Robust layout optimization for intelligent reflecting surfaces-based visible light communication systems.

Due to the inherent tendency to be blocked by obstacles, reliability is a major challenge for visible light communication (VLC). The intelligent reflective surface (IRS) is an effective way to reduce or eliminate the influence of blockage in the VLC system. However, the complexity increases correspondingly due to complex shadow analysis when access points (APs), IRSs, and obstacles coexist. We proposed a robust layout optimization scheme for the IRS-VLC system to resist blockages. First, we model the random obstructions based on spatial geometry methods. Second, we build the optimization problem model considering consistent illumination, achievable data rate (ADR), the positions of the APs, and the directions of the IRS array. In order to achieve this objective, we develop an anti-occlusion method based on the non-dominated sorting genetic algorithm-II (NSGA-II) to get the Pareto front and use enhanced measurement functions (ASFs) to extract the best solution. Simulation results show that the proposed scheme works well in the IRS-VLC system. It is noteworthy that the rectangle layout has always demonstrated superior performance in the IRS-VLC system compared to other traditional layouts.

Tumor microenvironment activated mussel-inspired hollow mesoporous nanotheranostic for enhanced synergistic photodynamic/chemodynamic therapy.

Anti-tumor therapies reliant on reactive oxygen species (ROS) as primary therapeutic agents face challenges due to a limited oxygen substrate. Photodynamic therapy (PDT) is particularly hindered by inherent hypoxia, while chemodynamic therapy (CDT) encounters obstacles from insufficient endogenous hydrogen peroxide (H2O2) levels. In this study, we engineered biodegradable tumor microenvironment (TME)-activated hollow mesoporous MnO2-based nanotheranostic agents, designated as HAMnO2A. This construct entails loading artemisinin (ART) into the cavity and surface modification with a mussel-inspired polymer ligand, namely hyaluronic acid-linked poly(ethylene glycol)-diethylenetriamine-conjugated (3,4-dihydroxyphenyl) acetic acid, and the photosensitizer Chlorin e6 (mPEG-HA-Dien-(Dhpa/Ce6)), facilitating dual-modal imaging-guided PDT/CDT synergistic therapy. In vitro experimentation revealed that HAMnO2A exhibited ideal physiological stability and enhanced cellular uptake capability via CD44-mediated endocytosis. Additionally, it was demonstrated that accelerated endo-lysosomal escape through the pH-dependent protonation of Dien. Within the acidic and highly glutathione (GSH)-rich TME, the active component of HAMnO2A, MnO2, underwent decomposition, liberating oxygen and releasing both Mn2+ and ART. This process alleviates hypoxia within the tumor region and initiates a Fenton-like reaction through the combination of ART and Mn2+, thereby enhancing the effectiveness of PDT and CDT by generating increased singlet oxygen (1O2) and hydroxyl radicals (•OH). Moreover, the presence of Mn2+ ions enabled the activation of T1-weighted magnetic resonance imaging. In vivo findings further validated that HAMnO2A displayed meaningful tumor-targeting capabilities, prolonged circulation time in the bloodstream, and outstanding efficacy in restraining tumor growth while inducing minimal damage to normal tissues. Hence, this nanoplatform serves as an efficient all-in-one solution by facilitating the integration of multiple functions, ultimately enhancing the effectiveness of tumor theranostics.

Application of photo-crosslinkable gelatin methacryloyl in wound healing.

Wound healing is a complex and coordinated biological process easily influenced by various internal and external factors. Hydrogels have immense practical importance in wound nursing because of their environmental moisturising, pain-relieving, and cooling effects. As photo-crosslinkable biomaterials, gelatine methacryloyl (GelMA) hydrogels exhibit substantial potential for tissue repair and reconstruction because of their tunable and beneficial properties. GelMA hydrogels have been extensively investigated as scaffolds for cell growth and drug release in various biomedical applications. They also hold great significance in wound healing because of their similarity to the components of the extracellular matrix of the skin and their favourable physicochemical properties. These hydrogels can promote wound healing and tissue remodelling by reducing inflammation, facilitating vascularisation, and supporting cell growth. In this study, we reviewed the applications of GelMA hydrogels in wound healing, including skin tissue engineering, wound dressing, and transdermal drug delivery. We aim to inspire further exploration of their potential for wound healing.

Oxygen-Generating Organic/Inorganic Self-Assembled Nanocolloids for Tumor-Activated Dual-Model Imaging-Guided Photodynamic Therapy.

Tumor phototheranostics is usually compromised by the hypoxic tumor microenvironment and poor theranostic efficiency. The interplay between organic polymers and inorganic nanoparticles in novel nanocomposites has proven to be advantageous, overcoming previous limitations and harnessing their full potential through activation via the tumor microenvironment. This study successfully fabricated hypoxia-activated nanocolloids called HOISNDs through a process of self-assembly involving superparamagnetic iron oxide nanoparticles (SPIONs) and an organic polymer ligand called tetrakis(4-carboxyphenyl) porphyrin (TCPP)-engineered organic polymer ligand [methoxy poly(ethyleneglycol)-block-poly(dopamine-ethylenediamine-conjugated-4-nitrobenzyl chloroformate)-l-glutamate, mPEG-b-P(Dopa-EDA-co-NBCF)LG-TCPP)]. The SPIONs act as an oxygen generator to overcome the challenges posed by hypoxic tumors and enable the use of hypoxic-activatable MR/fluorescence dual-modal imaging-guided photodynamic therapy (PDT). The colloid stability of these HOISNDs proved to be exceptional in diverse biomimetic environments. Furthermore, they not only augment T2-weighted contrast capability as an MRI contrast agent but also function as an oxygen-producing device to amplify the generation and release of reactive oxygen species (ROS). The HOISNDs can significantly target to tumor sites through the enhanced permeability and retention (EPR) effect with prolonged blood circulation time and subsequently are effectively endocytosed into a hypoxic intracellular environment that "turn on" the imaging function and photodynamic activity. Moreover, HOISNDs possess the ability to effectively decompose naturally occurring H2O2 into oxygen (O2) within the tumor utilizing the Fenton reaction. This method can mitigate the impact of hypoxia on oxygen-dependent PDT. The outcomes of in vivo diagnostic and therapeutic evaluations indicated that HOISNDs are a highly promising tool for dual-model imaging-guided cancer theranosis by ameliorating hypoxic conditions and augmenting PDT efficiency.

Hydrophyte Debris Induced Sedimentary Phosphorus Release in Tuojiang Rivers, China.

Hydrophyte debris decomposition may contribute to phosphorus (P) release from the sediments in riverine systems, but the transport and transformation of organic phosphorus during this process has not been studied well. Here, a ubiquitous hydrophyte in southern China (Alternanthera philoxeroides, A. philoxeroides) was selected to identify the processes and mechanisms of sedimentary P release in late autumn or early spring by laboratory incubation. The results showed that the physio-chemical interactions changed quickly during the beginning of the incubation, where the redox potential and dissolved oxygen at the water-sediment interface decreased rapidly, reaching reducing (299 mV) and anoxic (0.23 mg∙L-1) conditions, respectively. Soluble reactive P, dissolved total P and total P concentrations in overlying water all increased with time from 0.011, 0.025 and 0.169 mg∙L-1 to 0.100, 0.100 and 0.342 mg∙L-1 on average, respectively. Furthermore, the decomposition of A. philoxeroides induced sedimentary organic P release to overlying water, including phosphate monoester (Mono-P), and orthophosphate diesters (Diesters-P). The proportions of Mono-P and Diesters-P were higher at 3 to 9 days than at 11 to 34 days, being 29.4% and 23.3 for Mono-P, 6.3% and 5.7% for Diesters-P, respectively. Orthophosphate (Ortho-P) increased from 63.6 to 69.7% during these timeframes, which indicated the transformations of both Mono-P and Diester-P to bio-available orthophosphate (Ortho-P), causing the rising P concentration in the overlying water. Our results revealed that hydrophyte debris decomposition in river systems might lead to autochthonous P contribution even without external P import from the watershed, accelerating the trophic state of receiving waterbodies.

