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Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011–2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR7 − phthalates: 1.56 and WQS OR8 − phthalates: 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.

Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential.

By employing 5-(pyridin-3-yl)-1H-pyrazole-3-carboxylic acid ligand, a new coordination polymer [Cd(HPPC−)2(H2O)2]n (1) has been prepared via the one-pot solvothermal reation with CdI2 and structurally characterized via elemental analysis, FT-IR spectroscopy, single-crystal X-ray diffraction analysis and X-ray powder diffraction. The results represented that 1 is a three-dimensional (3D) framework based on the 2D corrugated layers and Cd–O pillars, which can be considered as a (3,6)-connected trl topology with Schlafli symbol of {4·62}2{42·610·83}. In this work, the photoluminescence and electrogenerated chemiluminescence (ECL) behavior of complex 1 were investigated and thermal stability was confirmed by TGA analysis. Meanwhile, the Brunauer–Emmett–Teller measurement of 1 was also conducted to address the porosity of this 3D structure. Complex 1 exhibited high intense ECL in dimethyl sulfoxide and after eight circulations the ECL efficiency still remained stable, thus providing the possibility for construction of potential polymers ECL materials. In addition, Hirshfeld surface analysis for 1 mapped with various functions and 2D fingerprint plots revealed that the H···H and O···H contacts outnumbered the other contacts in 1 (25.3% and 23.0% of the total interactions, respectively).

Cardiomyocyte apoptosis is critical for the development of viral myocarditis (VMC), which is one of the leading causes of cardiac sudden death in young adults. Our previous studies have demonstrated that elevated calpain activity is involved in the pathogenesis of VMC. This study aimed to further explore the underlying mechanisms. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin were infected with coxsackievirus B3 (CVB3) to establish a VMC model. Apoptosis was detected with flow cytometry, TUNEL staining, and western blotting. Cardiac function was measured using echocardiography. Mitochondrial function was measured using ATP assays, JC-1, and MitoSOX. Mitochondrial morphology was observed using MitoTracker staining and transmission electron microscopy. Colocalization of dynamin-related protein 1 (Drp-1) in mitochondria was examined using immunofluorescence. Phosphorylation levels of Drp-1 at Ser637 site were determined using western blotting analysis. We found that CVB3 infection impaired mitochondrial function as evidenced by increased mitochondrial ROS production, decreased ATP production and mitochondrial membrane potential, induced myocardial apoptosis and damage, and decreased myocardial function. These effects of CVB3 infection were attenuated by inhibition of calpain both by PD150606 treatment and calpastatin overexpression. Furthermore, CVB3-induced mitochondrial dysfunction was associated with the accumulation of Drp-1 in the outer membrane of mitochondria and subsequent increase in mitochondrial fission. Mechanistically, calpain cleaved and activated calcineurin A, which dephosphorylated Drp-1 at Ser637 site and promoted its accumulation in the mitochondria, leading to mitochondrial fission and dysfunction. In summary, calpain inhibition attenuated CVB3-induced myocarditis by reducing mitochondrial fission, thereby inhibiting cardiomyocyte apoptosis. Calpain is activated by CVB3 infection. Activated calpain cleaves calcineurin A and converts it to active form which could dephosphorylate Drp-1 at Ser637 site. Then, the active Drp-1 translocates from the cytoplasm to mitochondria and triggers excessive mitochondrial fission. Eventually, the balance of mitochondrial dynamics is broken, and apoptosis occurs.

A new Trichoderma asperellum strain, TasT1, was isolated from the rhizosphere of Malus sieversii in Xinjiang Region of China. Its antifungal ability was evaluated by controlling root rot Fusarium oxysporum (Fox68) of M. sieversii. The results showed that TasT1 inhibited the growth of Fox68, with an inhibition rate of 66.7%. After treating Arabidopsis thaliana seedlings with different concentrations of TasT1 fermentation liquor, the root hair density of the seedlings changed significantly. Treatment with 60% fermentation liquor caused the root length to increase by 21%, and the fresh weight by 80%. Furthermore, TasT1 fermentation liquor improved the detoxification ability of A. thaliana seedlings against Fox68 toxin and greatly alleviated leaf wilting. Defense-related enzymes (e.g., peroxidase, POD) activity and malondialdehyde content of A. thaliana increased significantly. In addition, in the TasT1 + Fox68 group, the expression levels of PDF1.2B, PDF1.2C, and PR1 were upregulated by 5.2, 5.1, and 2.2 times respectively after treatment for 3 d. Meanwhile, we used GC–MS analysis of chemical component of TasT1 fermentation liquor and found that TasT1 fermentation liquor include 49 kinds of ingredients which contain a lot of antibacterial substances. Our findings suggest that TasT1 fermentation liquor could induce the accumulation of defense-related enzymes to improve disease resistance and growth of A. thaliana seedlings. TasT1 has the potential to control F. oxysporum (Fox68) and protect M. sieversii.

