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Chemodynamic therapy (CDT) is an emerging and promising therapeutic strategy that suppresses tumor growth by catalytically converting intracellular hydrogen peroxide (H2O2) into highly-reactive hydroxyl radicals (•OH). However, the inherent substrate of H2O2 is relatively insufficient to achieve desirable CDT efficacy. Therefore, searching for integrated therapeutic methods with synergistic therapeutic modality is especially vital to augment therapeutic outcomes. Herein, we reported nanodot- CuxMnySz @BSA@ICG (denoted as CMS@B@I) and bovine serum albumin (BSA)-based biomineralization CuxMnySz (CMS) loaded with photodynamic agent-indocyanine green (ICG). CMS@B@I converts endogenous hydrogen peroxide (H2O2) into highly active hydroxyl radical (•OH) via Fenton reaction, and effectively produces reactive oxygen species (ROS) after being exposed to 808 nm laser irradiation, attributable to the excellent photodynamic agent-ICG. This results in eliciting a ROS storm. Additionally, CMS@B@I exhibits a superior photothermal effect under NIR-II 1064 nm laser irradiation to enhance tumor CDT efficacy. The NIR-II fluorescence imaging agent of ICG and the excellent photothermal effect of CMS@B@I are highly beneficial to NIR-II fluorescence and infrared thermal imaging, respectively, resulting in tracing the fate of CMS@B@I. This study attempts to design a bimodal imaging-guided and photothermal-enhanced CDT nanoagent for augmenting tumor catalytic therapy.

Based on the actor-partner interdependence model, this paper studied the relationship between marital commitment, sacrifice behavior and marital quality of military couples. A convenience sample of 171 Chinese military couples from Guangdong, Jiangsu and Sichuan province was used. All participants completed the self-report questionnaires independently including the Dimension of Commitment Inventory (DCI), the Couples Sacrifice Behavior Scale (CSBS) and the Evaluation and Nurturing Relationship Issues, Communication and Happiness (ENRICH). Results showed that the scores of marital commitment and marital quality of male soldiers were significantly higher than that of their spouses. Compared to their spouses, male soldiers reported higher frequency of sacrifice behaviors and perceiving sacrifice behaviors of spouses. Furthermore, the marital commitment of military couples had significant influence on their own marital quality and frequency of perceiving each other’s sacrifice behavior Military couples’ perception of the frequency of each other’s sacrifice behavior partially mediated the effect of marital commitment on their marital quality. Male soldiers’ perception of spouse’s sacrifice behavior frequency significantly predicted the marital quality of their spouses.

Chemodynamic therapy (CDT) is an emerging and promising therapeutic strategy that suppresses tumor growth by catalytically converting intracellular hydrogen peroxide (H

Improving the aquaculture production efficiency by appropriate diets is an essential approach to meeting the increasing market demand for sea cucumbers. The feces of sea urchins, which contains various enzymes and microorganisms, is a potentially cost-effective food for sea cucumbers. To assess the usability of the fecal diet, a five-week laboratory simulation is conducted to investigate behaviors, digestion ability, growth and resistance ability of the sea cucumber Apostichopus japonicus fed with fecal diet at water temperatures of 15°C and 5°C. In the present study, A. japonicus fed with fecal diet shows an obvious preference to fecal diet rather than prepared feed at water temperatures of both 15°C and 5°C, which suggests that the feces is an applicable diet for A. japonicus. Furthermore, small A. japonicus fed with feces (group F) shows significant advantages in intestinal community richness, community diversity and intestine protease activity to A. japonicus fed with prepared feed (group S) at 15°C. These results indicate that the fecal diet provides benefits to digestion ability of small A. japonicus at 15°C. Weight gaining rate is significantly higher in the A. japonicus fed with feces than that in A. japonicus that were fed with feed or not fed with food (group C), which suggests that the direct improvement of the production efficiency at 15°C. The advantages in intestinal bacteria, protease activity, and growth are consistently found in group F compared with group S at 5°C. In addition, the composition of intestinal bacteria indicates that sea cucumbers may inherit the intestinal bacteria of sea urchins through fecal consumption. This suggests that the fecal diet enhances the digestion ability and enzyme activity at low water temperature and thus improves the growth of sea cucumbers. Furthermore, sea cucumbers fed with sea urchin feces have the highest survival rate among the three groups in exposure to an acute salinity decrease at both 5 and 15°C, indicating a better resistance to low salinity. This provides a new insight into the geographical expansion to low-salinity areas in sea cucumber aquaculture. In conclusion, the present study suggests that sea urchin feces have a great potential for the application in improving the production efficiency of sea cucumber aquaculture.

BackgroundActive-empathic listening (AEL) is the active and emotional involvement of a listener that can take place in at least three key stages of the listening process. Bodie has developed and validated a self-reported, 11-item, three-factor active-empathic listening scale (AELS) in English with good reliability (Cronbach’s alpha = 0.86) to assess AEL abilities. Nevertheless, a Chinese version of the AELS had not been established and validated yet.ObjectiveThe objective of the present study was to examine the reliability and validity of the Chinese version of the AELS.MethodsAfter translating the scale into the Chinese version, 834 college students completed the test. After 4 weeks, 206 participants were tested again on the Chinese AELS to examine retest reliability. The critical ratio method and the item-total correlations were used for the item analysis. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to examine the construct validity. The internal consistency of the scale was analyzed with Cronbach’s alpha and McDonald’s Omega. Interclass correlation coefficient (ICC) was used to examine the scale’s retest reliability. The Interpersonal Reactivity Index (IRI) was used to examine the convergent validity. Pearson correlation analysis was conducted.ResultsEach item of the Chinese AELS had a good discrimination, and the item-total correlation of each item ranged from 0.51 to 0.73. EFA extracted three factors with characteristic root values greater than 1, which could explain 70.72% of the total variance. CFA indicated an adequate fit of the three-factor model (χ2/df = 2.250, root mean square error of approximation [RMSEA] = 0.055, the comparative fit index [CFI] = 0.971, the Tucker-Lewis index [TLI] = 0.959, and the goodness of fit index [GFI] = 0.959). The internal consistency reliability was acceptable (sensing: α = 0.79/ω = 0.78, processing: α = 0.83/ω = 0.83, responding: α = 0.79/ω = 0.79, and AELS: α = 0.87/ω = 0.87). Retest reliability of the scale at 4-week intervals by an ICC was 0.563. The Chinese AELS was significantly correlated with each dimension of IRI.ConclusionThe reliability and validity of the Chinese AELS met the basic psychometrics requirements. Therefore, the scale can be potentially used to assess the active empathic listening abilities of people in China.

