NRF2 Dysregulation in Hepatocellular Carcinoma and Ischemia: A Cohort Study and Laboratory Investigation.

Background Intermediate stage hepatocellular carcinomas (HCCs) are treated by inducing ischemic cell death with transarterial embolization (TAE) or transarterial chemoembolization (TACE). A subset of HCCs harbor nuclear factor E2-related factor 2 (NRF2), a major regulator of the oxidative stress response implicated in cell survival after ischemia. NRF2-mutated HCC response to TAE and/or TACE is unknown. Purpose To test whether ischemia resistance is present in individuals with NRF2-mutated HCC and if this resistance can be overcome by means of NRF2 inhibition in HCC cell lines. Materials and Methods This was a combined retrospective review of an institutional database (from January 2011 to December 2018) and prospective study (from January 2014 to December 2018) of participants with HCC who underwent TAE and a laboratory investigation of HCC cell lines. Imaging follow-up included liver CT or MRI at 1 month after the procedure followed by 3-month interval scans. Tumor radiologic response was assessed on the basis of follow-up imaging. The time to local progression after TAE for individuals with and individuals without NRF2 pathway alterations was estimated by using competing risk analysis (Gray test). The in vitro response to ischemia in four HCC cell lines with and without NRF2 overexpression was evaluated, and the combination of ischemia with NRF2 knockdown by means of short hairpin RNA or an NRF2 inhibitor was tested. Doubling time estimates, dose response curve regression, and comparison analyses were performed. Results Sixty-five individuals (median age, 69 years [range, 19-84 years]; 53 men) were evaluated. HCCs with NRF2 pathway mutation had a shorter time to local progression after TAE compared to those without mutation (6-month cumulative incidence of local progression, 56% [range, 19%-91%] vs 22% [range, 12%-34%], respectively; P < .001) and confirmed ischemia resistance in NRF2-overexpressing HCC cell lines. However, ischemia and NRF2 knock-down worked synergistically to decrease proliferation of NRF2-overexpressing HCC cell lines. Dose response curves of ML385, an NRF2 inhibitor, showed that ischemia induces addiction to NRF2 in cells with NRF2 alterations. Conclusion Hepatocellular carcinoma with nuclear factor E2-related factor 2 (NRF2) alterations showed resistance to ischemia, but ischemia simultaneously induced sensitivity to NRF2 inhibition. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Weiss and Nezami in this issue.

A novel lncRNA LOC101927746 accelerates progression of colorectal cancer via inhibiting miR-584-3p and activating SSRP1.

An increasing number of reports have indicated that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, many lncRNAs remain unidentified in CRC, and their functions are yet to be elucidated. In this study, we investigated the function of lncRNA LOC101927746 in CRC progression. We found that LOC101927746 expression was significantly increased in CRC tissues according to the GEO dataset. Moreover, LOC101927746 expression was positively correlated with tumor stage and metastasis. Additionally, the high expression of LOC101927746 predicted poor prognosis in CRC patients. Functionally, we demonstrated that LOC101927746 silencing significantly suppressed the proliferation, migration, and invasion of CRC cells. In terms of its mechanism, LOC101927746 could serve as a competing endogenous RNA to inhibit miR-584-3p and activate its target gene SSRP1. The expression of miR-584-3p was inversely correlated with either LOC101927746 or SSRP1 in CRC tissues. The overexpression of SSRP1 or inhibition of miR-584-3p could reverse the effects of LOC101927746 knockdown in CRC cells. Taken together, our results suggest that the LOC101927746/miR-584-3p/SSRP1 axis modulates CRC progression.

Pirfenidone inhibits cryoablation induced local macrophage infiltration along with its associated TGFb1 expression and serum cytokine level in a mouse model.

