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Rabbit coccidiosis is a very serious disease caused by protozoan parasites of the genus Eimeria, which increases the production rate of free radicals, especially reactive oxygen species. When the generation of free radicals exceeds the scavenging capacity of the body’s antioxidant system, the oxidant-antioxidant balance is broken, resulting in oxidative stress. This study was designed to investigate the effect on the oxidant-antioxidant status of rabbits infected with E. intestinalis and E. magna. To this end, eighteen 30-d-old weaned rabbits were randomly allocated into three groups as follows: the E. intestinalis infection group with 3×103 sporulated oocysts of E. intestinalis, the E. magna infection group with 20×103 sporulated oocysts of E. magna, and the uninfected control group. We measured the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and the contents of malondialdehyde (MDA) in rabbits’ small intestinal tissues (duodenum, jejunum and ileum) of the three groups on day 8. The results showed that CAT activity and MDA levels significantly increased, while the activities of SOD, GSH-Px and T-AOC decreased after E. intestinalis and E. magna infection. Besides, the jejunum and ileum were particularly damaged in the rabbits. It is concluded that the pathological oxidative stress occurs during the E. intestinalis and E. magna infection process and the body’s oxidant-antioxidant balance is disrupted.

It is significant to design, synthesise and optimise flavonoid derivatives with better anti-inflammatory activity. This study aims to design and synthesise a series of novel 2-phenyl-4H-chromen-4-one compounds with anti-inflammatory; among them, compound 8 was discovered as the best one. And then, the effects of compound 8 on the TLR4/MAPK signalling pathway was carried out in vivo, the results indicated that compound 8 could downregulate NO, IL-6, and TNF-α expression, and suppress LPS-induced inflammation by inhibiting the TLR4/MAPK pathways. Furthermore, compound 8 reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo. The results suggest that compound 8 has the potential against inflammation through regulating TLR4/MAPK pathway and can be assessed further for drug development.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with increasing incidence. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin has been used for the treatment of T2DM worldwide. Although sitagliptin has excellent therapeutic outcome, adverse effects are observed. In addition, previous studies have suggested that sitagliptin may have pleiotropic effects other than treating T2DM. These pieces of evidence point to the importance of further investigation of the molecular mechanisms of sitagliptin, starting from the identification of sitagliptin-binding proteins. In this study, by combining affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), we discover seven high-confidence targets that can interact with sitagliptin. Surface plasmon resonance (SPR) assay confirms the binding of sitagliptin to three proteins, i. e., LYPLAL1, TCP1, and CCAR2, with binding affinities (K D) ranging from 50.1 μM to 1490 μM. Molecular docking followed by molecular dynamic (MD) simulation reveals hydrogen binding between sitagliptin and the catalytic triad of LYPLAL1, and also between sitagliptin and the P-loop of ATP-binding pocket of TCP1. Molecular mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis indicates that sitagliptin can stably bind to LYPLAL1 and TCP1 in active sites, which may have an impact on the functions of these proteins. SPR analysis validates the binding affinity of sitagliptin to TCP1 mutant D88A is ~10 times lower than that to the wild-type TCP1. Our findings provide insights into the sitagliptin-targets interplay and demonstrate the potential of sitagliptin in regulating gluconeogenesis and in anti-tumor drug development.

Abstract Background Colorectal cancer is the third most common cause of death among cancers in the world. Although improvements in various treatments have greatly improved the survival time of colorectal cancer patients, since colorectal cancer is often at an advanced stage when diagnosed, the prognosis of patients is still very poor. Since the ceRNA regulatory network was proposed in 2011, it has greatly promoted the study of the molecular mechanism of colorectal cancer occurrence and development. Objective Exploring the new molecular mechanism of colorectal cancer occurrence and development and providing new targets for the diagnosis and treatment of colorectal cancer. Method We analyzed the RNA-seq data of CRC from TCGA, such as differential expression analysis, weighted gene co-expression network analysis (WGCNA) and construction of ceRNA regulatory network. Results We constructed a ceRNA network using RNA-seq data of CRC from TCGA. In the ceRNA regulatory network, 19 hub molecules with significant prognostic effects were ultimately identified, including 8 lncRNAs, 2 mRNAs and 9 miRNAs. These hub molecules constitute the lncRNA-miRNA, miRNA-mRNA or lncRNA-miRNA-mRNA axis. Conclusion In this article, some new ceRNA regulatory axes have been discovered, which may potentially disclose new molecular mechanisms for the occurrence and development of colorectal cancer, thereby providing an important blueprint for the treatment and prognosis assessment of CRC patients.

