Effects of Water and Nitrogen on Growth, Rhizosphere Environment, and Microbial Community of Sophora alopecuroides: Their Interrelationship.

The effective management of water and nitrogen is crucial in the artificial cultivation of medicinal plants. Sophora alopecuroides, a perennial herbaceous plant in the Fabaceae family, is extensively used in medicine, with alkaloids as its primary bioactive constituents. Nevertheless, there remains a significant knowledge gap regarding how rhizospheric microbial communities respond to varying water and nitrogen conditions and their intricate relationships with soil environments and the growth of S. alopecuroides. In this study, two-year-old S. alopecuroides were used in a two-factor, three-level water-nitrogen interaction experiment. The irrigation levels included W1 (30-35% of maximum water holding capacity), W2 (50-55%), and W3 (70-75%), while nitrogen levels comprised N1 (32 mg/kg), N2 (64 mg/kg), and N3 (128 mg/kg). The study assessed plant growth indicators, total alkaloid content, and rhizospheric soil physicochemical parameters of S. alopecuroides. High-throughput sequencing (16S rRNA and ITS) was employed to analyze variations in rhizospheric microbial community composition and structure. The results showed that Proteobacteria and Ascomycota are the predominant bacterial and fungal phyla in the rhizosphere microbial community of S. alopecuroides. The highest biomass and alkaloid accumulation of S. alopecuroides were observed under the N1W3 treatment (50% nitrogen application and 70-75% of maximum water holding capacity). Specifically, six bacterial genus-level biomarkers (TRA3_20, MND1, env_OPS_17, SBR1031, Haliangium, S0134_terrestrial_group) and six fungal genus-level biomarkers (Pseudeurotium, Rhizophagus, Patinella, Pseudeurotium, Patinella, Rhizophagus) were identified under the N1W3 treatment condition. In the partial least squares path modeling (PLS-PM), water and nitrogen treatments demonstrated markedly positive direct effects on soil physicochemical parameters (p < 0.01), while showing significant negative direct impacts on alkaloid accumulation and plant growth indicators (p < 0.05). Soil physicochemical parameters, in turn, significantly negatively affected the rhizosphere fungal community (p < 0.05). Additionally, the rhizosphere fungal community exhibited highly significant negative direct effects on both the plant growth indicators and total alkaloid content of S. alopecuroides (p < 0.01). This study provides new insights into the interactions among rhizosphere soil environment, rhizosphere microbiota, plant growth, and alkaloid accumulation under water and nitrogen regulation, offering a scientific basis for the water and nitrogen management in the cultivation of S. alopecuroides.

Impacts of Climate Change on the Habitat Suitability and Natural Product Accumulation of the Medicinal Plant Sophora alopecuroides L. Based on the MaxEnt Model.

Sophora alopecuroides L., a perennial herb in the arid and semi-arid regions of northwest China, has the ecological functions of windbreaking and sand fixation and high medicinal value. In recent years, global warming and human activities have led to changes in suitable habitats for S. alopecuroides, which may affect the accumulation of natural products. In this study, MaxEnt 3.4 and ArcGIS 10.4 software were used to predict the distribution of potentially suitable habitats for S. alopecuroides in China under climate change. Furthermore, the geographical distribution of S. alopecuroides as affected by human activities, the differences in the content of natural products of S. alopecuroides between different suitable habitats, and the correlation between natural products and environmental factors were analyzed. The results showed that suitable habitats for S. alopecuroides were projected to expand in the future, and the major environmental factors were temperature (Bio1), rainfall (Bio18), and soil pH (pH). When Bio1, Bio18, and pH were 8.4283 °C, 7.1968 mm, and 9.9331, respectively, the distribution probability (P) of S. alopecuroides was the highest. After adding a human activity factor, the accuracy of the model prediction results was improved, and the area of suitable habitats was greatly reduced, showing a fragmented pattern. Meanwhile, habitat suitability had a specific effect on the content of natural products in S. alopecuroides. Specifically, the content of natural products in S. alopecuroides in wild habitats was higher than that in artificial cultivation, and highly suitable habitats showed higher contents than those in non-highly suitable habitats. The contents of total alkaloids and total flavonoids were positively correlated with human activities and negatively correlated with land use types. Among them, total alkaloids were negatively correlated with aspect, and total flavonoids were positively correlated with aspect. In addition, it is suggested that Xinjiang should be the priority planting area for S. alopecuroides in China, and priority should be given to protection measures in the Alashan area. Overall, this study provides an important foundation for the determination of priority planting areas and resource protection for S. alopecuroides.

Pre-S1 Mutations as Indicated by Serum Pre-S1 Antigen Negative is Associated with an Increased Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients.