PURPOSE: To investigate the effects of pirfenidone (PFD) on post-cryoablation inflammation in a mouse model. MATERIALS AND METHODS: In this IACUC-approved study, eighty Balb/c mice were randomly divided into four groups (20/group): sham + vehicle, sham + PFD, cryoablation + vehicle, and cryoablation + PFD. For cryoablation groups, a 20% freeze rate cryoablation (20 s to less than -100 °C) was used to ablate normal muscle in the right flank. For sham groups, the cryoprobe was advanced into the flank and maintained for 20 s without ablation. PFD or vehicle solution was intraperitoneally injected (5 mg/kg) at days 0, 1, 2, 3, and then every other day until day 13 after cryoablation. Mice were euthanized at days 1, 3, 7, and 14. Blood samples were used for serum IL-6, IL-10, and TGFß1 analysis using electrochemiluminescence and ELISA assays, respectively. Immunohistochemistry-stained ablated tissues were used to analyze macrophage infiltration and local TGFß1 expression in the border region surrounding the cryoablation-induced coagulation zone. RESULTS: Cryoablation induced macrophage infiltration and increased TGFß1 expression in the border of the necrotic zone, and high levels of serum IL-6, peaking at days 7 (70.5 ±â€¯8.46/HPF), 14 (228 ±â€¯18.36/HPF), and 7 (298.67 ±â€¯92.63), respectively. Animals receiving PFD showed reduced macrophage infiltration (35.5 ±â€¯16.93/HPF at day 7, p < 0.01) and cytokine levels (60.2 ±â€¯7.6/HPF at day 14, p < 0.01). PFD also significantly reduced serum IL-6 levels (p < 0.001 vs. all non-PFD groups). CONCLUSIONS: PFD mitigates cryoablation induced muscle tissue macrophage infiltration, increased IL-6 levels, and local TGFß1 expression in a small animal model.

Contributions of long-term tillage systems on crop production and soil properties in the semi-arid Loess Plateau of China.

BACKGROUND: This study determined the long-term effect of tillage systems on soil properties and crop yields in a semi-arid environment. Field pea (Pisum sativum L.) and spring wheat (Triticum aestivum L.) were alternately grown in six tillage systems at Dingxi (35° 28' N, 104° 44' E), north-west China starting in 2001. RESULTS: After the first 6 years of experiments, conventional tillage with stubble incorporating (TS) and no-till with stubble cover (NTS) increased soil organic matter by 9.9% and 13.0%, respectively, compared to the conventional tillage with stubble removed (T); both TS and NTS also increased soil microbial counts, available K and P, and total N. No-till with stubble removed (NT), NTS and NTP (no-till with plastic mulching) had 20.7%, 62.6% and 43.7% greater alkaline phosphatase activity compared to the T treatment. Soil catalase, urease and invertase activities were all greater in the no-till treatments than in the T treatment. Averaged across 6 years, both wheat and pea achieved highest grain yields under NTS treatment. CONCLUSION: No-till with stubble retention is the most promising system for improving soil physical, biological and chemical properties, and increasing crop yields, and thus, this system can be adopted in areas with conditions similar to the semi-arid north-west China. © 2015 Society of Chemical Industry.

Establishing and clinically validating a machine learning model for predicting unplanned reoperation risk in colorectal cancer.

BACKGROUND: Colorectal cancer significantly impacts global health, with unplanned reoperations post-surgery being key determinants of patient outcomes. Existing predictive models for these reoperations lack precision in integrating complex clinical data. AIM: To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients. METHODS: Data of patients treated for colorectal cancer (n = 2044) at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected. Patients were divided into an experimental group (n = 60) and a control group (n = 1984) according to unplanned reoperation occurrence. Patients were also divided into a training group and a validation group (7:3 ratio). We used three different machine learning methods to screen characteristic variables. A nomogram was created based on multifactor logistic regression, and the model performance was assessed using receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis. The risk scores of the two groups were calculated and compared to validate the model. RESULTS: More patients in the experimental group were ≥ 60 years old, male, and had a history of hypertension, laparotomy, and hypoproteinemia, compared to the control group. Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation (P < 0.05): Prognostic Nutritional Index value, history of laparotomy, hypertension, or stroke, hypoproteinemia, age, tumor-node-metastasis staging, surgical time, gender, and American Society of Anesthesiologists classification. Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility. CONCLUSION: This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer, which can improve treatment decisions and prognosis.

Comparative study of immune response to local tumor destruction modalities in a murine breast cancer model.

Introduction: Immunotherapy is revolutionizing the management of multiple cancer types. However, only a subset of patients responds to immunotherapy. One mechanism of resistance is the absence of immune infiltrates within the tumor. In situ vaccine with local means of tumor destruction that can induce immunogenic cell death have been shown to enhance tumor T cell infiltration and increase efficacy of immune checkpoint blockade. Methods: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed. Results: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery. Conclusion: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.

