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Abstract Background Bigleaf hydrangea (Hydrangea macrophylla) is a widely cultivated ornamental plant species. Leaf spot disease, caused by Corynespora cassiicola, poses a significant threat to the ornamental quality and economic value of hydrangeas. However, the disease resistance breeding of hydrangea is limited due to the lacking of resistant varieties and genes. Results This study evaluated ten hydrangea varieties for their resistance to leaf spot disease. Among them, ‘White Angel’ and ‘Ocean Heart’ were screened out as representative varieties for resistance and susceptibility, respectively, on the basis of evaluation. Physiological and biochemical indices, phytohormones, and transcriptomic changes were measured in the leaves of both varieties at 0 and 24 h post inoculation with C. cassiicola. The results showed that C. cassiicola infection significantly increased abscisic acid (ABA) contents in both varieties; however, the increase was significantly higher in the susceptible variety ‘Ocean Heart’ compared to the resistant variety ‘White Angel’ (p

Abstract Personalized music teaching in universities improves students’ learning and efficiency through adaptive guidance. This adaptability requires large study data and intelligent decisions based on the learner’s ability. This article introduces a Definitive Teaching Support System (DTSS) exclusive to music learning to augment this concept. This system is designed to increase the adaptability of music learning based on student interest and ability. The system is powered by a fuzzy decision system for identifying maximum teaching adaptability to personalized processes. Low-to-high-sorted personalization provides new endorsements for further music sessions in the fuzzy derivative process. Maximum adaptability is the target for new personalized sessions in the universities. This differs for various students from which a common adaptability level for monotonous recommendations is identified. The identified adaptability is set as a global maximum solution towards music learning personalization. The defuzzification reduces the chances of low adaptability by expelling the stationary adaptability outcomes.

Abstract NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.

In this study, three sequencing batch biofilter granular reactors (SBBGRs) were employed to treat model lignin wastewater containing different lignin models (2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin). After 40 days of cultivation, uniform-shaped aerobic granular sludge (AGS) was successfully developed through nutrient supplementation with synthetic wastewater. During the acclimation stage, the chemical oxygen demand (COD) reduction efficiencies of the three reactors showed a trend of initial decreasing (5–20%) and then recovering to a high reduction efficiency (exceeding 90%) in a short period of time. During the stable operation stage, all three reactors achieved COD reduction efficiencies exceeding 90%. These findings indicated the cultivated AGS's robust resistance to changes in lignin models in water. UV–Vis spectra analysis confirmed the effective degradation of the three lignin models. Microbiological analysis showed that Proteobacteria and Bacteroidetes were always the dominant phyla. At the genus level, while Acinetobacter (15.46%) dominated in the inoculation sludge, Kapabacteriales (7.93%), SBR1031 (11.77%), and Chlorobium (25.37%) were dominant in the three reactors (for 2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin) after degradation, respectively. These findings demonstrate that AGS cultured with SBBGR effectively degrades lignin models, with different dominant strains observed for various lignin models. HIGHLIGHTS The aerobic granular sludge cultivated in SBBGR was applied to treat lignin models and demonstrated excellent impact resistance.; The high sludge concentration and diverse microbial community enable effective lignin model degradation.; Different strains dominated the cultured AGS in three reactors that degraded 2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin, respectively.;

Abstract Esophageal cancer is a common type of cancer that poses a significant threat to human health. While the pro-inflammatory cytokine IL-1β has been known to contribute to the development of various types of tumors, its role in regulating esophageal cancer progression has not been extensively studied. Our studies found that the expression of IL-1β and FOXO3A was increased in esophageal squamous cell carcinoma (ESCC). IL-1β not only increased the proliferation, migration, and invasion of two ESCC cell lines but also promoted tumor growth and metastasis in nude mice. We also observed that IL-1β and FOXO3A regulated the process of epithelial-mesenchymal transition (EMT) and autophagy. The PI3K/AKT pathway was found to be involved in the changes of FOXO3A with the expression level of IL-1β. The AKT agonist (SC79) reversed the reduction of FOXO3A expression caused by the knockdown of IL-1β, indicating that IL-1β plays a role through the PI3K/AKT/FOXO3A pathway. Furthermore, the knockdown of FOXO3A inhibited ESCC development and attenuated the pro-cancer effect of overexpressed IL-1β. Targeting IL-1β and FOXO3A may be potentially valuable for the diagnosis and treatment of ESCC.

