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Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has a therapeutic effect on bupivacaine-induced neurotoxicity. The aim of this study was to determine the underlying mechanisms of bupivacaine-induced neurotoxicity and the potential neuroprotective role of GM1. A rat spinal cord neurotoxicity model was established by injecting bupivacaine (5%, 0.12 μL/g) intrathecally. The protective effect of GM1 (30 mg/kg) was evaluated by pretreating the animals with it prior to the bupivacaine regimen. The neurological and locomotor functions were assessed using standard tests. The histomorphological changes, neuron degeneration and apoptosis, and endoplasmic reticulum stress (ERS) relevant markers were analyzed using immunofluorescence, quantitative real-time PCR, and Western blotting. Bupivacaine resulted in significant neurotoxicity in the form of aberrant neurolocomoter functions and spinal cord histomorphology and neuronal apoptosis. Furthermore, the ERS specific markers were significantly upregulated during bupivacaine-induced neurotoxicity. These neurotoxic effects were ameliorated by GM1. Pretreatment with GM1 protects against bupivacaine-induced neurotoxicity via the inhibition of the GRP78/PERK/eIF2α/ATF4-mediated ERS.

In this paper, we develop a novel enriched Galerkin (EG) method for the steady incompressible Navier-Stokes equations in rotational form, which is both pressure-robust and parameter-free. The EG space employed here, originally proposed in [1], differs from traditional EG methods: it enriches the first-order continuous Galerkin (CG) space with piecewise constants along edges in two dimensions or on faces in three dimensions, rather than with elementwise polynomials. Within this framework, the gradient and divergence are modified to incorporate the edge/face enrichment, while the curl remains applied only to the CG component, an inherent feature that makes the space particularly suitable for the rotational form. The proposed EG method achieves pressure robustness through a velocity reconstruction operator. We establish existence, uniqueness under a small-data assumption, and convergence of the method, and confirm its effectiveness by numerical experiments.

We propose a novel parameter-free and locking-free enriched Galerkin (EG) method for solving the linear elasticity problem in both two and three dimensions. Unlike existing locking-free EG methods, our method enriches the first-order continuous Galerkin (CG) space with piecewise constants along edges in two dimensions or faces in three dimensions. This enrichment acts as a correction to the normal component of the CG space, ensuring the locking-free property and delivering an oscillation-free stress approximation without requiring post-processing. Our theoretical analysis establishes the well-posedness of the method and derives optimal error estimates. Numerical experiments further demonstrate the accuracy, efficiency, and robustness of the proposed method.

Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry. It is unknown whether the H7N9 viruses can acquire additional mutations during their circulation in nature and become lethal to poultry and more dangerous for humans. Here, we evaluated the evolution of H7N9 viruses isolated from avian species between 2013 and 2017 in China and found 23 different genotypes, 7 of which were detected only in ducks and were genetically distinct from the other 16 genotypes that evolved from the 2013 H7N9 viruses. Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin （HA） cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet. H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.

Rubus chingii Hu. is a versatile plant valued for its medicinal and edible properties. Its fruits are rich in flavonoids, with unripe fruits exhibiting higher flavonoid content. This study identified the WRKY gene family in this plant and explored its regulatory mechanisms in flavonoid synthesis. In total, 52 members of the RcWRKY family were identified; they were unevenly distributed on six chromosomes and all located in the nucleus. Based on the phylogenetic tree, these 52 members were divided into seven subgroups, and the motifs and gene structures of different subgroups were highly consistent. Their promoters were rich in elements such as light and jasmonic acid methyl response elements. Additionally, 20 collinear gene pairs were identified in the genome, most of which underwent purifying selection. Whole-genome duplication was the main cause of expansion of the RcWRKY family, and most members showed obvious collinearity with dicotyledonous plants. Transcriptome analysis revealed that 47 RcWRKY members were differentially expressed during fruit ripening, and 11 were highly expressed at the mature green (MG) stage with high flavonoid content. Additionally, the 30 identified flavonoid synthesis-related genes were highly expressed in the MG period, with six RcWRKY members being significantly positively correlated with most flavonoid synthesis genes. Reverse transcription-quantitative polymerase chain reaction and subcellular localization confirmed that RcWRKY34 and RcWRKY37 were highly expressed in the MG period and located in the nucleus. Dual-luciferase assay showed that both RcWRKY34 and RcWRKY37 positively regulated the flavonoid synthesis gene LG07.48 . Overall, this study lays a foundation for enhancing the medicinal value of palm-leaved R. chingii .

