Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Nitrate leaching characteristics of red soils from different parent materials in subtropical China.

Globally, nitrate (NO3-) leaching from agroecosystems has been of major concern. There is evidence that NO3- leaching exhibits intense seasonal variation in subtropical regions. However, influencing factors to the seasonal dynamics remain unclear. In this study, a two-year field lysimeters experiment was conducted with three red soils derived from different parent materials (Quaternary red clay (QR), red sandstone (RS), and basalt (BA)). An N fertilizer (15N-enriched urea, 10 atom% excess) of 200 kg N ha-1 yr-1 was applied for maize. The effect of parent material on NO3- leaching characteristics was examined in surface (0-20 cm) and subsoil (20-100 cm) layers. The results showed due to the weakening of abundant drainage, there was no significant effect of parent materials on NO3- leaching characteristics in surface layers. Environmental factors (precipitation and temperature) and fertilization together led to obvious seasonal characteristics, i.e. abundant NO3- leaching during both crop growth and fallow periods. In subsoil layers, NO3- leaching characteristics were completely different among three soils. The concentrations and δ15N of NO3- in QR and RS soils showed a continuous increase after first year's fertilization, while those in BA soil remained relatively stable after reaching peak levels around harvest in first year. Meanwhile, the NO3- leaching amount in BA soil was significantly lower than in the other two soils. These might be explained by different NO3- adsorption capacities caused by the differences in mineral composition and free iron and aluminium contents. These elucidated in subsoil layers, NO3- leaching characteristics highly depended on parent materials. Meanwhile, adsorption capacity was limited and cannot slow NO3- leaching in the long run. Our results suggest that seasonal variation of NO3- leaching in surface layers and temporary retardant effect from NO3- adsorption capacity in subsoil layers should receive much attention when calculating and predicting NO3- leaching in subtropical regions.

Soil acidification in a tailing area of ionic rare earth in Southeast China.

Ionic rare earth ores are now commonly mined using the ammonium sulfate in situ leaching method, causing soil acidification in tailings. To evaluate the degree of soil acidification in tailings and the influence of mining activities on acidification, we selected an ionic rare earth tailing and a nearby unmined area in Southeast China. This tailing had been closed for 12 years. We sampled the soil from the surface to the bedrock in layers and determined soil properties related to soil acidification. The results showed that the average soil pH was 5.0 in the unmined area and 4.5 in the mined area (tailing area). Rare earth mining led to a decrease in soil pH of 0.47 units per 10 years, which was 2-5 times higher than that of other land uses. The shallow soil acidification in the mined area is not affected by mining. Deep soils were significantly acidified and the H+ concentration in the soil solution was approximately nine times that of the unmined area soil. Deep soil acidification is influenced very little by natural factors. The average soil ammonium­nitrogen (NH4+-N) and nitrate­nitrogen contents in the mined area were 58.34 mg kg-1 and 8.19 mg kg-1, respectively, 84 times and 21 times that of the unmined area. There were large amounts of NH4+, NO3-, and H+ in the soil of the mined area, indicating that soil acidification is closely related to exogenous NH4+-N input and nitrogen transformation. Nitrification is the most important driver of soil acidification in mining areas. Continued nitrification of excess NH4+-N will continue to produce H+ and migrate with water, which will cause long-term harm to the soil and surrounding environment in the mining area. Therefore, it is necessary to remove the enriched NH4+-N in tailings soil to avoid further soil acidification.

Soil organic carbon content increase in the east and south of China is accompanied by soil acidification.

