Adaptation Strategies of Seedling Root Response to Nitrogen and Phosphorus Addition.

The escalation of global nitrogen deposition levels has heightened the inhibitory impact of phosphorus limitation on plant growth in subtropical forests. Plant roots area particularly sensitive tissue to nitrogen and phosphorus elements. Changes in the morphological characteristics of plant roots signify alterations in adaptive strategies. However, our understanding of resource-use strategies of roots in this environment remains limited. In this study, we conducted a 10-month experiment at the Castanopsis kawakamii Nature Reserve to evaluate the response of traits of seedling roots (such as specific root length, average diameter, nitrogen content, and phosphorus content) to nitrogen and phosphorus addition. The aim was to reveal the adaptation strategies of roots in different nitrogen and phosphorus addition concentrations. The results showed that: (1) The single phosphorus and nitrogen-phosphorus interaction addition increased the specific root length, surface area, and root phosphorus content. In addition, single nitrogen addition promotes an increase in the average root diameter. (2) Non-nitrogen phosphorus addition and single nitrogen addition tended to adopt a conservative resource-use strategy to maintain growth under low phosphorus conditions. (3) Under the single phosphorus addition and interactive addition of phosphorus and nitrogen, the roots adopted an acquisitive resource-use strategy to obtain more available phosphorus resources. Accordingly, the adaptation strategy of seedling roots can be regulated by adding appropriate concentrations of nitrogen or phosphorus, thereby promoting the natural regeneration of subtropical forests.

miR-552 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma by targeting FOXO1.

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly malignant cancer. Few effective systemic targeted therapies are available for patients with unresectable ICC, but there exists an urgent need to explore mechanisms underlying the initiation and progression of ICC. MicroRNA (miRNA) plays vital roles in the initiation, progression, and drug resistance of different cancers. Recently, the biological function of a novel miRNA, miR-552, has been widely analyzed in hepatocellular carcinoma and colorectal, cervical, gastric, and other cancers. However, its role in ICC has not yet been elucidated. In this study, we found that miR-552 expression was upregulated in ICC and that miR-552 predicted poor prognosis. Using functional studies, we found that miR-552 enhanced the proliferation and invasion ability of ICC cells. Mechanistic research identified that forkhead box O1 (FOXO1) is the target of miR-552 in ICC. Moreover, the combined panels of miR-552 and FOXO1 exhibited a better prognostic value for ICC patients than did miR-552 alone. In conclusion, these findings demonstrated that the miR-552/FOXO1 axis drove ICC progression, further suggesting that targeting this axis could be a novel therapeutic strategy for ICC.

Postoperative Prognosis of Non-alcoholic Fatty Liver Disease-Associated Intrahepatic Cholangiocarcinoma: a Multi-center Propensity Score Matching Analysis.

BACKGROUND AND AIMS: The incidence of intrahepatic cholangiocarcinoma (ICC) in non-alcoholic fatty liver disease (NAFLD) is increasing gradually. The prognosis of NAFLD-ICC has not been well studied. We aim to investigate the prognosis of patients with NAFLD-ICC after curative-intent partial hepatectomy (PH). METHODS: Multi-center data from January 2003 to January 2014 were retrospectively analyzed. The prognosis of ICC was analyzed using PSM and compared with hepatitis B virus (HBV)-related ICC. RESULTS: A total of 898 patients with ICC were included in this study. Of them, 199 (22.2%) were NAFLD-ICC, and 699 (77.8%) were HBV-ICC. Multivariate analysis showed that CA19-9 ≥ 37 U/mL, microvascular invasion, tumor size > 5 cm, multiple tumors, and lymph node (LN) metastasis were independent risk factors for early recurrence (ER) in ICC patients. After a 1:1 PSM, NAFLD-ICC has worse 5-year overall survival (OS) (24.0% vs. 48.9%), 5-year recurrence (80.9% vs. 55.0%), and ER (58.5% vs. 30.0%) than that of HBV-ICC (all P < 0.01). Multivariable analysis showed NAFLD was an independent risk factor for OS (hazard ratio [HR] 2.26, 95% CI 1.63-3.13, P < 0.001), tumor recurrence (HR 2.24, 95%CI 1.61-3.10, P < 0.001) and ER (HR 2.23, 95%CI 1.60-3.09, P < 0.001) in patients with ICC after PH. The sensitivity analysis indicated that NAFLD-ICC patients were more likely to experience ER. CONCLUSION: Compared with HBV-ICC, NAFLD-ICC has a worse prognosis and was more likely to relapse early. More frequent surveillance should be considered.

Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC). AIM: To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC. METHODS: This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. RESULTS: Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings. CONCLUSIONS: Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.

[Responses of chlorophyll fluorescence and non-structural carbohydrate accumulation of Castanopsis kawakamii seedlings to seed dispersal positions]. / æ ¼æ°æ ²å¹¼è‹—å¶ç»¿ç´ è§å ‰å’Œéžç»“æž„æ€§ç¢³æ°´åŒ–åˆç‰©ç§¯ç´¯å¯¹ç§å­æ•£å¸ƒä½ç½®çš„å“åº”.

