Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice. Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

In vitro outcomes of quercetin on Candida albicans planktonic and biofilm cells and in vivo effects on vulvovaginal candidiasis. Evidences of its mechanisms of action.

BACKGROUND AND PURPOSE: Candida albicans is a fungus that produces common fungal infection in humans, including vulvovaginal candidiasis (VVC). While quercetin (QC) has potential antifungal activities against C. albicans, studies on the in vivo anti-VVC activity of QC are limited. This study evaluated the antifungal capacity of QC against cultured C. albicans strain SC5314 or in C. albicans-infected mice. METHODS: Microdilution and XTT reduction assay were used to determine the minimum inhibitory concentration (MIC) and biofilm formation of QC on C. albicans, respectively. Immunofluorescence was performed to detect the anti-invasive capacity of QC upon co-culturing C. albicans with VK2/E6E7 cells. The potential anti-VVC effects of QC were assessed in C. albicans-infected mice with VVC. Further, inflammatory cytokine levels were determined using ELISA. PAS and Papanicolaou staining were used to detect C. albicans cells and polymorphonuclear leukocytes (PMNs) in vaginal tissues. Western blotting and immunohistochemistry were performed to measure the expression of MAPK, ERK, JUN, and P38. RESULTS: MIC and minimal fungicidal concentration (MFC) of QC for C. albicans were 128 µM and > 512 µM, respectively. QC concentration lower than 128 µM (32-128 µM) could not inhibit C. albicans. QC (16 µM) notably inhibited C. albicans biofilm formation and suppressed the adhesion and invasion of C. albicans to VK2/E6E7 cells. In addition, the pharmacokinetic parameters of orally administered QC in mice showed rapid absorption (approximately 1 h) and slow elimination (approximately 6 h). Oral QC showed an effective protective function against C. albicans infection with no toxic effects a in mouse VVC model. QC significantly reduced IL-1α, TNF-α, IL-22 and IL-23 levels in vaginal lavage solution, inhibited invasive C. albicans and PMN infiltration in vaginal tissue, and effectively protected the integrity of vaginal mucosa. CONCLUSIONS: The present study showed that QC has rapid oral absorption, slow elimination, good viral distribution, and a lack of toxicity. QC not only inhibited biofilm formation, adhesion, and invasion of C. albicans in vitro, but also ameliorated C. albicans-induced inflammation and protected the integrity of the vaginal mucosa in vivo, suggesting that QC has the potential for the treatment of candidiasis.

Efficacy of acupuncture for endometriosis-associated pain: a multicenter randomized single-blind placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain. DESIGN: A multicenter, randomized, single-blind, placebo-controlled trial. INSTITUTIONS: Four tertiary hospitals in Jiangxi and Hainan Provinces. SUBJECTS: Women with endometriosis-associated pain aged between 20 and 40 years. INTERVENTION: Subjects were assigned randomly to receive either acupuncture or sham acupuncture treatment for 12 weeks, starting one week before each expected menstruation and administered as a 30-minute session once per day, 3 times a week. During the menstruation period, acupuncture was administered daily when pelvic pain associated with endometriosis occurred. After acupuncture or sham acupuncture treatment, the subjects were followed for another 12 weeks. MAIN OUTCOME MEASURES: Changes in maximum pain as assessed with the visual analog scale (VAS) for various pelvic pain, duration of dysmenorrhea, and scores on the Multidimensional Pain Inventory, Beck Depression Inventory, Profile of Mood States, and Endometriosis Health Profile from baseline to week 12 and week 24. RESULTS: A total of 106 women were assigned randomly to the acupuncture and sham groups. In the acupuncture group, the reduction in the dysmenorrhea VAS score was significantly greater after treatment, but not at the end of the trial, compared to the sham group. The duration of pain was significantly shorter in the acupuncture group. All test scores were improved to a significantly greater extent in the acupuncture group than in the sham group at week 12 but not at week 24. Changes in nonmenstrual pelvic pain and dyspareunia VAS scores were not different between the groups. No severe adverse events or differences in adverse events were recorded. CONCLUSION: Acupuncture is an effective and safe method of relieving dysmenorrhea, shortening the pain duration, and improving wellbeing and quality of life in women with endometriosis-associated pain, although its efficacy fades after treatment is discontinued. CLINICAL TRIAL REGISTRATION NUMBER: NCT03125304.

Natural product evodiamine-inspired medicinal chemistry: Anticancer activity, structural optimization and structure-activity relationship.

