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Tumor immunotherapy has emerged as a promising approach to tumor treatment. Currently, immune adjuvant-based therapeutic modalities are rarely curative in solid tumors owing to challenges including the low permeability and extremely poor water solubility of these adjuvants, limiting their ability to effectively promote dendritic cell (DC) maturation. Herein, we employed ultrasound-mediated cavitation (UMC) to promote the delivery of Toll-like receptor agonist (R837)-loaded pH-responsive liposomes (PEOz-Lip@R837) to tumors. The tumor-associated antigens (TAAs) produced by UMC treatment exhibited vaccinal activity, particularly in the presence of immune adjuvants, together promoting the maturation of DC and inducing cytokine production. Importantly, UMC can down-regulate immune checkpoint molecules, like Cd274, Foxp3 and Ctla4, synergistically stimulating the activation and proliferation of T cells in the body to facilitate tumor treatment. This UMC-enhanced PEOz-Lip@R837 approach was able to induce a robust antitumor immune response capable of arresting primary and distant tumor growth, while also developing immunological memory, protecting against tumor rechallenge following initial tumor clearance. Overall, these results highlight a promising UMC- and pH-sensitive immune adjuvant delivery-based treatment for tumors with the potential for clinical application.

Background and aim Diagnosing NASH is challenging. This study intended to explore the diagnostic value of multiple technical acoustic measurements in the diagnosis of NASH, and to establish a diagnostic model combining technical acoustic measurements with clinical parameters to improve the diagnostic efficacy of NASH. Methods We consecutively enrolled 75 patients with clinically suspected NAFLD who underwent percutaneous liver biopsy in our hospital from June 2020 to December 2021. All cases underwent multiple advanced acoustic measurements for liver such as SWD, SWS, ATI, NLV, and Ratio examination before liver biopsies. A nomogram prediction model combining the technical acoustic measurements and clinical parameters was established and the model is proposed to improve the diagnostic performance of NASH. Results A total of 75 cases were included in this study. Classification of Pathological grade for NASH was as follows: normal liver, (n=15, 20%), NAFL, (n=44, 58.7%), and NASH, (n=16, 21.3%). There were statistically significant differences in SWS (p=0.002), AC (p=0.018), NLV (p=0.033), age (p=0.013) and Glucose (Glu) (p=0.049) between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH, and the calibration curves showed good calibrations in both training and validation sets. The AUCs of the combined nomogram model for the training set and validation set were 0.8597 and 0.7794, respectively. Conclusion There were statistically significant differences in SWS, AC, NLV, age and Glu between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH. The predictive model has a higher diagnostic performance than a single factor model in the diagnosis of NASH, and has a good clinical application prospect.

Inefficient intracellular gene release and transfection limit nonviral gene delivery applications in cancer therapy. Reactive oxygen species (ROS) responsive nonviral gene delivery is the most widely explored strategy for such applications, yet the development of fast and safe ROS responsive nanocarriers proves to be a challenge because of the intracellular chemical equilibrium of high ROS and glutathione levels. Here, we report an ultrasound-enhanced ROS responsive charge-reversal polymeric nanocarrier (BTIL) for fast and efficient pancreatic cancer gene delivery. The BTIL is composed of B-PDEAEA/DNA polyplex-based cores and IR780-loaded liposome coatings. The IR780 is able to produce an excess of ROS under low intensity ultrasound irradiation, thus disequilibrating the chemical equilibrium of ROS and glutathione, and promoting the ROS-responsive positive-to-negative charge-reversal of the B-PDEAEA polymer. This charge conversion results in fast polyplex dissociation and intracellular gene release, inducing efficient gene transfection and cancer cell apoptosis. Moreover, following the intravenous administration, BTIL maintains a stable and long circulation in the bloodstream, achieves orthotopic pancreatic ductal adenocarcinoma distribution, and exhibits potent antitumor activity with negligible side effects. Our results reveal the proposed strategy to be both promising and universal for the development of fast and safe ROS responsive nonviral gene delivery in cancer therapy.

Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis.

To describe the safety rules of various industrial process data and explore the characteristics of unsafe behaviour, the association rules of unsafe behaviour based on pan-scene were proposed in this study. First, based on the scene data theory, unsafe behaviour was described by eight dimensions (time, location, behavioural individual, unsafe action, behavioural attribute, behavioural trace, professional category and risk level) to achieve scene data description and structural transformation. Second, the Apriori algorithm was used to explore the distribution rules of unsafe behaviour dimensions and the interaction between different dimensions from two perspectives: single-dimensional statistical analysis and multidimensional association rule mining. Finally, through SPSS Modeler software, an empirical analysis of pan-scene data for subway construction was conducted, and the association rules between type of work, construction stage, working time and unsafe action were identified. Some strong association rules were produced by the association analysis. For example, during the 13:00-17:00 of the excavation floor stage, the most frequent unsafe action of machine operators is the irregular binding of lifting objects. This result could explain why some unsafe actions are prone to occur in different construction stages and working times for workers of different types, which can be controlled and managed in a targeted manner, thus reducing the possibility of accidents.

Summary: During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment. Key Words: apoptosis-induced apoptosis, atherosclerotic plaque, endothelial cell, macrophage, neovascularization, sonodynamic therapy

Atherosclerotic cerebrocardiovascular disease is the major cause of acute ischemic diseases in humans. Impaired efferocytosis contributes to the progression of atherosclerosis. Pathological and apoptotic cells fail to undergo effective phagocytic clearance, leading to increased inflammation and necrotic core formation. Previously, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy (SDT) promotes apoptotic cell efferocytosis via ATP release in atherosclerotic plaques. However, the exact signaling molecule involved in this process is still unknown. In the present study, sinoporphyrin sodium-mediated SDT (DVDMS-SDT) was applied to balloon-denuded rabbits in vivo to observe changes in the composition of atherosclerotic lesions. Cultured human THP-1-derived and mouse peritoneal macrophage-derived foam cells were used for in vitro mechanistic studies. Three days after DVDMS-SDT treatment, macrophage efferocytosis was significantly enhanced whereas local inflammation was attenuated in rabbit atherosclerotic lesions. At days 7 and 28, the histopathological analysis showed that DVDMS-SDT inhibited the progression of atherosclerosis, reduced the macrophage content, and increased the smooth muscle cell content in a time-dependent manner. Mechanistically, DVDMS-SDT activated mitochondria-caspase apoptosis in foam cells. Interestingly, activated by DVDMS-SDT, caspase-3 a key factor of apoptosis, reduced the expression of the anti-phagocytic molecule CD47 in foam cells. Of great importance, the promotion of macrophage efferocytosis by DVDMS-SDT can be eliminated by the overexpression of CD47. Overall, these results demonstrated that DVDMS-SDT effectively boosted efferocytosis via deactivation of CD47 expression, thereby reducing inflammation in advanced atherosclerotic plaques.

An edible green algal species Caulerpa lentillifera J. Agardh is reported from China for the first time. The species was collected from the southwest of Hainan Island and morphologically identified...

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium‐mediated sonodynamic therapy (DVDMS‐SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging‐guided SDT in plaque angiogenesis theranostics, termed PFP–HMME@PLGA/MnFe2O4–ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2O4), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid‐glycolic acid (PLGA) shells and is conjugated to an anti‐VEGFR‐2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP‐mediated SDT promotes mitochondrial‐caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP‐mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP‐mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP‐mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis., A clinical non‐invasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. In this article, the strategy of “multi‐modality imaging‐guided SDT” to inhibit plaque neovascularization is proposed, which is more convenient for clinical use and makes SDT more accurate and efficient.