A Potential Fungicide against Pseudoperonospora Cubensis: Design, Synthesis and 3D-QSAR of New Pyrazole-5-Carboxamide Derivatives.

BACKGROUND: Downy mildew is one of the major fungi causing significant economic losses to crops. The resistance of this fungus to current fungicides is increasing and new fungicides with a unique mode of action are needed. OBJECTIVE: To find a novel pyrazole amide derivative as a potential fungicide. METHODS: A series of pyrazole-5-carboxamide derivatives containing a diaryl ether were designed and synthesized by the Intermediate derivatization method (IDM). Their fungicidal activities against Pseudoperonospora cubensis (P. cubensis, cucumber downy mildew) were evaluated in the greenhouse. RESULTS: Bioassays indicated that several compounds exhibited excellent fungicidal activity against P. cubensis in vivo. In particular, T24 (EC50 = 0.88 mg L-1) had the highest activity compared with Dimethomorph and Fluazinam and other analogues. The relationship between the activity and the structure of these derivatives was analyzed, and an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established to determine that electrostatic and steric fields had important effects on the improvement of fungicidal activity. CONCLUSION: The novel pyrazole-5-carboxamide derivative T24 can be considered a potential fungicide for P. cubensis control.

A Star-Shaped Copolymer with Tetra-Hydroxy-Phenylporphyrin Core and Four PNIPAM-b-PMAGA Arms for Targeted Photodynamic Therapy.

The novel thermosensitive star-shaped tetra-hydroxy-phenylporphyrin-cored (THPP) double hydrophilic poly(N-isopropylacrylamide)-b-poly(methylacrylamide glucose) block copolymers (THPP-(PNIPAM-b-PMAGA)4) were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization. Notably, the low critical solution temperatures (LCSTs) of THPP-(PNIPAM-b-PMAGA)4 were above normal body temperature (37 °C) which depended on the hydrophilic PMAGA contents of copolymers. When the temperature was higher than the LCST of the copolymer, the copolymer could be neutralized into micelles in aqueous and could be coated with antitumor drugs and released around tumor cells. The MTT study indicated that THPP-(PNIPAM-b-PMAGA)4 had a low toxicity to L929 and HeLa cells in the absence of light. However, THPP-(PNIPAM-b-PMAGA)4 showed a high toxicity with HeLa cells under light irradiation which could be used as a potential photosensitizer for photodynamic therapy (PDT). In addition, THPP-(PNIPAM-b-PMAGA)4 showed specific a recognition function with Concanavalin A (Con A) to achieve active targeted drug delivery. This work provides a new approach for the development of tumor targeting and chemotherapy/PDT.

Two-dimensional power allocation scheme for NOMA-based underwater visible light communication systems.

In this work, a two-dimensional power allocation scheme combining fractional transmit power allocation (FTPA) and the sine cosine algorithm (SCA) is proposed for non-orthogonal multiple access (NOMA)-based underwater visible light communication (UVLC) systems. Considering the proposed power allocation scheme, a downlink NOMA-based UVLC system using blue-light-emitting diodes in the deep-sea environment is set up to evaluate the influence of the FTPA coefficient and SCA on system communication performance. The simulation results demonstrate that the two-dimensional power allocation scheme can effectively reduce the impact of user pairing on system performance and improve the system transmission rate compared with the conventional power allocation scheme.

CRISPR/dCas-mediated gene activation toolkit development and its application for parthenogenesis induction in maize.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems can be engineered as programmable transcription factors to either activate (CRISPRa) or inhibit transcription. Apomixis is extremely valuable for the seed industry in breeding clonal seeds with pure genetic backgrounds. We report here a CRISPR/dCas9-based toolkit equipped with dCas9-VP64 and MS2-p65-HSF1 effectors that may specifically target genes with high activation capability. We explored the application of in vivo CRISPRa targeting of maize BABY BOOM2 (ZmBBM2), acting as a fertilization checkpoint, as a means to engineer parthenogenesis. We detected ZmBBM2 transcripts only in egg cells but not in other maternal gametic cells. Activation of ZmBBM2 in egg cells in vivo caused maternal cell-autonomous parthenogenesis to produce haploid seeds. Our work provides a highly specific gene-activation CRISPRa technology for target cells and verifies its application for parthenogenesis induction in maize.

Experimental apparatus for resistivity measurement of gas hydrate-bearing sediment combined with x-ray computed tomography.

Natural gas hydrate has sparked worldwide interest due to its enormous energy potential. Geophysical surveys are commonly used in gas hydrate exploration, and resistivity logging plays an important role in this field. Nevertheless, the electrical response mechanism as a result of the gas hydrate growth in sediment is not well understood. This study develops an apparatus for the in situ resistivity testing of gas hydrate-bearing sediment combined with x-ray computed tomography scanning. Using this equipment, the gas hydrate samples can be synthesized under high-pressure and low-temperature conditions. The sample resistivities of three different layers can also be measured in situ during the gas hydrate formation. Moreover, x-ray computed tomography scanned gray images are acquired, which can be used to calculate the saturation and analyze the microscopic distribution of gas hydrate. A series of experiments are performed to validate the feasibility of the apparatus. The results show that the sample resistivity shows three distinct stages of variation as the gas hydrate grows. The most sensitive saturation range to the electrical response is ∼10.50%-22.34%. Very few gas hydrate particles will not significantly change the pore connectivity. By contrast, too many gas hydrate particles will hinder the pore network blocking. Both situations will not result in a significant change in resistivity.

The performance of OPC water model in prediction of the phase equilibria of methane hydrate.

Molecular dynamics (MD) simulations were performed to determine the three-phase coexistence line of sI methane hydrates. The MD simulations were carried out at four different pressures (4, 10, 40, and 100 MPa) by using the direct phase coexistence method. In current simulations, water was described by either TIP4P/Ice or "optimal" point charge (OPC) models and methane was described as a simple Lennard-Jones interaction site. Lorentz-Berthelot (LB) combining rules were used to calculate the parameters of the cross interactions. For the OPC model, positive deviations from the energetic LB rule were also considered based on the solubility of methane in water. For the TIP4P/Ice water model, the obtained three phase coexistence temperatures showed good agreement with experiment data at higher pressures, which is consistent with previous predictions. For the OPC water model, simulations using the classic and the modified LB parameters both showed negative deviations to the experimental values. Our results also indicated that the deviation of the T3 prediction by the OPC model was not closely correlated with the predicted melting point of ice. At 4 MPa, the modified OPC model showed a better prediction of hydrate equilibrium temperature, even better than the prediction by TIP4P/Ice. Considering the relatively higher accuracy in biomolecular MD of the OPC model, it is suggested that this model may have a better performance in hydrate MD simulations of biomolecule-based additives.

pH-responsive dynamically cross-linked nanogels with effective endo-lysosomal escape for synergetic cancer therapy based on intracellular co-delivery of photosensitizers and proteins.

Co-delivery of photosensitizers (PSs) and protein drugs represents great potentiality for enhancing the efficiency of synergistic cancer therapy. However, the intricate tumor-microenvironment and the lack of nanoplatforms to co-deliver both into cancer cells and activate their functions significantly hinder the clinical translation of this combined approach for cancer treatment. Herein, a chlorine e6 (Ce6)-functionalized and pH-responsive dynamically cross-linked nanogel (Ce6@NG) is fabricated by formation of benzoic imine linkages between Ce6-modified methoxy poly (ethyleneglycol)-block-poly (diethylenetriamine)-L-glutamate-Ce6 [MPEG-b-P(Deta)LG-Ce6] and terephthalaldehyde as cross-linkers for effective intracellular co-delivery of Ce6 and cytochrome c (CC), which could form a novel combination therapy system (CC/Ce6@NGs). The pH-sensitive benzoic imine bonds in the CC/Ce6@NGs endow them with excellent systemic stability under normal physiological environment while this nanosystem can be further cationized to enhance cell uptake in acidic extracellular environment. Upon cellular internalization, CC/Ce6@NGs can rapidly escape from the endo/lysosomal compartments and subsequently activate Ce6 to generate cytotoxic singlet oxygen upon laser irradiation and release of CC to induce programmed cell death by complete cleavage of benzoic imines at more acidic intracellular environments. Importantly, the catalase-like activity of CC can decompose H2O2 to produce O2 for hypoxia alleviation and improvement of the photodynamic therapy (PDT) of cancer. Moreover, this enhanced synergistic anticancer activity is confirmed both in vitro and in vivo. In view of the versatile chemical conjugation, this research offers a promising and smart nanosystem for intracellular co-delivery of PSs and therapeutic proteins.