Hiatal hernia repair (HHR) during sleeve gastrectomy (SG) is recommended when hiatal hernia (HH) is found intraoperatively. However, its effect on gastroesophageal reflux disease (GERD) remains controversial. To evaluate the effect of concomitant SG and HHR on GERD in patients with obesity. Web of Science, PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were searched for all studies reporting the efficacy of SG+HHR for patients with obesity and GERD up to March 2021. A total of 18 studies totaling 937 patients met the inclusion criteria. The results of meta-analysis showed that after SG+HHR, there was a significant reduction in GERD symptoms (OR: 0.20; 95% CI: 0.10 to 0.41; P < 0.00001), improvement in esophagitis (OR: 0.12, 95% CI: 0.05 to 0.26, P < 0.001), and decrease in GERD-HRQL (MD: 19.13, 95% CI: −3.74 to 34.51; P=0.01). The incidence of GERD remission after SG+HHR was 68.0% (95% CI: 55.0–80.9%), de novo GERD was 12% (95% CI: 8–16%), and HH recurrence was 11% (95% CI: 4 to 19%). SG+HHR was superior to SG alone in GERD remission (OR: 2.97, 95% CI: 1.78 to 4.95, P < 0.0001). However, there was no significant difference in de novo GERD after SG+HHR compared with SG alone. SG+HHR can positively affect weight loss, GERD resolution, esophagitis reduction, and GERD-HRQL improvement. SG+HHR seems to have a promising future in patients with obesity and GERD. However, further studies based on objective assessment are warranted to evaluate these results better.

Elliptical fin-and-tube heat exchangers are commonly used in air conditioning, heating, refrigeration industries, and ventilation. This study numerically investigates the effect of vortex generators on the performance of elliptical fin-and-tube heat exchanger under different inclination angles. In this study, air flow that is in the transitional regime is selected as the working fluid. Reynolds numbers at the inlet are varied in a range of 1300 to 2100, and the shear stress transport k-ω turbulence model is selected to solve the non-closure of basic turbulence equations. The ellipticity ratios of the tubes which are used for the analysis are between 0.6 and 1.0, and the inclination angles are varied from 15° to 75°. The effects of different inclination angles of vortex generators on the Colburn factor j, friction factor f, and efficiency index j/f are analyzed. The friction and Colburn factors are observed to increase with increasing vortex generator inclination angles. It is found that the efficiency factors for a 15° vortex generator inclination angle at 0.6, 0.7, 0.8, and 0.9 ellipticity ratios improve compared to the corresponding cases with no vortex generator. However, the vortex generator cannot improve the efficiency factor of the circular tube heat exchanger. The 3D CFD method employed by this study has great potential for use in optimally designing the arrangement of the vortex generators to enhance the performance of heat exchangers.

The Japanese flying squid (Todarodes pacificus) is an important fishery resource in East Asia, including Japan, China, and Korea. Recent studies have suggested that it exhibits significant interannual variation with a close relationship with environmental variables, among which water temperature has an apparent influence on its spawning, hatching, and growth. Therefore, we need to understand how the Japanese flying squid in the Japan Sea (JS) will be affected by global warming. Based on particle tracking methods, we simulated migration and individual growth of Japanese flying squid from spawning to juveniles (182 days) in six cases: one for high-level catch years (1960–1966), one for low-level catch years (2008–2014), and four for the future, including two for 50 years (2056–2062) and two for 100 years from now (2104–2110) under the warming scenario of RCP2.6 and RCP8.5, respectively. The simulations showed that the number of squid increased with warming. The main reason for the increase was the warming of the JS, which increased the survival rate of autumn- and winter-spawning cohorts. In addition, the model also demonstrated the potential effects of warming on the physiological process of the early life stage of the Japanese flying squid.

Roux-en-Y gastric bypass (RYGB) is one of the most frequently performed bariatric procedures worldwide. Remnant gastric cancer after RYGB is a rare complication. There were about seventeen cases reported in the world. The location of the tumor in these cases occurs mainly in the gastric antrum, followed by the body, then the pylorus and linitis plastica, and the last was fundus of the stomach. To the best of our knowledge, this is the first case that gastric cancer located in the cardia of stomach after RYGB. A 68-year-old male patient had chronic esophagitis, bile reflux gastritis, and erosive antral gastritis 5 years after RYGB and now developed to aggressive carcinoma in the gastric pouch. In spite of having chemotherapy and traditional Chinese medicine therapy, the patient died of multiple organ failure after 15 months. This case report highlights the importance to have gastroscopy to observe the proximal small remnant stomach after RYGB in long-term follow-up. Attention must be paid when patients develop symptoms like abdominal pain or excessive weight loss after RYGB. For patients at high risk such as those who have a family history of gastric cancer or presenting abnormal levels of tumor markers should rather undergo Sleeve Gastrectomy plus Jejunojejunal Bypass (SGJB) instead of RYGB.

Background Sex is an important covariate of epigenome-wide association studies due to its strong influence on DNA methylation patterns across numerous genomic positions. Nevertheless, many samples on the Gene Expression Omnibus (GEO) frequently lack a sex annotation or are incorrectly labelled. Considering the influence that sex imposes on DNA methylation patterns, it is necessary to ensure that methods for filtering poor samples and checking of sex assignment are accurate and widely applicable. Results Here we presented a novel method to predict sex using only DNA methylation beta values, which can be readily applied to almost all DNA methylation datasets of different formats (raw IDATs or text files with only signal intensities) uploaded to GEO. We identified 4345 significantly (p Conclusions This proposed sex classifier not only can be used for sex predictions but also applied to identify samples with sex chromosome aneuploidy, and it is freely and easily accessible by calling the ‘estimateSex’ function from the newest wateRmelon Bioconductor package (https://github.com/schalkwyk/wateRmelon).

Photothermal therapy has attracted extensive attentions in cancer treatment due to its precise spatial-temporal controllability, minimal invasiveness, and negligible side effects. However, two major deficiencies, unsatisfactory heat conversion efficiency and limited tissue penetration depth, hugely impeded its clinical application. In this work, hollow carbon nanosphere modified with polyethylene glycol-graft-polyethylenimine (HPP) was elaborately synthesized. The synthesized HPP owns outstanding physical properties as a photothermal agent, such as uniform core-shell structure, good biocompatibility and excellent heat conversion efficiency. Upon NIR-II laser irradiation, the intracellular HPP shows excellent photothermal activity towards cancer cell killing. In addition, depending on the large internal cavity of HPP, the extended biomedical application as drug carrier was also demonstrated. In general, the synthesized HPP holds a great potential in NIR-II laser-activated cancer photothermal therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-00884-7.