Objective: Pre-S1 antigen (pre-S1) is a component of hepatitis B virus large surface antigen (L-HBsAg). This study aimed to investigate the association between clinical pre-S1 antigen (pre-S1) status and adverse prognostic events in chronic hepatitis B (CHB) patients. Methods: This study retrospectively enrolled 840 CHB patients with comprehensive clinical data, including 144 patients with multiple follow-up of pre-S1 status. All patients were tested for serum pre-S1 and divided into pre-S1 positive and negative groups. Single factor and logistic multiple regression analyses were performed to explore the association between pre-S1 and other HBV biomarkers with the risk of hepatocellular carcinoma (HCC) in CHB patients. The pre-S1 region sequences of HBV DNA were obtained from one pre-S1 positive and two pre-S1 negative treatment-naïve patients using polymerase chain reaction (PCR) amplification followed by Sanger sequencing. Results: The quantitative HBsAg level was significantly higher in the pre-S1 positive group than that in the pre-S1 negative group (Z=-15.983, P<0.001). The positive rate of pre-S1 increased significantly with the increase in HBsAg level (χ 2=317.963, P<0.001) and HBV DNA load (χ 2=15.745, P<0.001). The pre-S1 negative group had a higher HCC risk than the pre-S1 positive group (Z=-2.00, P=0.045, OR=1.61). Moreover, patients in the sustained pre-S1 negative group had a higher HCC risk (Z=-2.56, P=0.011, OR=7.12) than those in the sustained pre-S1 positive group. The sequencing results revealed mutations in the pre-S1 region from samples of pre-S1 negative patients, including frameshift and deletion mutations. Conclusion: Pre-S1 is a biomarker that indicates the presence and replication of HBV. Pre-S1 sustained negativity attributed to pre-S1 mutations in CHB patients may be associated with a higher risk of HCC, which has clinical significance and warrant further investigations.

Lightweight Chain-Typed Magnetic Fe3O4@rGO Composites with Enhanced Microwave-Absorption Properties.

A lightweight microwave-absorbing material with a strong electromagnetic-absorption capability of practical significance in the field of electromagnetic compatibility was obtained by adjusting the ratio of Fe3O4 and rGO. A nanoparticle material with a chain-typed structure consisting of a combination of Fe3O4 and rGO was produced by a hydrothermal method under an applied magnetic field. The electromagnetic loss property of the Fe3O4@rGO composites is studied in the frequency range from 2 to 18 GHz. In addition, the reflection loss and the mechanism of microwave absorption are explored. By changing the amounts of rGO, the electromagnetic loss of the Fe3O4@rGO composites can be effectively regulated, which obtain better reflection loss. The minimum reflection loss of the Fe3O4@rGO composites is -49.4 dB at 16.2 GHz only with a thickness of 1.75 mm. Thus, the Fe3O4@rGO composites have an extremely thin thickness and a strong electromagnetic wave absorption capacity, which is a candidate for the development of lightweight magnetic absorbing materials.

Diagnostic and prognostic nomograms for newly diagnosed intrahepatic cholangiocarcinoma with brain metastasis: A population-based analysis.

Brain metastasis (BM) is one of the rare metastatic sites of intrahepatic cholangiocarcinoma (ICC). ICC with BM can seriously affect the quality of life of patients and lead to a poor prognosis. The aim of this study was to establish two nomograms to estimate the risk of BM in ICC patients and the prognosis of ICC patients with BM. Data on 19,166 individuals diagnosed with ICC were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors and prognostic factors were identified by the logistic and the Cox regression, respectively. Next, two nomograms were developed, and their discrimination was estimated by concordance index (C-index) and calibration plots, while the clinical benefits of the prognostic nomogram were evaluated using the receiver operating characteristic (ROC) curves, the decision curve analysis (DCA), and the Kaplan-Meier analyses. The independent risk factors for BM were T stage, N stage, surgery, alpha-fetoprotein (AFP) level, and tumor size. T stage, surgery, radiotherapy, and bone metastasis were prognostic factors for overall survival (OS). For the prognostic nomogram, the C-index was 0.759 (95% confidence interval (CI) = 0.745-0.773) and 0.764 (95% CI = 0.747-0.781) in the training and the validation cohort, respectively. The calibration curves revealed a robust agreement between predictions and actual observations probability. The area under curves (AUCs) for the 3-, 6-, and 9-month OS were 0.721, 0.727, and 0.790 in the training cohort and 0.702, 0.777, and 0.853 in the validation cohort, respectively. The DCA curves yielded remarkable positive net benefits over a wide range of threshold probabilities. The Kaplan-Meier analysis illustrated that the nomogram could significantly distinguish the population with different survival risks. We successfully established the two nomograms for predicting the incidence of BM and the prognosis of ICC patients with BM, which may assist clinicians in choosing more effective treatment strategies.

Corrigendum: Development and Validation of Novel Nomograms to Predict the Overall Survival and Cancer-Specific Survival of Cervical Cancer Patients With Lymph Node Metastasis.

