Phosphorus fertilization enhances terrestrial carbon cycling in phosphorus-deficient ecosystems.

Anthropogenic phosphorus (P) input into terrestrial soils have been greatly increased, with potential effects on both above- and belowground carbon (C) cycling processes. However, uncertainty about how plant-soil-microbe systems respond to P fertilization makes it difficult to predict the effects of anthropogenic P input on the terrestrial C cycling. In this study, we conducted a global meta-analysis, examining 1183 observations from 142 publications. The findings revealed that P fertilization consistently promoted C cycling variables in plant-soil-microbe systems, resulting in improvements ranging from 7.6% to 49.8% across various ecosystem types. Notably, these positive effects of P fertilization were more pronounced with higher application rates and longer experimental durations. As the background P contents increased, the functions of P fertilization in C cycling variables shifted from positive to negative. Structural equation modeling demonstrated that changes in plant inputs predominantly drove the positive impacts of P fertilization rate and experimental duration, as well as the negative impacts of background P contents on soil respiration and microbial biomass C responses to P fertilization. Our study demonstrated the coherent responses of terrestrial C cycling processes to P fertilization and highlighted the significance of P fertilization boosting C cycling processes in P-deficient ecosystems. We suggested that minimizing the application of P fertilization in P-rich environments would enhance C sequestration and reduce P-induced environmental pollution.

Phosphorus additions imbalance terrestrial ecosystem C:N:P stoichiometry.

Carbon (C):nitrogen (N):phosphorus (P) stoichiometry in plants, soils, and microbial biomass influences productivity and nutrient cycling in terrestrial ecosystems. Anthropogenic inputs of P to ecosystems are increasing; however, our understanding of the impacts of P addition on terrestrial ecosystem C:N:P ratios remains elusive. By conducting a meta-analysis with 1413 paired observations from 121 publications, we showed that P addition significantly decreased plant, soil, and microbial biomass N:P and C:P ratios, but had negligible effects on C:N ratios. The reductions in N:P and C:P ratios became more evident as the P application rates and experimental duration increased. The P addition effects on terrestrial ecosystem C:N:P stoichiometry did not vary with ecosystem types or climates. Moreover, the responses of N:P and C:P ratios in soil and microbial biomass were associated with the responses of soil pH and fungi:bacteria ratios. Additionally, P additions increased net primary productivity, microbial biomass, soil respiration, N mineralization, and N nitrification, but decreased ammonium and nitrate contents. Decreases in plant N:P and C:P ratios were both negatively correlated to net primary productivity and soil respiration, but positively correlated to ammonium and nitrate contents; microbial biomass, soil respiration, ammonium contents, and nitrate contents all increased with declining soil N:P and C:P ratios. Our findings highlight that P additions could imbalance C:N:P stoichiometry and potentially impact the terrestrial ecosystem functions.

Meta-analysis shows that plant mixtures increase soil phosphorus availability and plant productivity in diverse ecosystems.

Soil phosphorus (P) availability is critical to plant productivity in many terrestrial ecosystems. How soil P availability responds to changes in plant diversity remains uncertain, despite the global crisis of rapid biodiversity loss. Our meta-analysis based on 180 studies across various ecosystems (croplands, grasslands, forests and pot experiments) shows that, on average, soil total P, phosphatase activity and available P are 6.8%, 8.5% and 4.6%, respectively, higher in species mixtures than in monocultures. The mixture effect on phosphatase activity becomes more positive with increasing species and functional group richness, with more pronounced increases in the rhizosphere than in the bulk soil. The mixture effects on soil-available P in the bulk soil do not change, but with increasing species or functional group richness these effects in the rhizosphere soil shift from positive to negative. Nonetheless, enhanced soil phosphatase activity stimulated available P in diverse species mixtures, offsetting increased plant uptake effects that decrease soil-available P. Moreover, the enhancement effects of species richness on soil phosphatase activity are positively associated with increased plant productivity. Our findings highlight that preserving plant diversity could increase soil phosphatase activity and P availability, which sustain the current and future productivity of terrestrial ecosystems.

Plant mixture balances terrestrial ecosystem C:N:P stoichiometry.