Wound healing is a complex, dynamic and difficult process. Much effort and attempt has been made to accelerate this process. The purpose of this study is to prepare nanoparticles loaded with vaccarin (VAC-NPS)hydrogel and evaluate its effect on promoting wound healing. In the present study, the physicochemical properties of VAC-NPS were characterized. Transmission electron microscopy (TEM) was used to observe the morphology of VAC-NPS. Human umbilical vein endothelial cells (HUVEC) was employed to assessment the biocompatibility of VAC-NPS in vitro. The wound healing function of VAC-NPS hydrogels was evaluated in the full-thickness dermal wound in a rat model. The results indicated that VAC-NPS was spherical like particles with uniform particle size distribution and no obvious aggregation with a diameter of (216.6 ± 10.1)nm. The loading capacity and encapsulation efficiency of VAC in the nanoparticles were (14.3 ± 1.2) % and (51.7 ± 1.7) % respectively. MTT assay demonstrated that the VAC-NPS had no cytotoxicity and could promote HUVEC proliferation and migration. In vivo results showed that VAC-NPS promotes wound healing, and the mechanism may be through up-regulating IL-1β and PDGF-BB, promoting angiogenesis. VAC-NPS might have a potential application value for the treatment of the wound healing and a promising performance in bio-medically relevant systems.

The effects of flow velocity on the fitness-related behaviours of Mesocentrotus nudus remain largely unknown, greatly hampering the efficiency of stock enhancement. To explore the appropriate velocities for stock enhancement, we investigated dislodgement and immobilization velocities up to 90 cm s−1. The experimental results showed that M. nudus (test diameter of ~30 mm) were dislodged at 73.50 ± 7.7 cm s−1 and that M. nudus movement occurred only when the flow velocity was less than 33.40 ± 2.7 cm s−1. Three flow velocities less than 33.40 ± 2.7 cm s−1 (2, 10 and 20 cm s−1) were subsequently used to study the effects of flow velocities on covering behaviour and the righting response time of M. nudus. The downstream movement velocity of M. nudus was significantly larger than that upstream at 2 cm s−1 (P = 0.016) and 10 cm s−1 (P = 0.008), but not at 20 cm s−1 (P = 0.222). The righting response time of M. nudus was significantly longer at 20 cm s−1 than that at 2 cm s−1 (P = 0.015). The present study indicates that a flow velocity less than 20 cm s−1, preferably 2–10 cm s−1, is probably appropriate for the stock enhancement of M. nudus. Notably, the current study is a laboratory investigation without considering the hydrographic complexity in the field. Further studies should be carried out to investigate the long-term effects of water flow on feeding and growth of M. nudus both in the laboratory and the field.

Lung cancer always ranks first in the number of cancer deaths every year, accounting for 18.4% of total cancer deaths in 2018. Metastasis is the main cause of death in lung cancer patients. The identification of bioactive components of traditional Chinese medicine is very important for the development of novel reagents against non-small cell lung cancer (NSCLC). Rosthorin A has originated from Rabdosia rosthornii (Diels) Hara which excerpts from 'Chinese materia medica', and is known to have 'clear heat phlegm' properties in the folk. Little is known about the biological functions and mechanisms of Rosthorin A in cancer cells at present. The role of EMT in metastasis of a tumor cell is self-evident. Slug is an important EMT inducer, which is related to the development of lung cancer. Cell growth, clone assay, cell migration, cell invasion, and protein expression, and NSCLC transplanted tumor growth were performed in A549, H1299, and H1975 cells. Rosthorin A significantly inhibited the growth of NSCLC cells, it could prolong the survival of nude mice. Rosthorin A inhibited the migration and invasion of A549, H1299, and H1975 cells. Rosthorin A up-regulated E-cadherin expression level and down-regulated the expression of β-catenin, N-cadherin, vimentin, Slug, and Twist. Rosthorin A could promote the expression of E-cadherin and inhibit the development of EMT by downregulating Slug, to inhibit the development and metastasis of NSCLC cells. In summary, Rosthorin A could be used as a promising candidate for the treatment of NSCLC patients with recurrence and metastasis.

In the present study, the maximum entropy model (MaxEnt) based on the data of sea surface temperature (SST) and published information was used to assess the site suitability for the aquaculture expansion of the sea cucumber Apostichopus japonicus and the sea urchin Strongylocentrotus intermedius in China. According to the current assessment, the coastal areas of Hebei province and Tianjin have great prospects for A. japonicus aquaculture, while is currently being underutilized. In the south, more than 94% of the coastal areas in Zhejiang, Fujian, and Guangdong provinces are suitable for the growth of A. japonicus for six months, especially the coastal areas of Lianjiang, Changle, Fuqing and Putian in Fujian province. The water temperatures in more than 94% of China's coastal areas are higher than 25 °C in July and August, which probably results in the mortality of S. intermedius in aquaculture. This clearly indicates that high water temperature is the bottleneck of S. intermedius aquaculture and well explains the limited expansion of this commercially important exotic species since the introduction in 1989. We suggest a new aquaculture model of S. intermedius that extends the seed production to November to avoid the mass mortality in summer. In the south, 64% of coastal areas in Zhejiang and Fujian provinces are suitable for the transplantation of S. intermedius to the south. The present study suggests the ecological niche model MaxEnt based on the data of SST and published information as a new tool for the assessment of the site suitability of sea cucumbers and sea urchins in China. This provides new insights into the aquaculture expansion of native and exotic species.