Increased soil organic carbon (OC) in China has been reported in the past two decades, suggesting the sequestration of atmospheric carbon dioxide into soil, mitigating climate change and improving soil health. On the other hand, soil pH decrease had also been reported nationwide. If the two are related, the strategy of increasing soil OC could negatively affect soil quality for food production and the environment. We investigate this thread based on large-scale soil survey data from two provinces with typical soil and cropping patterns in the east and south of China, Jiangsu (102,600 km2) and Guangdong (177,900 km2). The data include >5000 observations from soil surveys conducted over the past four decades, i.e., the 1980s, 2006-2007, and 2010-2011. Using spatiotemporal modelling, we show that across Jiangsu province, the topsoil OC on average has increased from 8.5 g kg-1 to 9.9 g kg-1 from 1980 to 2000 and a further increase to 12.6 g kg-1 in 2010. This increase was accompanied by a decrease in average pH from 7.63 to 6.90. In Guangdong, there was an overall increase in average topsoil OC content from 14.2 g kg-1, 16.5 g kg-1, and 20.2 g kg-1 with a decrease in average pH from 5.58, 4.90, and 4.98. Based on the spatiotemporal modelling results, the structural equation modelling analysis shows that OC and pH changes were significantly correlated and linked by increased soil N content. On croplands, soil N content was mainly attributed to N fertiliser application. The pH decrease was particularly significant in the east of China where the soils were neutral in pH. We recommend that more revolutionary means be taken to sequestrate atmospheric carbon into soil as the current OC increase due to increasing crop productivity via a high rate of nitrogen application may have a potential acidification effect.

Deep accumulation of soluble organic nitrogen after land-use conversion from woodlands to orchards in a subtropical hilly region.

Accumulation of soluble organic nitrogen (SON) in soil poses a significant threat to groundwater quality and plays an important role in regulating the global nitrogen cycle; however, most related studies have focused only on the upper 100-cm soil layers. Surface land-use management and soil properties may affect the vertical distribution of SON; however, their influence is poorly understood in deep soil layers. Therefore, this study assessed the response of SON concentration, pattern, and storage in deep regoliths to land-use conversion from woodlands to orchards in a subtropical hilly region. Our results showed that the SON stocks of the entire soil profile (up to 19.5 m) ranged from 254.5 kg N ha-1 to 664.1 kg N ha-1. Land-use conversion not only reshaped the distribution pattern of SON, but also resulted in substantial accumulation of SON at the 0-200 cm soil profile in the orchards compared to that in the woodlands (124.1 vs 190.5 kg N ha-1). Land-use conversion also altered the SON/total dissolved nitrogen ratio throughout the regolith profile, resulting in a relatively low (<50 %) ratio in orchard soils below 200 cm. Overall, 76.8 % of SON (338.4 ± 162.0 kg N ha-1) was stored in the layers from 100 cm below the surface to the bedrock. Regolith depth (r = -0.52 and p < 0.05) was found to be significantly correlated with SON concentration, explaining 17.8 % of the variation in SON, followed by total nitrogen (14.4 %), total organic carbon/total nitrogen ratio (10.1 %), and bulk density (9.3 %). This study provides insights into the estimation of terrestrial nitrogen and guidance for mitigation of groundwater contamination risk due to deep accumulation of SON.

Mapping high resolution National Soil Information Grids of China.

Soil spatial information has traditionally been presented as polygon maps at coarse scales. Solving global and local issues, including food security, water regulation, land degradation, and climate change requires higher quality, more consistent and detailed soil information. Accurate prediction of soil variation over large and complex areas with limited samples remains a challenge, which is especially significant for China due to its vast land area which contains the most diverse soil landscapes in the world. Here, we integrated predictive soil mapping paradigm with adaptive depth function fitting, state-of-the-art ensemble machine learning and high-resolution soil-forming environment characterization in a high-performance parallel computing environment to generate 90-m resolution national gridded maps of nine soil properties (pH, organic carbon, nitrogen, phosphorus, potassium, cation exchange capacity, bulk density, coarse fragments, and thickness) at multiple depths across China. This was based on approximately 5000 representative soil profiles collected in a recent national soil survey and a suite of detailed covariates to characterize soil-forming environments. The predictive accuracy ranged from very good to moderate (Model Efficiency Coefficients from 0.71 to 0.36) at 0-5 cm. The predictive accuracy for most soil properties declined with depth. Compared with previous soil maps, we achieved significantly more detailed and accurate predictions which could well represent soil variations across the territory and are a significant contribution to the GlobalSoilMap.net project. The relative importance of soil-forming factors in the predictions varied by specific soil property and depth, suggesting the complexity and non-stationarity of comprehensive multi-factor interactions in the process of soil development.

Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases.

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

Soil acidification and loss of base cations in a subtropical agricultural watershed.