Mitochondrial diseases are disorders caused primarily by mutations in mitochondrial DNA, with the mitochondrial 3243A > G (m.3243A > G) mutation being one of the most common pathogenic mutations. Here, a pluripotent stem cell line with high m.3243A > G mutation load was generated by reprogramming the skin fibroblasts from a patient with mitochondrial disease. This cell line exhibited pluripotency, multilineage differentiation potential and normal karyotype, representing a valuable cell resource for studying the pathogenesis of mitochondrial diseases and screening drugs.

Jasmine (Jasminum sambac Aiton) is a well-known cultivated plant species for its fragrant flowers used in the perfume industry and cosmetics. However, the genetic basis of its floral scent is largely unknown. In this study, using PacBio, Illumina, 10× Genomics and high-throughput chromosome conformation capture (Hi-C) sequencing technologies, a high-quality chromosome-level reference genome for J. sambac was obtained, exploiting a double-petal phenotype cultivar ‘Shuangbanmoli’ (JSSB). The results showed that the final assembled genome of JSSB is 580.33 Mb in size (contig N50 = 1.05 Mb; scaffold N50 = 45.07 Mb) with a total of 39 618 predicted protein-coding genes. Our analyses revealed that the JSSB genome has undergone an ancient whole-genome duplication (WGD) event at 91.68 million years ago (Mya). It was estimated that J. sambac diverged from the lineage leading to Olea europaea and Osmanthus fragrans about 28.8 Mya. On the basis of a combination of genomic, transcriptomic and metabolomic analyses, a range of floral scent volatiles and genes were identified involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways. The results provide new insights into the molecular mechanism of its fragrance biosynthesis in jasmine.

Steel slag is an industrial solid waste produced during the steelmaking process. To explore the application of steel slag in the agricultural field, the present experiment was carried out to study the effect of substrates with different contents of steel slag on the growth of Hydrangea macrophylla cuttings. The conventional substrate (perlite: vermiculite: peat = 1:1:1) was used as the control (CK), and the treatments were designed as T1 (steel slag: perlite: vermiculite: peat = 1:3:3:3, v/v/v/v), T2 (steel slag: perlite: vermiculite: peat = 1:2:2:2, v/v/v/v), T3 (steel slag: perlite: vermiculite: peat = 1:1:1:1, v/v/v/v), and T4 (steel slag: perlite: vermiculite: peat = 1:0:0:0, v/v/v/v). The results showed that the addition of steel slag significantly increased the substrate’s bulk density, EC, and pH and improved its water retention capacity to a certain extent. There were significant differences among different treatments in morphological indicators, root growth and development, and physiological and biochemical characteristics of cutting seedlings. All traits, including plant height, fresh weight, dry weight, root length, root surface area, root volume, the number of root tips, root activity, and soluble protein content of seedlings grown in T3 were significantly higher than those in other substrates. The results indicated that the appropriate addition of steel slag is helpful to hydrangea cuttings’ growth, and the optimal mixing ratio is steel slag: perlite: vermiculite: peat = 1:1:1:1 (v/v/v/v). This is a significant innovation in applying steel slag in agricultural production.

Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host’s health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions. Interactions between the gut microbiota and host have not been fully explored in pigs. Specific pathogen-free (SPF) pigs are ideal non-primate large animals to study the interactions between the gut microbiota and the host. In this study, we performed high-throughput sequencing analysis of the gut microbiota and the gut tissue transcriptome of six SPF pigs to provide a systematic understanding of the composition, function, and spatial distribution of gut microbiota in SPF pigs. We identified significant differences in microbial diversity and functionality among different gastrointestinal tract sites. Metagenomics data analysis revealed significant differences in alpha diversity and beta diversity of microbiota in different gastrointestinal sites of SPF pigs. Additionally, transcriptomic data indicated significant differences in gene expression as well as KEGG and GO functional enrichment between the small intestine and large intestine. Furthermore, by combining microbial metagenomics and host transcriptomics analyses, specific correlations were found between gut microbiota and host genes. These included a negative correlation between the TCN1 gene and Prevotella dentalis, possibly related to bacterial metabolic pathways involving vitamin B12, and a positive correlation between the BDH1 gene and Roseburia hominis, possibly because both are involved in fatty acid metabolism. These findings lay the groundwork for further exploration of the co-evolution between the microbiota and the host, specifically in relation to nutrition, metabolism, and immunity. In conclusion, we have elucidated the diversity of the gut microbiota in SPF pigs and conducted a detailed investigation into the interactions between the gut microbiota and host gene expression. These results contribute to our understanding of the intricate dynamics between the gut microbiota and the host, offering important references for advancements in life science research, bioproduct production, and sustainable development in animal husbandry.