It is a well-known phenomenon that natural products can serve as powerful drug leads to generate new molecular entities with novel therapeutic utility. Evodiamine (Evo), a major alkaloid component in traditional Chinese medicine Evodiae Fructus, is considered a desirable lead scaffold as its multifunctional pharmacological properties. Although natural Evo has suboptimal biological activity, poor pharmacokinetics, low water solubility, and chemical instability, medicinal chemists have succeeded in producing synthetic analogs that overshadow the deficiency of Evo in terms of further clinical application. Recently, several reviews on the synthesis, structural modification, mechanism pharmacological actions, structure-activity relationship (SAR) of Evo have been published, while few reviews that incorporates intensive structural basis and extensive SAR are reported. The purpose of this article is to review the structural basis, anti-cancer activities, and mechanisms of Evo and its derivatives. Emphasis will be placed on the optimizing strategies to improve the anticancer activities, such as structural modifications, pharmacophore combination and drug delivery systems. The current review would benefit further structural modifications of Evo to discover novel anticancer drugs.

Inhibitory effect of methylene blue mediated photodynamic therapy combined with berberine on Porphyromonas gingivalis in vitro / 国际生物医学工程杂志

Objective:To investigate the in vitro inhibitory effect of methylene blue mediated photodynamic therapy (PDT) combined with berberine on Porphyromonas gingivalis (P.g). Methods:P.g was cultured until the middle to late log phase, and methylene blue was added to P.g suspension at different mass concentrations for 5 min, and a laser (wavelength 660 nm, power 140 mW/cm 2) was irradiated for 2 min to find the optimal concentration of methylene blue combined with the laser for in vitro inhibition of P.g. The effect of methylene blue mediated PDT on the in vitro inhibition of P.g and the effect of berberine on the growth curve of P.g were observed. The inhibitory effect of methylene blue mediated PDT and berberine on P.g was investigated by successive combined applications. The effect of methylene blue mediated PDT on P.g morphology was observed by scanning electron microscopy. The absorption peaks of each component were measured by ultraviolet spectrophotometer. Results:The best inhibition was achieved at a methylene blue mass concentration of 24.414 1 μg/ml under 660 nm laser excitation. The differences were statistically significant in both the methylene blue and PDT groups compared with the control group (all P<0.001). 0.05 mg/ml berberine had an inhibitory effect on the planktonic bacteria of P.g. After P.g was treated with methylene blue mediated PDT, the bacterial cell walls were crumpled into clusters. Compared with the control group, the number of colonies was reduced in the 0.05 mg/ml berberine group, and the difference was statistically significant ( P<0.01). The difference between the 0.05 mg/ml berberine + light group and the control group was not statistically significant ( P>0.05). When PDT was combined with berberine, there was a synergistic inhibitory effect on P.g. PDT followed by berberine shows a better inhibitory effect on bacteria, and the differences were statistically significant (all P<0.01). After the berberine treatment, the bacterial surface became smooth, and the length of the bacterial body increased compared with the control group. Conclusions:Methylene blue mediated PDT has an inhibitory effect on P.g. When combined with berberine, it has a synergistic inhibitory effect on P.g., and the inhibition effect is better when PDT is applied first and then berberine is applied in combination.

Blood and synovial tissue metabolomics of rheumatoid arthritis rats treated with less polar ginsenosides / 中华风湿病学杂志

Objective:The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied, and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods:Rats were randomly divided into the control group, the model group, methotrexate treatment group, and high dose, medium dose, and low dose less polar ginsenosides groups. After 30 days of oral administration, less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis. Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography (UPLC) tandem mass spectrometry (MS) to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results:Compared with the model group, erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides ( P<0.01). Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively. The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively. Major differential metabolites were identified in the model group of rats, including arachidonic acid, valine, linoleic acid, and guanine nucleoside, etc. The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides, including linoleic acid, betaine, eicosapentaenoic acid, alanine, methionine sulfoxide, isoleucine, etc. Conclusion:The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism, valine, leucine and isoleucine degradation, arachidonic acid metabolism. Less polar ginsenosides regulatethe linolenic acid metabolism, methionine metabolism and glucose alanine cycle.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Effect of pectin oligosaccharides supplementation on infant formulas: The storage stability, formation and intestinal absorption of advanced glycation end products.

