Cyanobacterial Bloom Formation by Enhanced Ecological Adaptability and Competitive Advantage of Microcystis-Non-Negligible Role of Quorum Sensing.

Microcystis-dominated cyanobacterial blooms (MCBs) frequently occur in freshwaters worldwide due to massive Microcystis colony formation and severely threaten human and ecosystem health. Quorum sensing (QS) is a direct cause of Microcystis colony formation that drives MCBs outbreak by regulating Microcystis population characteristics and behaviors. Many novel findings regarding the fundamental knowledge of the Microcystis QS phenomenon and the signaling molecules have been documented. However, little effort has been devoted to comprehensively summarizing and discussing the research progress and exploration directions of QS signaling molecules-mediated QS system in Microcystis. This review summarizes the action process of N-acyl homoserine lactones (AHLs) as major signaling molecules in Microcystis and discusses the detailed roles of AHL-mediated QS system in cellular morphology, physiological adaptability, and cell aggregation for colony formation to strengthen ecological adaptability and competitive advantage of Microcystis. The research progress on QS mechanisms in Microcystis are also summarized. Compared to other QS systems, the LuxI/LuxR-type QS system is more likely to be found in Microcystis. Also, we introduce quorum quenching (QQ), a QS-blocking process in Microcystis, to emphasize its potential as QS inhibitors in MCBs control. Finally, in response to the research deficiencies and gaps in Microcystis QS, we propose several future research directions in this field. This review deepens the understanding on Microcystis QS knowledge and provide theoretical guidance in developing strategies to monitor, control, and harness MCBs.

People who seem disgusting seem more immoral.

Despite unresolved questions about replicability, a substantial number of studies find that disgust influences and arises from evaluations of immoral behavior and people. Departing from prior emphases, the current research examines a novel, related question: Are people who are viewed as disgusting (i.e., people whose habits seem disgusting) perceived as more immoral than typical or unusual people? Four experiments examined this, also exploring the downstream impacts of moral character judgments. Adults who seemed disgusting were regarded as more immoral for purity and non-purity violations (Experiment 1) and less praiseworthy for prosocial acts (Experiment 2). In Experiment 3, an 8-year-old with typical (but seemingly disgusting) habits was rated as "naughtier" and likelier to misbehave than an atypical child who loved vegetables and disliked sweets. Experiment 4 revealed how, when no behavioral information is available, beliefs about target disgust influence beliefs about future behavior, helping explain why seemingly disgusting targets are viewed as more immoral, but not always more punishable for their bad behavior.

Modifying luteolin's algicidal effect on Microcystis by virgin and diversely-aged polystyrene microplastics: Unveiling novel mechanisms through microalgal adaptive strategies.

Luteolin has shown great potential in inhibiting Microcystis-dominated cyanobacterial blooms. However, widespread microplastics (MPs) in natural aquatic systems often serve as substrates for cyanobacterial growth, which could impact cyanobacterial resistance to external stresses and interfere with luteolin's algicidal effect. This study explored the influence of virgin and diversely-aged polystyrene microplastics (PS-MPs) on inhibitory effect of luteolin on Microcystis growth and its microcystins (MCs) production/release. Moreover, the underlying mechanisms were also revealed by jointly analyzing SEM image, antioxidant response, exopolymeric substances (EPSs) production, and functional gene expression. Results suggested that 0.5, 5, and 50 mg/L virgin and diversely-aged PS-MPs almost weakened growth inhibition and oxidative damage of two doses of luteolin against Microcystisby stimulating its EPSs production and inducing self-aggregation of Microcystis cells and/or hetero-aggregation between Microcystis cells and PS-MPs. Compared to virgin PS-MPs, photo-aged PS-MPs possessed rougher flaky surfaces, and hydrothermal-aged PS-MPs showed internal cracking. These characteristics led to greater stimulation of EPS production and exhibited more significant protective effects on Microcystis. Notably, PS-MPs also decreased MCs content in aqueous phase, likely because they adsorbed some MCs. Such toxigenic hetero-aggregates formed by MCs, MPs, and Microcystis cells would directly poison grazing organisms that consume them and create more pathways for MCs into food web, posing greater eco-risks. This is the first study to clarify the influence and mechanisms of virgin and diversely-aged MPs on allelopathic algicidal effects from the perspective of microalgal inherent adaptive strategies.

Meta-analysis for systematic review of global micro/nano-plastics contamination versus various freshwater microalgae: Toxicological effect patterns, taxon-specific response, and potential eco-risks.