Soil acidification along with base cations loss degrades soil quality and is a major environmental problem, especially in agroecosystems with extensive nitrogen (N) fertilization. So far, the rates of proton (H+) production and real soil acidification (loss of base cations) remain unclear in subtropical agricultural watersheds. To assess the current status and future risk of soil acidification in subtropical red soil region of China, a two-year monitoring was conducted in a typical agricultural watershed with upland, paddy fields, and orchards where high N fertilizers are applied (320 kg N ha-1 yr-1). H+ production, neutralization and base cations losses were quantified based on the inputs (rainwater, inflow of water, and fertilizer) and outputs (outflow of water, groundwater drainage, and plant uptake) of major elements (K+, Ca2+, Na+, Mg2+, Al3+, NH4+, NO3-, SO42-, Cl-, and H+). The result showed that total H+ production in the watershed was 5152 molc ha-1 yr-1. N transformation was the most important H+ source (68%), followed by excess plant uptake of cations (25%) and H+ deposition (7%). Base cations exchange and weathering of minerals (3842 molc ha-1 yr-1) dominated H+ neutralization, followed by SO42- adsorption (1081 molc ha-1 yr-1), while H+ and Al3+ leaching amounted to 431 molc ha-1 yr-1, only. These results state clearly that despite significant soil acidification, the acidification of surface waters is minor, implying that soils have buffered substantially the net H+ addition. As a result of soil buffering, there was abundant loss of base cations, whose rate is significantly higher than the previously reported weathering rate of minerals in red soils (3842 vs 230-1080 molc ha-1 yr-1). This suggests that the pool of exchangeable base cations is being depleted in the watershed, increasing the vulnerability of the watershed, and posing a serious threat to future recovery of soils from acidification.

Significant loss of soil inorganic carbon at the continental scale.

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and CO2 release. However, to date, few studies have addressed these processes. Here, we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon (SIC) stocks in China. We observe an overall decrease in SIC stocks in topsoil (0-30 cm) (11.33 g C m-2 yr-1) from the 1980s to the 2010s. Total SIC stocks have decreased by ∼8.99 ± 2.24% (1.37 ± 0.37 Pg C). The average SIC losses across China (0.046 Pg C yr-1) and in cropland (0.016 Pg C yr-1) account for ∼17.6%-24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland, respectively. Nitrogen deposition and climate change have profound influences on SIC cycling. We estimate that ∼19.12%-19.47% of SIC stocks will be further lost by 2100. The consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration, which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.

Copper migration and isotope fractionation in a typical paddy soil profile of the Yangtze Delta.

To decipher Cu migration in paddy soils, which is important for understanding Cu supply in rice cultivation, Cu concentrations and isotope compositions were measured in a paddy soil profile in Suzhou, Eastern China, in the central Yangtze Delta. The results show that the variations in δ65Cu values and Cu concentrations are not coupled along the profile. From top to bottom, the δ65Cu values show small variations (0.07 ± 0.03‰ to 0.25 ± 0.01‰) in the upper layers (Ap-Br1), with a decrease in the subsurface Br2 layer (from 0.16 ± 0.04‰ to -0.19 ± 0.02‰), are almost homogeneous in the transitional Br3-BCrg layers (-0.01 ± 0.01‰ to -0.10 ± 0.02‰), and further decrease to -0.33 ± 0.01‰ in the permanently submerged G1 and G2 layers. Copper concentrations in the Ap layer show some fluctuations (25.8 to 29.0 µg/g), increase in the Br2 and Br3 layers (23.9 µg/g to 31.9 µg/g), and then decrease to 15.1 µg/g in the lower layers. The lack of coupling between δ65Cu values and Cu concentrations may be ascribed to various physicochemical conditions in different layers. In the upper layers, Cu(I) enriched in light isotopes migrates downward with soil solutions under flooded conditions, leaving the soils of the Ap and Br1 layers enriched in heavy Cu isotopes. In the Br2 layer, the readsorption of light Cu isotopes on clay minerals results in decreased δ65Cu values and increased Cu concentrations. In the Br3-BCrg layers, Cu(I) can be oxidized to Cu(II). The homogeneous Cu isotopes in these layers may mainly result from equilibrium adsorption of Cu on clay minerals. The decreased δ65Cu values and Cu concentrations in the G layer are mainly attributed to groundwater transport in this layer. This study represents the Cu isotope variations in a paddy soil profile and the possible mechanism of Cu isotope fractionation.

Seasonal dynamics of soil pH and N transformation as affected by N fertilization in subtropical China: An in situ 15N labeling study.