Diversity of Anaerobic Methane Oxidizers in the Cold Seep Sediments of the Okinawa Trough.

Active cold seeps in the Okinawa Trough (OT) have been widely identified, but the sediment microbial communities associated with these sites are still poorly understood. Here, we investigated the distribution and biomass of the microbial communities, particularly those associated with the anaerobic oxidation of methane (AOM), in sediments from an active cold seep in the mid-Okinawa Trough. Methane-oxidizing archaea, including ANME-1a, ANME-1b, ANME-2a/b, ANME-2c, and ANME-3, were detected in the OT cold seep sediments. Vertical stratification of anaerobic methanotrophic archaea (ANME) communities was observed in the following order: ANME-3, ANME-1a, and ANME-1b. In addition, the abundance of methyl coenzyme M reductase A (mcrA) genes corresponded to high levels of dissolved iron, suggesting that methane-metabolizing archaea might participate in iron reduction coupled to methane oxidation (Fe-AOM) in the OT cold seep. Furthermore, the relative abundance of ANME-1a was strongly related to the concentration of dissolved iron, indicating that ANME-1a is a key microbial player for Fe-AOM in the OT cold seep sediments. Co-occurrence analysis revealed that methane-metabolizing microbial communities were mainly associated with heterotrophic microorganisms, such as JS1, Bathy-1, and Bathy-15.

Methanogenesis pathways of methanogens and their responses to substrates and temperature in sediments from the South Yellow Sea.

Although coastal sediments are major contributors to the production of atmospheric methane, the effects of environmental conditions on methanogenesis and the community of methanogenic archaea are not well understood. Here, we investigated the methanogenesis pathways in nearshore and offshore sediments from the South Yellow Sea (SYS). Moreover, the effects of the supply of methanogenic substrates (H2/CO2, acetate, trimethylamine (TMA), and methanol) and temperature on methanogenesis and the community of methanogenic archaea were further determined. Methylotrophic, hydrogenotrophic and acetotrophic methanogenesis were found to be responsible for biogenic methane production in nearshore sediments. In the offshore sediments, methylotrophic methanogenesis was the predominant methanogenic pathway. The changes in methanogenic community structure under different substrate amendments were characterized. Lower diversities were detected in substrate-amended samples with methanogenic activity. Hydrogenotrophic Methanogenium, multitrophic Methanosarcina, methylotrophic Methanococcoide, Methanococcoide or methylotrophic Methanolobus were dominant in H2/CO2-, acetate-, TMA- and methanol-amended sediment slurries, respectively. PCoA showed that the methanogen community in H2/CO2 and acetate amendments exhibited greater differences than those in other treatments. Lower temperature (10 °C) limits hydrogenotrophic and acetoclastic methanogenesis, but methylotrophic methanogenesis is much less affected. The response of methanogen diversity to the incubation temperature varied among the different substrate-amended slurries. The multitrophic methanogen Methanosarcina became increasingly abundant in H2/CO2- and acetate-amended sediment slurries when the temperature increased from 10 to 30 °C.

Artificial intelligence-assisted system for precision diagnosis of PD-L1 expression in non-small cell lung cancer.