Pectin oligosaccharides with a molecular weight greater than 700 Da was obtained from the pomace of kiwi (Actinidia arguta). Based on characteristics analysis and inhibitory activity of advanced glycation end products (AGEs) formation in vitro, the target pectin oligosaccharides was added to infant formulas and then subjected to accelerated storage. Results showed that pectin oligosaccharides supplementation inhibited the browning of infant formulas and glassy transition of lactose, and slowed down the increase of water activity under accelerated storage conditions. Pectin oligosaccharides also inhibited the formation of AGEs in infant formulas, such as 5-(hydroxymethyl)furfural, Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine, methylglyoxal hydromidazolones, glyoxal hydromidazolones, glyoxal-lysine dimer, methylglyoxal-lysine dimer and pyrraline. Besides, permeability studies using Caco-2 cell monolayer also showed that pectin oligosaccharides supplementation inhibited the intestinal absorption of AGEs, especially 5-(hydroxymethyl)furfural, Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine and glyoxal hydromidazolones. These results provide a reliable theoretical basis for the application of pectin oligosaccharides in infant formulas.

Effect of submerged plant coverage on phytoplankton community dynamics and photosynthetic activity in situ.

Restoration of submerged plants in eutrophic lakes can reduce nutrients and phytoplankton biomass in the water body. However, the effect of submerged plants on phytoplankton communities and their photosynthetic activity in situ are still poorly understood. Here, we studied the response of phytoplankton community structure and fluorescence parameters to different submerged plants coverage, the relationship of phytoplankton community and fluorescence parameters with submerged plants coverage and water physicochemical parameters were analysed in sampling area of Hangzhou West Lakes. The results showed that the coverage and biomass of submerged plants were negatively correlated with nitrogen and phosphorus contents in water body but positively correlated with total phenol content. The ratio of nitrogen to phosphorus in the study site changed greatly (32.25-124.54). In spring and summer, Oscillatoria and Leptolyngbya (Cyanophyta) were the dominant species, while in autumn and winter, the dominant species were Cyclotella (Chlorophyta), and Melosira and Cymbella (Bacillariophyta). Compared with Chlorophyta and Bacillariophyta, fluorescence parameters of Cyanophyta were more sensitive to total phosphorus, N:P ratio, total phenols, pH, and electric conductivity. Fluorescence parameters of Chlorophyta and Bacillariophyta were only affected by underwater light. Total phosphorus (TP) and N:P had a negative effect on the maximum photochemical electron yield of Cyanophyta. Furthermore, Cyanophyta was inhibited by total phenols from submerged plants. When phytoplankton were under stress, photochemical electron yield decreased significantly, whereas non-photochemical quenching increased. The structural equation model showed that the coverage of submerged plants might indirectly affect the fluorescence parameters of Cyanophyta by affecting nitrogen, phosphorus, and total phenol contents in the water body. These findings contribute to the understanding of the mechanisms underlying the impact of submerged plant restoration on phytoplankton community dynamics in subtropical eutrophic shallow lakes and provide a theoretical basis for the management of lakes.

[Spatial Distribution Characteristics of Phosphorus Fractions and Release Risk in Sediments of Honghu International Importance Wetland].

According to a spatial distribution analysis of phosphorus in sediments from Honghu Wetland, it was found that TP content in sediments at the mouth of Honghu Lake was 781.31-1955.84 mg·kg-1 and the average value was(1287.21±437.28)mg·kg-1. TP content in sediments in the open water area was 438.33-1554.04 mg·kg-1, with an average value of(718.10±238.15)mg·kg-1. The TP content of sediments in lake inlet was significantly higher than that of sediments in the open water area(P<0.05), and that in the enclosed aquaculture was higher than in the open water area, although no significant difference was observed (P>0.05). The TP content of sediments to the northwest and northeast of Honghu Lake was higher than that to the southwest of Honghu Lake, and the TP content of sediments in The Four-lake main canal was significantly higher than that of Luoshan main canal(P<0.05). The phosphorus input in the Four-lake main canal may be the main source of phosphorus in Honghu Lake sediments. The phosphorus fraction composition in sediments from different sampling sites were significantly different. Fe/Al-P and Ca-P were the main forms of phosphorus in sediments from the lake inlet, while OP and Ca-P were the main forms of phosphorus in sediments from the open water area. The variation in spatial phosphorus form composition was related to the influence of human activity and the distribution of aquatic plants. Fe/Al-P and OP contents were used to estimate the content of biological available phosphorus (BAP) in evaluated sediments, and the proportion of BAP in TP was used to estimate the risk of phosphorus release in Honghu sediments. BAP/TP was 39.8%-69%, with an average of(56.5±7.23)%, indicating a high risk of phosphorus release. OP and BAP were significantly correlated with TP in overlying water(P<0.01), and the correlation between BAP and phosphate in the overlying water was the highest. The results showed that phosphorus concentration in the overlying water may be related to the release of Fe/Al-P and OP into water bodies.