Nitrogen (N)-induced soil acidification has received much attention worldwide. Nitrification and soil N mineralization are two key N cycle processes that affect soil acidification. However, the seasonal dynamics of soil pH under their combined influence is unclear. We studied the effect of N fertilization on soil pH and N transformations using 15N tracing in field lysimeters with soils developed from different parent materials (Quaternary red clay, sandstone, and basalt). Maize was planted with 200 kg N ha-1 yr-115N-labeled urea addition. During 7-45 days after fertilization, proton (H+) production due to nitrification of fertilizer N, nitrate (NO3-) leaching, and plant uptake exceeded H+ consumption by base cations mobilization and leaching, resulting in a significant soil pH decline. When nitrification activity decreased (after 45 days), due to exhausted ammonium (NH4+) availability, soil pH rose again. During the fallow period, acid neutralization due to base cation mobilization, and ammonification of soil organic N (SON) offset H+ production caused by nitrification of mineralized SON, leading to a sustained rise in soil pH. After the one-year experiment, no significant soil pH decrease was observed in any of the soils. Parent material had little effect on the seasonal dynamics of soil acidification, which appeared to be controlled by fertilization, environmental factors (temperature and moisture), and plant uptake. In subtropical regions, monitoring of soil pH on an annual basis may mask the effect of N fertilization on soil acidification.

Nitrate runoff loss and source apportionment in a typical subtropical agricultural watershed.

Nitrate (NO3-) loss and enrichment in water bodies caused by fertilization are a major environmental problem in agricultural areas. However, the quantitative contribution of different NO3- sources, especially chemical fertilizers (CF) and soil organic nitrogen (SON), to NO3- runoff loss remains unclear. In this study, a systematic investigation of NO3- runoff and its sources was conducted in a subtropical agricultural watershed located in Yujiang County, Jiangxi Province, China. A semi-monthly sampling was performed at the inlet and outlet from March 2018 to February 2019. Hydrochemical and dual NO3- isotope (15 N and 18O) approaches were combined to estimate the NO3- runoff loss and quantify the contribution of different sources with a Bayesian isotope mixing model. Source apportionment by Stable Isotope Analysis in R (SIAR) suggested that NO3- in runoff was mainly derived from nitrification of ammonium (NH4+) mineralized from SON (37-52%) and manure/sewage (M&S) (25-47%), while the contribution of CF was relatively small (14-25%). The contribution of various sources showed seasonal variations, with a greater contribution of CF in the wet growing season (March to August). Compared with the inlet which contributed 37-40% to runoff NO3-, SON contributed more at the outlet (49-52%). Denitrification in the runoff was small and appeared to be confined to the dry season (September to February), with an estimated NO3- loss of 2.73 kg N ha-1. The net NO3- runoff loss of the watershed was 34.5 kg N ha-1 yr-1, accounting for 15% of the annual fertilization rate (229 kg N ha-1 yr-1). Besides M&S (22%), fertilization and remineralization of SON (CF + SON) were the main sources for the NO3- runoff loss (78%), suggesting accelerated nitrification of NH4+ from CF (24%) and SON mineralization (54%). Our study indicates that NO3- runoff loss in subtropical agricultural watersheds is dominated by nonpoint source pollution from fertilization. SON played a more important role than CF. Besides, the contribution of sewage should not be neglected. Our data suggest that a combination of more rational fertilizer N application (CF), better management of SON, and better treatment of domestic sewage could alleviate NO3- pollution in subtropical China.

A Hypercoagulable Hematological Metastasis Breast Cancer Model.

BACKGROUND: The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. METHODS: Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. RESULTS: The multiple linear regression model was constructed as log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 17) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. CONCLUSIONS: In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.

Potentially Overestimated Efficacy of Nanoparticle Albumin-bound Paclitaxel compared with Solvent-based Paclitaxel in Breast Cancer: A Systemic Review and Meta-analysis.