Plant and soil C:N:P ratios are of critical importance to productivity, food-web dynamics, and nutrient cycling in terrestrial ecosystems worldwide. Plant diversity continues to decline globally; however, its influence on terrestrial C:N:P ratios remains uncertain. By conducting a global meta-analysis of 2049 paired observations in plant species mixtures and monocultures from 169 sites, we show that, on average across all observations, the C:N:P ratios of plants, soils, soil microbial biomass and enzymes did not respond to species mixture nor to the species richness in mixtures. However, the mixture effect on soil microbial biomass C:N changed from positive to negative, and those on soil enzyme C:N and C:P shifted from negative to positive with increasing functional diversity in mixtures. Importantly, species mixture increased the C:N, C:P, N:P ratios of plants and soils when background soil C:N, C:P, and N:P were low, but decreased them when the respective background ratios were high. Our results demonstrate that plant mixtures can balance terrestrial plant and soil C:N:P ratios dependent on background soil C:N:P. Our findings highlight that plant diversity conservation does not only increase plant productivity, but also optimizes ecosystem stoichiometry for the diversity and productivity of today's and future vegetation.

Effects on the structure and properties of native corn starch modified by enzymatic debranching (ED), microwave assisted esterification with citric acid (MCAE) and by the dual ED/MCAE treatment.

Native corn starch was modified by enzymatic debranching (ED), microwave assisted citric acid esterification (MCAE), and by dual ED/MCAE. The structure and properties of native starch (NS), and the resulting debranched starch (DS), microwave assisted citric acid esterified starch (MCS), and microwave assisted citric acid debranched starch (MCDS) were determined and compared. Both the morphology and crystalline regions of the modified starches were changed by ED and MCAE. ED increased significantly the amylose content and transparency, but decreased the in vitro enzymatic digestibility, freeze thaw stability and relative crystallinity of DS compared to those of NS. MCAE produced a decrease in amylose content, transparency, in vitro enzymatic digestibility, and relative crystallinity, but increased the freeze-thaw stability of MCS compared to NS, and of MCDS compared to DS. The A-type crystalline structure of NS and DS was changed to B-type crystalline structure after MCAE treatment, and a new FTIR characteristic band at 1735 cm-1 was observed for MCS and MCDS. This work provides insights for producing esterified corn starches by a combined enzyme, microwave and organic acid novel technology.

Artificial intelligence in tongue diagnosis: Using deep convolutional neural network for recognizing unhealthy tongue with tooth-mark.

Tongue diagnosis plays a pivotal role in traditional Chinese medicine (TCM) for thousands of years. As one of the most important tongue characteristics, tooth-marked tongue is related to spleen deficiency and can greatly contribute to the symptoms differentiation and treatment selection. Yet, the tooth-marked tongue recognition for TCM practitioners is subjective and challenging. Most of the previous studies have concentrated on subjectively selected features of the tooth-marked region and gained accuracy under 80%. In the present study, we proposed an artificial intelligence framework using deep convolutional neural network (CNN) for the recognition of tooth-marked tongue. First, we constructed relatively large datasets with 1548 tongue images captured by different equipments. Then, we used ResNet34 CNN architecture to extract features and perform classifications. The overall accuracy of the models was over 90%. Interestingly, the models can be successfully generalized to images captured by other devices with different illuminations. The good effectiveness and generalization of our framework may provide objective and convenient computer-aided tongue diagnostic method on tracking disease progression and evaluating pharmacological effect from a informatics perspective.

Microenvironment Remodeling Micelles for Alzheimer's Disease Therapy by Early Modulation of Activated Microglia.

Current strategies for Alzheimer's disease (AD) treatments focus on pathologies in the late stage of the disease progression. Poor clinical outcomes are displayed due to the irreversible damages caused by early microglia abnormality which triggers disease development before identical symptoms emerge. Based on the crosstalk between microglia and brain microenvironment, a reactive oxygen species (ROS)-responsive polymeric micelle system (Ab-PEG-LysB/curcumin (APLB/CUR)) is reported to normalize the oxidative and inflammatory microenvironment and reeducate microglia from an early phase of AD. Through an ß-amyloid (Aß) transportation-mimicked pathway, the micelles can accumulate into the diseased regions and exert synergistic effects of polymer-based ROS scavenging and cargo-based Aß inhibition upon microenvironment stimuli. This multitarget strategy exhibits gradual correction of the brain microenvironment, efficient neuroprotection, and microglia modulation, leading to decreased Aß plaque burdens and consequently enhanced cognitive functions in APPswe/PSEN1dE9 model mice. The results indicate that microglia can be exploited as an early target for AD treatment and their states can be controlled via microenvironment modulation.

Double-sided effect of tumor microenvironment on platelets targeting nanoparticles.

The cancer cells and stromal cells in tumor microenvironment secrete cytokines and recruit "homing" cells (macrophage, lymphocytes, platelets, etc.). Platelets can interact with tumor microenvironment and specifically aggregate at tumor sites. Surprising, we observed different "homing" effects of activated platelets in breast cancer model and pancreatic cancer model which is highly related with the blood supply of tumors. Besides, platelets targeting magnetic nanoparticles (MNPs) can home to breast cancer but be repelled from pancreatic cancer. We observed the targeting effect of MNPs is highly related with the expressions of collagen Ⅰ (marker of extracellular matrix) and CD34 (marker of tumor neovascularization). The homing nanoparticles such as platelets targeting MNPs could realize the tumor targeting ability, photo-thermal effect and tumor immunotherapeutic ability in the accessible tumor (e.g. breast cancer) but not the hypovascular tumor (e.g. pancreatic cancer).

