients, contributing to pretreatment decision-making.

A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging.

Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle's performance and biocompatibility support the further translational development of liver-specific MRI contrast agents.

Postoperative radioiodine therapy impact on survival in poorly differentiated thyroid carcinoma: a population-based study.

PURPOSE: The true impact of postoperative radioiodine therapy on survival has been controversial for patients with poorly differentiated thyroid carcinoma (PDTC). We aimed to determine the impact of postoperative radioiodine on survival in PDTC through a population-based study. METHODS: Data on patients with PDTC were collected from the US SEER database (2004 to 2015). Patients were divided into the radioiodine group and nonradioiodine group. Survival comparison between groups was evaluated by Kaplan-Meier curves, log-rank test and multivariate Cox regression analysis. Akaike information criterion was used to select variables in the nomogram. The performance of the nomogram was assessed by discrimination (C-index) and calibration plots. RESULTS: The radioiodine group had more aggressive features, such as advanced tumor node metastasis stage and radical surgery, compared to the nonradioiodine group. PDTC patients receiving radioiodine therapy had a significant survival advantage in terms of overall survival (OS) (P = 0.001) but not in terms of cancer-specific survival (P = 0.083). Multivariate analysis revealed radioiodine therapy was an independent favorable factor for OS in PDTC patients (hazard ratio = 0.57; 95% CI, 0.44-0.75, P < 0.001). Subgroup analysis identified patients' characteristics favoring radioiodine therapy. The nomogram (age, tumor size, extension, neck lymph nodes metastasis and radioiodine therapy) of OS for predicting 3-, 5- and 10-year OS probability showed good discrimination (C-index, 0.797) and calibration power. CONCLUSION: Postoperative radioiodine therapy can prolong the long-term OS in patients with PDTC, and is an independent favorable prognostic factor for those patients. Further prospective studies are warranted.

18F-FDG PET/CT Imaging in Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma. We present a 53-year-old man with a hepatic IV/VIII segment neoplasm whose tumor markers were all in the reference range. The neoplasm presented intense uptake of 18F-FDG and was confirmed as sarcomatoid hepatocellular carcinoma by immunohistochemistry. After 6 cycles of PD-1 treatment, no recurrence or metastasis was found by follow-up CT over 2 years. Thus, we reported a case of sarcomatoid hepatocellular carcinoma with complete remission to PD-1 treatment and provided some help for the diagnosis and treatment of sarcomatoid hepatocellular carcinoma.

Immune-Related RNA-Binding Protein-Based Signature With Predictive and Prognostic Implications in Patients With Lung Adenocarcinoma.

Background: Dysregulation of RNA-binding proteins (RBPs) in cancers is associated with immune and cancer development. Here, we aimed to profile immune-related RBPs in lung adenocarcinoma (LUAD) and construct an immune-related RBP signature (IRBPS) to predict the survival and response to immunotherapy. Methods: A correlation analysis was performed to establish a co-expression network of RBPs and immune-related genes (IRGs) to characterize immune-related RBPs in the TCGA-LUAD cohort (n = 497 cases). Then, a combination of the Random survival forest (RSF) and Cox regression analysis was performed to screen the RBPs and establish IRBPS. This was followed by independent validation of IRBPS in GSE72094 (n = 398 cases), GSE31210, (n = 226 cases), and GSE26939 (n = 114 cases). Differences between the low- and high-risk groups were compared in terms of gene mutations, tumor mutation burden, tumor-infiltrating lymphocytes, and biomarkers responsive to immunotherapy. Results: DDX56, CTSL, ZC3H12D, and PSMC5 were selected and used to construct IRBPS. The high-risk scores of patients had a significantly worse prognosis in both training and testing cohorts (p < 0.0001 and p < 0.05, respectively), and they tended to be older and have an advanced TNM stage. Furthermore, IRBPS was a prognostic factor independent of age, gender, smoking history, TNM stage, and EGFR mutation status (p = 0.002). In addition, high-risk scores of IRBPS were significantly correlated with tumor-infiltrating lymphocytes (p < 0.05). They also had a high level of PD-L1 protein expression (p < 0.01), number of neoantigens (p < 0.001), and TMB (p < 0.001), implying the possible prediction of IRBPS in the immunotherapy of LUAD. Conclusion: The currently established IRBPS encompassing immune-related RBPs might serve as a promising tool to predict survival, reflect the immune microenvironment, and predict the efficacy of immunotherapy among LUAD patients.