The energetic link in the benthic community is based on physiological characteristics of the low food absorption efficiency of sea urchins. Low food absorption efficiency of sea urchins is correlated with the activity of digestive enzymes and the duration of food in their gut. Thus, the digestive enzymes activities (pepsin and amylase enzyme activities) and gut emptying are important indicators in assessing nutrient digestion and absorption in sea urchins. In the present study, the relationship between these indicators and molecules related to digestive physiology were quantified in sea urchins. We found (1) an inter-regulatory relationship existed between Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and serotonin (5-hydroxytryptamine; 5-HT) in the gut of Strongylocentrotus intermedius; (2) digestive enzyme activities were negatively correlated with the TRPA1 and concentration of 5-HT in the gut of S. intermedius; (3) gut emptying rate was positively correlated with TRPA1 and concentration of 5-HT in the gut of S. intermedius. The present study revealed that the digestion and absorption of food are correlated with the TRPA1 and 5-HT in the gut of S. intermedius, which provides valuable information about the digestive physiology of sea urchins. This novel finding is relevant to understanding the low food digestibility of sea urchins. It also provides valuable information to the digestive physiology of sea urchins, which are key to maintaining the stability of food webs in the marine ecosystem.

The energetic link in the benthic community is based on physiological characteristics of the low food absorption efficiency of sea urchins. Low food absorption efficiency of sea urchins is correlated with the activity of digestive enzymes and the duration of food in their gut. Thus, the digestive enzymes activities (pepsin and amylase enzyme activities) and gut emptying are important indicators in assessing nutrient digestion and absorption in sea urchins. In the present study, the relationship between these indicators and molecules related to digestive physiology were quantified in sea urchins. We found (1) an inter-regulatory relationship existed between Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and serotonin (5-hydroxytryptamine; 5-HT) in the gut of

Sea urchin aggregation is a common phenomenon in coastlines. However, it remains controversial whether sea urchins form resource aggregations or behavioral aggregations in a non-spawning season. To clarify, we studied the aggregative responses to food and predators in the sea urchin Mesocentrotus nudus when high fitness areas (HFAs) were scarce versus sufficient. By taking the occupied area of each sea urchin (test diameter + spines = 4.5 cm) as a square (4.5 cm × 4.5 cm), we set scarce HFAs for the sea urchins in Experiment 1 (the squares of HFAs: the area occupied by experimental sea urchins = 1:1) and sufficient HFAs for the sea urchins in Experiment 2 (the squares of HFAs: the area occupied by experimental sea urchins = 2:1). If M. nudus form resource aggregations, they would aggregate passively under the scarce HFAs conditions, but not in the sufficient HFAs conditions. Conversely, if M. nudus form behavioral aggregation, aggregation would occur in both scarce and sufficient HFAs. The present results showed that in the scarce HFAs, M. nudus in the food and predator groups were significantly closer to the food and further from predators, and had significantly more aggregated numbers in HFAs than those in the control group. Sea urchins did not aggregate in response to food or predators under the sufficient HFAs, although significantly more sea urchins of the experimental group was found in HFAs than that of the control group. Sea urchins (at least M. nudus) form resource aggregations that are driven by the scarce HFAs. This provides valuable information into the mechanisms of the aggregation of sea urchins.

Sea urchins and sea cucumbers are mutually beneficial organisms in kelp ecosystem. As herbivores, sea urchins process kelp through feeding and egestion, providing inaccessible food for benthic consumers such as sea cucumbers. Sea urchins in turn profit from the sediment cleaned by sea cucumbers. However, behavioral interactions between them remain poorly understood, which greatly hampers our understanding on the relationship between ecologically important benthic species in marine ecosystems and the regulating mechanism. The present study investigated behavioral interactions between sea urchins Strongylocentrotus intermedius and sea cucumbers Apostichopus japonicus in laboratory conditions. We revealed that the presence of sea urchins caused significant higher speed movement of A. japonicus. Interestingly, the negative effects of S. intermedius on A. japonicus were significantly reduced in the shared macroalgal area. For the first time, we found the interspecific responses to alarm cues between sea cucumbers and sea urchins. Conspecific responses were significantly larger than the interspecific responses in both sea urchins and sea cucumbers. This indicates that interspecific response to alarm cues is an efficient approach to anti-predation and coexistence in mutually beneficial organisms. The present study shed light on the interspecific relationships and coexistence between sea urchins and sea cucumbers in kelp ecosystem.

Cost-effective reefs improve the yield of sea cucumber Apostichopus japonicas cultured in ponds. The reaction to reef models was studied in laboratory experiments regarding selectivity and fitness-related behaviors (crawling, feeding and defecation) in different roughness (rough and smooth), angles (30°, 60° and 90°) and heights (3.5, 7, 10.5 and 14 cm). The present study found that significantly more sea cucumbers selected the rough model, with significantly better crawling frequency, tentacles activity frequency and defecation behavior compared with those on the smooth model. This indicates that rough materials in artificial reefs are appropriate for the fitness-related behaviors of sea cucumbers. Regarding the angles, the 30° model attracted significantly more sea cucumbers than those of 60° and 90°. Among the three angles, sea cucumbers in the 30° model showed significantly better defecation behavior, while showed higher frequencies of crawling and tentacles activity in comparison with the 90° model. In other words, the models of 30° and 60° serve as the "toilet" and the "kitchen" of sea cucumbers better in defecation and food intake. No significant difference was found in the number of sea cucumbers selecting any model of three heights. The 7-cm model sees significantly higher frequencies of crawling and tentacles activity than the ones of 3.5 and 14 cm. These results indicate that the higher reef may not necessarily be valuable in the pond culture and a shorter one may help boost the feeding efficiency of sea cucumbers.