Bacterial community succession in aerobic-anaerobic-coupled and aerobic composting with mown hay affected C and N losses.

The primary objective of this work was to investigate how the dominant microbial species change and affect C and N losses under aerobic and aerobic-anaerobic-coupled composting of mown hay (MH, ryegrass) and corn stover (CS) mix. Results showed that C and N losses in aerobic compost of MH-CS were significantly decreased by 19.57-31.47% and 29.04-41.18%, respectively. 16S rRNA gene sequencing indicated that the bacterial microbiota showed significant differences in aerobic and aerobic-anaerobic-coupled composting. LEfSe analyses showed that aerobic composting promoted the growth of bacteria related to lignocellulosic degradation and nitrogen fixation, while aerobic-anaerobic-coupled composting promoted the growth of bacteria related to denitrification. Correlation analysis between bacterial community and environmental factors indicated that moisture content (MC) was the most important environmental factor influencing the differentiation of bacterial growth. KEGG analysis showed that aerobic composting enhanced the amino acid, carbohydrate, and other advantageous metabolic functions compared to that of aerobic-anaerobic-coupled composting. As a conclusion, the addition of 10-20% corn stover (w/w) to new-mown hay (ryegrass) appeared to inhibit anaerobic composting and prompt aerobic composting in MH-CS mix, which led to the effective utilization of mown hay as a resource for composting.

A comparative study of Cd(ii) adsorption on calcined raw attapulgite and calcined aluminium hydroxide-modified attapulgites in aqueous solution.

In this study, raw attapulgite and two aluminium hydroxide-modified attapulgites prepared using different aluminium salts were calcined at 600 °C to successfully prepare three novel adsorbents (C-ATP, C-ATP-SO4 2- and C-ATP-Cl-). The three adsorbents were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis and X-ray photoelectron spectroscopy (XPS). Batch experiments revealed that the Cd(ii) adsorption capacity of the three adsorbents increased with increasing pH, increasing the initial concentration of Cd(ii) in solution, and with longer adsorption times. The order of adsorption capacity was always C-ATP > C-ATP-Cl- > C-ATP-SO4 2-. C-ATP and C-ATP-Cl- were better described by the Langmuir model, while C-ATP-SO4 2- was better described by the Freundlich model. The three adsorbents reached adsorption equilibrium within 2 h, and all followed pseudo-second order kinetics. The adsorption of Cd(ii) onto the three adsorbents was physisorption, as suggested by the calculated thermodynamic parameters. Although the adsorption of Cd(ii) on C-ATP and C-ATP-Cl- was exothermic, the adsorption on C-ATP-SO4 2- was endothermic. Ion exchange and cadmium precipitation were the primary mechanisms of cadmium adsorption on the three adsorbents analysed by XPS. The presence of SO4 2- in C-ATP-SO4 2- may result in weaker binding of Cd(ii) by the adsorbent than C-ATP-Cl-.

Nano zero-valent iron loaded corn-straw biochar for efficient removal of hexavalent chromium: remediation performance and interfacial chemical behaviour.

To improve the poor stability of nano zero-valent iron (nZVI), corn-straw biochar (BC) was used as a support for the synthesis of composites of nZVI-biochar (nZVI/BC) in different mass ratios. After a thorough characterization, the obtained nZVI/BC composite was used to remove hexavalent chromium [Cr(vi)] in an aquatic system under varying conditions including composite amount, Cr(vi) concentration, and pH. The obtained results show that the treatment efficiency varied in the following order: nZVI-BC (1 : 3) > nZVI-BC (1 : 5) > nZVI alone > BC alone. This order indicates the higher efficiency of composite material and the positive effect of nZVI content in the composite. Similarly, the composite dosage and Cr(vi) concentration had significant effects on the removal performance and 2 g L-1 and 6 g L-1 were considered to be the optimum dose at a Cr(vi) concentration of 20 mg L-1 and 100 mg L-1, respectively. The removal efficiency was maximum (100%) at pH 2 whereas solution pH increased significantly after the reaction (from 2 to 4.13). The removal kinetics of Cr(vi) was described by a pseudo-second-order model which indicated that the removal process was mainly controlled by the rate of chemical adsorption. The thermodynamics was more in line with the Freundlich model which indicated that the removal was multi-molecular layer adsorption. TEM-EDS, XRD, and XPS were applied to characterize the crystal lattice and structural changes of the material to specify the interfacial chemical behaviour on the agent surface. These techniques demonstrate that the underlying mechanisms of Cr(vi) removal include adsorption, chemical reduction-oxidation reaction, and co-precipitation on the surface of the nZVI-BC composite. The results indicated that the corn-straw BC as a carrier material highly improved Cr(vi) removal performance of nZVI and offered better utilization of the corn straw.