Objectives: To analyze and describe the spatiotemporal trends of Low back pain (LBP) burdens from 1990 to 2019 and anticipate the following decade’s incidence.Methods: Using data from the Global Burden of Disease (GBD) 2019 Study, we described net drifts, local drifts, age effects, and period cohort effects in incidence and forecasted incidence rates and cases by sex from 2020 to 2029 using the Nordpred R package.Results: LBP remained the leading cause of the musculoskeletal disease burden globally and across all socio-demographic index (SDI) regions. China is the top country. For recent periods, high-SDI countries faced unfavorable or worsening risks. The relative risk of incidence showed improving trends over time and in successively younger birth cohorts amongst low-middle-, middle- and high-middle-SDI countries. Additionally, the age-standardized incidence rates (ASIR) of LBP in both sexes globally showed a decreasing trend, but the incident cases would increase from 223 to 253 million overall in the next decade.Conclusion: As the population ages, incident cases will rise but ASIR will fall. To minimise LBP, public awareness and disease prevention and control are needed.

Osteoporosis is the result of osteoclast formation exceeding osteoblast production, and current osteoporosis treatments targeting excessive osteoclast bone resorption have serious adverse effects. There is a need to fully understand the mechanisms of osteoclast-mediated bone resorption, identify new drug targets, and find better drugs to treat osteoporosis. Gar C (Gar C) is a major naturally occurring phytochemical isolated from mangosteen, and is a derivative of the naturally occurring phenolic antioxidant lutein. We used an OP mouse model established by ovariectomy (OVX). We found that treatment with Gar C significantly increased bone mineral density and significantly decreased the expression of TRAP, NFATC1 and CTSK relative to untreated OP mice. We found that Garcinone C could disrupt osteoclast activation and resorption functions by inhibiting RANKL-induced osteoclast differentiation as well as inhibiting the formation of multinucleated osteoclasts. Immunoblotting showed that Gar C downregulated the expression of osteoclast-related proteins. In addition, Gar C significantly inhibited RANKL-induced ROS production and affected NF-κB activity by inhibiting phosphorylation Formylation of P65 and phosphorylation and degradation of ikba. These data suggest that Gar C significantly reduced OVX-induced osteoporosis by inhibiting osteoclastogenesis and oxidative stress in bone tissue. Mechanistically, this effect was associated with inhibition of the ROS-mediated NF-κB pathway.

Seaweed aquaculture is vital in protecting the marine eco-environment and mitigating climate change. China generates more than half of the world’s total seaweed production. However, despite multiple local studies, accurate and reliable information on broad-scale seaweed farms is still scarce. Using an object-based method to classify 3 m spatial resolution Planet Scope images along offshore China, a total of 129,494 ha of cultured seaweed was identified and delineated with an overall accuracy of 95.70% and a KAPPA index of 0.912, respectively. Then, a seaweed map in offshore China in 2018–2019 was developed. The results provided basic information about seaweed farms in China. The approach reported in this work is accurate and efficient, which can be used to replace the conventional method to obtain the culture seaweed information. This study can be of reference for mapping seaweed on a broader or global scale.

Summary: This study found that the level of neuroepithelial cell-transforming gene 1 protein (NET1) was significantly increased in a mouse cardiac fibrosis model. Moreover, the expression level of NET1 was increased in cardiac fibrosis induced by TGF-β1, suggesting that NET1 was involved in the pathological process of cardiac fibrosis. Overexpression of NET1 promoted β-catenin expression in the nucleus and significantly increased the proliferation and migration of cardiac fibroblasts. NET1 may form a complex with β-catenin through GSK3β. Knockdown of β-catenin alleviated the effects of NET1 overexpression on collagen production and cell migration. In the heart of NET1 knockout mice, NET1 knockout can reduce the expression of β-catenin, α-SMA, and collagen content induced by MI. In conclusion, NET1 may regulate the activation of Wnt/β-catenin and TGF/Smads signaling pathway, promote collagen synthesis in fibroblasts, and participate in cardiac fibrosis. Thus, NET1 may be a potential therapeutic target in cardiac fibrosis.

Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. have always been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itself has a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types of functional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates the speed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bone metabolism mechanism is complicated, the research duration is long and difficult, which significantly restricts the progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro with the help of tissue engineering technology based on biological theory, can simulate the complex biological functions of organs in vivo. Once proposed, it shows broad application prospects in the research of organ development, drug screening, mechanism study, and so on. As a complex and special organ, bone organoid construction itself is quite challenging. This review will introduce the characteristics of bone microenvironment, the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for bone organoid construction, study direction, and application prospects.

Chlorinated paraffins (CPs), a group of chlorinated alkane mixtures, are frequently detected in various environmental matrices and human bodies. Recently, CPs have garnered considerable attention owing to their potential to induce health hazards in wildlife and human. Several reviews have discussed short-chain CPs (SCCPs) induced ecological risk; however, a comprehensive understanding of the underlying toxic mechanisms and a comparison among SCCPs, medium-, and long-chain CPs (MCCPs and LCCPs, respectively) are yet to be established. This review summarizes the latest research progress on the toxic effects and the underlying molecular mechanisms of CPs. The main toxicity mechanisms of CPs include activation of several receptors, oxidative stress, disturbance of energy metabolism, and inhibition of gap junction-mediated communication. The sensitivity of different species to CP-mediated toxicities varies markedly, with aquatic organisms exhibiting the highest sensitivity to CP-induced toxicity. The toxicity comparison analysis indicated that MCCPs may be unsafe as potential substitutes for SCCPs.

Abstract Background Hydrangea macrophylla var. Maculata ‘Yinbianxiuqiu’ (YB) is an excellent plant species with beautiful flowers and leaves with silvery white edges. However, there are few reports on its leaf color characteristics and color formation mechanism. Results The present study compared the phenotypic, physiological and transcriptomic differences between YB and a full-green leaf mutant (YM) obtained from YB. The results showed that YB and YM had similar genetic backgrounds, but photosynthesis was reduced in YB. The contents of pigments were significantly decreased at the edges of YB leaves compared to YM leaves. The ultrastructure of chloroplasts in the YB leaves was irregular. Transcriptome profiling identified 7,023 differentially expressed genes between YB and YM. The expression levels of genes involved in photosynthesis, chloroplast development and division were different between YB and YM. Quantitative real-time PCR showed that the expression trends were generally consistent with the transcriptome data. Conclusions Taken together, the formation of the silvery white leaf color of H. macrophylla var. maculata was primarily due to the abnormal development of chloroplasts. This study facilitates the molecular function analysis of key genes involved in chloroplast development and provides new insights into the molecular mechanisms involved in leaf coloration in H. macrophylla.

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1β (39.42 ± 3.076 ng/L, p

Currently, the failure rate for internal fixation in patients with osteoporosis can be reduced by antiosteoporosis therapy alone. However, the administration of anti-osteoporotic drugs is not a complete solution. Therefore, it is necessary to investigate other causes of surgical failure, such as inflammation. In recent years, the inflammation caused by macrophage M1 polarization has garnered wide attention. The purpose of this research is to explore the inhibitory effect of avicularin (AL) on macrophage M1 polarization, by which it ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis and bone metabolic index analysis. In in vitro experiments, bone marrow derived macrophages (BMDM) and RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS), and analyzed by immunofluorescence (IF) staining, Western blot (WB) and flow cytometry. WB was also used to analyze the nuclear factor kappa-B (NF-κB) pathway. In addition, the expression levels of inflammatory cytokines were detected in cell supernatant using ELISA kits. Through observation of this experiments, we found that AL can inhibit M1 polarization of macrophages. Moreover, it can significantly inhibit the release of inflammatory factors to improve multiple mouse femur parameters. Furthermore, AL inhibited the phosphorylation of IKBα and P65 in the NF-κB pathway. The above data indicate that AL ameliorates inflammatory responses by inhibiting macrophage M1 polarization via its inhibitory effect on the NF-κB pathway, thus alleviating the instability of implants in mice with osteoporosis.