The changing characteristics of phytoplankton community and biomass in subtropical shallow lakes: Coupling effects of land use patterns and lake morphology.

The community composition and biomass of phytoplankton in shallow lakes are impacted by many environmental factors including water quality physicochemical parameters, land use in the watershed, and lake morphology. However, few studies have simultaneously evaluated the relative importance of these factors on the effect of community composition and biomass of phytoplankton. The relative importance of the water quality physicochemical parameters (water temperature [WT], total nitrogen [TN], total phosphorus [TP], pH, dissolved oxygen [DO], electrical conductivity [EC], turbidity and Secchi depth [SD]), land use (built-up land, farmland, waters, forest, grassland, and unused land) in the watershed, and lake morphology (area and depth) on the composition and biomass of phytoplankton communities were assessed in 29 subtropical shallow lakes in Wuhan, China, during different seasons from December 2017 to November 2018. The results showed that phytoplankton in all 29 lakes was mainly composed of Cyanophyta, Chlorophyta, and Bacillariophyta. Phytoplankton abundance was highest in summer and lowest in winter. We analyzed the relative importance of the three groups of variables to the community composition of the phytoplankton by variance decomposition. The results showed that the three groups of environmental variables had the highest explanation rate (> 80%) for the composition of the phytoplankton community in summer and autumn, and the explanation rates in spring and winter were 42.1% and 39.8%, respectively. The water quality physicochemical parameters were the most important variables affecting the composition of phytoplankton communities, followed by land use in the watershed. Through generalized additive model and structural equation model analysis, we found that the land use and lake morphology had minimal direct impact on the Chl-a and cell density of phytoplankton, mainly by altering the TN, TP, turbidity, SD, DO, and EC, which indirectly affected phytoplankton. WT and nutrients were still the main predictors of phytoplankton abundance. Built-up land was the main source of nitrogen and phosphorus in lakes. Correlation analysis found that forest and grassland had positive impacts on reducing lake nitrogen and phosphorus contents. This showed that increasing grassland and forest in the watershed could reduce the pollutants entering the lake. Our findings will contribute to water quality management and pollution control for subtropical shallow lakes.

3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration.

Hydrophilic bone morphogenetic protein 2 (BMP2) is easily degraded and difficult to load onto hydrophobic carrier materials, which limits the application of polyester materials in bone tissue engineering. Based on soybean-lecithin as an adjuvant biosurfactant, we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone) and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction, avoiding the use of exogenous cells. The optimized bioactive osteo-polyester scaffold (BOPSC), i.e. SBMP-10SC, had a high BMP2 entrapment efficiency of 95.35%. Due to its higher porosity of 83.42%, higher water uptake ratio of 850%, and sustained BMP2 release with polymer degradation, BOPSCs were demonstrated to support excellent in vitro capture, proliferation, migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells (mADSCs), and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds (10SCs). Furthermore, in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells, which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months. The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.

Hydrogen peroxide modification affects the structure and physicochemical properties of dietary fibers from white turnip (Brassica Rapa L.).

Turnip (Brassica rapa L.) is widely consumed as a vegetable and traditional Chinese medicine with high dietary fiber content. Soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were obtained from white turnips, and the IDF was modified with alkaline hydrogen peroxide to obtain modified IDF (MIDF) and modified SDF (MSDF). The compositional, structural, and functional properties of the four samples were investigated. After modification, the modified dietary fibers (MDFs) showed smaller particle sizes and lower contents of pectin and polyphenol than those of unmodified dietary fibers (DFs) The results of scanning electron microscopy (SEM), Fourier transformed infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) showed that compared to the DFs, the MDFs were smaller and had more exposed hydroxyl groups. Analysis of the microrheological behaviors showed that the MDFs had higher viscosity than that of the DFs, with a looser structure for the MSDF and a stable structure for the MIDF. Therefore, due to structural changes, the physical and functional properties of the MDFs were improved compared to those of the unmodified DFs. Pearson correlation analysis showed that the particle size was positively correlated with the pectin content. The water holding capacity (WHC), oil adsorption capacity (OAC) and water swelling capacity (WSC) showed positive correlations with each other. This work indicated that white turnip could be a potential new source of DFs, which presented desirable functional properties after modification.