Bacterial Diversity and Potential Functions in Response to Long-Term Nitrogen Fertilizer on the Semiarid Loess Plateau.

Bacterial diversity and its functions are essential to soil health. N fertilization changes bacterial communities and interferes with the soil biogeochemical N cycle. In this study, bacterial community and soil physicochemical properties were studied in 2018 after applying N fertilizers (0, 52.5, 105, 157.5, and 210 kg N ha-1) for a long (2003-2018) and a short (2003-2004) duration in a wheat field on the Loess Plateau of China. Soil bacteria were determined using 16S rRNA Illumina-MiSeq®, and the prediction function was analyzed through PICRUSt. The study showed that N fertilizer significantly changed the diversity and abundance of bacterial communities. The phyla Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi were most abundant, accounting for 74-80% of the bacterial community abundance. The optimum rates of N fertilizer application (N105) maintain soil health by promoting soil microbial diversity and abundance. The bacterial population abundance was higher after short-term N application than after N application for a long duration and lowest with the high N-fertilizer treatment (N210). High N enrichment led to more heterotrophic N-fixing microorganisms (Alphaproteobacteria), in which metabolism and genetic information processing dominated, while cellular processes, genetic information processing, metabolism, and organismal systems were the main functional categories under low N. The phyla Gemmatimonadetes, Actinobacteria, Bacteroidetes, and Chloroflexi were the key bacteria in the co-occurrence network. The genus Saccharimonadales of the superphylum Patescibacteria has a more significant impact under low N treatment. Long-term N fertilization affected the soil pH, NO3-N, and other physicochemical properties, and soil NO3-N was the highest indicator, contributing 81% of the bacterial community function under different N fertilizer treatments.

Changes in Ammonia-Oxidizing Archaea and Bacterial Communities and Soil Nitrogen Dynamics in Response to Long-Term Nitrogen Fertilization.

Ammonia oxidizing archaea (AOA) and bacteria (AOB) mediate a crucial step in nitrogen (N) metabolism. The effect of N fertilizer rates on AOA and AOB communities is less studied in the wheat-fallow system from semi-arid areas. Based on a 17-year wheat field experiment, we explored the effect of five N fertilizer rates (0, 52.5, 105, 157.5, and 210 kg ha-1 yr-1) on the AOA and AOB community composition. This study showed that the grain yield of wheat reached the maximum at 105 kg N ha-1 (49% higher than control), and no further significant increase was observed at higher N rates. With the increase of N, AOA abundance decreased in a regular trend from 4.88 × 107 to 1.05 × 107 copies g-1 dry soil, while AOB abundance increased from 3.63 × 107 up to a maximum of 8.24 × 107 copies g-1 dry soil with the N105 treatment (105 kg N ha-1 yr-1). Application rates of N fertilizer had a more significant impact on the AOB diversity than on AOA diversity, and the highest AOB diversity was found under the N105 treatment in this weak alkaline soil. The predominant phyla of AOA and AOB were Thaumarchaeota and Proteobacteria, respectively, and higher N treatment (N210) resulted in a significant decrease in the relative abundance of genus Nitrosospira. In addition, AOA and AOB communities were significantly associated with grain yield of wheat, soil potential nitrification activity (PNA), and some soil physicochemical parameters such as pH, NH4-N, and NO3-N. Among them, soil moisture was the most influential edaphic factor for structuring the AOA community and NH4-N for the AOB community. Overall, 105 kg N ha-1 yr-1 was optimum for the AOB community and wheat yield in the semi-arid area.