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has exhibited clinical efficacy in breast cancer treatment, but toxicities can be yielded more at the same time. We did this meta-analysis aiming to unambiguously compare nab-PTX with conventional solvent-based paclitaxel (sb-PTX) in breast cancer patients of all stages. Method: Pubmed, Embase and Cochrane Library were searched for head-to-head randomized controlled trials of nab-PTX and sb-PTX in breast cancer. Risk ratio (RR) with 95% confidence interval was used for dichotomous variables while Hazard ratio (HR) was used for time-to-event outcomes. Results: Our review finally included 9 studies with 3508 patients. Nab-PTX showed a benefit on objective response rate (ORR) (RR=1.22 [1.04-1.43], P=0.01) as well as non-inferiority compared with sb-PTX in disease control rate (DCR) (RR=1.01 [0.98-1.04], P=0.44), overall survival (OS) (HR=0.99 [0.93-1.05], P=0.81) and disease free survival/progression free survival (DFS/PFS) (HR=0.92 [0.81-1.05], P=0.21). However, when it comes to toxicities (fatigue, nausea or vomiting, peripheral sensory neuropathy and adverse event related discontinuation), results favored sb-PTX (RR=2.89 [1.07-7.8], 3.15 [1.78-5.59], 2.11 [1.32-3.37], 2.02 [1.61-2.53]; P<0.05). Patients with metastatic tumors or undergoing conventional schedule responses better to nab-PTX than the compared groups (RR of ORR in metastatic vs early or locally advanced patients: 1.46 [1.09-1.96] vs 1.01 [0.94-1.08]; conventional vs dose dense group: 1.59 [1.23-2.06] vs 1.01 [0.91-1.12]). Conclusions: Nab-PTX can improve ORR compared with paclitaxel and should be given priority to when aiming to reduce tumor load in breast cancer. Sb-PTX of dose dense schedule is recommended when toxicity of nab-PTX is hard to bear for breast cancer patients.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

SANT, a novel Chinese herbal monomer combination, decreasing tumor growth and angiogenesis via modulating autophagy in heparanase overexpressed triple-negative breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

Deep Nitrate Accumulation in a Highly Weathered Subtropical Critical Zone Depends on the Regolith Structure and Planting Year.

Nitrate accumulated deep (>100 cm) in the regolith (soil and saprolite) threatens groundwater quality, but most studies focus only on nitrate nearer the surface (<100 cm). Surface soil management versus regolith interactions affect deep nitrate leaching, but their combined impact remains unclear. This study measured how deep nitrate accumulation was affected by crop practices including orchard/cropland planting years, regolith structure, and soil properties in highly weathered subtropical red soils. Deep nitrate storage varied from 43.6 to 1116.3 kg ha-1. Regolith thickness was positively correlated with nitrate storage (R2 = 0.43, p < 0.05). Reticulated red clay (110-838 cm) had 81% of the accumulated nitrate and overlapped with 79% of the nitrate accumulation layer. All of the nitrate accumulation parameters (except for peak depth (PD)) generally increased with the planting years. The difference in peak nitrate concentration (9.0-20.0 mg kg-1) with planting year gradient (3-58 years) varied by 2.2 times, and the difference in nitrate storage (43.6-425.7 kg ha-1) varied by 9.8 times. Texture and pH explain 41.6% of the variation in nitrate concentration. As soil management practices interact with deeper regolith to control the spatial pattern of nitrate accumulation, vulnerable regions could be identified to avoid high accumulation.

Heparanase from triple­negative breast cancer and platelets acts as an enhancer of metastasis.

Triple­negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia­inducible factor­1a (HIF-1a)/vascular endothelial growth factor­a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti­Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

Iron Stable Isotopes in Bulk Soil and Sequential Extracted Fractions Trace Fe Redox Cycling in Paddy Soils.

In paddy soils, iron (Fe) forms are highly influenced by the seasonal redox changes and leave detectable isotope signals because of fractionation between different Fe forms. Here, we present Fe concentrations and Fe isotope compositions (expressed as δ56Fe values) in a paddy soil profile from Suzhou, China. Light Fe isotopes were enriched in two iron-accumulation layers (Br3 and G1) with high Fe concentrations. In particular, large shifts in both Fe concentrations and δ56Fe values were found at the Br2 and Br3 boundaries, showing fast and efficient transformation between these horizons. With sequential extraction, we show that Fe isotopes in the short-range-ordered Fe minerals and crystalline Fe oxides were lighter than those in the residual silicate minerals. Iron enriched in light isotopes was leached from the Ap horizon and subsequently moved to Br horizon, quickly precipitating there as Fe oxides.