Micro/nano-plastics (MNPs), as emerging persistent pollutants, are threatening freshwater ecosystems worldwide. Microalgae are important primary producers at the base of trophic level and susceptible to MNPs contamination, possibly resulting in further contamination in higher trophic levels and water quality. This study conducted a systematic review of 1071 observations from 63 publications, utilizing meta-analysis and subgroup analysis to investigate the toxicological effect patterns of MNPs parameters (size, concentration, and type) on microalgae. We also explored the potential eco-risks of certain specific MNPs parameters and subtle variations in the response of various microalgae taxa to MNPs. Results suggested that microplastics significantly inhibited microalgal photosynthesis, while nano-plastics induced more severe cell membrane damage and promoted toxin-release. Within a certain range of concentrations (0∼50 mg/L), rising MNPs concentration progressively inhibited microalgal growth and chlorophyll-a content, and progressively enhanced toxin-release. Among MNPs types, polyamide caused higher growth inhibition and more severe lipid peroxidation, and polystyrene induced more toxin-release, whereas polyethylene terephthalate and polymethyl methacrylate posed minimal effects on microalgae. Moreover, Bacillariophyta growth was inhibited most significantly, while Chlorophyta displayed strong tolerance and Cyanophyta possessed strong adaptive and exceptional resilience. Particularly, Komvophoron, Microcystis, Nostoc, Scenedesmus, and Gomphonema were more tolerant and might dominate freshwater microalgal communities under MNPs contamination. These results are crucial for acquiring the fate of freshwater microalgae under various MNPs contamination, identifying dominant microalgae, and reasonably assessing and managing involved eco-risks.

Effect of initial moisture content, resulting from different ratios of vegetable waste to maize straw, on compost was mediated by composting temperatures and microbial communities at low temperatures.

Owing to the huge amounts and perishable character of vegetable wastes, composting is one of the best options for recycling vegetable wastes post-harvest. The initial moisture content (MC) is critical for optimizing composting process, but the effect of high MC in undehydrated vegetable wastes on composting was rarely reported. For this, the plant-scale windrows were prepared by mixing cauliflower waste and maize straw at different ratios to control initial MC of 70 % (T1-70) and 80 % (T2-80), respectively, and composted in winter. As composting progressed, substantial organic matter degradation, progressive humification, decreases in electrical conductivity and increases of pH and germination index (GI) were observed in both treatments. Nonetheless, T1-70 accelerated heating rate early during composting, prolonged high temperature period (>50 °C) by 30 d, thus increased the harmless level of composting, and significantly improved the humification of end-products compared to T2-80. Results also revealed that T1-70 activated more indigenous microbes and enhanced microbial interactions early during composting, with the fungi enriched in T1-70 playing an important role in accelerating the composting process. Remarkably, the difference in composting temperatures, humification degree, and microbial communities between the two treatments was most significant during the maturation phase. In this phase, MWH_CFBk5, Planktosalinus, Pseudopedobacter, and Luteimonas enriched in T1-70 were positively correlated with humification indices. It is suggested that the effect of initial MC, resulting from different ratios of vegetable waste to maize straw, on their composting was mediated by the composting temperature and microbial communities at low temperatures.

Deep Learning-Assisted Automated Multidimensional Single Particle Tracking in Living Cells.

The translational and rotational dynamics of anisotropic optical nanoprobes revealed in single particle tracking (SPT) experiments offer molecular-level information about cellular activities. Here, we report an automated high-speed multidimensional SPT system integrated with a deep learning algorithm for tracking the 3D orientation of anisotropic gold nanoparticle probes in living cells with high localization precision (<10 nm) and temporal resolution (0.9 ms), overcoming the limitations of rotational tracking under low signal-to-noise ratio (S/N) conditions. This method can resolve the azimuth (0°-360°) and polar angles (0°-90°) with errors of less than 2° on the experimental and simulated data under S/N of ∼4. Even when the S/N approaches the limit of 1, this method still maintains better robustness and noise resistance than the conventional pattern matching methods. The usefulness of this multidimensional SPT system has been demonstrated with a study of the motions of cargos transported along the microtubules within living cells.

Reaction-Initiated Single-Molecule Tracking of Mass Transfer in Core-Shell Mesoporous Silica Particles.