[Distribution and enrichment characteristics of soil nutrients in the nebkhas profile of Nitraria tangutorum in Gahai Lake Area, Qaidam Basin.] / æŸ´è¾¾æœ¨ç›†åœ°å°•æµ·æ¹–åŒºç™½åˆºçŒä¸›æ²™å †å‰–é¢åœŸå£¤å »åˆ†çš„åˆ†å¸ƒå’Œå¯Œé›†ç‰¹å¾.

As a special bio-geomorphic landscape in the Qaidam desert area, Nitraria tangutorum nebkhas play a critical role in fixing quicksand, improving soil quality, and maintaining the stability of regional ecological environment. Taking the N. tangutorum nebkhas with coverage of approximately 15%, 25%, 45% and 60% in Gahai Lake area of Qaidam Basin as the research objects, we analyzed the vertical distribution and enrichment characteristics of soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the contents of SOM, TN, TP, TK, AN, AP and AK varied in the range of 1.67-10.22 g·kg-1, 0.05-0.42 g·kg-1, 0.31-0.54 g·kg-1, 15.87-18.84 g·kg-1, 2.26-11.68 mg·kg-1, 0.80-15.00 mg·kg-1 and 45-161 mg·kg-1, respectively. Vertically, soil nutrients in the N. tangutorum nebkhas with 15% coverage showed a decreasing trend first then increased, and then decreased again with the increase of soil depth, except for TP, which did not show any significant change. In the nebkhas with 25%, 45% and 60% coverage, SOM, TN, AN, TP and AP all showed a decreasing trend with increasing soil depth ,whereas TK and AK did not change significantly with soil layer. Above the nebkhas ground level of N. tangutorum, SOM, TN, TK, AN, AP and AK were all enriched, especially in the surface layer.Aamong all the nutrients, the enrichment rate of AN reached 5.19. In addition, below the nebkhas ground level of N. tangutorum, TN, AN, TK, AK and AP also showed enrichment. SOM, TN, AN, TP, AP, TK and AK were all significantly positively correlated with soil water content, and negatively correlated with altitude. All nutrients except TP were mainly affected by altitude. In conclusion, soil nutrient content of N. tangutorum nebkhas was the highest in the surface layer, the enrichment effect of which was not only reflected in the interior of the nebkhas, but also below the ground level of the nebkhas. Our results could provide reference for the scientific utilization of N. tangutorum nebkhas and ecological environment protection in Qaidam Basin area.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Matrine injection inhibits pancreatic cancer growth via modulating carbonic anhydrases- a network pharmacology-based study with in vitro validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Matrine injection is a complex mixture of plant bioactive substances extracted from Sophora flavescens Aiton and Smilax glabra Roxb. Since its approval by the Chinese Food and Drug Administration (CFDA) in 1995, Matrine injection has been clinically used as a complementary and alternative treatment for various cancers; however, the underlying mechanism of pancreatic cancer treatment is yet to be elucidated. AIM OF THE STUDY: The present study explores the potential mechanism of matrine injection on pancreatic cancer through network pharmacology technique and in vitro experimental validation. MATERIALS AND METHODS: Genes differentially expressed in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database (GSE101448). The potential active components of matrine injection were selected following a literature search, and target prediction was performed by the SwissTarget Prediction database. Overlapping genes associated with survival were screened by the Gene Expression Profiling Interactive Analysis (GEPIA) database. In vitro experimental validation was performed with cell counting kit-8 (CCK-8) assay, apoptosis detection, cell cycle analysis, immunoblotting, and co-immunoprecipitation of the identified proteins. RESULTS: One thousand seven hundred genes differentially expressed among pancreatic tumor and non-tumor tissues were screened out. Sixteen active components and 226 predicted target genes were identified in matrine injection. A total of 25 potential target genes of matrine injection for the treatment of pancreatic cancer were obtained. Among them, the prognostic target genes carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) based on the GEPIA database are differently expressed in tumors compared to adjacent normal tissue. In vitro experiments, the results of CCK-8 assay, apoptosis and cell cycle analysis, immunoblotting, and co-immunoprecipitation showed that matrine injection inhibited Capan-1 and Mia paca-2 proliferation, arrested the cell cycle at the S phase, and induced apoptosis through up-regulated CA12 and down-regulated CA9. CONCLUSIONS: In this study, bioinformatics and network pharmacology were applied to explore the treatment mechanism on pancreatic cancer with matrine injection. This study demonstrated that matrine injection inhibited proliferation, arrested the cell cycle, and induced apoptosis of pancreatic cancer cells. The mechanism may be related to the induction of CA12 over-expression, and CA9 reduced expression. As novel targets for pancreatic cancer treatment, Carbonic anhydrases require further study.