[This corrects the article DOI: 10.3389/fonc.2022.857375.].

Development and Validation of Novel Nomograms to Predict the Overall Survival and Cancer-Specific Survival of Cervical Cancer Patients With Lymph Node Metastasis.

Objective: The objective of this study was to establish and validate novel individualized nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in cervical cancer patients with lymph node metastasis. Methods: A total of 2,956 cervical cancer patients diagnosed with lymph node metastasis (American Joint Committee on Cancer, AJCC N stage=N1) between 2000 and 2018 were included in this study. Univariate and multivariate Cox regression models were applied to identify independent prognostic predictors, and the nomograms were established to predict the OS and CSS. The concordance index (C-index), calibration curves, and receiver operating characteristic (ROC) curves were applied to estimate the precision and discriminability of the nomograms. Decision-curve analysis (DCA) was used to assess the clinical utility of the nomograms. Results: Tumor size, log odds of positive lymph nodes (LODDS), radiotherapy, surgery, T stage, histology, and grade resulted as significant independent predictors both for OS and CSS. The C-index value of the prognostic nomogram for predicting OS was 0.788 (95% CI, 0.762-0.814) and 0.777 (95% CI, 0.758-0.796) in the training and validation cohorts, respectively. Meanwhile, the C-index value of the prognostic nomogram for predicting CSS was 0.792 (95% CI, 0.767-0.817) and 0.781 (95% CI, 0.764-0.798) in the training and validation cohorts, respectively. The calibration curves for the nomograms revealed gratifying consistency between predictions and actual observations for both 3- and 5-year OS and CSS. The 3- and 5-year area under the curves (AUCs) for the nomogram of OS and CSS ranged from 0.781 to 0.828. Finally, the DCA curves emerged as robust positive net benefits across a wide scale of threshold probabilities. Conclusion: We have successfully constructed nomograms that could predict 3- and 5-year OS and CSS of cervical cancer patients with lymph node metastasis and may assist clinicians in decision-making and personalized treatment planning.

Tgfb3 and Mmp13 regulated the initiation of liver fibrosis progression as dynamic network biomarkers.

Liver fibrogenesis is a complex scar-forming process in the liver. We suggested that the liver first responded to chronic injuries with gradual changes, then reached the critical state and ultimately resulted in cirrhosis rapidly. This study aimed to identify the tipping point and key molecules driving liver fibrosis progression. Mice model of liver fibrosis was induced by thioacetamide (TAA), and liver tissues were collected at different time-points post-TAA administration. By dynamic network biomarker (DNB) analysis on the time series of liver transcriptomes, the week 9 post-TAA treatment (pathologically relevant to bridging fibrosis) was identified as the tipping point just before the significant fibrosis transition, with 153 DNB genes as key driving factors. The DNB genes were functionally enriched in fibrosis-associated pathways, in particular, in the top-ranked DNB genes, Tgfb3 negatively regulated Mmp13 in the interaction path and they formed a bistable switching system from a dynamical perspective. In the in vitro study, Tgfb3 promoted fibrogenic genes and down-regulate Mmp13 gene transcription in an immortalized mouse HSC line JS1 and a human HSC line LX-2. The presence of a tipping point during liver fibrogenesis driven by DNB genes marks not only the initiation of significant fibrogenesis but also the repression of the scar resolution.

Serum amyloid A levels in patients with liver diseases.

BACKGROUND: Serum amyloid A (SAA) is an acute phase protein mainly synthesized by the liver. SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells, the major scar forming cells in the liver. However, few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases. AIM: To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B (CHB) patients. METHODS: Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study. The patients included 205 with CHB, 22 with active autoimmune liver disease (AILD), 21 with nonalcoholic steatohepatitis (NASH), 14 with drug-induced liver injury (DILI), and 16 with pyogenic liver abscess. Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level. Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls. Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error (alpha = 0.05/6 = 0.008). For statistical tests of other variables, P < 0.05 was considered statistically significant. Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis. RESULTS: All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients, with the highest SAA level found in patients with pyogenic liver abscess (398.4 ± 246.8 mg/L). Patients with active AILD (19.73 ± 24.81 mg/L) or DILI (8.036 ± 5.685 mg/L) showed higher SAA levels than those with active CHB (6.621 ± 6.776 mg/L) and NASH (6.624 ± 4.891 mg/L). Single (P < 0.001) and multivariate logistic regression analyses (P = 0.039) for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L. Serum levels of SAA and CRP (C-reactive protein) were positively correlated in patients with CHB (P < 0.001), pyogenic liver abscess (P = 0.045), and active AILD (P = 0.02). Serum levels of SAA (0.80-871.0 mg/L) had a broader fluctuation range than CRP (0.30-271.3 mg/L). CONCLUSION: Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess. It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.