Periprosthetic osteolysis (PPO), caused by wear particles, has become a major cause of joint replacement failure. Secondary surgery after joint replacement poses a serious threat to public health worldwide. Therefore, determining how to effectively inhibit wear particle-induced PPO has become an urgent issue. Recently, the interaction between osteogenic inhibition and wear particles at the biological interface of the implant has been found to be an important factor in the pathological process. Previous studies have found that the central nervous system plays an important role in the regulation of bone formation and bone remodeling. Dopamine (DA), an important catecholamine neurotransmitter, plays an integral role in the physiological and pathological processes of various tissues through its corresponding receptors. Our current study found that upregulation of dopamine first receptors could be achieved by activating the Wnt/β-catenin pathway, improving osteogenesis in vivo and in vitro, and significantly reducing the inhibition of titanium particle-induced osteogenesis. Overall, these findings suggest that dopamine first receptor (D1R) may be a plausible target to promote osteoblast function and resist wear particle-induced PPO.

Jasmine [Jasminum sambac (L.) Aiton] is a commercially important cultivated plant species known for its fragrant flowers used in the perfume industry, medicine and cosmetics. In the present study, we obtained a draft genome for the J. sambac cultivar ‘Danbanmoli’ (JSDB, a single-petal phenotype). We showed that the final genome of J. sambac was 520.80 Mb in size (contig N50 = 145.43 kb; scaffold N50 = 145.53 kb) and comprised 35,363 genes. Our analyses revealed that the J. sambac genome has undergone only an ancient whole-genome duplication (WGD) event. We estimated that the lineage that has given rise to J. sambac diverged from the lineage leading to Osmanthus fragrans and Olea europaea approximately 31.1 million years ago (Mya). On the basis of a combination of genomic and transcriptomic analyses, we identified 92 transcription factors (TFs) and 206 genes related to heat stress response. Base on a combination of genomic, transcriptomic and metabolomic analyses, a range of aroma compounds and genes involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways were identified. In the newly assembled J. sambac genome, we identified a total of 122 MYB, 122 bHLH and 69 WRKY genes. Our assembled J. sambac JSDB genome provides fundamental knowledge to study the molecular mechanism of heat stress tolerance, and improve jasmine flowers and dissect its fragrance.

Hydrangea (Hydrangea macrophylla (Thunb.) Ser.) is a famous ornamental plant species with high resistance to aluminum (Al). The aluminum-activated malate transporter (ALMT) family encodes anion channels, which participate in many physiological processes, such as Al tolerance, pH regulation, stomatal movement, and mineral nutrition. However, systematic studies on the gene family have not been reported in hydrangea. In this study, 11 candidate ALMT family members were identified from the transcriptome data for hydrangea, which could be divided into three clusters according to the phylogenetic tree. The protein physicochemical properties, phylogeny, conserved motifs and protein structure were analyzed. The distribution of base conservative motifs of HmALMTs was consistent with that of other species, with a highly conserved WEP motif. Furthermore, tissue-specific analysis showed that most of the HmALMTs were highly expressed in the stem under Al treatment. In addition, overexpression of HmALMT5, HmALMT9 and HmALMT11 in yeasts enhanced their tolerance to Al stress. Therefore, the above results reveal the functional role of HmALMTs underlying the Al tolerance of hydrangea. The present study provides a reference for further research to elucidate the functional mechanism and expression regulation of the ALMT gene family in hydrangea.

Epidemiologic data reveal that diabetes patients taking metformin exhibit lower incidence of stroke and better functional outcomes during post-stroke neurologic recovery. We previously demonstrated that chronic post-ischemic administration of metformin improved functional recovery in experimental cerebral ischemia. However, few beneficial effects of metformin on the acute phase of cerebral ischemia were reported either in experimental animals or in stroke patients, which limits the application of metformin in stroke. We hypothesized that slow cellular uptake of metformin hydrochloride may contribute to the lack of efficacy in acute stroke. We recently developed and patented a novel metformin derivative, metformin threonate (SHY-01). Pharmacokinetic profile in vivo and in cultured cells revealed that metformin is more rapidly uptaken and accumulated from SHY-01 than metformin hydrochloride. Accordingly, SHY-01 treatment exhibited more potent and rapid activation of AMP-activated protein kinase (AMPK). Furthermore, SHY-01 elicited a stronger inhibition of microglia activation and more potent neuroprotection when compared to metformin hydrochloride. SHY-01 administration also had superior beneficial effects on neurologic functional recovery in experimental stroke and offered strong protection against acute cerebral ischemia with reduced infarct volume and mortality, as well as the improved sensorimotor and cognitive functions in rats. Collectively, these results indicated that SHY-01 had an improved pharmacokinetic and pharmacological profile and produced more potent protective effects on acute stroke and long-term neurological damage. We propose that SHY-01 is a very promising therapeutic candidate for cerebral ischemic stroke.