Antioxidant, hepatoprotective and antifungal activities of black pepper (Piper nigrum L.) essential oil.

The essential oil extracted from the black Piper nigrum L. (BPEO) was analyzed for antioxidant, hepatoprotective and antifungal activities. BPEO is rich in total phenolics, total flavonoids and proanthocyanidins, and showed good free radicals and lipid peroxidation scavenging capacities. In a CCl4-induced liver injury mice model, the BPEO treated groups showed increases in the catalase (CAT), glutathione (GSH) and total superoxide dismutase (T-SOD) activities present in the liver and kidney, and reverses the CCl4-elevated total bilirubin (TBIL), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and malondialdehyde (MDA) level, which were confirmed in further analyses of kidney tissue sections. BPEO can effectively inhibit the growth of Aspergillus flavus spoilage fungus in maize. Further analyses indicated that BPEO disrupt the permeability barrier of the cell membrane and lead to mitochondrial dysfunction in A. flavus. Therefore, the current study proved BPEO's potential as hepatoprotective products and natural food preservatives.

Potential ecological implication of Cladophora oligoclora decomposition: Characteristics of nutrient migration, transformation, and response of bacterial community structure.

During decay, the sediment microenvironment and water quality are severely affected by excessive proliferation of harmful algae such as filamentous green algae (FGA). The frequency of this FGA is increased through global warming and water eutrophication. In the present study, the degradation processes of a common advantage FGA Cladophora oligoclora and its effect on nitrogen and phosphorus nutrient structure and bacterial community composition at the sediment-water interface were investigated by stable isotope labelling and high-throughput sequencing. The results showed that the decomposition process of C. oligoclona was fast, stable, and difficult to degrade. The changes in sediment δ15N values reached 66.68 ‰ on day 40, which indicated that some of the nitrogen had migrated to the sediment from C. oligoclona litter. TN and NH4+-N in the overlying water rapidly increased between days 0-10, NH4+-N rose to 78.21% of TN on day 40, resulting in severe pollution of ammonia in the overlying water. The nitrogen forms and contents in the sediment are mainly derived from the increasing ammonia nitrogen release. The TP and IP in the overlying water increased to the highest concentrations of 6.68±0.64, 6.59±0.79 mg·L-1 during the decomposition process, respectively, resulting in the migration of phosphate to the sediments with increasing phosphorus content. The abundance of the main dominant bacterial communities, such as Acinetobacter (0.08%-62.48%) and Pseudomonas (0.13%-20.36%) in sediments and overlying water has changed significantly. The correlation analysis results suggested that the phosphorus was mainly related to the bacterial community in the overlying water, while the various forms of nitrogen demonstrated a high relevance with the bacterial community in the sediment. Our research results will be valuable in evaluating the potential ecological risk of FGA decomposition and provide scientific support for shallow lake management and submerged vegetation restoration.

Response of Vallisneria natans to aluminum phytotoxicity and their synergistic effect on nitrogen, phosphorus change in sediments.

Increasing aluminum (Al) use and its effects on aquatic systems have been a global issue, however the Al impacts on submerged plants and their ecological functions were poorly understood. Aquatic simulation experiments were performed to study Al-toxicity on the germination and seedling morphological and physiological characteristics of Vallisneria natans, and investigate their synergistic effect on nitrogen (N), phosphorus (P) change and microbial community in sediment. The seeds germination characteristics, growth and physiological parameters of seedlings, including root activity, were significantly affected by alum treatments and the inhibition levels increased with Al3+ concentration. The Al accumulation in roots and leaves were significantly different. Al3+ concentration above 0.3 mg/L showed toxic to V. natans. TN, TP, IP, Fe/Al-P contents in sediments varied markedly under co-existence of Al and V. natans. Additionally, the relative abundance of sediment microbial community related to N, P cycle was effected. Results concluded that the increasing aquatic Al-concentration inhibits growth and propagation of submerged plants and the ecological restoration effect, and exerts synergistic effect with submerged plants on N, P components in sediments. Such findings were helpful for Al ecological evaluation, and were instructive for the submerged plants restoration in shallow eutrophic lakes with Al input.

Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis.