Although the potential link exists between behavioral responses to UV-B radiation and the maximization of fitness, molecular mechanisms of these UV-B induced behaviors remain poorly understood. For the first time, we investigated the transcriptomes of covered (CB), sheltered (SB) and non-protected (NA) sea urchins Strongylocentrotus intermedius exposed to UV-B radiation. A total of 330 differentially expressed genes were revealed by transcriptome comparisons. By comparing with the group NA, we found 79 up-regulated and 118 down-regulated genes in SB group, as well as 26 up-regulated and 67 down-regulated genes in group CB. There were 34 up-regulated genes and 52 down-regulated genes in group SB, compared with group CB. These differentially expressed genes failed to enrich either Gene Ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG), only except an enrichment in KEGG. We highlighted TRPA1 and Opsin as key neurobiological genes involved in the molecular mechanisms of covering and sheltering behaviors of sea urchins exposed to UV-B radiation. What's more, other identified genes provide valuable resources for future investigations on the molecular basis of covering and sheltering behaviors of sea urchins.

Accumulating studies have confirmed the crucial role of long non-coding RNAs (ncRNAs) as favorable biomarkers for cancer diagnosis, therapy, and prognosis prediction. In our recent study, we established a robust model which is based on multi-gene signature to predict the therapeutic efficacy and prognosis in glioblastoma (GBM), based on Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. lncRNA-seq data of GBM from TCGA and CGGA datasets were used to identify differentially expressed genes (DEGs) compared to normal brain tissues. The DEGs were then used for survival analysis by univariate and multivariate COX regression. Then we established a risk score model, depending on the gene signature of multiple survival-associated DEGs. Subsequently, Kaplan-Meier analysis was used for estimating the prognostic and predictive role of the model. Gene set enrichment analysis (GSEA) was applied to investigate the potential pathways associated to high-risk score by the R package “cluster profile” and Wiki-pathway. And five survival associated lncRNAs of GBM were identified: LNC01545, WDR11-AS1, NDUFA6-DT, FRY-AS1, TBX5-AS1. Then the risk score model was established and shows a desirable function for predicting overall survival (OS) in the GBM patients, which means the high-risk score significantly correlated with lower OS both in TCGA and CGGA cohort. GSEA showed that the high-risk score was enriched with PI3K-Akt, VEGFA-VEGFR2, TGF-beta, Notch, T-Cell pathways. Collectively, the five-lncRNAs signature-derived risk score presented satisfactory efficacies in predicting the therapeutic efficacy and prognosis in GBM and will be significant for guiding therapeutic strategies and research direction for GBM.

Interaction among sea urchins remains largely uninvestigated, although the aggregation of sea urchins is common. In the present study, 1, 15 and 30 sea urchins Strongylocentrotus intermedius (11.06 ± 0.99 mm in test diameter) were placed in a 1 m2 circular tank, respectively. Movement behaviors were recorded for 12 min to investigate potential interactions among sea urchins. After the 12-min control period, we added food cues into the tank and recorded the changes in sea urchins’ behaviors. For the first time, we here quantified the interactions among sea urchins in laboratory and found that the interactions varied with food cues and with different densities. The sea urchins dispersed in random directions after being released. There was no significant difference in the movement speed and the displacement of sea urchins among the three density groups (1, 15 and 30 ind/m2). The interaction occurred when sea urchins randomly contacted with the conspecifics and slowed down the movement speed. The speed of sea urchins after physical contacts decreased by an average of 40% in the density of 15 ind/m2 and 17% in the density of 30 ind/m2. This interaction resulted in significantly higher randomness in the movement direction and lower movement linearity in 15 and 30 ind/m2 than in 1 ind/m2. After the introduction of food cues, the movement speed, displacement and dispersal distance of sea urchin groups decreased significantly in all the three densities. The dispersal distance and expansion speed of sea urchins were significantly lower in 30 ind/m2 than those in 15 ind/m2. The present study indicates that the interaction among sea urchins limits the movement of individual sea urchin and provides valuable information into how large groups of sea urchins are stable in places where food is plentiful.

The detection of light intensity and subsequent phototaxis are essential for the fitness of sea urchins in intertidal and shallow subtidal waters, where light intensity varies in accordance with the depth and other hydrographic conditions. The molecular basis of photoresponse, however, remains largely unknown. We compared the expression of SiOpsin4, SiPax6, and SiOpsin5 among tube feet, coelomocytes, gonads, and gut of the sea urchin Strongylocentrotus intermedius. All three genes showed the significantly highest expression in tube feet. To test whether r‐opsin genes (for example, Opsin4) and Pax6 in tube feet, rather than chaopsin genes (for example, Opsin5), are involved in the molecular responses to light intensity, we investigated the expression of Opsin4, Pax6, and Opsin5 among four light intensities. Both Opsin4 and Pax6 expressions were significantly higher in the sea urchins at 1,500 lx than at 100, 300, and 700 lx, indicating a co‐upregulation of Opsin4 and Pax6 expressions in sea urchins exposed to the high light intensity (for example, 1,500 lx). However, there was no significant difference of SiOpsin5 expression among the four light intensity groups. Consistent with our hypothesis, there was no significant difference in either Opsin4 or Pax6 expression between the two light intensity environments (low light intensity environment: 50–100 lx; high light intensity environment: 330–1400 lx). This indicates that positive phototaxis and negative phototaxis probably regulate the expression of Opsin4 and Pax6 to a similar level when sea urchins are exposed to the high and low light intensities, respectively. The present study provides new insights into the molecular basis of light intensity detection and subsequent phototaxis of eyeless species.

Understanding the ecological role of shelters is greatly hampered by the scarcity of long-term laboratory experiments on the trade-off between fitness benefits and costs. This lack probably leads to an underestimation of the negative and/or positive effects on behaviors and growth of marine invertebrates in benthic ecosystems. Although our previous study revealed a significant effect on fitness-related traits of Glyptocidaris crenularis after 31 months, the present study extended it and investigated fitness benefits and/or costs of long-term sheltering on sea urchins to over 7 years. The present long-term study suggests that the previously reported reduction in feeding rate probably resulted from a reduction in reflexive feeding motions (Aristotle’s lantern reflex) rather than changes in foraging behavior. Actively seeking sheltering behavior was negatively impacted in individuals with continuous access to shelters. However, covering and righting behaviors did not differ in sheltered sea urchins, indicating that these behaviors are maintained to escape from adverse environments regardless of shelter. Body size of sea urchins in the group with shelters was significantly lower than those without shelters after 7 years. Weights of gonads and gut were not significantly different after 7 years despite previous observations of differences after ~2.5 years. The present study provides valuable information on the trade-off between fitness benefits and costs to sea urchins residing in shelters. However, the present study is only a laboratory investigation for one urchin species (G. crenularis) which does not consider the complexity of natural environments. Field studies should be carried out with G. crenularis and other sea urchin species, before a more universal conclusion can be drawn.