We propose and experimentally demonstrate an ultra-compact, low-loss polarization-independent directional coupler on the silicon-on-insulator (SOI) platform. By exploiting subwavelength gratings in the directional coupler, the coupling strength could be made equal for both transverse-electric and transverse-magnetic polarizations. The demonstrated polarization-independent directional coupler has a device length of only 4.5 μm and achieves complete cross-coupling with a low excess loss of

Since the 1980s, Sargassum fusiforme has been cultivated in Zhejiang, South China, and nowadays it becomes one of the important commercial seaweeds in China. With traditions of eating habits in the East Asian countries, this brown alga is used as food, because it contained functional oligo/polysaccharides and chemical components. and was regarded playing roles in antioxidant activities and regulating immunology. Through over 15 years’ selection, breeding and cultivation, we obtained three strains with good traits and testified their characters during the production, which included the cultivars with high yield and other two good characters, either all the selected strains were applied in the Sargassum production. To avoid confusion during the selection and nursery, it was preferred to establish one fingerprint for distinguishing the Sargassum cultivars from different strains. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) methods were adopted to analyze the genetic diversities of the selected S. fusiforme strains. With that, one fingerprint with RAPD markers was constructed, and one sequence characterized amplified region (SCAR) marker to S. fusiforme was obtained. It is indicated that the applied fingerprint could be valid in S. fusiforme genetic and germplasm justification, and will be positive to molecular marker assistance in its selection and cultivation.

Saccharina angustata and S. longissima are ecologically and economically important seaweeds. So far, no microsatellite marker was available to S. angustata and S. longissima due to a lack of genomic data. Here, we developed polymorphic simple sequence repeats (SSRs) in S. longissima and S. angustata and applied these markers for further population genetic analysis. Cross-amplification tests showed that 11 SSR loci exhibited high amplification rate in S. angustata and S. longissima. Polymorphic information content values (PIC) of 11 loci showed 10 loci (PIC = 0.552–0.908), except for SJ31 (PIC = 0.482), have high polymorphism (PIC > 0.5). Polymorphism tests indicated that 10 loci have high polymorphism in three varieties of S. japonica and two related species. Genetic diversity analysis confirmed the validation of these markers in accessing the genetic diversity level of these kelps. STRUCTURE and NJ tree results indicated these 10 microsatellites are effective in evaluating the genetic relationship among different kelp populations. As results, these 10 polymorphic microsatellite markers are valid to Saccharina genetic analysis.

Brown algae play a dominant role in the primary productivity of coastal ecosystems and may have an efficient carbon fixation. In this work, 56 genes involved in inorganic carbon fixation were identified from the Saccharina japonica genome. Sequence structure analysis of these genes showed the existence of corresponding function domains and active amino acid sites highly conserved with other stramenopile species. The predicted subcellular localizations showed that Calvin cycle-related enzymes predominantly reside in the plastid and that putative C4-related enzymes are mainly distributed in the mitochondrion. We determined the transcriptional profiles and enzymatic activities of these C4-related enzymes in response to the KHCO3 concentrations and light intensities. Pyruvate orthophosphate dikinase (PPDK) presented the greatest response to low HCO3− concentrations and high light intensity. Phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated at low HCO3− concentrations to compensate for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and might be the crucial decarboxylase in this kelp. We propose that S. japonica might possess a PPDK- and PEPCK-dependent C4-like pathway that enables its rapid growth in natural coastal environments.