Keep a watchful eye on methionine adenosyltransferases, novel therapeutic opportunities for hepatobiliary and pancreatic tumours.

Methionine adenosyltransferases (MATs) synthesize S-adenosylmethionine (SAM) from methionine, which provides methyl groups for DNA, RNA, protein, and lipid methylation. MATs play a critical role in cellular processes, including growth, proliferation, and differentiation, and have been implicated in tumour development and progression. The expression of MATs is altered in hepatobiliary and pancreatic (HBP) cancers, which serves as a rare biomarker for early diagnosis and prognosis prediction of HBP cancers. Independent of SAM depletion in cells, MATs are often dysregulated at the transcriptional, post-transcriptional, and post-translational levels. Dysregulation of MATs is involved in carcinogenesis, chemotherapy resistance, T cell exhaustion, activation of tumour-associated macrophages, cancer stemness, and activation of tumourigenic pathways. Targeting MATs both directly and indirectly is a potential therapeutic strategy. This review summarizes the dysregulations of MATs, their proposed mechanism, diagnostic and prognostic roles, and potential therapeutic effects in context of HBP cancers.

Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear. AIM OF THE STUDY: This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro. MATERIALS AND METHODS: The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting. RESULTS: A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment. CONCLUSIONS: QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

Magnetic hyperthermia induces effective and genuine immunogenic tumor cell death with respect to exogenous heating.

Immunogenic cell death (ICD) can improve the therapeutic effects of cancer immunotherapy by initiating adaptive immune responses. Unlike the exogenous hyperthermia modality in clinics, magnetic hyperthermia (MH) is characterized by an iron oxide nano-agent acting as a heating source and the effects induced by heating acting at the intracellular region. However, the immunological effects of endogenous heating generated during MH and exogenous heating, and the difference in damage-associated molecular pattern (DAMP) emissions correlating with the ICD are unclear; whether MH elicits genuine ICD remains unknown. Herein, we have identified 10 distinct DAMP correlates of ICD induced by intracellular MH, and found that only heat shock proteins 70/90 were expressed after water bath heating (exogenous hyperthermia) in human triple-negative breast cancer (TNBC) MDA-MB-231 cells, murine TNBC 4T1 cells, and surgically resected specimens of ductal breast cancer from patients. In vivo vaccination assays were performed in immunocompetent BALB/c mice. The results demonstrated that MH with endogenous heating could stimulate the genuine ICD on 4T1 cells and achieved optimal therapeutic effects on 4T1 tumors, whereas exogenous heating under the same conditions failed to elicit these effects. These findings with regard to the MH induced genuine ICD with high efficiency are critical for the development of safe and effective therapeutics to amplify the therapeutic responses of cancer immunotherapy.