Future climate change will affect the environmental fate of hydrophobic organic contaminants (HOCs) and associated human health risks, yet the extent of these effects remains unknown. Here, we couple a high-resolution environmental multimedia model with a bioaccumulation model to study the multimedia distribution of 16 priority polycyclic aromatic hydrocarbons (PAHs), a group of HOCs, and assess future PAH-related human health risks under varying climate change scenarios over China at a continental scale. After removing the effects of PAH emission changes, we find that the total PAH concentrations would decrease in the air, freshwater, sediment, soil, and organisms, while the high-molecular-weight PAH would increase in the air with climate warming from 1.5°C to 4°C. Consequently, the multi-pathway exposure human health risks predominately influenced by dietary ingestion are expected to decrease by 1.7%–20.5%, while the respiratory risks are projected to rise by 0.2%–5.8% in the future. However, the persistently high multi-pathway human health risks underscore the need for reducing future PAH emissions by 69% compared with 2009 levels in China. Our study demonstrates the urgency of limiting PAH emissions under future climate change for public health and highlights the importance of including the contribution of dietary ingestion in human health risk assessment.

Oxalis triangularis ‘Purpurea’ has significant ornamental value in landscaping. There is a critical necessity to elucidate the gene functions of O. triangularis ‘Purpurea’ and dissect the molecular mechanisms governing key ornamental traits. However, a reliable genetic transformation method remains elusive. In this study, our investigation revealed that various transformation parameters, including recipient material (petioles), pre-culture time (2–5 days), acetosyringone (AS) concentration (100–400 μM), Agrobacterium concentrations (OD600 = 0.4–1.0), infection time (5–20 min), and co-culture time (2–5 days), significantly impacted the stable genetic transformation in O. triangular ‘Purpurea’. Notably, the highest genetic transformation rate was achieved from the leaf discs pre-cultured for 3 days, treated with 200 μM AS infected with Agrobacterium for 11 min at OD600 of 0.6, and subsequently co-cultured for 3 days. This treatment resulted in a genetic transformation efficiency of 9.88%, and it only took 79 days to produce transgenic plants. Our transformation protocol offers advantages of speed, efficiency, and simplicity, which will greatly facilitate genetic transformation for O. triangular ‘Purpurea’ and gene function studies.

Abstract Lithium‐ion batteries (LIBs) are one of the most exciting inventions of the 20th century and have been widely employed in modern society. LIBs have powered many of our electronics, such as laptop computers, smartphones, and even large‐scale energy storage systems. With the development of modern technology, next‐generation LIBs with higher energy density are in demand. A number of electrode materials with high theoretical capacity, including Sn, Si, Li metal anode, and S cathode materials, have been explored. Nevertheless, they usually suffer from structural or interface failure during cycling, limiting their practical application. Ga‐based liquid metals (LMs) possess self‐healing capability, fluidity, and metallic advantages so they have been employed as self‐healing skeletons or interfacial protective layers to minimize the negative impact of volume expansion or dendritic growth on the electrode materials. Herein, the features of Ga‐based LMs are briefly discussed to indicate their potential for battery systems. In addition, recent developments on Ga‐based LMs applied in LIBs have been summarized, including from the aspects of anodes, cathodes, and electrolytes. Finally, future opportunities and challenges for the development of Ga‐based LMs in LIBs are highlighted.

The moisture-conserving effect of straw mulch-based no-tillage (SMNT) is expected to increase fertile spikes and grain yield in environments with rainfall less than 200 mm. However, the mechanisms underlying the positive effect of SMNT on wheat tillering are not fully elucidated. A split-plot experiment was designed to investigate the combined effects of SMNT and cultivars on tillering of dryland wheat grown under both dry and favorable climates. Application of SMNT to a cultivar with 1–2 tillers exploited both tillering and kernel-number plasticity, increasing the mean grain yield by 20.5%. This increase was attributed primarily to an increased first-tiller emergence rate resulting from increased N uptake, leaf N content, and N remobilization from tillers to their grain. The second and third tillers, as transient sinks, contributed to the tiller survival rate, which depends on tiller leaf number. The increased total N uptake by SMNT also increased the dry mass yield of tillers and the C:N ratio, reducing the asymmetric competition between main stem and tillers. Owing to these beneficial effects, reduced mitogen-activated protein kinase (MAPK) and abscisic acid signals were observed under SMNT, whereas indole-3-acetic acid (IAA) signals and genes involved in DNA replication and mismatch repair were increased. These signals activated three critical transcription factors (the calmodulin-binding transcription activator, GRAS domain, and cysteine-2/histidine-2 family) and further increased rapid drought response and tiller maintenance after stem extension. Phenylpropanoid biosynthesis, sphingolipid biosynthesis, and galactose metabolism were most relevant to increased tillering under SMNT because of their critical role in drought response and lignin biosynthesis. Our results suggest that straw mulch-based no-tillage activates rapid drought response and improved wheat tillering by coordinating root N uptake, N remobilization, and asymmetric competition between main stem and tillers.