The manipulation of bile acid (BA) homeostasis by blocking the ileal apical Na(+)-dependent bile salt transporter (ASBT/SLC10A2) may have therapeutic effects in nonalcoholic fatty liver disease. We developed a novel ASBT inhibitor, an N-(3,4-o-dichlorophenyl)−2-(3-trifluoromethoxy) benzamide derivative referred to as IMB17–15, and investigated its therapeutic effects and the molecular mechanisms underlying the effects. Syrian golden hamsters were challenged with high-fat diet (HFD) to induce NAFLD and were subsequently administered 400 mg/kg IMB17–15 by gavage daily for 21 days. Serum, liver, and fecal samples were collected for further analysis. Plasma concentration-time profiles of IMB17–15 were also constructed. The human hepatocyte cell line HL-7702 was treated with Oleic acid (OA) with or without IMB17–15. Western blotting and real-time PCR were used to study the molecular mechanisms of IMB17–15. We found that IMB17–15 inhibited ASBT and subsequently suppressed ileal farnesoid X receptor (FXR) and FXR-activated fibroblast growth factor15/19 (FGF15/19) expression, which reduced the hepatic phosphorylated extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) levels and upregulated the cholesterol 7α-hydroxylase (CYP7A1) activity. Additionally, IMB17–15 stimulated adenosine monophosphate (AMP)-activated protein kinase (AMPKα) phosphorylation and enhanced peroxisome proliferator activated receptor α (PPARα) expression and thus promoted triglyceride (TG) oxidation and high-density lipoprotein cholesterol (HDL-c) metabolism through an ASBT-independent mechanism. In conclusion, a novel ASBT inhibitor known as IMB17–15 protected hamsters against HFD-induced NFALD by manipulating BA and lipid homeostasis. IMB17–15 also reduced lipid deposition in human hepatic cell lines, indicating that it may be useful as a therapy for NAFLD patients.

MYB plays vital roles in regulating proliferation and differentiation of hematopoietic progenitor cells, dysregulation of MYB has been implicated in the pathogenesis of leukemia. Although the transcription of MYB has been well studied, its detailed underlying regulatory mechanisms still remain elusive. Here, we detected the long-range interaction between the upstream regions, −34k and −88k, and the MYB promoter in K562, U937, and HL-60 cells using circularized chromosome conformation capture (4C) assay, which declined when MYB was downregulated during chemical-induced differentiation. The enrichment of enhancer markers, H3K4me1 and H3K27ac, and enhancer activity at the −34k and −88k regions were confirmed by ChIP-qPCR and luciferase assay respectively. ChIP-qPCR showed the dynamic binding of GATA1, TAL1, and CCAAT/enhancer-binding protein (C/EBPβ) at −34k and −88k during differentiation of K562 cells. Epigenome editing by a CRISPR-Cas9-based method showed that H3K27ac at −34k enhanced TF binding and MYB expression, while DNA methylation inhibited MYB expression. Taken together, our data revealed that enhancer elements at −34k are required for MYB expression, TF binding, and epigenetic modification are closely involved in this process in human myeloid leukemia cells.

The TabZIP15 gene encoding a 396 amino acid (aa) polypeptide in the fungus Trichoderma asperellum ACCC30536 was cloned and characterised. The protein includes a basic region motif (NR-x2-QR-x2-R) and has a pillar-like structure. The 25 basic region/leucine zipper transcription factors (TFs) identified in the T. asperellum genome were divided into YAP (14 TFs), ATF2 (5), GCN4 (2), Zip1 (2), BRLZ (1) and u1 (1) subfamilies based on conserved domains. T. asperellum was cultured in minimal media (MM) control, C-Hungry and N-Hungry medium (to simulate nutrient competition and interaction with pathogens, respectively), and differential expression analysis showed that 14 TabZIP genes (including TabZIP15) were significantly altered under both conditions; TabZIP23 responded strongly to N-Hungry media and TabZIP24 responded strongly to C-Hungry media. However, only YAP genes TabZIP15, TabZIP12 and TabZIP2 were significantly upregulated under both conditions, and expression levels of TabZIP15 were highest. T. asperellum was also cultured in the presence of five fungal pathogenic toxins, and RT-qPCR results showed that TabZIP15 was significantly upregulated in four of the five toxin stress conditions (MM + Rhizoctonia solani, MM + Fusarium oxysporum, MM + Alternaria alternata and MM + Cytospora chrysosperma).

Background Angiosarcomas (AS) have poor prognosis and often metastasize to distant sites. The potential predictors of metastatic angiosarcomas (MAS) have not been extensively investigated. The main objective of this study was to identify survival predictors of MAS. Methods Surveillance, Epidemiology, and End Results (SEER) datasets were used to identify patients with MAS from 2010 to 2016. Risk predictors were determined with the aid of Kaplan-Meier and Cox regression model analyses. Results A total of 284 MAS patients met the study entry criteria. Among these, 121 patients (42.6%) were diagnosed with metastasis in bone, 26 in brain (9.2%), 86 in liver (30.3%) and 171 in lung (60.2%). Overall, 96 patients (33.8%) had two or more metastatic sites. The 1- and 3-year overall survival (OS) rates were 20.8 and 3.8% while 1- and 3-year cancer-specific survival (CSS) rates were 22.0 and 5.2%, respectively. Cox regression analysis revealed chemotherapy, radiation treatment (RT) and tumor size ≤10 cm as independent favorable predictors of OS. In terms of CSS, tumor grade IV, tumor size > 10 cm and absence of chemotherapy were independent adverse predictors. Surgery did not prolong survival outcomes (both OS and CSS) in the current cohort. Conclusion MAS is associated with extremely poor survival. Chemotherapy, RT, and tumor size are independent predictors of OS. Chemotherapy and tumor size are independent prognostic factors of CSS. Chemotherapy is therefore recommended as the preferred treatment option for MAS patients.

This study investigates the biocontrol potential of Trichoderma asperellum mutants against Rhizoctonia solani, Alternaria alternata, and Fusarium oxysporum and growth promotion of Populus davidiana × P. alba var. pyramidalis (PdPap poplar) seedlings. A T-DNA insertion mutant library of T. asperellum was constructed using Agrobacterium tumefaciens-mediated transformation. Sixty-five positive transformants (T1–T65) were obtained. Growth rates of the mutants T39 and T45 were the same, 39.68% faster than the WT. In toxin tolerance tests, only T39 had greater tolerance to A. alternata fermentation broth than the WT, but mutant T45 had the same tolerance as the WT to all fermentation broths. Furthermore, T39 and T45 had a greater antagonistic ability than the WT strain against R. solani and A. alternata. The inhibition rate of the mutants T39 and T45 against A. alternata are 73.92% and 80.76%, respectively, and 63.51% and 63.74%, respectively. Furthermore, the three strains increased the activities of superoxide dismutases, peroxidase, catalase (CAT) and phenylalanine ammonia lyase (PAL) in PdPap seedling leaves. CAT and PAL activity in the PdPap seedling leaves was 11.25 and 5.50 times higher, respectively, in the presence of T39 than in the control group and 12 and 6.35 times higher, respectively, in the presence of T45 than in the control group. All three strains promoted seedling growth and the root and stem development, especially mutant T45. Mutants T39 and T45 reduced the incidence of pathogenic fungi in poplar and stimulated poplar seedling growth.

The transcription factor BplMYB46 has been identified as a regulator of abiotic stress responses and promoter of secondary wall deposition in Betula platyphylla. To investigate the downstream targets of BplMYB46, the expression profiles of genes in stems from BplMYB46-overexpressing (OE) and BplMYB46-silencing (SE) plants were studied. In OE stems, 952 genes were upregulated, and 1469 were downregulated in comparison to SE stems. In a KEGG pathway enrichment analysis of differentially expressed genes (DEGs), 1387 differentially expressed genes were annotated for 117 metabolic pathways. DEGs were abundant for metabolic pathway, secondary metabolite biosynthesis, plant hormone signal transduction, phenylpropanoid and flavonoid biosynthesis. DEGs were implicated lignin or cellulose biosynthesis, cell wall modification, xylem development, disease resistance, stress responses, and anthocyanin biosynthesis. These results suggested that BplMYB46 regulates cell wall development and stress resistance by affecting the expression of these genes. Our study further elucidates the mechanism by which BplMYB46 mediates abiotic stress responses and secondary cell wall biosynthesis in birch.

This retrospective cohort study aims to evaluate the effects of introducing the O-arm-based navigation technique into the traditional posterior lumbar interbody fusion (PLIF) procedure treating elderly patients with three-level lumbar degenerative diseases. Forty-one consecutive elderly patients were enrolled according to the criteria. There were 21 patients in the free-hand group and 20 patients in the O-arm group. Both two groups underwent the PLIF with or without the O-arm-based navigation technique. The demographic features, clinical data and outcomes, and radiological information were collected for further analysis. The average follow-up time was 18.3 (range, 12–28) months in the free-hand group and 16.7 (range, 12–24) months in the O-arm group. Comparison between two groups revealed no significant difference regarding demographic features. The operation time took in the navigation group was significantly less than that in the free-hand group (222.55 ± 38.00 mins versus 255.19 ± 40.26 mins, P

Using a three-dimensional coupled biophysical model, we simulated the responses of a low-trophic ecosystem in the East China Sea (ECS) to long-term changes in nutrient load from the Changjiang (Yangtze) River over the period of 1960–2005. Two major factors affected changes in nutrient load: changes in river discharge and the concentration of nutrients in the river water. Increasing or decreasing Changjiang discharge induced different responses in the concentrations of nutrients, phytoplankton, and detritus in the ECS. Changes in dissolved inorganic nitrogen (DIN), silicate (SIL), phytoplankton, and detritus could be identified over a large area of the ECS shelf, but changes in dissolved inorganic phosphate (DIP) were limited to a small area close to the river mouth. The high DIN:DIP and SIL:DIP ratios in the river water were likely associated with the different responses in DIN, DIP, and SIL. As DIP is a candidate limiting nutrient, perturbations in DIP resulting from changes in the Changjiang discharge are quickly consumed through primary production. It is interesting that an increase in the Changjiang discharge did not always lead to an increase in phytoplankton levels in the ECS. Phytoplankton decreases could be found in some areas close to the river mouth. A likely cause of the reduction in phytoplankton was a change in the hydrodynamic field associated with the river plume, although the present model is not suitable for examining the possibility in detail. Increases in DIN and DIP concentrations in the river water primarily led to increases in DIN, DIP, phytoplankton, and detritus levels in the ECS, whereas decreases in the SIL concentration in river water led to lower SIL concentrations in the ECS, indicating that SIL is not a limiting nutrient for photosynthesis, based on our model results from 1960 to 2005. In both of the above-mentioned cases, the sediment accumulation rate of detritus exhibited a large spatial variation near the river mouth, suggesting that core sample data should be carefully interpreted.

Peroxiredoxins (Prxs) are ubiquitous thiol-specific antioxidant enzymes that are critically involved in cell defense and protect cells from oxidative damage. In this study, a putative Type II Prx (ThPrx1) was identified and characterized from Tamarix hispida. The expression of ThPrx1 is highly induced in response to hydrogen peroxide (H2O2) and methyl viologen (MV) stresses. When expressed ectopically, ThPrx1 showed enhanced tolerance against oxidative stress in yeast and Arabidopsis. In addition, transgenic Arabidopsis plants overexpressing ThPrx1 displayed improved seedling survival rates and increased root growth and fresh weight gain under H2O2 and MV treatments. Moreover, transgenic Arabidopsis plants showed decreased accumulation of H2O2, superoxide (O2•−) and malondialdehyde (MDA), increased superoxide dismutase (SOD) activity compared to wild-type (WT) plants under oxidative stress. Moreover, transgenic plants maintained higher photosynthesis efficiency and lower electrolyte leakage rates than that of WT plants under stress conditions. These results clearly indicated that ThPrx1 plays an important role in cellular redox homeostasis under stress conditions, leading to the maintenance of membrane integrity and increased tolerance to oxidative stress.

A bio-inspired layered material of reduced graphene oxide (RGOs) and calcium carbonate was synthesized via a one-pot strategy in DMF/H2O mixed solvent. The experimental results show that the product is a layered material of wrinkled RGOs networks and micron-sized calcium carbonate particles with uniform granular diameter and homogeneous morphology, which are distributed between the layered gallery of the graphene scaffold. The polymorph and the morphology of the in-situ produced calcium carbonate particles can be manipulated by simply changing the temperature scheme. Besides, the graphene oxide was reduced to a certain extent, and the hierarchical wrinkles were generated in the RGOs layer by the in-situ formation of the calcium carbonate particles. This work provides a facile and controllable strategy for synthesizing layered material of RGOs and carbonates, and also presents a platform for making three-dimensional porous wrinkled RGOs networks.

Our study found that birch employs different physiological pathways to tolerance salt stress in roots and leaves, and the genes closely correlated with these physiological changes were identified. Birches are fast-growing woody plants that are adapted to adverse environments, and are widely distributed from north Europe to northeast Asia. However, the salt stress tolerance mechanism of birch has little been studied. Here, we investigated the physiological and molecular response of white birch (Betula Platyphylla) to salt stress. Long-term salt stress inhibited photosynthetic activity, and decreased stomatal conductance of birch. Abscisic acid was induced in birch during the early salt stress period, and Ca2+ level was increased slowly but maintained at a higher level for a long time. Under salt conditions, the salt-overly-sensitive pathway was activated in birch roots; reactive oxygen species (ROS) was highly accumulated, and superoxide dismutase is the main ROS scavenger in roots, while peroxidase is the main ROS scavenger in leaves. Proline plays a role in salt tolerance in both roots and leaves; however, soluble sugars and trehalose also have roles in salt stress tolerance, but mainly in leaves. Additionally, the genes that might have essential roles in controlling some of these physiological changes were identified, which represent good candidate genes to characterize the salt tolerance mechanism of birch. This study increased our understanding of the salt tolerance mechanism of birch plants.

Identification of the upstream regulators of a gene is important to characterize the transcriptional pathway and the function of the gene. Previously, we found that a zinc finger protein (ThZFP1) is involved in abiotic stress tolerance of Tamarix hispida. In the present study, we further investigated the transcriptional pathway of ThZFP1. Dof motifs are abundant in the ThZFP1 promoter; therefore, we used them to screen for transcriptional regulators of ThZFP1. A Dof protein, ThDof1.4, binds to the Dof motif specifically, and was hypothesized as the upstream regulator of ThZFP1. Further study showed that overexpression of ThDof1.4 in T. hispida activated the expression of GUS controlled by the ThZFP1 promoter. In T. hispida, transient overexpression of ThDof1.4 increased the transcripts of ThZFP1; conversely, transient RNAi-silencing of ThDof1.4 reduced the expression of ThZFP1. Chromatin immunoprecipitation indicated that ThDof1.4 binds to the ThZFP1 promoter. Additionally, ThDof1.4 and ThZFP1 share similar expression patterns in response to salt or drought stress. Furthermore, like ThZFP1, ThDof1.4 could increase the proline level and enhance ROS scavenging capability to improve salt and osmotic stress tolerance. Together, these results suggested that ThDof1.4 and ThZFP1 form a transcriptional regulatory cascade involved in abiotic stress resistance in T. hispida.

ANAC069 binds to the DNA sequence of C[A/G]CG[T/G] to regulate the expression of genes, resulting in decreased ROS scavenging capability and proline biosynthesis, which contribute to increased sensitivity to salt and osmotic stress. NAM-ATAF1/2 and CUC2 (NAC) proteins are plant-specific transcription factors that play important roles in abiotic stress responses. In the present study, we characterized the physiological and regulatory roles of Arabidopsis thaliana ANAC069 in response to abiotic stresses. Arabidopsis plants overexpressing ANAC069 displayed increased sensitivity to abscisic acid, salt, and osmotic stress. Conversely, ANAC069 knockdown plants showed enhanced tolerance to salt and osmotic stress, but no change in ABA sensitivity. Further studies showed that ANAC069 inhibits the expression of SOD, POD, GST, and P5CS genes. Consequently, the transcript level of ANAC069 correlated negatively with the reactive oxygen species (ROS) scavenging ability and the proline level. The genes regulated by ANAC069 were further studied using a gene chip on a genome-wide scale, and 339 and 226 genes up- and downregulated by ANAC069 were identified. Analysis of the promoters of the genes affected by ANAC069 suggested that ANAC069 regulates the expression of genes mainly through interacting with the DNA sequence C[A/G]CG[T/G] in response to abiotic stresses. Collectively, our data suggest that ANAC069 could recognize C[A/G]CG[T/G] sequences to regulate the expression of genes that negatively regulates salt and osmotic stress tolerance by decreasing ROS scavenging capability and proline biosynthesis.

In this study, the material and electrical properties of La2O3/SiO2/4H-SiC metal–oxide–semiconductor (MOS) capacitors are systematically characterized. Thermal oxidization SiO2 with varying thickness (0 nm, 3.36 nm, 5 nm, 8 nm, and 30 nm) were coated with La2O3 using atomic layer deposition on n-type 4H-SiC. The stacking oxides were measured using atomic force microscopy, transmission electron microscopy, and x-ray photoelectron spectroscopy, and the MOS capacitors were measured by capacitance–voltage and current–voltage measurements. The results demonstrate that the main gate current leakage mechanisms are dependent on the thickness of the SiO2 oxide under the applied electric field. The primary mechanism for current leakage from the La2O3/4H-SiC MOS capacitor follows the Schottky emission mechanism due to its low conduction band offset. In contrast, the current leakage mechanism for the capacitor with a 3.36 nm SiO2 layer follows the Poole–Frenkel emission mechanism on account of its high trap charge density in the gate dielectric and at the interface. When the thickness of the SiO2 layer increases to 8 nm, lower leakage current is observed by reason of the low trap charge density and high conduction band offset when E ≤ 5 MV/cm. As the electric field strength increases to 5 MV/cm and 5.88 MV/cm (30 nm SiO2: 4.8 MV/cm), the main current leakage mechanism changes to the Fowler–Nordheim tunneling mechanism, which indicates that the La2O3/SiO2 stacking structure can improve the properties of MOS capacitors.

Ethylene response factors (ERFs) are plant-specific transcription factors that function as multiple regulators in various stress-responsive pathways. In the current study, to investigate the transcription patterns of ERFs in response to salt and drought treatments, four ERF genes were cloned and identified from Japanese white birch (Betula platyphylla). The real-time quantitative polymerase chain reaction (qPCR) results showed that these four BpERF genes all responded to NaCl and PEG stress. Most BpERF genes were significantly induced in roots and leaves, but not in stems, such as BpERF 1,4 under NaCl treatment, and exhibited tissue-specific expression profiles in response to different abiotic stress. Further, we cloned the four BpERF genes into pYES2 vector, transformed and expressed these genes in yeast Saccharomyces cerevisiae to investigate their tolerance to salt and drought stress. Compared with the control (yeast transformed with empty pYES2), yeast cells expressing BpERF genes showed improved tolerance to salt and drought stress, indicating that these BpERFs could confer salt and drought tolerance to transgenic yeast cells. These results suggested that these BpERF genes play important roles in abiotic stress tolerance in B. platyphylla.

The ethylene-responsive factor family is one of the largest families of plant-specific transcription factors that are involved in plant development and stress responses. Previously, we demonstrated that the gene ThERF1, encoding a novel ethylene-responsive factor from Tamarix hispida, negatively modulates abiotic stress tolerance. In the present study, Arabidopsis plants overexpressing ThERF1 had decreased oxidative tolerance and increased transpirational water loss rate compared with wild-type plants, leading to sensitivity to abiotic stress. Real-time RT-PCR showed that the upstream regulator of ThERF1, ThWRKY2, is involved in responses to different abiotic stresses. Furthermore, both ThWRKY2 and ThERF1 shared similar expression patterns in the stems and leaves of T. hispida when exposed to salinity, drought and abscisic acid. Chromatin immunoprecipitation assays further confirmed that ThWRKY2 can directly bind to the promoter of ThERF1 and regulate its expression. This study revealed the regulatory mechanism of ThERF1 expression in response to abiotic stresses in T. hispida.

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

Osteoporosis results from the imbalance between bone resorption and bone formation, and restoring the normal balance of bone remodeling is highly desirable for identification of better treatment. In this study, using a cell-based high-throughput screening model representing Runt-related transcription factor 2 (RUNX2) transcriptional activity, we identified a novel small-molecular-weight compound, T63, as an efficient up-regulator of osteogenesis. T63 increased the alkaline phosphatase (ALPL) activity and mineralization as well as gene expression of Alpl and other osteogenic marker genes in mouse osteoblasts and mesenchymal stem cell-like cells. Upon induction of osteoblast differentiation, T63 inhibited adipogenic differentiation in the pluripotent mesenchymal cells. Consistently, T63 up-regulated RUNX2 mRNA and protein levels, and knockdown of RUNX2 reduced the osteogenic role of T63. Mechanistically, T63 activated both BMPs and WNT/β-catenin signaling pathways. Inhibition of either signaling pathway with specific inhibitor suppressed T63-induced RUNX2 expression and the osteogenic phenotypes. Moreover, T63 markedly protected against bone mass loss in the ovariectomized and dexamethasone treated rat osteoporosis model. Collectively, our data demonstrate that T63 could be a promising drug candidate and deserves further development for potential therapeutics in osteoporosis.