Deep learning, which is a subfield of machine learning, has opened a new era for the development of neural networks. The auto-encoder is a key component of deep structure, which can be used to realize transfer learning and plays an important role in both unsupervised learning and non-linear feature extraction. By highlighting the contributions and challenges of recent research papers, this work aims to review state-of-the-art auto-encoder algorithms. Firstly, we introduce the basic auto-encoder as well as its basic concept and structure. Secondly, we present a comprehensive summarization of different variants of the auto-encoder. Thirdly, we analyze and study auto-encoders from three different perspectives. We also discuss the relationships between auto-encoders, shallow models and other deep learning models. The auto-encoder and its variants have successfully been applied in a wide range of fields, such as pattern recognition, computer vision, data generation, recommender systems, etc. Then, we focus on the available toolkits for auto-encoders. Finally, this paper summarizes the future trends and challenges in designing and training auto-encoders. We hope that this survey will provide a good reference when using and designing AE models.

With the rapid development of urbanization, fire risk factors have increased greatly, indicating a higher requirement for urban firefighting security. Fire rescue capabilities can be effectively improved by the scientific layout of fire stations, and therefore, the optimal spatial arrangement of fire stations has practical implications for urban safety. In this paper, a method for planning the locations of urban fire stations is presented, taking into account the fire risk points of interest (POIs) data, road networks and fire station planning principles. The combined model method is validated against the nearest facility point model, and the service area model is proposed for the coverage of POIs and regional areas of planned new sites. The efficacy of the model is demonstrated through an improvement in the coverage of crosspoints of the regional area and points of interest (POIs), with increases of 10.20% and 12.43%, respectively. We applied the combined model method to Fengdong New Town, Shaanxi Province, China. A total of 11 new potential sites were proposed to improve the efficiency of spatial coverage, and subsequently, the coverage rate of the POIs and regional area reached 97.66% and 84.80%, respectively. This study provides application guidelines for the decision-making of fire services and the allocation of firefighting resources.

ABSTRACT Phaeocystis globosa causes severe marine pollution by forming harmful algal blooms and releasing hemolytic toxins and is therefore harmful to marine ecosystems and aquaculture industries. In this study, Microbulbifer sp. YX04 exerted high algicidal activity against P. globosa by producing and secreting metabolites. The algicidal activity of the YX04 supernatant was stable after exposure to different temperatures (−80 to 100°C) and pH values (4 to 12) for 2 h, suggesting that algicidal substances could temporarily be stored under these temperature and pH value conditions. To explore the algicidal process and mechanism, morphological and structural changes, oxidative stress, photosynthesis, autophagic flux, and global gene expression were investigated. Biochemical analyses showed that the YX04 supernatant induced reactive oxygen species (ROS) overproduction, which caused lipid peroxidation and malondialdehyde (MDA) accumulation in P. globosa. Transmission electron microscopy (TEM) observation and the significant decrease in both maximum photochemical quantum yield (Fv/Fm) and relative electron transfer rate (rETR) indicated damage to thylakoid membranes and destruction of photosynthetic system function. Immunofluorescence, immunoblot, and TEM analyses indicated that cellular damage caused autophagosome formation and triggered large-scale autophagic flux in P. globosa. Transcriptome analysis revealed many P. globosa genes that were differentially expressed in response to YX04 stress, most of which were involved in photosynthesis, respiration, cytoskeleton, microtubule, and autophagosome formation and fusion processes, which may trigger autophagic cell death. In addition to P. globosa, the YX04 supernatant showed high algicidal activity against Thalassiosira pseudonana, Thalassiosira weissflogii, Skeletonema costatum, Heterosigma akashiwo, and Prorocentrum donghaiense. This study highlights multiple mechanisms underlying YX04 supernatant toxicity toward P. globosa and its potential for controlling the occurrence of harmful algal blooms. IMPORTANCE P. globosa is one of the most notorious harmful algal bloom (HAB)-causing species, which can secrete hemolytic toxins, frequently cause serious ecological pollution, and pose a health hazard to animals and humans. Hence, screening for bacteria with high algicidal activity against P. globosa and studies on the algicidal characteristics and mechanism will contribute to providing an ecofriendly microorganism-controlling agent for preventing the occurrence of algal blooms and reducing the harm of algal blooms to the environment. Our study first reported the algicidal characteristic and mechanism of Microbulbifer sp. YX04 against P. globosa and demonstrated that P. globosa shows different response mechanisms, including movement ability, antioxidative systems, photosynthetic systems, gene expression, and cell death mode, to adapt to the adverse environment when algicidal compounds are present.

Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.

Prorocentrum donghaiense, a marine dinoflagellate, causes harmful algal blooms (HABs) characterised by the highest outbreak frequency and most extensive coverage among similar species in the East China Sea. Highly efficient and ecofriendly biocontrol strategies should be developed for HAB control. Prodigiosin is an efficient biological algicide that demonstrated strong algicidal activity towards P. donghaiense. However, the mechanism of its toxicity to P. donghaiense is unknown. These factors were investigated to evaluate potential use of prodigiosin for control of P. donghaiense blooms. Photosynthetic electron transport rate, maximum quantum yield and respiration rate of P. donghaiense decreased significantly upon exposure to prodigiosin, indicating that prodigiosin rapidly exerted adverse effects on the chloroplasts and mitochondria. Furthermore, a significant increase in dichlorofluorescein fluorescence intensity indicated an overproduction of reactive oxygen species (ROS). The antioxidant system of P. donghaiense scavenged ROS; however, an increase in malondialdehyde concentrations indicated that excessive ROS were still able to initiate lipid peroxidation. Thus, ROS production resulted in the formation of lipids with a reduced degree of unsaturation. Lipid peroxidation decreased lipid fluidity and rigidified the membrane system, causing serious functional destruction of the membrane. Flow cytometry analysis indicated that prodigiosin arrested the cell cycle of P. donghaiense. However, surviving algal cells were able to repair the damaged functions and resume the cell cycle after prodigiosin was removed by photodegradation. Otherwise, P. donghaiense cells lost their membrane integrity and died. To begin an evaluation of ecological safety of prodigiosin, we tested four marine organisms at various trophic levels. The results of these tests indicated that Chlorella vulgaris, Photobacterium phosphoreum, Artemia salina and Lateolabrax japonicus were less sensitive to prodigiosin than P. donghaiense. Toxicity to all five organisms declined after prodigiosin was exposed to sunlight for 6 h. Considering the toxic doses of prodigiosin to various organisms and its photodegradation characteristics, we suggest that prodigiosin has potential in controlling P. donghaiense blooms but should be applied at night, in small doses, with multiple applications.

In order to better understand the changes in fruit quality and soluble sugar components in wild Actinidia eriantha at the soft ripening stage, this study explored the fruit quality indexes, soluble sugar components, sucrose metabolism-related enzyme activities and the expression of sucrose metabolism-related enzyme genes in wild A. eriantha germplasm resources. The results showed that the fruit quality of wild A. eriantha at the soft ripening stage was quite different, and the coefficient of variation of fructose content was the largest, followed by sucrose and glucose. Principal component analysis and systematic clustering analysis showed that the comprehensive performance of fruit quality indexes of M28 and M10 was the most prominent. The accumulation and composition of soluble sugar components in different wild A. eriantha varieties (lines) were not consistent. The activities of sucrose metabolism enzymes among wild A. eriantha varieties (lines) were different to some extent. The sucrose metabolism-related enzyme genes among wild A. eriantha germplasm resources had different expression patterns. The results will contribute to understanding the fruit quality changes and the mechanism of sugar metabolism in wild A. eriantha at the soft ripening stage, and lay a foundation for the protection and utilization of wild A. eriantha germplasm resources.