A targeting theranostics nanomedicine as an alternative approach for hyperthermia perfusion.

Real-time monitoring drug-release is often regarded crucial in theranostics nanomedicine design, since it provides precise establishment of spatio-temporal activation of the drug-release in vitro and in vivo. A symmetrical self-immolative drug-dye conjugation (DDC) prodrug is developed in this study with disulfide bond as the trigger. The prodrug can be escorted by targeting PEG-PLGA micelles and hereby accumulated in the tumor by both active and passive targeting effect. Glutathione (GSH) with higher concentration in the tumor microenvironment can readily cleave the disulfide bond to initiate a subsequent decomposition of DDC, where the drug and dye can be released simultaneously in a strict one-to-one mode. Upon the disintegration, the "Turned-On" probe can emit near-infrared (NIR) fluorescence, with the aim of providing accurate and real-time information for the prodrugs' activation and biodistribution in vivo in a non-invasive way. Furthermore, the released dye can meanwhile act as a photothermic sensitizer, which can in-situ assist a deep penetration for the released drug in the tumor tissue with enhanced therapeutic efficiency. This "babysitting" strategy provides new reference for designing versatile theranostic nanomedicines for preclinical evaluations and an alternative approach for hyperthermia perfusion in clinic.

Protective effects of calycosin against CCl4-induced liver injury with activation of FXR and STAT3 in mice.

PURPOSE: Investigating the hepatoprotective effect of calycosin against acute liver injury in association with FXR activation and STAT3 phosphorylation. METHODS: The acute liver injury model was established by intraperitoneal injection of CCl4 in C57BL/6 mice. Serum alanine aminotransferase, aspartate aminotransferase, HE staining and TUNEL assay were used to identify the amelioration of the liver histopathological changes and hepatocytes apoptosis after calycosin treatment. ELISA kit and 5-bromo-2-deoxyuridine immunohistochemistry were used to measure the liver bile acid concentration and hepatocyte mitotic rate in vivo. The relation between calycosin and activation of FXR and STAT3 was comfirmed using the Luciferase assay, Molecular docking, Real-time PCR and Western Blot in vitro. RESULTS: The liver histopathological changes, hepatocytes apoptosis, liver bile acid overload and hepatocyte mitosis showed significant changes after calycosin treatment. Calycosin promoted the expression of FXR target genes such as FoxM1B and SHP but the effect was reversed by FXR suppressor guggulsterone. Molecular docking results indicated that calycosin could be embedded into the binding pocket of FXR, thereby increasing the expressions of STAT3 tyrosine phosphorylation and its target genes, Bcl-xl and SOCS3. CONCLUSIONS: Calycosin plays a critical role in hepatoprotection against liver injury in association with FXR activation and STAT3 phosphorylation.

Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa.

Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1,000 biopsy specimens from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ERα) and secreted frizzled related protein-1 (SFRP1), using bisulfite pyrosequencing. We used generalized estimating equations regression analysis to examine the association between methylation and selected variables. For both ERα and SFRP1, percentage methylation was significantly higher in the rectum than in the right colon (P = 0.001). For each 10 years of age, we observed a 1.7% increase in methylation level for ERα and a 2.9% increase for SFRP1 (P < 0.0001). African Americans had a significantly lower level of ERα and SFRP1 methylation than Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ERα (P = 0.03) and SFRP1 methylation (P = 0.01). Our results suggest that CGI methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults, given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia.

Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.

BACKGROUND: Global loss of methylated cytosines in DNA, thought to predispose to chromosomal instability and aneuploidy, has been associated with an increased risk of colorectal neoplasia. Little is known about the relationships between global hypomethylation and lifestyle, demographics, dietary measures, and genetic factors. METHODS: Our data were collected as part of a randomized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas. At a surveillance colonoscopy approximately 3 years after the qualifying exam, we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon. Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 (long interspersed nucleotide elements) repeats. RESULTS: The analysis included data from 388 subjects. There was relatively little variability in LINE methylation overall. Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side (P < 0.0001). No significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes. Race, dietary folic acid, and plasma B(6) showed associations with global methylation that differed between the right and the left bowel. The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation, and we found no association between LINE-1 methylation and risk of adenomas. CONCLUSIONS: LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite.