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Hydrogels have been extensively used in agriculture to improve crop yields for their excellent properties. However, they are currently used either as pesticide delivery platforms or water retention agents alone; the combination of these two functions into one agricultural hydrogel formulation has never been reported, which is crucial to promote sustainable development in agriculture. Herein, using poly(β-cyclodextrin) and adamantane-grafted poly(acrylic acid) (PAA-Ada) as the host and guest, respectively, an easy operating, multi-responsive, and safer hydrogel delivery system for insecticides is fabricated by the host-guest interaction between cyclodextrin and adamantane, which can load uniformly dispersed insecticides (fipronil, imidacloprid, and thiamethoxam) up to 60%. Benefiting from the carboxyl and hydroxyl groups on polymer chains, different temperatures (25, 35, and 45 °C) and pH values (5.0, 6.8, and 10.0) change the intermolecular forces within the hydrogel network and then the diffusion of the content, finally resulting in controlled release behaviors. Besides, this platform can rapidly release the insecticides in the presence of amyloglucosidase due to its ring-opening effect on cyclodextrin. Moreover, this platform exhibits high water-retaining capacity toward soil, which can increase the maximum water absorption of nutrient soil and quartz sand by 31.6 and 13.9%, respectively, and slows down the water loss. Compared with commercial formulation, this smart system reduces the acute toxicity to non-target organism earthworms by 52.4% and improves the efficacy against target organism aphids by 47.3%, showing better durability, lower environmental toxicity, and higher efficiency. To our knowledge, this is the first idea that simultaneously adopts the water-retaining capacity and controlled release ability of hydrogels to improve insecticide efficacy. In this regard, this smart hydrogel platform holds great potentials as slow-release granules with water-holding ability for protection against insect pests, providing an alternative platform for the sustainable development in green agriculture.

Lipid droplets (LDs), as crucial organelles, play a significant role in some physiological processes. Monitoring the concentration of LDs and dynamic behaviors between LDs and other organelles during some physiological processes is important for studying their biological function and medical diagnosis. Herein, we report a series of aggregation-induced emission (AIE) probes AIE-Cbz-LD-C

Structure-based design and optimization were performed to develop small-molecule β-catenin/B-cell lymphoma 9 (BCL9) inhibitors and improve their inhibitory activities. Compound ZL3138 with a novel 1-benzoyl 4-phenoxypiperidine scaffold was discovered to disrupt the β-catenin/BCL9 protein-protein interaction (PPI) with a Ki of 0.96 μM in AlphaScreen competitive inhibition assays and displayed good selectivity for β-catenin/BCL9 over β-catenin/E-cadherin PPIs. The binding mode of new inhibitors was characterized by structure-activity relationship and site-directed mutagenesis studies. Protein pull-down assays indicate that this series of compounds directly binds with β-catenin. Cellular target engagement and co-immunoprecipitation experiments demonstrate that ZL3138 binds with β-catenin and disrupts the β-catenin/BCL9 interaction without affecting the β-catenin/E-cadherin interaction in living cells. Further cell-based studies show that ZL3138 selectively suppresses transactivation of Wnt/β-catenin signaling, regulates transcription and expression of Wnt target genes, and inhibits the growth of Wnt/β-catenin-dependent cancer cells.

Mural is an important component of culture and art of Dunhuang in China. Unfortunately, these murals had been ruined or are being ruined by some diseases such as cracking, hollowing, falling off, mildew, dirt, and so on. Existing image restoration algorithms have problems such as incomplete repair and disharmonious texture during large-area repair, so the effect of mural image disease area repair is poor. Due to lack of a standard mural datasets, Dunhuang mural datasets are created in the paper. Meanwhile, our network architecture SeparaFill is proposed which connects two generators based on U-Net. Based on the characteristics of the painting, the contour line pixel area of the mural image is innovatively separated from the content pixel area. Firstly, the contour restoration generator network with skip connect and hierarchical residual blocks is employed to repair contour lines. Then, the color mural image is repaired by the content completion network with guide of the repaired contour. Full resolution branches and generator branches of the U type are exploited in content completion generators. Convolution layers of different kernel sizes are fused to improve the reusability of the underlying features. Finally, global and local discriminant networks are applied to determine whether the repaired mural image is authentic in terms of both the modified and unmodified areas. The proposed SeparaFill shows good performance in restoring the line structure of the damaged mural images and retaining the contour information of the mural images. Compared with existing restoration algorithms in mural real damage repair experiment, our algorithm increases the peak signal-to-noise ratio (PSNR) by an average of 1.1–4.3 dB and the structural similarity (SSIM) values were slightly improved. Experimental results reveal the good performance of the proposed model, which can contribute to digital restorations of ancient murals.