Standardized programmed death-ligand 1 (PD-L1) assessment in non-small cell lung cancer (NSCLC) is challenging, owing to inter-observer variability among pathologists and the use of different antibodies. There is a strong demand for the development of an artificial intelligence (AI) system to obtain high-precision scores of PD-L1 expression in clinical diagnostic scenarios. We developed an AI system using whole slide images (WSIs) of the 22c3 assay to automatically assess the tumor proportion score (TPS) of PD-L1 expression based on a deep learning (DL) model of tumor detection. Tests were performed to show the diagnostic ability of the AI system in the 22c3 assay to assist pathologists and the reliability of the application in the SP263 assay. A robust high-performance DL model for automated tumor detection was devised with an accuracy and specificity of 0.9326 and 0.9641, respectively, and a concrete TPS value was obtained after tumor cell segmentation. The TPS comparison test in the 22c3 assay showed strong consistency between the TPS calculated with the AI system and trained pathologists (R = 0.9429-0.9458). AI-assisted diagnosis test confirmed that the repeatability and efficiency of untrained pathologists could be improved using the AI system. The Ventana PD-L1 (SP263) assay showed high consistency in TPS calculations between the AI system and pathologists (R = 0.9787). In conclusion, a high-precision AI system is proposed for the automated TPS assessment of PD-L1 expression in the 22c3 and SP263 assays in NSCLC. Our study also indicates the benefits of using an AI-assisted system to improve diagnostic repeatability and efficiency for pathologists.

Among Multiple Needle Core Biopsy Samples, the One with the Highest Tumor Proportion Score Best Represents the PD-L1 Status of the Whole Surgical Specimen in Non-Small Cell Lung Cancer.

The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor has not been well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non-small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

A testing assembly for combination measurements on gas hydrate-bearing sediments using x-ray computed tomography and low-field nuclear magnetic resonance.

Studying the pore-scale characteristics of gas hydrate-bearing sediments (GHBS) is very important for a deep understanding of (i) how fluid flows therein and (ii) the corresponding gas production. Micro X-ray computed tomography (X-CT) and low-field nuclear magnetic resonance (NMR) are often used independently to characterize the pore structure of GHBS. Here, we present a new testing assembly that combines X-CT scans and low-field NMR tests to determine the pore-scale characteristics of GHBS in situ. The main parts of the testing assembly are a removable core holder made of polyether ether ketone, an X-CT system, and a low-field NMR system. The core holder allows for independent pressure control for the formation/dissociation of gas hydrates, which is xenon hydrate here. X-CT scans and low-field NMR tests are conducted successively to obtain not only the hydrate pore-scale behavior but also the transverse relaxation time distributions of GHBS. Correlation analysis between the pore size distributions and the transverse relaxation time curves gives the transverse surface relaxivity of xenon hydrate-bearing sediments during hydrate dissociation. The results show that the hydrate pore occurs as a mixture of grain-coating, cementing, pore-filling, and patchy clusters in a gas-dissolved solution. The peak pore size at the maximum frequency ratio increases with decreasing hydrate saturation. In addition, the transverse surface relaxivity dependence on hydrate pore occurrences is in the range of 67.1-129.3 µm/s when the hydrate saturation is lower than 0.4. The combination measurements for GHBS have a promising potential in understanding the structure evaluation of pore space during gas recovery.

Smad7 down-regulation via ubiquitin degradation mediated by Smurf2 in fibroblasts of hypertrophic scars in burned patients.