Objective: The topoisomerase inhibitor CPT-11 has been applied in treatment of multiple cancer types. Here, we probed into the possible mechanism of CPT-11 in affecting growth and metastasis of lung cancer (LC) cells, with involvement of the EGFR/MAPK pathway. Methods: The target protein of CPT-11 was screened through bioinformatics analysis, and the LC-related microarray datasets GSE29249, GSE32863 and GSE44077 were obtained for differential analysis for identifying the target protein. A subcutaneous xenograft tumor model and a metastatic tumor model were constructed in nude mice for in vivo mechanism verification of the regulatory role of CPT-11 in LC through modulation of EGRF/MAPK pathway. Results: Bioinformatics analysis showed that EGFR was the target protein of CPT-11. In vivo animal experiments confirmed that CPT-11 enhanced LC cell growth and metastasis in nude mice. CPT-11 could inhibit activation of EGFR/MAPK pathway. EGFR promoted LC cell growth and metastasis in nude mice through activation of the MAPK pathway. Conclusion: The topoisomerase inhibitor CPT-11 may prevent LC growth and metastasis by inhibiting activation of EGFR/MAPK pathway.

Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aβ aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aβ plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aβ and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aβ-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Heterophyllidiae, one of the main subgenus of Russula (Russulaceae, Russulales), is both ecologically and economically important. Although many studies have focused on subgenus Heterophyllidiae in China, the diversity, taxonomy, and molecular phylogeny still remained incompletely understood. In the present study, two new species, R. discoidea and R. niveopicta, and two known taxa, R. xanthovirens and R. subatropurpurea, were described based on morphology and molecular phylogenetic analyses of ITS and 28S DNA sequences with new collections of subgenus Heterophyllidiae from southern China. Both morphological and phylogenetic analyses consistently confirmed that R. niveopicta and R. xanthovirens belong to the subsect. Virescentinae, R. discoidea and R. subatropurpurea come under subsect. Heterophyllae, and R. prasina is synonymized with R. xanthovirens.

ABSTRACT: The microbiota has received plenty of attention in recent years due to its influence on host health and productivity. The striped eggs have reduced hatching performance and resulted in economic loss. The reasons are still unknown. Microbiota is one of the potentially important factors contributing to striped egg formation. This study investigates the relationship between the microbiota and striped eggs. The litter samples, feed samples, and cloacal swab samples of female ducks that produce striped eggs and normal eggs were performed for microbial diversity and composition using 16S rRNA sequencing. The results showed that there was no significant difference between feed microbiota and cloacal swab microbiota by alpha diversity, whereas, the number of microorganisms in the litter samples of female ducks that produced striped eggs was less than those of female ducks with normal eggs. There were compositional differences in litter microbiota of female ducks between the striped egg and the normal eggs. Among them, the abundance of Staphylococcus, Corynebacterium, and Brevibacterium in the litter of female ducks that produced striped eggs was significantly higher than that produced normal eggs. And these differential bacteria maybe affect the health of female ducks and cause abnormalities in the formation process of duck eggs. Therefore, the reduction of harmful bacteria may protect the reproductive health of female ducks and decrease the proportion of striped eggs. It provides an important reference to explore why female ducks produce striped eggs.

ObjectiveTo compare measures and effectiveness of case detection, transmission control, and vaccination for containment of coronavirus disease 2019 (COVID-19) epidemic in Australia, South Korea, Singapore, Israel, and India for providing evidences to the development of strategies on worldwide prevention and control of the epidemic. MethodsThe data on COVID-19 epidemic from January 1st 2020 through 2021 in the five countries were retrieved from the website of Our World in Data. Country-specific effects of non-pharmacological interventions (NPIs) and vaccinations on infectious source tracing, intercepting transmission, and protecting susceptible populations in the five countries were assessed by comparing correlations between the daily numbers of testing and incidence cases, the Oxford-stringency index and daily incidences, and the number of fully vaccinated persons per 100 population and daily mortalities. ResultsThe severity of COVID-19 epidemic was controlled by increased daily number of detection in a certain extent and the daily number of confirmed incidence cases decreased after the day with the highest detection number. The Oxford-stringency index increased with the worsening of COVID-19 epidemic but decreased somewhat with the weakening of the epidemic and the decrease in the index could relate to a rebound of the epidemic. The case-fatality rate of COVID-19 decreased with the increase of fully vaccination rate. ConclusionCountries around the world should actively learn from international experience, follow the laws of epidemiology, start from controlling the source of infection, cutting off the transmission route and protecting susceptible people, adapt NPIs and promote booster vaccination universally, further research and development, for coping effectively with the global public health challenge.