Studies of postglacial range shifts could enhance our understanding of seaweed species’ responses to climate change and hence facilitate the conservation of natural resources. However, the distribution dynamics and phylogeographic diversification of the commercially and ecologically important kelp Saccharina japonica in the Northwest Pacific (NWP) are still poorly surveyed. In this study, we analyzed the evolutionary history of S. japonica using two mitochondrial markers and 24 nuclear microsatellites. A STRUCTURE analysis revealed two partially isolated lineages: lineage H, which is scattered along the coast of Japan; and lineage P, which occurs along the west coast of the Japan Sea. Ecological niche modeling projections to the Last Glacial Maximum (LGM) revealed that the southern coasts of the Japan Sea and the Pacific side of the Oshima and Honshu Peninsulas provided the most suitable habitats for S. japonica, implying that these regions served as ancient refugia during the LGM. Ancient isolation in different refugia may explain the observed divergence between lineages P and H. An approximate Bayesian computation analysis indicated that the two lineages experienced post‐LGM range expansion and that postglacial secondary contact occurred in Sakhalin. Model projections into the year 2,100 predicted that S. japonica will shift northwards and lose its genetic diversity center on the Oshima Peninsula in Hokkaido and Shimokita Peninsula in Honshu. The range shifts and evolutionary history of S. japonica improve our understanding of how climate change impacted the distribution range and diversity of this species and provide useful information for the conservation of natural resources under ongoing environmental change in the NWP.

Natural hybridization can play a significant role in evolutionary processes and influence the adaptive diversification and speciation of brown seaweeds. However, this phenomenon is as yet unknown inSaccharinakelps.Saccharina angustataand two varieties ofSaccharina japonica(S. japonicavar.japonicaandS. japonicavar.diabolica) partly overlap in distribution along the Pacific coast of Hokkaido, which makes them a good model system to study hybridization and introgression among species of the genusSaccharina. Based on 13 highly variable nuclear microsatellites and a mitochondrial marker, we assessed the genetic diversity levels ofS. angustatafor the first time and populations from Muroran to Shiranuka (western part of the Pacific coast in Hokkaido) exhibited highest genetic diversity. Genetic diversity ofS. japonicawas higher inS. japonicavar.japonicaas compared withS. japonicavar.diabolica. There was significant genetic differentiation (F-ST > 0.25,p < 0.05) betweenS. japonicaandS. angustatabased on both markers. Moreover, there was poor genetic connectivity and limited interspecific hybridization among these closely relatedSaccharinaspecies. Ecological niche models projected a northward expansion of bothS. japonicaandS. angustataunder future climate scenarios and a range overlap between two species along the coast of Okhotsk Sea in Kamchatka Peninsula. The interspecific hybridization and genetic diversity among these kelps provide insights for kelp selection and cultivation as well as future conservation strategies of wild stocks. National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31900279] Shandong Provincial Natural Science FoundationNatural Science Foundation of Shandong Province [ZR2019BC024] Bilateral Joint Research Project between China and Japan [2017YFE0130900] Foundation for Science and Technology (FCT) of PortugalPortuguese Foundation for Science and Technology [UID/Multi/04326/2020, DL57/2016/CP1361/CT0035] info:eu-repo/semantics/publishedVersion

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)−/− mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron‐overload‐induced foam‐cell formation and pro‐inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)‐nuclear factor erythroid 2‐related factor 2 (Nrf2)‐FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS‐Nrf2‐FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

Aureochrome, a blue-light receptor specifically found in photosynthetic stramenopiles, plays an important role in algal growth and development. It holds a reversed effector-sensor topology for the reception of blue light, acting as a candidate of optogenetic tool in transcriptional regulation. However, the inner regulatory mechanism of aureochrome is still unclear. In this study, we explored the potential regulatory relationship between microRNAs (miRNAs) and mRNAs by small RNA, transcriptome and degradome sequencing in Saccharina japonica. Through screening miRNA-mRNA interaction networks at the whole-genome level, we found that 18 miRNAs perfectly paired with aureochrome. Among these screened miRNAs, miR8181 was negatively correlated with aureochrome5 with high credibility, exhibiting tissue-specific expression in sporophyte of S. japonica. Degradome analysis further revealed the exact cleavage site of miR8181 on aureochrome5, confirming their targeting relationship. For the 54 target genes of miR8181, nine genes that exhibited similar expression to that of aureochrome5 competed for the same binding site, thus establishing a competing endogenous RNA network. Functional enrichment of the target genes revealed that miR8181 was involved in the regulation of cell differentiation and development in S. japonica. Moreover, overexpression of miR8181 resulted in significant decreases in the cell growth rates of Phaeodactylum tricornutum, suggesting negative roles of miR8181 in regulating cell growth. Our study revealed that miR8181, the targeting miRNA of aureochrome5, played negative roles in cell growth and development.

Disruption of re-endothelialization and haemodynamic balance remains a critical side effect of drug-eluting stents (DES) for preventing intimal hyperplasia. Previously, we found that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) suppressed macrophage-mediated inflammation in atherosclerotic plaques. However, the effects on intimal hyperplasia and re-endothelialization remain unknown. In this study, 56 rabbits were randomly assigned to control, ultrasound, ALA and ALA-SDT groups, and each group was divided into two subgroups (n = 7) on day 3 after right femoral artery balloon denudation combined with a hypercholesterolemic diet. Histopathological analysis revealed that ALA-SDT enhanced macrophage apoptosis and ameliorated inflammation from day 1. ALA-SDT inhibited neointima formation without affecting re-endothelialization, increased blood perfusion, decreased the content of macrophages, proliferating smooth muscle cells (SMCs) and collagen but increased elastin by day 28. In vitro, ALA-SDT induced macrophage apoptosis and reduced TNF-α, IL-6 and IL-1β via the ROS-PPARγ-NF-κB signalling pathway, which indirectly inhibited human umbilical artery smooth muscle cell (HUASMC) proliferation, migration and IL-6 production. ALA-SDT effectively inhibits intimal hyperplasia without affecting re-endothelialization. Hence, its clinical application combined with bare-metal stent (BMS) implantation presents a potential strategy to decrease bleeding risk caused by prolonged dual-antiplatelet regimen after DES deployment.

Background: Breast cancer (BRCA) is the most commonly diagnosed cancer of women, which is aggressive cancer and has a mortality rate. CD52 and its monoclonal antibody (Alemtuzumab) play a critical role in inflammatory diseases, but the relationship between CD52 and BRCA is not clear.Methods: We first used the random forest algorithm to find the most critical genes related to the prognosis of BRCA patients. Then, according to the analysis of RNA sequence and clinical data of the TCGA dataset, we explored the relationship between CD52 with immune response-related pathways and immune metagenes. The pan-cancer analysis shows the importance of CD52 in a variety of tumorsResults:CD52 was related to the prognosis of BRCA patients (p < 0.001). Subsequent analysis based on RNA-seq and clinical data from the TCGA dataset revealed that CD52 is positively correlated with immune response-related pathways and immune metagenes. TIMER analysis showed that CD52 expression was positively correlated with immune infiltrating levels of B, CD4+ T, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in BRCA (r = 0.466, r = 0.645, r = 0.483, r = 0.149, r= 0.542,r = 0.665, respectively; p < 0.001). CpG sites (cg16068833, cg19743891, cg19743891, cg16664472, cg19677267, cg22517705, and cg27430637) were negatively correlated with CD52 expression (r = -0.662, r = -0.629, r =- 0.598, r = -0.519, r= -0.492, r = -0.445, respectively; p < 0.001). Furthermore, the expression of CD52 was significantly correlated with the following pathological stages (T stage, N stage, and survival state; p=0.024, p=0.047, and p=0.007, respectively). The results of the pan-cancers study suggest that CD52 may play an important role in the occurrence, development, and prognosis of multiple tumors.Conclusions: These findings suggested that CD52 is a promising immunotherapy target and prognostic prediction value for BRCA.