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

Aluminum distribution heterogeneity and relationship with nitrogen, phosphorus and humic acid content in the eutrophic lake sediment.

Increasing amount of aluminum (Al) gets into aquatic ecosystem through anthropogenic activity, but the knowledge about Al migration and relationships with sediments possessing different physico-chemical properties in eutrophic lakes is limited. Here, the Al migration rule and relationships with sediment nutritions in the Hangzhou West Lake, China was investigated, where a certain amount of residual Al-salts can enter because of the pre-treatment of the Qiantang River diversion project every day. Results revealed the obvious spatial distribution heterogeneity of Al in sediment vertical direction and horizontal direction following water flow. The Al content in sediment ranged 0.463-1.154 g kg-1 in Maojiabu Lake, and ranged 9.862-40.442 g kg-1 in Xiaonanhu Lake. Higher Al content distributed in upper layer sediment in lake with more disturbance. Total nitrogen (TN) contents were higher 0.917-3.387 mg g-1 and 0.627-0.786 mg g-1 in upper layer sediment than that in lower layer in Maojiabu Lake and Xiaonanhu Lake, respectively. Total phosphorus (TP) content ranged 0.779-2.580 mg g-1, in which IP and Fe/Al-P contributed 24.9-80.8% and 17.0-51.6%, respectively. Correlations between Al content with nutrition, humic acid (HA) etc. of sediment regionally varied in Maojiabu and Xiaonanhu Lake. Spatial distribution of Al-salt in eutrophic lakes closely related with the physico-chemical characteristics of nutrients, humus, human disturbance and water division parameters. Results provides new insight into Al-salts migration and references for Al-risk evaluating in eutrophic lakes.

Three-dimensional printing beta-tricalcium phosphate scaffold loaded with icariin particles for repairing osteonecrosis of the femoral head in rabbits / 中国组织工程研究

BACKGROUND: Preliminary study has prepared three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin. OBJECTIVE: To investigate the role of three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin in the repair of rabbit models of osteonecrosis of the femoral head. METHODS: New Zealand white rabbits (provided by Qinglongshan Laboratory Animal Center of Nanjing) were selected to establish the steroid-induced osteonecrosis of the femoral head. The 27 model rabbits underwent core decompression and debridement, were randomly divided into three groups, and then implanted with autologous bone, β-tricalcium phosphate scaffold, three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin (composite scaffold group) , respectively. The micro-CT scanning and pathological observation were performed at 4, 8, and 12 weeks after implantation. RESULTS AND CONCLUSION: (1) Micro-CT showed that at 4 weeks after implantation, trabecular bone was observed around and in implants in each group. In the autologous bone group, there were a large number of trabecular bones in the grafting area at 8 weeks, and the trabecular bone structure was dense at 12 weeks after implantation. In the tricalcium phosphate and composite scaffold groups, the scaffolds were well integrated with the bone interface. At 4 weeks after implantation, there was a certain amount of trabecular bone surrounding the scaffold, and trabecular grew into the scaffold until 8 weeks in the composite scaffold group. At 4 weeks after implantation, few thin trabecular bone was visible, and extensive trabecular bone formation was observed around the scaffold at 8 weeks in the tricalcium phosphate group. (2) Hematoxylin-eosin staining results showed that there were many mature osteoblasts, and few cartilage matrix, newly born bones integrated well to the implants at 12 weeks in the autologous bone and tricalcium phosphate groups. In the composite scaffold group, there were many cartilage matrixes, and newly born bones integrated poorly to the implants. (3) Masson staining showed that at 12 weeks after implantation, the osteogenic capacity in the composite scaffold group was lower than that in the autologous bone group (P < 0.05) , but higher than that in the tricalcium phosphate group (P < 0.05) . (4) TRAP staining results at 12 weeks after implantation revealed that the amount of osteoclast in composite scaffold group was less than that in the tricalcium phosphate group (P < 0.05) , and was not significantly different from the autologous bone group (P> 0.05) . (5) Immunohistochemical staining at 12 weeks after implantation revealed that the positive rate of vascular endothelial growth factor in the composite scaffold group was higher than that in the tricalcium phosphate group (P < 0.05) , and lower than that in the autologous bone group (P < 0.05) . (6) In summary, three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin implanted into the rabbit model of osteonecrosis of the femoral head can promote the proliferation and differentiation of osteoblasts, inhibit the viability of osteoclasts, promote the angiogenesis, and contribute to the repair of osteonecrosis of the femoral head in rabbits.