[Soil nematode community characteristics of alfalfa field with different growing ages in the semi-arid Loess Plateau of Central Gansu, Northwest China]. / 陇中黄土高原半干旱区不同种植年限紫花苜蓿土壤线虫群落分布特征.

To clarify the impacts of long-term alfalfa plantation on the soil nematode community, soil samples were collected from different alfalfa growing ages (2 a, 9 a, 18 a) in the semi-arid area of Loess Plateau in Central Gansu by Illumina Miseq sequencing technology. The main controlling factors affecting its community change were also explored. The results showed that soil nematode belongs to 2 classes, 7 orders, 16 families and 21 genera. Among them, Chromadorea was the dominant group (44.6%-81.4%), the relative abundance of which decreased with alfalfa growing ages. Paratylenchus, Helicotylenchus, Xiphinema, Pristionchus, Ditylenchus, Panagrolaimus, Longidorus, Aprutides, Isolaimium and Aglenchus were the special nematode species of alfalfa, among which Paratylenchus (54.1%), Helicotylenchus (23.9%) and Xiphinema (21.9%) were the dominant nematodes in 2 a, 9 a and 18 a alfalfa soil respectively. Plant-parasitic nematode was the dominant group in alfalfa soil (31.8%-67.1%), and its relative abundance decreased at first and then increased with alfalfa growing ages. Results of redundancy analysis showed that soil available phosphorus and total nitrogen were the dominant environmental factors affecting community structure of soil nematodes in the region.

17α-Estradiol and genistein inhibit high fat diet induced prostate gene expression and prostate growth in the rat.

PURPOSE: High dietary fat and low phytoestrogen intake are associated with prostate cancer development and progression. Our previous study showed that exposure to a high fat diet significantly increased prostate 5α-reductase-2 mRNA and prostate growth in the rat. In the current experiments we determined the effects of genistein and 17α-estradiol on the modulation of dietary fat induced prostate 5α-reductase-2 and insulin-like growth factor-1 gene expression, and prostate growth. MATERIALS AND METHODS: At weaning male ACI/Seg rats (Harlan® Sprague-Dawley®) were fed a low or a high fat diet, with or without genistein or 17α-estradiol for 2, 4 or 10 weeks. The prostate was dissected and weighed. We determined the levels of prostate 5α-reductase-2 mRNA, insulin-like growth factor-1 mRNA, dihydrotestosterone, and plasma insulin-like growth factor-1, dihydrotestosterone and testosterone. RESULTS: Two-week exposure to a high fat diet significantly increased prostate insulin-like growth factor-1 mRNA without significant changes in plasma insulin-like growth factor-1, which was blocked by genistein and 17α-estradiol. Genistein but not 17α-estradiol also inhibited prostate 5α-reductase-2 mRNA and intraprostatic dihydrotestosterone induced by the high fat diet at 2 weeks. Genistein and 17α-estradiol completely blocked high fat diet induced prostate growth at 10 weeks of dietary treatment. However, neither genistein nor 17α-estradiol had any significant effect when co-administered with the low fat diet. CONCLUSIONS: Results indicate that genistein and 17α-estradiol can inhibit dietary fat induced changes in prostate 5α-reductase-2 and insulin-like growth factor-1 gene expression, and prostate growth in the rat. This may be beneficial to prevent dietary fat associated prostate diseases such as prostate cancer.

Inhibition of aberrant androgen receptor induction of prostate specific antigen gene expression, cell proliferation and tumor growth by 17α-estradiol in prostate cancer.

PURPOSE: Androgen independent prostate cancer growth and metastasis are a major cause of prostate cancer death. Aberrant androgen receptor activation due to androgen receptor mutation is an important mechanism of androgen independence. We determined the effectiveness and mechanism of 17α-estradiol (Sigma®) in blocking aberrant androgen receptor activation due to androgen receptor mutation. MATERIALS AND METHODS: We used LNCaP and MDA Pca-2b prostatic tumor cells (ATCC®) containing a mutated androgen receptor and WT estrogen receptor ß to test 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression and cell growth. Cotransfection analysis was used to further elucidate the mechanism of 17α-estradiol action. Xenograft animals with an LNCaP prostate tumor were prepared to study the in vivo effect of 17α-estradiol on tumor growth inhibition. RESULTS: In LNCaP cells 17α-estradiol produced a dose dependent inhibition of cyproterone acetate (Sigma) or dihydrotestosterone induced prostate specific antigen gene expression. In MDA Pca-2b cells 17α-estradiol inhibited cortisol (Sigma) induced prostate specific antigen expression and blocked dihydrotestosterone and cortisol induced cell proliferation in LNCaP and MDA Pca-2b cells, respectively. Cotransfection analysis showed that 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression was medicated via estrogen receptors. In xenograft mice with LNCaP prostate cancer 17α-estradiol but not 17ß-estradiol (Sigma) significantly inhibited tumor growth, although each estrogen tended to decrease tumor growth. CONCLUSIONS: Results suggest that 17α-estradiol with less classic estrogenic activity is a potential therapeutic agent for androgen independent prostate cancer due to androgen receptor mutation.