CRY-DASH, a new cryptochrome blue light receptor, can repair damaged DNA and regulate secondary metabolism and development of fungus. However, its role in regulation during the growth of Saccharina japonica is still unclear. After cloning the full-length of CRY-DASH from S. japonica (sjCRY-DASH), we deduced that its open reading frame was 1779 bp long and encoded 592 amino acids. sjCRY-DASH transcription was rapidly upregulated within 30 min in response to blue light and exhibited 24 h periodicity with different photoperiods. Moreover, sjCRY-DASH maintained the same periodicity in suitable growth temperature, suggesting a close relationship between this periodicity and circadian rhythm regulation. Novel-m3234-5p, which was targeted to sjCRY-DASH, decreased with increasing sjCRY-DASH transcription, acting as a negative modulator of sjCRY-DASH. Six long non-coding RNAs classified as long intergenic non-coding RNAs (lincRNAs) exhibited co-expression with sjCRY-DASH. A miRNA sjCRY DASH lincRNA network was consequently identified. By predicting the endogenous competing mRNAs of novel-m3234-5p, we found that sjCRY-DASH indirectly participated in the regulation of DNA damage repair, protein synthesis and processing, and actin transport. In conclusion, our results revealed that non-coding RNAs participate in the regulation of sjCRY-DASH, which played vital roles in the growth and early development of S. japonica.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). Currently, approximately 20–40% of individuals with diabetes are diagnosed with DN. Mesangial cells (MCs) are critical for maintaining and regulating glomerular filtration, and the abnormal proliferation of MCs causes the accumulation of mesangial extracellular matrix (ECM), further promoting glomerular dysfunction and renal diseases. Low molecular weight fucoidan (LMWF) extracted from Saccharina japonica could alleviate DN, but the mechanism was not analysed. Based on the ability of LMWF to ameliorate the human renal mesangial cell (HRMC) injury caused by advanced glycation end products (AGEs), we identified fibronectin (FN) as the most obviously impacted protein in the ECM-receptor interaction by proteomic analysis. The co-localization of LMWF and FN indicated direct interaction between them, and surface plasmon resonance (SPR) analysis confirmed the specific binding with a KD of 453.7 μmol L−1. Positively charged protamine sulfate (PS) promoted the combination of LMWF and HRMCs and further enhanced the effect of LMWF on HRMC injury. Our results indicated that LMWF alleviates the HRMC injury caused by AGEs via binding FN and inhibiting the ECM-receptor interaction pathway. These results provide a foundation for the in-depth analysis of the mechanism of polysaccharide functions.

Saccharina japonica is one of the most important seaweed resources for alginate and fucoidan extraction, and these extracted chemical products are used in foods, textiles, cosmetics, pharmaceuticals, and other applications. The synthesis pathways of alginate and fucoidan are complicated and most of genes and their functions are not clearly understood. Phosphomannomutase is an important enzyme that is involved in the synthesis of both alginate and F-fucoidan in the kelp and also fulfils a phosphoglucomutase function in polysaccharide synthesis. In this study, the full sequence of phosphomannomutase/phosphoglucomutase gene (Sjpmm/Sjpgm) was isolated from S. japonica and characterised. The open reading frame (ORF) of Sjpmm/Sjpgm was 756 bp long, encoded 252 amino acids, and belonged to the haloacid dehydrogenase (HAD) superfamily. The fusion enzyme SjPMM/SjPGM was expressed and purified, and its phosphomannomutase (PMM) and phosphoglucomutase (PGM) activities were determined. The optimal temperature for both PMM and PGM activities was 30 °C, and the optimal pH values were 7.5 and 7.0, respectively. The influences of Mg2+, Mn2+, Co2+, and Ni2+ on the activation of SjPMM/SjPGM were measured, and the maximum activity occurred with Mg2+. Under the optimal conditions, the Km values for the substrates glucose-1-phosphate (G1P) and mannose-1-phosphate (M1P) were 0.08 and 1.15 mM, respectively. In addition, high-temperature (25 °C) and high-light intensity (55 ± 5 μmol photons m−2 s−1) both significantly increased the transcription of Sjpmm/Sjpgm (up to 1.7-fold and 4.6-fold, respectively). These results implied that the SjPMM/SjPGM was closely related to the synthesis of alginate and F-fucoidan and was directly involved in the acclimatisation of S. japonica to light and temperature stress.