TGF-ß1 (transforming growth factor ß1) was considered to play a critical role in the forming of hypertrophic scars. Smad, as a kind of signal downstream mediators, can modulate the functions of TGF-ß1. Smad7 can regulate TGF-ß1/Smad pathway and present negative feedbacks, which prevents fibrosis mediated by TGF-ß1. Nonetheless, the mechanisms related to Smad7 activity in regulating hypertrophic scarring are hardly known. The studies have shown that Smad7 decrease induced by the increase of Smurf2 (Smad ubiquitination regulatory factor 2, an E3 ubiquitin ligase of Smad7) ubiquitination degradation plays a part in fibrosis. We thus made a hypothesis that Smad7 could not inhibit TGF-ß1 because Smurf2 ubiquitin degradation was increased in hypertrophic scar fibroblasts. In our research, it was discovered that there was an increase in Smad7 mRNA levels but no increase in Smad7 protein levels in the fibroblasts of hypertrophic scars after TGF-ß1 treatment. The ubiquitination activity and degradation of Smad7 protein were increased in the fibroblasts of hypertrophic scars compared with the fibroblasts of normal skin. Enhanced degradation of Smad7 protein in the fibroblasts of hypertrophic scars was prevented by proteasome inhibitors MG132 / MG115. Furthermore, it was found that TGF-ß1 stimulation increased Smad7 protein expression after silencing Smurf2 gene in hypertrophic scar fibroblasts, and enhanced Smad7 degradation was prevented in hypertrophic scar fibroblasts after Smurf2 was silenced. It was implied that ubiquitin degradation mediated by Smurf2 might contribute to decreased Smad7 protein levels following TGF-ß1 stimulation in the fibroblasts of hypertrophic scars.

Overexpression of three P450 genes is responsible for resistance to novel pyrimidine amines in Magnaporthe oryzae.

BACKGROUND: A series of pyrimidine amine derivatives has been synthesized by modifying the pyrimidine ring group of diflumetorim-a mitochondrial complex I inhibiting fungicide. One derivative, code number SYP-34773, is investigated in this study involving Magnaporthe oryzae, the causal agent of rice blast, which is the most devastating disease in rice. The response, resistance profile and mechanism of M. oryzae to SYP-34773 were investigated, which provides or provide?? important data for the registration and rational use of pyrimidine amines. RESULTS: SYP-34773 showed greater control efficacy than fungicide isoprothiolane in the field. The baseline sensitivity was established at a mean 50% effective concentration (EC50 ) of 0.08 µg ml-1 . Four stable SYP-34773-resistant isolates with reduced sensitivity were generated from one (S118) of ten sensitive isolates with a resistance factor of EC50 ranging from 7.00 to 15.00. Conidia production and pathogenicity were similar to that of S118, although there was a significant decrease in mycelial growth and conidial germination in resistant isolates. Positive cross-resistance was observed between SYP-34773 and diflumetorim; and the SYP-34773-resistant isolates were still sensitive to isoprothiolane, carbendazim, fluazinam, azoxystrobin, or prochloraz. RNA-Seq analyses revealed three cytochrome P450 genes were upregulated in the resistant isolate under the treatment with SYP-34773, as confirmed by quantitative real-time PCR. The SYP-34773 content was significantly reduced in the resistant isolate when compared with the parental isolate. CONCLUSION: The study demonstrated that SYP-34773 exhibits high activity against M. oryzae. Overexpression of three cytochrome P450 genes has an important role in the resistance of M. oryzae to novel pyrimidine amines. © 2020 Society of Chemical Industry.

Design, synthesis and herbicidal evaluation of novel uracil derivatives containing an isoxazoline moiety.

BACKGROUND: Glyphosate is the most widely used and successful herbicide discovered to date, but its utility is now threatened by the occurrence of several glyphosate-resistant weed species. Saflufenacil is a relatively new herbicide developed by BASF in 2010. It is a highly effective selective herbicide showing excellent control on broadleaf weeds (more than 90 species), significantly superior to other protoporphyrinogen oxidase (PPO) inhibitor herbicides at the level of weeds controlled. It is also effective against glyphosate-resistant Conyza canadensis if used in combination with glyphosate. A series of novel uracil-based PPO inhibitors containing an isoxazoline moiety were designed via the intermediate derivatization method, synthesized using a key saflufenacil raw material as starting material and evaluated for herbicidal activity. RESULTS: The target compounds were characterized by 1 H NMR and high-resolution electrospray mass spectra. Bioassays indicated that some title compounds can control efficiently and effectively both broadleaf weeds and grassy weeds at low doses, especially the glyphosate-resistant weeds C. canadensis and Eleusine indica. CONCLUSION: This work provides a basis for further studies of 9b for control of a wider range of weeds, particularly for glyphosate-resistant weeds.