When seeds fallen from the mother trees, their initial contact physical environment was litter or soil. The dispersal positions of seeds (seeds positioned on top of the litter, the soil surface and beneath the litter) determine the process of their natural regeneration. We simulated three different dispersal positions of Castanopsis kawakamii, including seeds positioned on top of the litter (2 and 4 cm litter was placed below the seed layer), soil surface (without litter), and seeds beneath the litter (2, 4, 6 and 8 cm litter covers in the upper layer of seeds). We examined the effects of seed dispersal position on the chlorophyll fluorescence characteristics, non-structural carbohydrate, specific leaf area, leaf dry matter content and nutrient content of seedlings. The results showed that leaf nitrogen content per area of seedlings had significantly positive correlation with soluble sugar content, non-structural carbohydrate content, and negative correlation with specific leaf area across different dispersal positions. Seedlings of the moderate litter cover (2 and 4 cm) adopted resource acquisitive strategies by increasing relative chlorophyll content, soluble sugar content, non-structural carbohydrate content, leaf dry matter content, leaf nitrogen content and phosphorus contents per area, and decreasing specific leaf area to achieve their demands for rapid growth. Seedlings grew on soil surface and beneath the deep litter (6 and 8 cm) adopted the resource conservative strategies with higher leaf nitrogen content per mass and specific leaf area, lower leaf dry matter content, and non-structural carbohydrate content to intercept more effective light resources to compensate for the shady environment brought by deep litter. This would further decrease the probability of seedling mortality due to 'carbon starvation'. Seedlings under litter layer stored starch in leaf, and reduced the energy consumption of photosynthetic tissues (low PSⅡ maximum photochemical efficiency) to maintain seedling growth. Comprehensive analysis of entropy method indicated that low amount of litter cover (2 cm) significantly promoted seedling growth of C. kawakamii. In the future, we could regulate the thickness of litter layer to promote the growth and regeneration of C. kawakamii seedlings in natural forest.

Bioinspired DNA nanocockleburs for targeted delivery of doxorubicin.

A variety of three-dimensional DNA assemblies have been proposed as drug carriers owing to their good biocompatibility and easy fabrication. In this study, inspired by the structure of cockleburs, a novel aptamer-tethered DNA assembly was developed for effective targeted drug delivery. The Apt-nanocockleburs were fabricated via a facile process of DNA base pairing: four complementary DNA single strands, including one aptamer-ended strand and three sticky-end strands, were applied to pair with each other. The main body of the nanocockleburs can load doxorubicin (Dox) whilst the covered aptamer spines bind to the target MCF-7 cells. The self-assembled Apt-nanocockleburs exhibit higher cell uptake as well as increased cytotoxicity to MCF-7 cells than DNA nanocockleburs without aptamers. This study provided a DNA constructing platform to produce new drug carriers with high selectivity for cancer targeted drug delivery.

Surgical repair of abdominal wall defect with biomimetic nano/microfibrous hybrid scaffold.

It is universal to repair abdominal wall defects with prosthetic materials in abdominal surgery worldwide, which are associated with high complications and organ damage. At present, the composite nanofibers composed of natural and synthetic polymers as the new type of nano structure scaffold have attracted considerable attention in the field of tissue engineering. In this study we examined the feasibility of using electrospun silk fibroin (SF)/poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hybrid scaffolds for repairing of abdominal wall defects. Both in vivo and in vitro characterization were evaluated to access efficacy of the nanofiber for tissue regeneration. Our results showed that the electrospun SF/PHBV nanofiber scaffolds could stimulate the expression of TGF-ß1 and Collagen I in fibroblasts in vitro and then promote granulation and connective tissue depositions, but not result in a strong foreign body reaction in vivo. Moreover, we conjectured the potential molecular biological mechanism of SF/PHBV hybrid scaffolds in the process of tissue regeneration. Thus, the SF/PHBV hybrid nanofiber scaffolds have high efficiency and biocompatibility to repair abdominal wall defects.

MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart disease and its role in heart development.

The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups. The expressions of miR-34a, NOTCH-1, Jagged1, Hes1, Hey2 and Csx in cardiac tissues and ECCs were determined by both RT-qPCR and western blotting methods. MTT assay and flow cytometry were conducted for cell proliferation and apoptosis measurement. A dual luciferase reporter assay was applied to demonstrate that NOTCH-1 was the target gene of miR-34a. In comparison to the normal group, the expressions of miR-34a, Jagged1, Hes1 and Hey2 displayed up-regulated levels, while the expressions of NOTCH-1 and Csx were down-regulated in the CHD group. Compared with the blank and NC groups, the miR-34a mimics and siRNA-NOTCH-1 groups displayed reduced expressions of NOTCH-1 and Csx as well as a decreased proliferation rate, higher miR-34a, Jagged1, Hes1 and Hey2 expressions and an increased rate of apoptosis; while an reverse trend was observed in the miR-34a inhibitors group. The expressions of MiR-34a recorded increased levels in the miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups, however no changes in the expressions of NOTCH-1, Jagged1, Hes1, Hey2, Csx, as well as cell proliferation and apoptosis were observed when compared to the blank and NC groups. The results of our study demonstrated that miR-34a increases the risk of CHD through its downregulation of NOTCH-1 by modulating the Notch signaling pathway.