Managing the trade-offs among yield, economic benefits and carbon and nitrogen footprints of wheat cropping in a semi-arid region of China.

It is critical to understand how farming practices affect the carbon and nitrogen footprints of agricultural production. Grain yield, economic return, and carbon and nitrogen footprints of spring wheat (Triticum aestivum L.) were examined under different tillage-mulch practices. Wheat was grown over 15 years (2002-2016) in the semi-arid region of the western Loess Plateau of China under six tillage-mulch practices: traditional plough with no straw mulching (T), no-till without straw mulching (NT), traditional plough with straw mulching (TS), no-till without straw mulching (NTS), traditional plough with plastic mulching (TP), no-till with plastic mulching (NTP). Average wheat yield over 15 years under NTS, NTP, TP and TS was increased by 28, 24, 22, and 13%, respectively, compared to T. Average net return was greatest under NTS and lowest under TP. The soils under all six tillage-mulch practices gained a considerably large amount of soil organic carbon (SOC) over the 15 yr. The increase in SOC in the 0-30 cm soil layer was greatest under NTS and lowest under T. When changes in soil C were included in the calculations, treatments of NT, TS, NTS, and NTP sharply reduced total greenhouse gas (GHG) emission compared to T. Compared to T, the carbon footprint was decreased by 180, 44, and 123% under NTS, NT, and TS, respectively, but was increased by 153% under TP. Compared to T, the nitrogen footprint was 24-26% lower in TP and NTP, but was not significantly different under NTS, NT, and TS. Therefore, NTS enhanced yield and net return, and reduced GHG and the carbon footprint without increasing the nitrogen footprint, and should be adopted to mitigate the environmental impacts of wheat production in the semiarid Loess Plateau.

Soil Bacterial Diversity and Potential Functions Are Regulated by Long-Term Conservation Tillage and Straw Mulching.

Soil physiochemical properties are regulated by cropping practices, but little is known about how tillage influences soil microbial community diversity and functions. Here, we assessed soil bacterial community assembly and functional profiles in relation to tillage. Soils, collected in 2018 from a 17-year field experiment in northwestern China, were analyzed using high-throughput sequencing and the PICRUSt approach. The taxonomic diversity of bacterial communities was dominated primarily by the phyla Proteobacteria (32-56%), Bacteroidetes (12-33%), and Actinobacteria (17-27%). Alpha diversity (Chao1, Shannon, Simpson, and operational taxonomic unit (OTU) richness) was highest under no-tillage with crop residue removed (NT). Crop residue retention on the soil surface (NTS) or incorporated into soil (TS) promoted the abundance of Proteobacteria by 16 to 74% as compared to conventional tillage (T). Tillage practices mainly affected the pathways of soil metabolism, genetic information processing, and environmental information processing. Soil organic C and NH4-N were the principal contributors to the diversity and composition of soil microbiota, whereas soil pH, total nitrogen, total P, and moisture had little effect. Our results suggest that long-term conservation practices with no-tillage and crop residue retention shape soil bacterial community composition through modifying soil physicochemical properties and promoting the metabolic function of soil microbiomes.

Multiple methods for the identification of heavy metal sources in cropland soils from a resource-based region.