Actinidia eriantha is a unique germplasm resource for kiwifruit breeding. Genetic diversity and nutrient content need to be evaluated prior to breeding. In this study, we looked at the metabolites of three elite A. eriantha varieties (MM-11, MM-13 and MM-16) selected from natural individuals by using a UPLC-MS/MS-based metabolomics approach and transcriptome, with a total of 417 metabolites identified. The biosynthesis and metabolism of phenolic acid, flavonoids, sugars, organic acid and AsA in A. eriantha fruit were further analyzed. The phenolic compounds accounted for 32.37% of the total metabolites, including 48 phenolic acids, 60 flavonoids, 7 tannins and 20 lignans and coumarins. Correlation analysis of metabolites and transcripts showed PAL (DTZ79_15g06470), 4CL (DTZ79_26g05660 and DTZ79_29g0271), CAD (DTZ79_06g11810), COMT (DTZ79_14g02670) and FLS (DTZ79_23g14660) correlated with polyphenols. There are twenty-three metabolites belonging to sugars, the majority being sucrose, glucose arabinose and melibiose. The starch biosynthesis-related genes (AeglgC, AeglgA and AeGEB1) were expressed at lower levels compared with metabolism-related genes (AeamyA and AeamyB) in three mature fruits of three varieties, indicating that starch was converted to soluble sugar during fruit maturation, and the expression level of SUS (DTZ79_23g00730) and TPS (DTZ79_18g05470) was correlated with trehalose 6-phosphate. The main organic acids in A. eriantha fruit are citric acid, quinic acid, succinic acid and D-xylonic acid. Correlation analysis of metabolites and transcripts showed ACO (DTZ79_17g07470) was highly correlated with citric acid, CS (DTZ79_17g00890) with oxaloacetic acid, and MDH1 (DTZ79_23g14440) with malic acid. Based on the gene expression, the metabolism of AsA acid was primarily through the L-galactose pathway, and the expression level of GMP (DTZ79_24g08440) and MDHAR (DTZ79_27g01630) highly correlated with L-Ascorbic acid. Our study provides additional evidence for the correlation between the genes and metabolites involved in phenolic acid, flavonoids, sugars, organic acid and AsA synthesis and will help to accelerate the kiwifruit molecular breeding approaches.

‘Ganlv 1’ is a new cultivar of Actinidia eriantha selected from the wild natural population, which has the advantages of moderate taste, high yield, easy peeling and high ascorbic acid (AsA) content. In this study, ‘Ganlv 1’ was used to explore the changes in fruit quality, soluble sugar components, sucrose metabolism-related enzymes activities and sucrose metabolism-related enzyme genes’ expression during the fruit’s development. The results showed that, except for AsA, the changes in the fruit quality index and fruit growth and development during the development of ‘Ganlv 1’ basically exhibited the same trend. The fruit shape index was different in the different development stages of the fruit, and tended to be stable with fruit growth and development. The dynamic changes of the dry matter content indicated that the best time for fruit harvest was about 160 days after full bloom. The main sugar components in the fruit were fructose, glucose and sucrose, and sucrose and glucose were the main sugars in the soft-ripening stage. The trend of sucrose accumulation, the activities of the sucrose metabolism-related enzymes and the expression of the sucrose metabolism-related genes indicated that 130–145 days after full bloom (DAFB) might be the critical period of sucrose metabolism. The results are of great significance for clarifying the developmental characteristics and dynamic changes in the sugar components in A. eriantha fruits, and lay a foundation for further studying of the mechanism of sugar metabolism in A. eriantha.

In this study, a dendrite-reinforced Mg-based amorphous alloy composite was prepared through an in situ precipitation strategy. After plasma electrolytic oxidation (PEO) treatment, the Mg85.1Zn12.7Ca2Cu0.2 amorphous alloy composite exhibited enhanced plasticity and corrosion resistance in a simulated body fluid solution (SBF). The PEO-treated composite showed a significant plastic strain of 10.5 ± 1.1%, as well as outstanding strain-hardening behavior. The enhancement of plasticity may be attributed to the in-situ formed coating, which can not only serve as a propagation barrier for shear bands but can also introduce nucleation sites in the bands as a result of stress mismatch and compositional heterogeneity. The corrosion density in the SBF decreased by three orders compared with the composite substrate. The spontaneous formation of apatite on the porous layer demonstrated that the prepared PEO coating has high bioactivity. The current work may provide a fundamental basis for developing biomedical Mg-based alloys with excellent comprehensive mechanical properties and corrosion resistance.