Pyropia haitanensis is an important laver species in China. Its quality traits are closely related to the content of glutamic acid. Glutamate dehydrogenase (GDH) is a crucial enzyme in the glutamic acid metabolism. In this study, two GDH genes from P. haitanensis, PhGDH1 and PhGDH2, were cloned and successfully expressed in Escherichia coli. The in vitro enzyme activity assay demonstrated that the catalytic activity of PhGDHs is mainly in the direction of ammonium assimilation. The measured Km values of PhGDH1 for NADH, (NH4)2SO4, and α-oxoglutarate were 0.12, 4.99, and 0.16 mM, respectively, while the corresponding Km values of PhGDH2 were 0.02, 3.98, and 0.104 mM, respectively. Site-directed mutagenesis results showed that Gly193 and Thr361 were important catalytic residues for PhGDH2. Moreover, expression levels of both PhGDHs were significantly increased under abiotic stresses. These results suggest that PhGDHs can convert α-oxoglutarate to glutamic acid, and enhance the flavor and stress resistance of P. haitanensis.

Background Long-term survival in isolated marginal seas of the China coast during the late Pleistocene ice ages is widely believed to be an important historical factor contributing to population genetic structure in coastal marine species. Whether or not contemporary factors (e.g. long-distance dispersal via coastal currents) continue to shape diversity gradients in marine organisms with high dispersal capability remains poorly understood. Our aim was to explore how historical and contemporary factors influenced the genetic diversity and distribution of the brown alga Sargassum thunbergii, which can drift on surface water, leading to long-distance dispersal. Results We used 11 microsatellites and the plastid RuBisCo spacer to evaluate the genetic diversity of 22 Sargassum thunbergii populations sampled along the China coast. Population structure and differentiation was inferred based on genotype clustering and pairwise F ST and allele-frequency analyses. Integrated genetic analyses revealed two genetic clusters in S. thunbergii that dominated in the Yellow-Bohai Sea (YBS) and East China Sea (ECS) respectively. Higher levels of genetic diversity and variation were detected among populations in the YBS than in the ECS. Bayesian coalescent theory was used to estimate contemporary and historical gene flow. High levels of contemporary gene flow were detected from the YBS (north) to the ECS (south), whereas low levels of historical gene flow occurred between the two regions. Conclusions Our results suggest that the deep genetic divergence in S. thunbergii along the China coast may result from long-term geographic isolation during glacial periods. The dispersal of S. thunbergii driven by coastal currents may facilitate the admixture between southern and northern regimes. Our findings exemplify how both historical and contemporary forces are needed to understand phylogeographical patterns in coastal marine species with long-distance dispersal. Electronic supplementary material The online version of this article (10.1186/s12862-017-1089-6) contains supplementary material, which is available to authorized users.

Cytosine methylation plays vital roles in regulating gene expression and plant development. However, the function of DNA methylation in the development of macroalgae remains unclear. Through the genome-wide bisulfite sequencing of cytosine methylation in holdfast, stipe and blade, we obtained the complete 5-mC methylation landscape of Saccharina japonica sporophyte. Our results revealed that the total DNA methylation level of sporophyte was less than 0.9%, and the content of CHH contexts was dominant. Moreover, the distribution of CHH methylation within the genes exhibited exon-enriched characteristics. Profiling of DNA methylation in three parts revealed the diverse methylation pattern of sporophyte development. These pivotal DMRs were involved in cell motility, cell cycle and cell wall/membrane biogenesis. In comparison with stipe and blade, hypermethylation of mannuronate C5-epimerase in holdfast decreased the transcript abundance, which affected the synthesis of alginate, the key component of cell walls. Additionally, 5-mC modification participated in the regulation of blade and holdfast development by the glutamate content respectively via glutamine synthetase and amidophosphoribosyl transferase, which may act as the epigenetic regulation signal. Overall, our study revealed the global methylation characteristics of the well-defined holdfast, stipe and blade, and provided evidence for epigenetic regulation of sporophyte development in brown macroalgae.