Background The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. Methods A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35–60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value Results 149 pregnancies were found in 143 women with PH. Overall, 46 pregnancies were elective abortions, remaining 49 and 54 pregnancies completing delivery in the pre-MDT group and post-MDT group, respectively. Five (10.2%) mother and seven (8.6%) neonatal died in the former, while no maternal deaths but 1.9% neonatal death occurred in the latter. In subgroup analysis, maternal and fetal/neonatal complications were higher in patients with severe PH and World Health Organization functional class (WHO FC) III/IV and all maternal deaths occurred in class III/IV women. In pre-MDT and post-MDT groups, there were 8 and 22 pregnant women receiving the pulmonary-specific therapy and completing delivery, respectively. The percentage of heart failure and urgent cesarean of pre-MDT group was higher than the post-MDT group (30.6% vs. 12.9%, p = 0.02; 40.8% vs. 14.8%, p = 0.01, respectively). Conclusion Implementing the MDT decreased the rate of urgent caesarean section and heart failure in patients with PH and no maternal deaths occurred in the post-MDT group. Pregnant women with severe PH and WHO FC III/IV might have a poor prognosis, whereas the use of pulmonary-specific therapy might improve outcomes of pregnancy.

The addition of a surfactant is a constructive strategy to enhance the deposition of pesticides on plant leaves in agriculture. However, currently used surfactants normally require to be used at high concentrations, and most of them are anionic or nonionic. In this work, we found that didecyldimethylammonium bromide (DDAB), a double-chain cationic surfactant, can not only inhibit droplets from receding and rebounding but also promote sufficient spreading on paraffin and Chenopodium album L. leaf surfaces at an ultralow concentration (0.05%), in comparison with widely reported sodium dodecyl sulfate (SDS) and bis(2-ethylhexyl)sulfosuccinate (AOT). This phenomenon is attributed to the fast adsorption kinetics of DDAB from the bulk to the newly created interface (mere 100 ms), decreasing the surface tension significantly. Field experiments further prove that the addition of DDAB can significantly improve the control efficiency of herbicides. Our findings provide a simple and effective way for improving the droplet deposition on hydrophobic plant surfaces, which may lead to economic and environmental benefits in the future.

Aberrant activation of the Wnt/β-catenin signaling circuit is associated with cancer recurrence and relapse, cancer invasion and metastasis, and cancer immune evasion. Direct targeting of β-catenin, the central hub in this signaling pathway, is a promising strategy to suppress hyperactive β-catenin signaling but has proven to be highly challening. Substantial efforts have been made to discover compounds that bind with β-catenin, block β-catenin-mediated protein–protein interactions (PPIs), and suppress β-catenin signaling. Herein, we characterize potential small-molecule binding sites in β-catenin, summarize bioactive small molecules that directly target β-catenin, and review structure-based inhibitor optimization, structure-activity relationship (SAR), and biological activities of reported inhibitors. This knowledge will benefit future inhibitor development and β-catenin-related drug discovery.

A novel strain, Nitratireductor sp. GZWM139 capable of efficient removal of SMX was isolated from mariculture sewage, and Nitratireductor was reported to conduct the removal of antibiotics for the first time. Strain GZWM139 exhibited desirable adaptations to environmental factors with SMX removal efficiencies more than 90 % at temperatures of 28-38 °C, pH values of 4.5-8.5, salinities of 20-30 ‰, SMX levels of 1-5 mg/L and shaking speeds of 20-260 rpm. SMX removal was a cooperated process implemented by intracellular enzymes and extracellular enzymes, and was achieved through four proposed biotransformation pathways with the occurrences of demethylation, hydroxylation, nitration, formylation, oxidation, bond cleavage and ring opening. Strain GZWM139 responded to the SMX removal process by altering properties of cell membrane and motivating activities of xenobiotic-metabolizing enzymes and antioxidant system. Genomic analysis proved the existence of functional genes relevant to the SMX removal in strain GZWM139 and provided echoing genetic insights for revealing the SMX removal mechanism. Strain GZWM139 performed efficient detoxification of SMX and accomplished simultaneous removal of SMX and nitrogen in both mariculture sewage and domestic sewage. The findings are significant to the effective elimination of SMX pollution and comprehensive cognitions on metabolic mechanisms of SMX removal.

Right heart failure and right ventricular (RV) remodeling were the main reason for mortality of pulmonary hypertension (PH) patients. Apolipoprotein AV (ApoA5) is a key regulator of plasma triglyceride and have multifunction in several target organs. We detected decreased ApoA5 in serum of patients with PH and both in serum and RV of monocrotaline-induced PH model. Exogenously, overexpression ApoA5 by adenovirus showed protective effects on RV failure and RV fibrosis secondary to PH. In addition, in vitro experiments showed ApoA5 attenuated the activation of fibroblast induced by transforming growth factor β1 and synthesis and secretion of extracellular matrix by inhibiting focal adhesion kinase-c-Jun N-terminal kinase-Smad3 pathway. Finally, we suggest that ApoA5 may potentially be a pivotal target for RV failure and fibrosis secondary of PH.

Mercury (Hg) is a heavy metal with high toxicity and easy migration; it can be enriched through the food chain, and cause serious threats to the natural environment and human health. So, the development of a method that can be used to detect mercury ions (Hg2+ ) in the environment, in cells, and in organisms is very important. Here, a new 7-hydroxycoumarin-derived carbonothioate-based probe (CC-Hg) was designed and synthesized for detection of Hg2+ . After addition of Hg2+ , a large fluorescence enhancement was observed due to the formation of 7-hydroxyl, which reinforced the intramolecular charge transfer process. The CC-Hg probe had good water solubility and selectivity. Moreover, the probe was able to detect Hg2+ quantitatively over the concentration range 0-2 μM and with a detection limit of 7.9 nM. Importantly, we successfully applied the probe to detect Hg2+ in water samples, in living cells, and in zebrafish. The experimental results demonstrated its potential value in practical applications.

A novel Golgi-targeting Cys-specific fluorescent probe (Gol-Cys) was synthesized. Probe Gol-Cys is not only sufficiently sensitive to native Cys in living cells and zebrafish, but also can be used for monitoring the Cys level during Golgi stress.

As a eukaryotic organelle, the Golgi apparatus plays an essential role in various physiological activities such as stress response. The Golgi stress response is an important physiological process of conferring cytoprotection by regulating the synthesis and metabolism of bioactive molecules. Therefore, the development of new suitable in situ analytical techniques for monitoring related small molecular substances in the stress reaction of the Golgi apparatus is very helpful for further study of the regulatory mechanism of the Golgi apparatus. Recent studies have shown that endogenous hydrogen sulfide (H2S) also possesses crucial bioregulatory and protective performances in the stress response. Therefore, the high-fidelity in situ mapping of H2S production under the Golgi stress response plays an important role not only in revealing cytoprotection functions of H2S in the stress response but also in further understanding the regulatory mechanism of the Golgi stress response. In this work, we designed a simple Golgi-targetable H2S fluorescent probe (Gol-H2S) that responds accurately and sensitively to H2S in the Golgi apparatus of living cells and zebrafish. On the basis of its superior bioimaging performances, probe Gol-H2S was successfully applied to the in situ visualization of H2S production under the Golgi stress response elicited by monensin, a specific-Golgi stressor. The related process of the Golgi stress response was validated by stimulation and inhibition experiments. These findings fully demonstrate that H2S is an alternative biomarker of the Golgi stress response. Moreover, probe Gol-H2S can also be used as a potential tool for disclosing the detailed H2S-cytoprotection mechanisms under the regulation of the Golgi stress response in related diseases.

A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR(1068) phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2–inhibitor binding. This compound with a −1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade.

(1) Background: Biochar and plant growth-promoting rhizobacteria (PGPR) are widely used as amendments to increase the availability of nutrients and the diversity of the bacterial community within soil. (2) Methods: In this study, we investigated the effects of biochar and PGPR amendments on plant performance, soil physicochemical property, and soil microbial diversity, as well as their relationship in a Eucalyptus (clone DH32−29) plantation in Guangxi, China. We determined the microbial AWCD, Simpson, Shannon, and McIntosh indices, and soil inorganic nitrogen (NH4+, NO3−), total phosphorus (TP), total potassium (TK), total nitrogen (TN), and plant growth and nutrient concentrations; (3) Results: Biochar-only had a significant impact on soil microbial community function, although the effects on plant performance were limited. PGPR plus biochar was found to significantly increase the diversity indices of soil microbes, as well as soil TK and TP. Besides, soil microbes displayed a preference for carbohydrates rather than other carbon sources. (4) Conclusion: Soil microbial functional diversity responded to changes in plant performance and, therefore, it could indicate soil ecological stability and ecosystem productivity. These findings may suggest that biochar and PGPR could potentially maintain ecological sustainability in the soil and improve plant performance through altering soil physicochemical properties in a eucalyptus plantation.

Jingyuan Chen, Jun Luo, Xiaojie Yang, Peng Luo, Yusi Chen, Zilu Li, Jiang Li Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of ChinaCorrespondence: Jiang LiDepartment of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of ChinaEmail lijiangcs@csu.edu.cnBackground: Pulmonary hypertension patients experienced a high financial burden due to the high cost of drug therapy, high incidence of comorbidities and hospitalizations. Endothelin receptor antagonists (ERAs) in PAH treatment showed a high cost. While ambrisentan has been covered by medical insurance of a local government of China, there has been a drug transition from bosentan to ambrisentan in treating PAH patients. We evaluated the safety, efficacy and tolerability of ambrisentan after drug transition.Methods: Liver and renal functions were inspected at baseline, month 1, 3 and 6. NT-proBNP, echocardiographic variables, WHO functional class (WHO-FC), 6-minute walking distance (6MWD) were measured in the baseline and month 6 to evaluate the safety and efficacy. Quality of life (QOL) scale was used in the baseline and month 6 to investigate the tolerability and quality of life of PAH patients.Results: Among 224 PAH patients, 49 stable PAH patients meet the inclusion criteria were enrolled, among which three patients discontinued during the study. Our results showed no difference in 6-minute walking distance (6MWD) of PAH patients from baseline and month 6. The liver and renal function, N-terminal pro-brain natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) showed no difference either. For echocardiography parameters, the left ventricular end-diastolic dimension (LVEDD) of month 6 decreased. Other parameters were no significant difference from the baseline. There was no difference in the QOL scale between baseline and month 6.Conclusion: Our results suggested that it is safe and tolerable for stable PAH patients to transition from bosentan to ambrisentan without influencing hematologic parameters or heart function.Keywords: pulmonary arterial hypertension, ambrisentan, bosentan, endothelin receptor antagonist, drug transition

In this work, by taking full advantage of the transformation of nitro group into amino moiety under the direct reduction of CO, a new metal-free colorimetric and near-infrared fluorescent probe NIR-CO for rapid and specific tracing of intracellular CO has been constructed, and it also become the first reaction-based near-infrared fluorescent probe for CO detection without additional reagents. Probe NIR-CO could quantitatively detect CO at the nanomolar level and the detection limit was calculated as low as 6.1 nM. Additionally, probe NIR-CO with preeminent sensing properties was successfully applied to monitor the fluctuations of endogenous CO levels in living systems. In particular, the up-regulation of heme oxygenase-1 (HO-1) caused by transient glucose deprivation (TGD) in living cells and the down-regulation of HO-1 inhibited by high glucose (HG) in zebrafish were confirmed for the first time via mapping the glucose-induced fluctuations of CO levels. Thus, we anticipate that probe NIR-CO not only can serve as a powerful tool to investigate the detailed biological functions of CO in the pathophysiological processes, but also possesses potential applications of in situ monitoring HO-1 activity in the complex biological systems.

Cell-selective imaging of some biological species is significant for the diseases research of a specific tissue or organ. Peroxynitrite (ONOO−) as a kind of reactive nitrogen species (RNS), plays extremely important roles in diverse physiological and pathological processes. Developing cell-specific fluorescent probes for tracing ONOO− in living systems remains a great challenge due to the complexity of internal environment and high autofluorescence. In this work, we developed a galactose-appended hepatoma-specific fluorescent probe Gal-NHP with hydroxynaphthalimide as the fluorophore and hydroquinone moiety as the responsive receptor for sensitively detecting endogenous ONOO− in live HepG2 cells. Probe Gal-NHP could selectively trace ONOO− without interference from other species such as HOCl and H2O2. In addition, the introduction of galactose enhanced the water solubility of this probe, and Gal-NHP could respond quickly to ONOO− in aqueous solution. The quantitative experiment showed the excellent sensitivity of this probe with a good linear relationship. Above all, fluorescence imaging results displayed it possessed excellent hepatoma-specific ability and could successfully detect endogenous ONOO− of hepatoma cells in real time. Thus, this newly developed probe would benefit to reveal the roles of ONOO− in hepatoma cells.

The precise cellular function of peroxynitrite (ONOO–) in biosystems remains elusive, primarily owing to being short of ultrasensitive techniques for monitoring its intracellular distribution. In t...

It is very important to detect native hypochlorous acid (HOCl) in the complex biosystems owing to the important roles of HOCl in the immune defense and the pathogenesis of numerous diseases. In this paper, a new p-aminophenylether-based fluorescent probe PAPE-HA was developed for specific detection of HOCl. Probe PAPE-HA could implement the quantitative detection of HOCl ranging from 0 to 1 μM and the detection limit was obtained as low as 1.37 nM. Additionally, probe PAPE-HA could reach a rapid response for HOCl (2 min). Importantly, probe PAPE-HA with preeminent specificity and ultrasensitivity was proven to possess powerful capability of tracking native HOCl in live cells and zebrafish, and we thus anticipate that probe PAPE-HA could be used as a novel promising tool for revealing diverse cellular functions of HOCl.

A water-soluble fluorescent probe for monitoring thiophenols based on a GFP-type TPC-OH fluorophore and a 2,4-dinitrophenyl ether recognition unit was designed. This probe possessed remarkable sensitivity and specificity toward thiophenols in an almost pure aqueous solution, and also showed good interference immunity to other related analytes including aliphatic mercaptans. Meanwhile, the probe displayed a prominent linear correlation between the thiophenol concentrations in the range of 0 to 20 μM and the fluorescence intensities at 492 nm, and the detection limit was as low as 33 nM. More strikingly, probe 1 was employed to visualize thiophenol in both living cells and zebrafish, which further demonstrated that probe 1 was a powerful practical tool in monitoring thiophenols in living systems.

Peroxynitrite (ONOO−) is a reactive and short-lived biological oxidant endogenously generated in biosystems, and its excessive production is related to various diseases. However, the functional mechanisms of ONOO− are not fully understood. Here, we present a novel ratiometric fluorescent probe CPD-ratio for the accurate detection of ONOO− under single wavelength excitation. This study showed that the probe CPD-ratio can achieve the ratiometric detection of ONOO− with rapid response, and it possessed excellent selectivity and sensitivity (detection limit was calculated to be 47 nM). These properties and its non-toxicity demonstrated that probe CPD-ratio could be potentially employed to accurately monitor ONOO− levels in biological systems. We have thoroughly demonstrated the utility of the probe CPD-ratio for ratiometric bioimaging, because it has been effectively used to trace the exogenous and endogenous ONOO− in live cells.

The detection of ionic mercury (Hg2+) is very important because it is a highly toxic environmental pollutant that could cause serious diseases and threaten human health. Herein, we designed a new carbonothioate-based far-red fluorescent probe, CBRB, with a seminaphthorhodafluor dye as the fluorophore for the detection of Hg2+. The CBRB probe by itself exhibited very weak fluorescence due to the enhanced photo-induced electron transfer (PET) effect and inhibited the intramolecular charge transfer (ICT) process caused by the carbonothioate moiety. Upon addition of Hg2+, a tremendous fluorescence enhancement was achieved, attributed to the removal of the carbonothioate group via a specific mercury-promoted desulfurization reaction. Moreover, the probe displayed a large Stokes shift (about 105 nm) and was used to quantitatively measure the concentration of Hg2+ for concentrations ranging from 0 to 1 μM (DL = 3.6 nM). In addition, CBRB in our experiments responded exclusively to Hg2+, even in the presence of high concentrations other ions. Gratifyingly, this probe was successfully used to monitor Hg2+ in environmental water samples and to image Hg2+ in living cells as well as in zebrafish.

A novel pH-sensitive fluorescent probe has been designed and synthesized for sensing intracellular pH. This probe showed excellent water solubility, it was sensitive toward the pH range from 4 to 12, and it was especially sensitive in alkaline environments. During the pH changes from acidic to alkaline environments, the color of the solution turned from yellow to purple, thus the difference in color can be used to distinguish between acidic and alkaline systems. The other major features of probe pH-DCN including high selectivity, low toxicity, good reversibility and stability allowed pH-DCN to visualize fluctuations of the pH in live cells. Moreover, probe pH-DCN has successfully discriminated cancer cells from normal cells by monitoring their different intracellular pH levels.

In this work, a simple dichlororesorufin-based colorimetric and fluorescent probe R-Hg with the recognition receptor of carbonothioate was designed, synthesized, and exploited to determine mercury ions in aqueous solution and living cells as well as in zebrafish. After a series of analytical tests, probe R-Hg showed some excellent characteristics, such as ultrasensitivity, high selectivity, and good water solubility. The probe solution exhibited a very large fluorescence enhancement (about 150-fold) upon addition of Hg2+. Additionally, probe R-Hg exhibited excellent sensitivity, which could quantificationally detect Hg2+ at the nanomolar level, and the detection limit was 0.49 nM. Moreover, probe R-Hg could be used as a “naked-eye” probe for monitoring Hg2+, because the color of its solution transformed remarkably from yellow into pink with the participation of Hg2+. Importantly, probe R-Hg has potential application value and has been successfully applied to the determination of Hg2+ in practical water sa...