Background: Diabetes mellitus is a growing global health issue nearly across the world. Diabetic patients who are prone to develop diabetes-related complications often exhibit progressive neuropathy (painless and sensory loss). It is usual for small wounds to progress to ulceration, which especially worsens with peripheral arterial disease and in the presence of anaerobic bacteria, culminating into gangrene. In our study, vaccarin (VAC), the main active monomer extracted from Chinese herb vaccariae semen, is proven to have a role in promoting diabetic chronic wound healing through a cytoprotective role under high glucose conditions. Materials and methods: We constructed a pressure ulcer on both VAC-treated and control mice based on a type 1 diabetes (T1DM) model. The wound healing index was evaluated by an experimental wound assessment tool (EWAT). We also determined the effect of VAC on the proliferation and cell migration of human microvascular endothelial cells (HMEC-1) by a cell counting kit (CCK-8), a scratch and transwell assay. Results: The results demonstrated that VAC could promote the proliferation and migration of high glucose-stimulated HMEC-1 cells, which depend on the activation of FOXP2/AGGF1. Activation of the angiogenic factor with G patch and FHA domains 1 (AGGF1) caused enhanced phosphorylation of serine/threonine kinase (Akt) and extracellular regulated protein kinases (Erk1/2). By silencing the expression of forkhead box p2 (FOXP2) protein by siRNA, both mRNA and protein expression of AGGF1 were downregulated, leading to a decreased proliferation and migration of HMEC-1 cells. In addition, a diabetic chronic wound model in vivo unveiled that VAC had a positive effect on chronic wound healing, which involved the activation of the above-mentioned pathways. Conclusions: In summary, our study found that VAC promoted chronic wound healing in T1DM mice by activating the FOXP2/AGGF1 pathway, indicating that VAC may be a promising candidate for the treatment of the chronic wounds of diabetic patients.

Ozone depletion induced by anthropogenic gases has been increasing the transmission of solar ultraviolet-B radiation (UV-B, 280–315 nm) through the atmosphere, which may impact the fitness of marine invertebrates in intertidal and shallow waters. To our knowledge, however, the responses of fitness related behaviors to UV-B radiation at different intensities have been rarely studied in marine invertebrates. For the first time, the present study investigated the effects of exposure of one hour to UV-B radiation at different intensities on foraging behavior, Aristotle’s lantern reflex and righting behavior of the sea urchin Strongylocentrotus intermedius. Exposure of one hour to UV-B radiation at 10 μW/cm2 significantly reduced foraging behavior. An intensity dependent effect of exposure to UV-B radiation was found in the duration of the Aristotle’s lantern reflex. Exposure to UV-B radiation at 20 μW/cm2 for one hour significantly reduced the duration of the Aristotle’s lantern reflex, but 10 μW/cm2 did not. There was no significant difference of righting response time among sea urchins exposed to 0, 10 and 20 μW/cm2 for one hour. To test potential carryover effects, the behavioral traits were re-measured three days later. We found significant carryover effects of UV-B radiation on foraging time and righting response time, but not on the duration of the Aristotle’s lantern reflex. The present study indicates that a brief exposure of one hour to UV-B radiation can significantly affect the duration of Aristotle’s lantern reflex, righting response time and foraging behavior of a sea urchin, although the immediate impacts and carryover effects were highly trait dependent. This study provides new information into the behavioral responses of marine invertebrates to exposure to UV-B radiation. Future studies should be carried out to investigate long-term carryover effects of UV-B radiation on behavioral and physiological fitness related traits.

Mass mortality of commercially cultured marine species in summer is the most serious problem for the longline culture. Reducing crowding stress induced by high stocking density on the basis of high biomass is proposed to be an important approach to solving this issue. A laboratory experiment with multi-layer culture (18 sea urchins total, 6 urchins in each layer) was conducted to investigate gonad yield, gonadal development, thermal tolerance (CTmax) and disease transmission for the juvenile sea urchins Strongylocentrotus intermedius for ~7 weeks at elevated temperatures. The present study found that precocious puberty occurred both in those sea urchins cultured in multi-layer and those not (control group), indicating that gonadal development is accelerated by crowding stress (even in a low density of 6 sea urchins/1834.56 cm3). The CTmax showed a significantly negative correlation with gonadal development, suggesting precocious puberty probably is responsible for the decrease of resistance ability. We further assessed whether segregation in multi-layer culture improves these important traits of sea urchins. This approach significantly reduced gonadal development, improved CTmax and lower mortality and morbidity after disease challenge assays in sea urchins than those not separated in multi-layer culture, which efficiently reduces the gametogenesis, improves resistance ability and decreases disease transmission. The present study establishes a new approach to improving the survival of cultured organisms in the longline culture at high temperatures.

A cost-effective approach to controlling foraging and feeding behaviors of sea urchins is essential for the management of kelp beds. Laboratory experiments were designed to investigate whether alarm cues from crushed conspecific urchins can effectively prevent the foraging and feeding behaviors of the sea urchin Mesocentrotus nudus under the static seawater condition. The present study found that the number of M. nudus that foraged successfully was significantly lower when alarm cues were placed between the kelp and the sea urchins. This result indicates that alarm cues could play an important role in critical kelp-bed areas. It probably prevents sea urchins from foraging by acting as a barrier. Further, we found that alarm cues around the kelp significantly affected foraging behavior of M. nudus, indicating that the alarm cues around the kelp are a potential effective way to prevent sea urchins from foraging for the kelp. In addition, the number of sea urchins that stopped feeding was significantly higher in the group in the presence of alarm cues than that in the control group. This indicates that alarm cues may have an application in stopping sea urchins from feeding. However, there was no significant difference of Aristotle’s lantern reflex between the groups with and without alarm cues. These results indicate that alarm cues greatly affect foraging behavior, but not Aristotle’s lantern reflex of M. nudus. All together, the present study suggests that alarm cues have an application potential in the management of the kelp beds as green engineering. Future studies are essential to further investigate the chemical basis of the alarm cues of sea urchins for the application in large-scale.