Understanding the host-guest interactions in porous materials is of great importance in the field of separation science. Probing it at the single-molecule level uncovers the inter- and intraparticle inhomogeneity and establishes structure-property relationships for guiding the design of porous materials for better separation performance. In this work, we investigated the dynamics of host-guest interactions in core-shell mesoporous silica particles under in situ conditions by using a fluorogenic reaction-initiated single-molecule tracking (riSMT) approach. Taking advantage of the low fluorescence background, three-dimensional (3D) tracking of the dynamics of the molecules inside the mesoporous silica pore was achieved with high spatial precision. Compared to the commonly used two-dimensional (2D) tracking method, the 3D tracking results show that the diffusion coefficients of the molecules are three times larger on average. Using riSMT, we quantitatively analyzed the mass transfer of probe molecules in the mesoporous silica pore, including the fraction of adsorption versus diffusion, diffusion coefficients, and residence time. Large interparticle inhomogeneity was revealed and is expected to contribute to the peak broadening for separation application at the ensemble level. We further investigated the impact of electrostatic interaction on the mass transfer of molecules in the mesoporous silica pore and discovered that the primary effect is on the fraction rather than their diffusion rates of resorufin molecules undergoing diffusion.

Rapid and robust bacterial species identification using hyperspectral microscopy and gram staining techniques.

Gram staining can classify bacterial species into two large groups based on cell wall differences. Our study revealed that within the same gram group (gram-positive or gram-negative), subtle cell wall variations can alter staining outcomes, with the peptidoglycan layer and lipid content significantly influencing this effect. Thus, bacteria within the same group can also be differentiated by their spectra. Using hyperspectral microscopy, we identified six species of intestinal bacteria with 98.1% accuracy. Our study also demonstrated that selecting the right spectral band and background calibration can enhance the model's robustness and facilitate precise identification of varying sample batches. This method is suitable for analyzing bacterial community pathologies.

Chemical approaches for the stereocontrolled synthesis of 1,2-cis-ß-D-rhamnosides.

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-ß-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain ß-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of ß-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in ß-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.

Inoculating exogenous bacterium Brevibacillus laterosporus ZR-11 at maturity stage accelerates composting maturation by regulating physicochemical parameters and indigenous bacterial community succession.

Brevibacillus laterosporus ZR-11, a bio-control strain, was innovatively inoculated at maturity stage of composting to clarify its effect on physicochemical parameters and indigenous bacterial community structure in compost pile. Results revealed that ZR-11 inoculum rapidly increased pile temperature to 52 ºC and raised germination index (GI) value to beyond 85% on day 3, thereby achieving higher pile temperature and GI in the inoculated group than the non-inoculated group almost along maturity stage, and also decreased C/N ratio of the inoculated group to below 20 by composting end (day 8). Also, ZR-11 succeeded in colonizing compost pile along maturity stage. These suggested that ZR-11 as inoculum at maturity stage could accelerate compost maturation and have a potential to participate in bio-fertilizer production. High-throughput sequencing indicated that bacterial community structure experienced substantial succession in the inoculated and non-inoculated groups, and Firmicutes, Proteobacteria, and Actinobacteria were the dominant phyla in the two groups during maturity stage, with their abundances higher in the inoculated group. Saccharomonospora and Ammoniibacillus abundance increased on day 3 while Actinomadura abundance increased on day 6 in the inoculated group. As verified statistically, pile temperature and pH were key factors closely linked to dominant genera abundance, where Saccharomonospora and Ammoniibacillus abundance were positively correlated to pile temperature, while Actinomadura abundance was positively correlated to pile pH. Thus, it was inferred that ZR-11 inoculum could improve parameters such as temperature and pH to modify dominant genera abundance, thus regulating indigenous bacterial community succession, which might in turn promote compost maturation.

Novel ecological implications of non-toxic Microcystis towards toxic ecotype in population-promoting toxic ecotype dominance at various N levels and cooperative defense against luteolin-stress.

Microcystin (MC)-producing (MC+) and MC-free (MC-) Microcystis always co-exist and interact during Microcystis-dominated cyanobacterial blooms (MCBs), where MC+Microcystis abundance and extracellular MC-content (EMC) determine the hazard extent of MCBs. The current study elucidated intraspecific interaction between MC+ and MC-Microcystis at various nitrogen (N) levels (0.5-50 mg/L) and how such N-mediated interaction impacted algicidal and EMC-inhibiting effect of luteolin, a natural bioalgicide. Conclusively, MC+ and MC-Microcystis were inhibited mutually at N-limitation (0.5 mg/L), which enhanced the algicidal and EMC-inhibiting effects of luteolin. However, at N-sufficiency (5-50 mg/L), MC-Microcystis promoted MC+ ecotype growth and dominance, and such intraspecific interaction induced the cooperative defense of two ecotypes, weakening luteolin's algicidal and EMC-inhibiting effects. Mechanism analyses further revealed that MC+Microcystis in luteolin-stress co-culture secreted exopolymeric substances (EPSs) for self-protection against luteolin-stress and also released more EMC to induce EPS-production by MC-Microcystis as protectants, thus enhancing their luteolin-resistance and promoting their growth. This study provided novel ecological implications of MC-Microcystis toward MC+ ecotype in terms of assisting the dominant establishment of MC+Microcystis and cooperative defense with MC+ ecotype against luteolin, which guided the application of bioalgicide (i.e. luteolin) for MCBs and MCs pollution mitigation in different eutrophication-degree waters.