Rice blast, caused by rice blast fungus ( Magnaporthe oryzae ), is a global threat to food security, with up to 50% yield losses. Panicle blast is a severe form of rice blast, and disease responses vary between cultivars with different genotypes. Reactive oxygen species (ROS)-mediated signaling reactions and the phenylpropanoid pathway are important defense mechanisms involved in recognizing and resisting against fungal infection. To understand rice- M . oryzae interactions in resistant and susceptible cultivars, we determined dynamic changes in the activities of five defense-related enzymes in resistant cultivar jingsui 18 and susceptible cultivar jinyuan 899 infected with M . oryzae from 4 to 25 days after infection. We then performed untargeted metabolomics analyses to profile the metabolomes of the cultivars under infected and non-infected conditions. Dynamic changes in the activities of five defense-related enzymes were closely related to panicle blast resistance in rice. Metabolome data analysis identified 634 differentially accumulated metabolites (DAMs) between resistant and susceptible cultivars following infection, potentially explaining differences in disease response between varieties. The most enriched DAMs were associated with lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, and lignans, neolignans, and related compounds. Multiple metabolic pathways are involved in resistance to panicle blast in rice, including biosynthesis of other secondary metabolites, amino acid metabolism, lipid metabolism, phenylpropanoid biosynthesis, arachidonic acid metabolism, arginine biosynthesis, tyrosine metabolism, tryptophan metabolism, tyrosine and tryptophan biosynthesis, lysine biosynthesis, and oxidative phosphorylation.

BACKGROUND: Low phosphorus (P) availability is a major constraint to soybean growth and production. Developing P-efficient soybean varieties that can efficiently utilize native P and added P in the soils would be a sustainable and economical approach to soybean production. SCOPE: This review summarizes the possible mechanisms for P efficiency and genetic strategies to improve P efficiency in soybean with examples from several case studies. It also highlights potential obstacles and depicts future perspectives in 'root breeding'. CONCLUSIONS: This review provides new insights into the mechanisms of P efficiency and breeding strategies for this trait in soybean. Root biology is a new frontier of plant biology. Substantial efforts are now focusing on increasing soybean P efficiency through 'root breeding'. To advance this area, additional collaborations between plant breeders and physiologists, as well as applied and theoretical research are needed to develop more soybean varieties with enhanced P efficiency through root modification, which might contribute to reduced use of P fertilizers, expanding agriculture on low-P soils, and achieving more sustainable agriculture.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Purpose To develop a streamlined strategy for pharmaceutical cocrystal preparation without knowledge of the stoichiometric ratio by preparing and characterizing the cocrystals of myricetin (MYR) with four cocrystal coformers (CCF). Methods An approach based on the phase solubility diagram (PSD) was used for MYR cocrystals preparation and the solid-state properties were characterized by differential scanning calorimetry (DSC), fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The ternary phase diagram (TPD) was constructed by combining the PSD and nuclear magnetic resonance (NMR) data. After that, the TPD was verified by traditional methods. The dissolution of MYR in the four cocrystals and pure MYR within three different media were also evaluated. Results A simple research method for MYR cocrystal preparation was obtained as follows: first, the PSD of MYR and CCF was constructed and analyzed; second, by transforming the curve in the PSD to a TPD, a region of pure cocrystals formation was exhibited, and then MYR cocrystals were prepared and identified by DSC, FT-IR, PXRD, and SEM; third, with the composition of the prepared cocrystal from NMR, the TPD of the MYR-CCF-Solvent system was constructed. The powder dissolution data showed that the solubility and dissolution rate of MYR was significantly enhanced by the cocrystals. Conclusions A novel strategy for pharmaceutical cocrystals preparation without knowledge of the stoichiometric ratio based on the TPD was established and MYR cocrystals were successfully prepared. The present study provides a systematic approach for pharmaceutical cocrystal generation, which benefits the development and application of cocrystal technology in drug delivery.

It is a novel promising technology that the advantages of vibration are applied to the plastic forming process. This study is prompted by the effect of the number of blows and dwell time on the forming properties of forgings when hammer forging impact is considered as vibration excitation. Taking Ti-6Al-4V alloy as the research object, this study investigates the forging quality and strength-toughness through hammer forging experiments. Then, a numerical model is established and verified by experiments. The results show that increasing the number of blows at constant total dwell time can obviously decrease the cumulative damage, stress concentration and residual stress in forgings, while improving the uniformity of forging deformation, average grain size and residual stress distribution. In addition, the proportion of fine grains in the forging is also increased. The adjustment of hammer forging impact parameters from the perspective of vibration excitation is effective in improving the performance of forgings, which can provide a theoretical basis for the future development of advanced hammer forging technology.