Hyperglycemia and insulin resistance drive intestinal barrier dysfunction in type 2 diabetes (T2DM). Vaccarin, the main active component in the semen of traditional Chinese medicine Vaccaria has a definite effect on T2DM mice. The purpose of this study was to investigate whether vaccarin can enhance the intestinal barrier function in T2DM.The T2DM mice model was established by streptozocin and high-fat diet. Vaccarin at a dose of 1 mg/kg/day was administered. We evaluated the effects of vaccarin on gut microbiota and intestinal barrier function by 16S rRNA sequencing, Western blot, quantitative fluorescent PCR (qPCR), and morphological observation. Moreover, we constructed a single layer of the human intestinal epithelium model to determine the effect of vaccarin in vitro.The experimental results showed that vaccarin alleviated inflammatory mediators in serum and intestinal tissue of mice (P 0.05), which may depend on the improvement of tight junctions and gut microbiota (P 0.05). Activation of extracellular regulated protein kinases (Erk1/2) stimulated myosin light chain kinase (MLCK). By inhibiting ERK expression (P 0.05), vaccarin had similar effects to ERK inhibitors. In addition, the regulation of tight junction barriers also involved the abovementioned pathways in vivo.Vaccarin could protect the intestinal barrier by inhibiting the ERK/MLCK signaling pathway and modulate the composition of the microbiota. These results suggested that vaccarin may be an effective candidate for improving intestinal barrier changes in T2DM.

It is important to study the fitness of marine invertebrates in exposure to high water temperature. We studied whether the long-term high temperatures work on the fitness-related traits (righting behavior, covering behavior, foraging behavior, Aristotle's lantern reflex, body size) of S. intermedius whose parents (males and females) were exposed to ambient or high temperatures (~3 °C higher than the ambient) for a long period of time. The present study found that test diameter, wet body weight and test weight of offspring were not significantly different between temperature treatments, indicating that the parental sea urchins in exposure to high temperatures develop no carryover effects on the body size of the offspring sea urchins. We found no significant difference in foraging behavior, Aristotle's lantern reflex, lantern length and lantern weight of sea urchins after their parents had experienced long-term high temperatures. In addition, no significant change was found in the righting and covering behaviors of sea urchins whose parents were at long-term high temperatures. These results indicate that no significant lasting effects exhibited in the fitness-related behaviors and tissue size after their parents were exposed to high temperatures for a long time. The crushing force of test and test thickness showed no significant difference in the offspring of S. intermedius, no matter whether their parents were exposed to long-term high temperatures or not. The current results enrich our understanding that the parental sea urchin experiencing long-term high temperatures probably develop no carryover effects on the test of their offspring. We found that sea urchins whose parents were exposed to long-term elevated temperatures showed a significantly higher lantern length/test diameter and a significantly lower test height/test diameter in offspring sea urchins due to the thermal experience of their parents, showing the plasticity of lantern and test of offspring sea urchins in response to the thermal experience of their parents. Together with our previous investigation, the present study indicates that small sea urchins are less susceptible to the carryover effects of high temperatures in comparison with the developmental stages of embryos and larvae.

Understanding the ecological role of shelters is greatly hampered by the scarcity of long-term laboratory experiments on the trade-off between fitness benefits and costs. This lack probably leads to an underestimation of the negative and/or positive effects on behaviors and growth of marine invertebrates in benthic ecosystems. Although our previous study revealed a significant effect on fitness-related traits of Glyptocidaris crenularis after 31 months, the present study extended it and investigated fitness benefits and/or costs of long-term sheltering on sea urchins to over 7 years. The present long-term study suggests that the previously reported reduction in feeding rate probably resulted from a reduction in reflexive feeding motions (Aristotle’s lantern reflex) rather than changes in foraging behavior. Actively seeking sheltering behavior was negatively impacted in individuals with continuous access to shelters. However, covering and righting behaviors did not differ in sheltered sea urchins, indicating that these behaviors are maintained to escape from adverse environments regardless of shelter. Body size of sea urchins in the group with shelters was significantly lower than those without shelters after 7 years. Weights of gonads and gut were not significantly different after 7 years despite previous observations of differences after ~2.5 years. The present study provides valuable information on the trade-off between fitness benefits and costs to sea urchins residing in shelters. However, the present study is only a laboratory investigation for one urchin species (G. crenularis) which does not consider the complexity of natural environments. Field studies should be carried out with G. crenularis and other sea urchin species, before a more universal conclusion can be drawn.

This study describes the chemical constituents of Albiziae Cortex and their ability to ameliorate steatosis and promote proliferation and anti-oxidation in vitro. Together, five known lignan glycosides, (7S,8R)-erythro-syringylglycerol-&beta, &ndash, O-4&prime, sinapyl ether 9-O-&beta, D-glucopyranoside (1), (+)-lyoniresinol-9&prime, O-gluco-side (2), (&minus, )-lyoniresinol-9&prime, O-glucoside (3), picraquassioside C (4), and icariside E5 (5), were isolated from the Albiziae Cortex. Their structures were elucidated by extensive NMR and high-resolution mass spectrometry analysis and compared with reported data. Oil Red O staining results revealed that compounds 1, 2, and 3 attenuated lipid accumulation and lipid metabolic disorders in FFAs (oleate/palmitate, 2:1 ratio, 0.3 mM)-exposed HepG2 cells. The Cell Counting Kit 8 (CCK-8) assay results revealed that compounds 1 and 5 can significantly promote human umbilical vein endothelial cell (HUVEC) proliferation, meanwhile, these compounds did not exhibit significant cytotoxicity against HUVECs. In addition, 2&prime, 7&prime, dichlorofluorescein diacetate (DCFH-DA) staining results revealed that high glucose (HG)-induced reactive oxygen species (ROS) production was abolished by compounds 1, 2, and 3. This is the first report of the isolation of lignan skeletons from the genus Albizzia julibrissin with the ability to ameliorate steatosis and promote proliferation and anti-oxidation activities.