Examination of heavy metal sources in soils from a resource-based region is essential for source identification and implementation of restoration strategies regarding soil contamination. A total of 1069 samples were collected from cropland soils in the Baiyin District (Loess Plateau, Northwest China), a characteristically resource-based region to investigate the sources of arsenic (As), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), and zinc (Zn). Source identification was analyzed by multiple methods including spatial deviation (SD), correlation analysis (CA), enrichment factor (EF), principal component analysis (PCA), geographic information system (GIS), and positive matrix factorization (PMF). The results showed the combined applications of PMF, GIS, and PCA were accurate, pragmatic, and effective for source apportionment. Three origins were identified and the contribution rates were calculated as follows: approximately 95% of As came from wastewater irrigation; 75, 88, 60, and 76% of Cr, Mn, Ni, and V were separately derived from natural origins; and 81, 93, and 70% of Cu, Pb, and Zn originated from industrial sources, respectively. Natural origins, industrial sources, and wastewater irrigation were the three main contributors of heavy metals to cropland soils in this region.

Inhibition of tumor growth and tumor metastasis by a Chinese herbal formula--ZYD88, in an animal model with metastatic Lewis lung carcinoma.

Tumor metastasis is the leading cause of cancer death. In the present study, we determined the effectiveness of ZYD88, a Chinese herbal formula, in the inhibition of tumor growth and distant tumor metastases to the lung and liver in an animal model with metastatic Lewis lung carcinoma (LLC). Treatment with ZYD88 in adult C57BL/6 mice with metastatic LLC produced dose-dependent deceases in primary tumor weight, the mitotic tumor cell number, microvessel density, distant tumor metastases and red blood cell immune complexes, while it significantly increased tumor necrosis, thymus cortical thickness, the thymus medullar reticular epithelial cell (REC) number, and the activity of red blood cell C3b receptors. Although cyclophosphamide inhibited tumor growth, it had no significant effects on distant tumor metastases, thymus cortical thickness, the thymus medullar REC number, red blood cell C3b receptor activity and red blood cell immune complexes. These results indicate that ZYD88 possesses significant anti-angiogenic, anti-tumor and anti-metastatic effects in this animal model, and warrants further investigation.

Pancreaticoduodenal arterial rupture and hemoabdomen in ACI/SegHsd rats with polyarteritis nodosa.

Many lesions associated with aging have been well-characterized in various strains of rats. Although documented in Sprague-Dawley and spontaneously hypertensive rats, polyarteritis nodosa has not previously been reported in ACI/SegHsd rats. ACII SegHsd rats were maintained on high-fat (40.5%), low-fat (11.6%), and high-fat to low-fat dietary protocols to examine the correlation between dietary fat and the regulation of prostate 5alpha-reductase gene expression and prostate cancer. Seven rats died unexpectedly with hemoabdomen and rupture of the pancreaticoduodenal artery secondary to polyarteritis nodosa (PAN). The purpose of this study was to analyze the pathologic findings in these and the remaining ACI/SegHsd rats and to correlate the level of dietary fat with the presence of PAN, arterial rupture, and hemoabdomen. Approximately 65% of the rats had evidence of PAN by histopathology, with a 24% incidence of arterial rupture. Additional lesions noted included an 88% incidence of chronic progressive nephropathy (CPN) and a 32% incidence of cartilaginous foci in the aortic valve. We found no association between the percentage of dietary fat and incidence of PAN, CPN, or cardiac cartilage. Although arterial rupture is a known complication of polyarteritis nodosa in humans, this case series is the first to document arterial rupture and hemoabdomen in rats with PAN.

Effects of male sex hormones on gender identity, sexual behavior, and cognitive function.

Androgens, the male sex hormones, play an essential role in male sexual differentiation and development. However, the influence of these sex hormones extends beyond their roles in sexual differentiation and development. In many animal species, sex hormones have been shown to be essential for sexual differentiation of the brain during development and for maintaining sexually dimorphic behavior throughout life. The principals of sex determination in humans have been demonstrated to be similar to other mammals. However, the hormonal influence on sexual dimorphic differences in the nervous system in humans, sex differences in behaviors, and its correlations with those of other mammals is still an emerging field. In this review, the roles of androgens in gender and cognitive function are discussed with the emphasis on subjects with androgen action defects including complete androgen insensitivity due to androgen receptor mutations and 5alpha-reductase-2 deficiency syndromes due to 5alpha-reductase-2 gene mutations. The issue of the complex interaction of nature versus nurture is addressed.