Aquaporins belong to the highly conserved major intrinsic protein family and are involved in the transcellular membrane transport of water and other small solutes. However, there has been little work on cloning aquaporin (AQP) family genes and characterizing their functions in plants under various environmental stimuli. In this study, a total of 18 full-length AQP genes were identified in Tamarix hispida, a woody halophyte. Sequence analysis showed that most of these AQP proteins have six transmembrane domains connected by five loops. Phylogenetic analysis revealed that the members of the AQP family can be divided into four groups based on their structural characteristics, including plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like intrinsic proteins (NIPs), and small basic intrinsic proteins (SIPs). Furthermore, the expression profiles of AQP genes were analyzed in the roots, stems, and leaves under salinity, drought, heavy metal, and abscisic acid (ABA) treatments using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The results demonstrated that the AQP were involved in abiotic stress responses, indicating that they play important roles in response to abiotic stress and are involved in ABA-dependent stress-signaling pathways. These data will be useful to elucidate the complexity of the AQP gene family and the molecular mechanisms of abiotic stress tolerance.

Thyroid hormone (TH) signaling plays critical roles in the differentiation, growth, metabolism, and physiological function of all organs or tissues, including heart and skeletal muscle. Due to the significant progress in our understanding of the molecular mechanisms that underlie TH action, it’s widely accepted that TH signaling is regulated at multiple levels. A growing number of discoveries suggest that microRNAs (miRNAs) act as fine-tune regulators of gene expression and adds sophisticated regulatory tiers to signaling pathways. Recently, some pioneering studies in cardiac and skeletal muscle demonstrating the interplay between miRNAs and TH signaling suggest that miRNAs might mediate and/or modulate TH signaling. This review presents recent advances involving the crosstalk between miRNAs and TH signaling and current evidence showing the importance of miRNA in TH signaling with particular emphasis on the study of muscle-specific miRNAs (myomiRs) in cardiac and skeletal muscle. Although the research of the reciprocal regulation of miRNAs and TH signaling is only at the beginning stage, it has already contributed to our current understanding of both TH action and miRNA biology. We also encourage further investigations to address the relative contributions of miRNAs in TH signaling under physiological and pathological conditions and how a group of miRNAs are coordinated to integrate into the complex hierarchical regulatory network of TH.

The fast densification method of combustion reaction plus quick pressing was adopted to prepare nanocrystalline ceramics. The densification process of magnesia compact with a particle size of 100 nm was investigated, under the applied pressure of up to 170 MPa, and the temperature range of 1740–2080 K with ultra-high heating rate (above 1700 K/min). High-purity magnesia ceramics with a relative density of 98.8% and an average grain size of 120 nm was obtained at 1740 K, and the grain growth during the densification process was effectively restrained. The characteristic morphology of evaporation-condensation was observed in the compact prepared at 2080 K, which revealed the actual process of mass transfer by gas diffusion. Moreover, the investigation on the microstructure evolution and mechanism of grain growth was carried out, on the basis of as-preserved nanocrystalline ceramics. The result indicated that the grain growth of the nanocrystalline MgO was controlled by the mechanism of evaporation-condensation rather than surface diffusion. Furthermore, the pressure had an influence of restraining the grain growth based on solid diffusion and strengthening the effect of gas diffusion with the increasing temperature. Under the particular conditions, there existed an appropriate temperature for the densification of nanocrystalline magnesia, while the excessive temperature would exaggerate grain growth and impede densification.

Although plant glutathione transferase (GST) genes are reported to be involved in responses to abiotic stress, few GST genes have been functionally characterized in woody halophytes. In the present study, a GST gene from Tamarix hispida, designated ThGSTZ1, was cloned and functionally characterized. Expression of ThGSTZ1 was downregulated by drought and salinity stress, and abscisic acid. Transgenic Arabidopsis thaliana plants with constitutive expression of ThGSTZ1 showed increased survival rates under drought and salinity stress. These transgenic Arabidopsis plants exhibited increased levels of GST, glutathione peroxidase, superoxide dismutase and peroxidase activity, along with decreased malondialdehyde content, electrolyte leakage rates and reactive oxygen species (ROS) levels under salt and drought stress conditions. Transgenic T. hispida that transiently overexpressed ThGSTZ1 showed increased GST and GPX activities under NaCl and mannitol treatments, as well as improved ROS scavenging ability. These results suggest that ThGSTZ1 can improve drought and salinity tolerance in plants by enhancing their ROS scavenging ability. Therefore, ThGSTZ1 represents a candidate gene with potential applications for molecular breeding to increase stress tolerance in plants.

Heat shock proteins (HSPs) play important roles in protecting plants against environmental stresses. Furthermore, small heat shock proteins (sHSPs) are the most ubiquitous HSP subgroup with molecular weights ranging from 15 to 42 kDa. In this study, nine sHSP genes (designated as ThsHSP1-9) were cloned from Tamarix hispida. Their expression patterns in response to cold, heat shock, NaCl, PEG and abscisic acid (ABA) treatments were investigated in the roots and leaves of T. hispida by real-time RT-PCR analysis. The results showed that most of the nine ThsHSP genes were expressed at higher levels in roots than in leaves under normal growth condition. All of ThsHSP genes were highly induced under conditions of cold (4 °C) and different heat shocks (36, 40, 44, 48 and 52 °C). Under NaCl stress, all nine ThsHSPs genes were up-regulated at least one stress time-point in both roots and leaves. Under PEG and ABA treatments, the nine ThsHSPs showed various expression patterns, indicating a complex regulation pathway among these genes. This study represents an important basis for the elucidation of ThsHSP gene function and provides essential information that can be used for stress tolerance genetic engineering in future studies.