Small sea urchins Strongylocentrotus intermedius (1–2 cm of test diameter) are exposed to different environments of light intensities after being reseeded to the sea bottom. With little information available about the behavioral responses of S. intermedius to different light intensities in the environment, we carried out an investigation on how S. intermedius is affected by three light intensity environments in terms of phototaxis, foraging and righting behaviors. They were no light (zero lx), low light intensity (24–209 lx) and high light intensity (252–2,280 lx). Light intensity had obvious different effects on phototaxis. In low light intensity, sea urchins moved more and spent significantly more time at the higher intensity (69–209 lx) (P = 0.046). S. intermedius in high light intensity, in contrast, spent significantly more time at lower intensity (252–690 lx) (P = 0.005). Unexpectedly, no significant difference of movement (average velocity and total distance covered) was found among the three light intensities (P > 0.05). Foraging behavior of S. intermedius was significantly different among the light intensities. In the no light environment, only three of ten S. intermedius found food within 7 min. In low light intensity, nine of 10 sea urchins showed successful foraging behavior to the food placed at 209 lx, which was significantly higher than the ratio of the number (two of 10) when food was placed at 24 lx (P = 0.005). In the high light intensity, in contrast, significantly less sea urchins (three of 10) found food placed at the higher light intensity (2,280 lx) compared with the lower light intensity (252 lx) (10/10, P = 0.003). Furthermore, S. intermedius showed significantly longer righting response time in the high light intensity compared with both no light (P = 0.001) and low light intensity (P = 0.031). No significant difference was found in righting behavior between no light and low light intensity (P = 0.892). The present study indicates that light intensity significantly affects phototaxis, foraging and righting behaviors of S. intermedius and that ~200 lx might be the appropriate light intensity for reseeding small S. intermedius.

This study describes the chemical constituents of Albiziae Cortex and their ability to ameliorate steatosis and promote proliferation and anti-oxidation in vitro. Together, five known lignan glycosides, (7S,8R)-erythro-syringylglycerol-β–O-4′-sinapyl ether 9-O-β-D-glucopyranoside (1), (+)-lyoniresinol-9′-O-gluco-side (2), (−)-lyoniresinol-9′-O-glucoside (3), picraquassioside C (4), and icariside E5 (5), were isolated from the Albiziae Cortex. Their structures were elucidated by extensive NMR and high-resolution mass spectrometry analysis and compared with reported data. Oil Red O staining results revealed that compounds 1, 2, and 3 attenuated lipid accumulation and lipid metabolic disorders in FFAs (oleate/palmitate, 2:1 ratio, 0.3 mM)-exposed HepG2 cells. The Cell Counting Kit 8 (CCK-8) assay results revealed that compounds 1 and 5 can significantly promote human umbilical vein endothelial cell (HUVEC) proliferation; meanwhile, these compounds did not exhibit significant cytotoxicity against HUVECs. In addition, 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining results revealed that high glucose (HG)-induced reactive oxygen species (ROS) production was abolished by compounds 1, 2, and 3. This is the first report of the isolation of lignan skeletons from the genus Albizzia julibrissin with the ability to ameliorate steatosis and promote proliferation and anti-oxidation activities.

Cardiovascular complications are a major leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Vascular endothelial dysfunction is a core pathophysiological event in the early stage of T2DM and eventually leads to cardiovascular disease. Vaccarin (VAC), an active flavonoid glycoside extracted from vaccariae semen, exhibits extensive biological activities including vascular endothelial cell protection effects. However, little is known about whether VAC is involved in endothelial dysfunction regulation under high glucose (HG) or hyperglycemia conditions. Here, in an in vivo study, we found that VAC attenuated increased blood glucose, increased glucose and insulin tolerance, relieved the disorder of lipid metabolism and oxidative stress, and improved endothelium-dependent vasorelaxation in STZ/HFD-induced T2DM mice. Furthermore, in cultured human microvascular endothelial cell-1 (HMEC-1) cells, we showed that pretreatment with VAC dose-dependently increased nitric oxide (NO) generation and the phosphorylation of eNOS under HG conditions. Mechanistically, VAC-treated HMEC-1 cells exhibited higher AMPK phosphorylation, which was attenuated by HG stimulation. Moreover, HG-triggered miRNA-34a upregulation was inhibited by VAC pretreatment, which is in accordance with pretreatment with AMPK inhibitor compound C (CC). In addition, both reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) and VAC abolished HG-evoked dephosphorylation of AMPK and eNOS, increased miRNA-34a expression, and decreased NO production. These results suggest that VAC impedes HG-induced endothelial dysfunction via inhibition of the ROS/AMPK/miRNA-34a/eNOS signaling cascade.

Small sea urchins Strongylocentrotus intermedius (1–2 cm of test diameter) are exposed to different environments of light intensities after being reseeded to the sea bottom. With little information available about the behavioral responses of S. intermedius to different light intensities in the environment, we carried out an investigation on how S. intermedius is affected by three light intensity environments in terms of phototaxis, foraging and righting behaviors. They were no light (zero lx), low light intensity (24–209 lx) and high light intensity (252–2,280 lx). Light intensity had obvious different effects on phototaxis. In low light intensity, sea urchins moved more and spent significantly more time at the higher intensity (69–209 lx) (P = 0.046). S. intermedius in high light intensity, in contrast, spent significantly more time at lower intensity (252–690 lx) (P = 0.005). Unexpectedly, no significant difference of movement (average velocity and total distance covered) was found among the three light intensities (P > 0.05). Foraging behavior of S. intermedius was significantly different among the light intensities. In the no light environment, only three of ten S. intermedius found food within 7 min. In low light intensity, nine of 10 sea urchins showed successful foraging behavior to the food placed at 209 lx, which was significantly higher than the ratio of the number (two of 10) when food was placed at 24 lx (P = 0.005). In the high light intensity, in contrast, significantly less sea urchins (three of 10) found food placed at the higher light intensity (2,280 lx) compared with the lower light intensity (252 lx) (10/10, P = 0.003). Furthermore, S. intermedius showed significantly longer righting response time in the high light intensity compared with both no light (P = 0.001) and low light intensity (P = 0.031). No significant difference was found in righting behavior between no light and low light intensity (P = 0.892). The present study indicates that light intensity significantly affects phototaxis, foraging and righting behaviors of S. intermedius and that ~200 lx might be the appropriate light intensity for reseeding small S. intermedius.