Long-term tracking robust removal of Microcystis-dominated bloom and microcystin-pollution risk by luteolin continuous-release microsphere at different nitrogen levels-Mechanisms from proteomics and gene expression.

Luteolin continuous-release microsphere (CRM) has promising algicidal effect against Microcystis, but how nitrogen (N) level impacted CRM effects on Microcystis growth and microcystins (MCs) pollution was never tracked along long term. This study revealed that luteolin CRM exerted long-term and robust inhibitory effects on Microcystis growth and MC-pollution by sharply decreasing extracellular and total MCs content at each N level, with growth inhibition ratio of 88.18%-96.03%, 92.91%-97.17% and 91.36%-95.55% at 0.5, 5 and 50 mg/L N, respectively, during day 8-30. Further analyses revealed that CRM-stress inhibited transferase, GTPase and ATPase activities, ATP binding, metal ion binding, fatty acid biosynthesis, transmembrane transport and disrupted redox homeostasis to pose equally robust algicidal effect at each N level. At lower N level, CRM-stress tended to induce cellular metabolic mode towards stronger energy supply/acquisition but weaker energy production/consumption, while triggered a shift towards stronger energy production/storage but weaker energy acquisition/consumption as N level elevated, thus disturbing metabolic balance and strongly inhibiting Microcystis growth at each N level. Long-term robust algicidal effect of CRM against other common cyanobacteria besides Microcystis was evident in natural water. This study shed novel insights into inhibitory effects and mechanisms of luteolin CRM on Microcystis growth and MC-pollution in different N-level waters.

Expression of PGRMC1 in patients with polycystic ovary syndrome and its molecular mechanism for regulating ovarian granulosa cell apoptosis and glucolipid metabolism. / PGRMC1åœ¨å¤šå›Šåµå·¢ç»¼åˆå¾æ‚£è€ ä¸­çš„è¡¨è¾¾åŠå ¶è°ƒæŽ§åµå·¢é¢—ç²’ç»†èƒžå‡‹äº¡å’Œç³–è„‚ä»£è°¢çš„åˆ†å­æœºåˆ¶.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism. METHODS: A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR. RESULTS: The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05). CONCLUSIONS: Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.

Phosphorus level impacts luteolin effect on Microcystis aeruginosa growth and microcystin-pollution risk - Novel perspective from correlation between exopolymers substances fractions and microcystin-production/release.

Luteolin as a phytogenic algicide can inhibit the growth and microcystins (MCs) release of Microcystis, a dominant genus during cyanobacterial blooms, but how phosphorus (P) level impacts luteolin effect on its growth and MC-pollution risk is unclear. By employing Microcystis aeruginosa as test alga, this study addressed this concern and explored response mechanisms from novel insights of relationship between extracellular polysaccharide (ex-poly) and protein (ex-pro) contents and MC-production/release. At each P level (0.05-5 mg/L), rising luteolin dose more greatly inhibited Microcystis growth and MC-pollution risk, with growth inhibition ratio of around 10%-30%, 20%-50% and 40%-90% for 3, 6 and 12 mg/L luteolin, respectively, but almost increasingly enhanced cellular ability of MC-production/conservation and total and bound ex-poly/ex-pro production. Rising P level promoted Microcystis growth and intracellular/extracellular MCs content (IMC, EMC) in test system at each luteolin dose, thus higher P level weakened algicidal and MC-removal effects of luteolin, indicating that P-decrease was required for stronger application outcome of luteolin. Total and bound ex-poly/ex-pro amount were positively correlated with cellular MC-production/conservation ability, IMC and EMC, which constituted cooperative stress-defense of Microcystis at each P level. Besides, rising luteolin dose posed stronger algicidal effect by inactivating gene expression involving peroxidase synthesis (especially at P-limitation), photosynthesis and P acquisition, while rising P level alleviated algicidal and MC-pollution inhibition effects of luteolin by enhancing gene expression involving N acquisition and peroxidase synthesis. This study shed novel insights for P-dependent effect and mechanisms of luteolin on toxigenic Microcystis growth and MC-pollution control, which guided to mitigating toxigenic Microcystis-dominated cyanobacterial blooms in different P-level water areas.