Secondary growth of stems is an important process for the radial increase of trees. To gain an insight into the molecular mechanisms underlying stem development from primary to secondary growth and to provide information for molecular research and breeding in Betula platyphylla (birch), the gene expression profiles of material from the first, third, and fifth internodes (IN) of 3-month-old seedlings were analyzed. Compared with the first IN, 177 genes were up-regulated and 157 genes down-regulated in the third IN; in the fifth IN, 180 genes were up-regulated and 275 genes were down-regulated. The expressions of 24 genes were up-regulated and 6 genes were down-regulated in the fifth IN relative to the third IN. The differentially expressed genes were annotated as having roles in cambium, xylem, and phloem development and formation; including cell wall expansion, cellulose biosynthesis, lignin biosynthesis and deposition, xylem extension, cell wall modification, and growth hormone responses. The expressions of genes related to cell wall expansion and cellulose biosynthesis in the primary cell wall were down-regulated in the third and fifth IN relative to the first IN. Genes involved in lignin biosynthesis, xylem extension, and cellulose synthesis in the secondary cell wall were up-regulated in the third and fifth IN relative to the first IN. These results described the patterns of gene expression during stem development in birch and provided candidate genes for further functional characterization.

In this study, we developed a simple and efficient transient transformation system, which can be used in homologous expression or reverse genetic study of the plants. A system for characterizing gene function in response to stress tolerance was also developed based on this transformation method. The overexpression and RNAi-silencing of a bZIP gene from Tamarix hispida, ThbZIP1, were performed in T. hispida using this transformation method. Real-time PCR showed that the expression of ThbZIP1 was highly up- and down-regulated in the plants with overexpression and RNAi-silenced expression of ThbZIP1, respectively, when compared with control plants (transiently transformed with empty pROK2). A physiological study showed that ThbZIP1 can enhance the activities of both peroxidase (POD) and superoxide dismutase (SOD), and decrease electrolyte leakage rate and levels of reactive oxygen species (ROS) and malondialdehyde (MDA) under salt stress conditions. Furthermore, ThbZIP1 is found to mediate stress tolerance by regulating the expression of SOD and POD genes. These results suggested that this transient transformation system is an effective method for determining the function of a gene in response to abiotic stress in plants.

The ethylene response factor (ERF) genes are a subfamily of transcription factors containing a single AP2/ERF domain, which play crucial roles in plant development and response to biotic and abiotic stresses. In the present study, 16 ERF genes (named ThERF1–ThERF16) were isolated from Tamarix hispida, and their expression in response to salt, drought and ABA treatment was investigated using real-time RT-PCR. The results showed that all 16 ERFs are expressed in root, stem and leaf tissues, but the individual transcript levels vary strongly in roots, stem or leaves. Among these ThERFs, ThERF1 is the most abundant in roots, stems and leaves, indicating that it may play a more important physiological role than the other ThERF genes. The 16 ThERF genes are all highly differentially expressed in leaves, stems or roots under salt and drought stress, demonstrating that they are involved in the salt and drought stress responses. Under ABA treatment, expression of the ThERF genes was mainly down-regulated in roots, but induced in leaves or stems, suggesting that they are also involved in the ABA stress response. These results strongly suggest that ThERFs are abiotic stress response genes that may play important roles in the stress tolerance of T. hispida.

NAC (NAM, ATAF1/2 and CUC2) domain proteins are plant-specific transcriptional regulators that play roles in diverse developmental processes and stress responses. However, there has been little work on cloning NAC family genes and characterizing their expression patterns in response to abiotic stresses in woody plants. In the present study, a total of 21 full-length NAC genes were identified in Tamarix hispida, a woody halophyte. Most of these NACs contained a complete NAC DNA-binding domain and a variable transcriptional regulation domain. Real-time RT-PCR showed that these ThNAC genes are all expressed in the roots, stems, and leaves of T. hispida in response to salinity, drought, heavy metal, or abscisic acid (ABA) stimuli, indicating that they play regulatory roles in the abiotic stress response and are involved in ABA-dependent stress-signaling pathways. This study may provide insight into the roles of NACs in abiotic stress tolerance and also contribute to the selection of candidate genes for using molecular breeding to improve plant stress tolerance.

Root tissue is the primary site of perception for stress from soil, and is the main tissue involved in stress response. Tamarix hispida is a woody halophyte that is highly tolerant to salt and drought stress, but little information available about gene expression in roots in response to abiotic stress. In this study, eight transcriptomes from roots of T. hispida treated with NaHCO3 for 0, 12, 24 and 48 h (two biological replicates were set at each time point) were built. In total, 47,324 unigenes were generated, and 6,267 differentially expressed genes (DEGs) were identified. There were 2,510, 3,690, and 2,636 genes significantly differentially expressed after stress for 12, 24 and 48 h, respectively. Co-expressed DEGs were clustered into ten classes (P

The occlusion effect of vascular targeted photodynamic therapy (V-PDT) for malformed vessels in port wine stains (PWS) often last for some time after the treatment. A relatively longer period after V-PDT is needed to accurately assess the final response of PWS microcirculation to the treatment. In this study, we intended to use laser speckle imaging (LSI) to assess the tissue perfusion changes of PWS at follow-up after V-PDT and preliminarily analyze the relationship between perfusion change and color bleaching. Seventeen patients with 40 PWS lesions were scanned by LSI before and 3–6 months after they received V-PDT. The speckle flow indices of PWS lesions and normal skin before and at follow-up after V-PDT were recorded. We also performed analyses on the correlation between perfusion changes and color bleaching. Before V-PDT, the 40 PWS lesions showed higher perfusion than the normal skin (1,421 ± 463 and 1,115 ± 386 perfusion unit (PU), respectively, P