Light is an important environmental factor for the fitness of small sea urchins. It is thus important to reveal the appropriate light environments for their stock enhancement. However, the effects of light spectra on fitness related behaviors of sea urchins remain mostly unknown. To reveal appropriate light spectra for stock enhancement of the sea urchin Strongylocentrotus intermedius, we investigated the effects of light spectra on the foraging behavior, phototaxis, Aristotle's lantern reflex of S. intermedius (test diameter: 10.35 ± 0.05 mm). There were five light spectra, including red (630–670 nm), yellow (570–600 nm), green (510–550 nm), blue (440–490 nm) and white light (a mix of blue-based and a little red). We found that successful foraging proportion under blue light (65 %) was obviously higher than those under other light spectra, although no significant difference was detected (P > 0.05). The foraging time of S. intermedius was significantly higher under red light than under blue (P 0.05). Light spectra showed no significant effect on phototaxis of S. intermedius (P > 0.05). This indicates that the effect of light spectra on the foraging behavior is not due to phototaxis and movement distance in S. intermedius. Further, Aristotle's lantern reflex of S. intermedius under white light was significantly higher than that under red light (P

Taking advantage of the seasonally appropriate water temperature in southern China is an important approach to expanding Strongylocentrotus intermedius aquaculture for the increasing market demand. However, appropriate diets remain largely uninvestigated and seed supply is in shortage, leaving the most serious problems of S. intermedius aquaculture in southern China unaddressed. Here, a feeding experiment was conducted for ∼6 months (from November 2018 to May 2019) to compare the somatic and gonadal growth, as well as gonadal development of S. intermedius (∼30 mm of test diameter) fed either macroalgae Gracilaria lemaneiformis or Saccharina japonica at the temperatures simulating water those off southern China coast (Fuzhou, 119°50′ E, 26°24′ N). Test size, wet body weight, specific growth rate, lantern size, wet gut weight and gonad yield of S. intermedius fed S. japonica were all significantly larger than those of sea urchins fed G. lemaneiformis. The present results indicate that long-term feeding G. lemaneiformis is unacceptable for aquacultural S. intermedius in southern China, because of the inefficiency of supporting somatic and gonadal growth. Saccharina japonica may suffice as a suitable diet for the aquaculture of S. intermedius in southern China. Further, spent gonads were observed in S. intermedius fed G. lemaneiformis in May 2019, meanwhile all gonads of individuals fed S. japonica remained in the premature stage. This suggests that G. lemaneiformis displays a promising potential for accelerating gonadal development of S. intermedius and subsequently supports the seed production of sea urchins in spring in southern China. The present study provides valuable information into the aquaculture management of S. intermedius in southern China.

Stock enhancement as an effective method of increasing production of Mesocentrotus nudus has prompted increasing interest in both China and Japan. It's essential to reveal the optimal temperature range for stock enhancement of M. nudus. In order to achieve this aim, we carried out a simulated laboratory experiment including three levels of water temperatures (10 °C, 15 °C and 20 °C) to investigate effects of different temperatures on the survival, food consumption, growth and behaviors of small, medium and large size M. nudus for ~50 days. According to our investigation, all the three size M. nudus exposed to 15 °C showed significantly better growth, faster righting speed among the three temperature levels. All the three size M. nudus exposed to 20 °C showed faster righting speed, better growth and longer movement distance than those exposed to 10 °C. We suggest aquafarmers to release M. nudus onto the sea floor when the natural water temperature reaches 15–20 °C for stock enhancement, which is more benefit for their survival, behavior and growth than the range of 10–15 °C.

Transgenerational effects, which involve both selection and plasticity, are important for the evolutionary adaptation of echinoderms in the changing ocean. Here, we investigated the effects of breeding design and water temperature for offspring on fertilization, hatchability, larval survival, size, abnormality and metamorphosis of the sea urchin Strongylocentrotus intermedius, whose dams and sires were exposed to long-term (~15 months) elevated temperature (~3 °C above ambient) or ambient temperature. There was no transgenerational effect on fertilization and metamorphosis of S. intermedius, while negative transgenerational effects were found in hatchability and most traits of larval size. Dam and sire effects were highly trait and developmental stage dependent. Interestingly, we found S. intermedius probably cannot achieve transgenerational acclimation to long-term elevated temperature for survival provided their offspring were exposed to an elevated temperature. The present study enriches our understanding of transgenerational effects of ocean warming on sea urchins.

Transgenerational effects are important for phenotypic plasticity and adaptation of marine invertebrates in the changing ocean. Ultraviolet-B (UV-B) radiation is an increasing threat to marine invertebrates. For the first time, we reported positive and negative transgenerational effects of UV-B radiation on egg size, fertilization, hatchability and larval size of a marine invertebrate.Strongylocentrotus intermediusexposed to UV-B radiation showed positive transgenerational effects and adaptation on egg size, hatching rate and post-oral arm length of larvae. Negative transgenerational effects were found in body length, stomach length and stomach width of larvae whose parents were exposed to UV-B radiation. Sires probably play important roles in transgenerational effects of UV-B. The present study provides valuable information into transgenerational effects of UV-B radiation on fitness related traits of sea urchins (at leastStrongylocentrotus intermedius).