The lack of targeted and high-efficiency drug delivery to the central nervous system (CNS) nidus is the main problem in the treatment of demyelinating disease. Extracellular vesicles (EVs) possess great promise as a drug delivery vector given their advanced features. However, clinical applications are limited because of their inadequate targeting ability and the “dilution effects” after systemic administration. Neural stem cells (NSCs) supply a plentiful source of EVs on account of their extraordinary capacity for self-renewal. Here, we have developed a novel therapeutic system using EVs from modified NSCs with high expressed ligand PDGF-A (EVPs) and achieve local delivery. It has been demonstrated that EVPs greatly enhance the target capability on oligodendrocyte lineage. Moreover, EVPs are used for embedding triiodothyronine (T3), a thyroid hormone that is critical for oligodendrocyte development but has serious side effects when systemically administered. Our results demonstrated that systemic injection of EVPs + T3, versus EVPs or T3 administration individually, markedly alleviated disease development, enhanced oligodendrocyte survival, inhibited myelin damage, and promoted myelin regeneration in the lesions of experimental autoimmune encephalomyelitis mice. Taken together, our findings showed that engineered EVPs possess a remarkable CNS lesion targeting potential that offers a potent therapeutic strategy for CNS demyelinating diseases as well as neuroinflammation.

Abstract Background Many seed plants produce winged diaspores that use wind to disperse their seeds. The morphology of these diaspores is directly related to the seed dispersal potential. The majority of winged diaspores have flat wings and only seeds; however, some angiosperms, such as Firmiana produce winged fruit with a different morphology, whose seed dispersal mechanisms are not yet fully understood. In this study, we observed the fruit development of F. simplex and determined the morphological characteristics of mature fruit and their effects on the flight performance of the fruit. Results We found that the pericarp of F. simplex dehisced early and continued to unfold and expand during fruit development until ripening, finally formed a spoon-shaped wing with multiple alternate seeds on each edge. The wing caused mature fruit to spin stably during descent to provide a low terminal velocity, which was correlated with the wing loading and the distribution of seeds on the pericarp. When the curvature distribution of the pericarp surface substantially changed, the aerodynamic characteristics of fruit during descent altered, resulting in the inability of the fruit to spin. Conclusions Our results suggest that the curved shape and alternate seed distribution are necessary for the winged diaspore of F. simplex to stabilize spinning during wind dispersal. These unique morphological characteristics are related to the early cracking of fruits during development, which may be an adaptation for the wind dispersal of seeds.

Hydrogen peroxide is an industrially highly demanded chemical, but its electrochemical synthesis still suffers from sluggish kinetics and imperfect selectivity. Here, the authors report a catalyst material comprising single cobalt atoms anchored on oxygen functionalized graphene oxide that produces 1.0 mg cm−2 h−1 of H2O2 with high selectivity and a low onset potential.

The effects of CeCu6 and Cu2S on microstructure, electrical conductivity and mechanical properties in as-cast pure copper were investigated by utilizing the microstructure analysis, conductivity test and tensile test with adding 300 ppm Ce and S elements in pure copper ingot (Ce and S elements, mainly existed in the form of CeCu6 and Cu2S). The results showed that the average grain sizes of as-cast pure copper, Cu-0.03Ce and Cu-0.03S were 376, 159 and 193 μm, respectively. The grain refining mechanism of the two phases (CeCu6 and Cu2S) were quite different. The grain refining mechanism of CeCu6 mainly rely on component supercooling; The grain refining mechanism of Cu2S mainly rely on inhibiting grain growth. After hot extrusion, the conductivity of as-cast pure copper, Cu-0.03Ce and Cu-0.03S were increased from 100.1, 100.2 and 95.5 to 101.3, 100.9 and 99.4 %IACS; and the elongation were 66.59, 49.17 and 34.23%, respectively. The disregistry between CeCu6/Cu2S and copper matrix was 10.24% (0 2 10¯)CeCu6‖(4¯ 11)Cu, 24.91% (14¯ 6 12)Cu2S‖(1¯ 31)Cu, respectively. The disregistry between CeCu6 and copper matrix was smaller than that between Cu2S and copper matrix, leading to the wettability, conductivity and interfacial bonding strength between CeCu6 and copper matrix were better. The conductivity of Cu-0.03S could be improved after hot extrusion, which attributed to the gap at the interface could be partially reduced by hot extrusion.