Research progress on the therapeutic effects of polysaccharides on non-alcoholic fatty liver diseases.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is a leading cause of cirrhosis and hepatocellular carcinoma. Due to its complex pathophysiology, there is currently no approved therapy. Polysaccharide, a kind of natural product, possesses a wide range of pharmacological activities. Numerous preclinical studies have confirmed that polysaccharides could interfere with the occurrence and development of NAFLD at multiple interrelated levels, such as improvement of glucose and lipid metabolism, antioxidation, anti-inflammation, and regulation of gut-liver axis, thus showing great potential as novel anti-NAFLD drugs. In this paper, we reviewed the polysaccharides with anti-NAFLD effect in recent years, and also systematically analyzed their possible pharmacological mechanisms.

Extraction and characterization of cyclic lipopeptides with antifungal and antioxidant activities from Bacillus amyloliquefaciens.

AIMS: This study aimed to isolate active substances from metabolites of Bacillus amyloliquefaciens SJ100001 and examine their antifungal activity against Fusarium oxysporum (F. oxysporum) SJ300024 screened from the root-soil of cucumber wilt. METHODS AND RESULTS: An active substance, anti-SJ300024, was obtained from the fermentation broth of strain SJ100001 by reversed-phase silica gel and gel chromatography, and further got its chemical structure as cyclic lipopeptide Epichlicin through nuclear magnetic resonance (NMR) and mass spectrometry (MS). In vitro experiments showed that Epichlicin had a better inhibitory rate (67.46%) against the strain SJ300024 than the commercially available fungicide hymexazol (45.10%) at the same concentration. The MTT assays proved that Epichlicin was non-cytotoxic, besides it also had good free radical scavenging ability and total reducing ability. CONCLUSIONS: Epichlicin isolated from strain SJ100001 can effectively control F. oxysporum SJ300024 screened from the root-soil of cucumber wilt. SIGNIFICANCE AND IMPACT OF THE STUDY: Epichlicin may be used as an environmentally friendly and efficient biocontrol agent for controlling Fusarium wilt of cucumber and reducing crop losses. More importantly, the non-cytotoxicity of Epichlicin can avoid harm to consumers. Additionally, Epichlicin has broad application prospects in medicine due to its antioxidant properties.

Nitrogen-dependent luteolin effect on Microcystis growth and microcystin-pollution risk - Novel mechanism insights unveiled by comparative proteomics and gene expression.

Phytogenic allelochemical luteolin has potential to mitigate Microcystis-dominated cyanobacterial blooms (MCBs), but its algicidal effect against toxigenic Microcystis may be impacted by natural factors, especially nitrogen (N) level in waters. This study innovatively explored N-dependent effect of luteolin on Microcystis growth and its microcystins (MCs) production/release, and elucidated underlying mechanisms from proteomics and gene expression views. Generally, at each N level, rising luteolin dose progressively inhibited Microcystis growth by inhibiting proteins syntheses and genes expression involving light-capturing, photosynthetic electron transfer, Calvin cycle and phosphorus (P) acquisition, according to comparative proteomics and gene expression. At higher luteolin dose and lower N level, Microcystis cell tended to increase microcystins (MCs) production and conservation ability, with the highest increase degree observed at 12 mg/L luteolin and 0.5 mg/L N on day 10, reaching 1.96 and 2.68 folds of luteolin-free control, respectively, but decrease MC-release as extracellular MCs content (EMC), with inhibition ratio of 72.86%, 73.57%, 74.45% and 40.58%, 45.28%, 60.00% at rising N level under 12 mg/L luteolin stress on day 10 and 16, respectively. These enabled cellular defensive response of Microcystis to stronger stress and N limitation. Under luteolin stress, higher N level more strongly up-regulated numerous processes (e.g., oxidoreductase activity, ATP binding and transmembrane transport, oxidative phosphorylation, tricarboxylic acid cycle, fatty acid biosynthesis, glycolysis/gluconeogenesis, pyruvate, amino acids metabolism, metal ion-binding, P acquisition) as compensative protective responses to progressively down-regulated photosynthetic and ribosomal processes at higher N level, thus causing faster Microcystis growth than lower N level. This study provided novel insights for N-dependent effect and mechanisms of luteolin on MCBs mitigation and MCs risk control, and guided algicidal application of luteolin in different eutrophic-degree waters.

Synthesis and application of phosphorylated saccharides in researching carbohydrate-based drugs.

Phosphorylated saccharides are valuable targets in glycochemistry and glycobiology, which play an important role in various physiological and pathological processes. The current research on phosphorylated saccharides primarily focuses on small molecule inhibitors, glycoconjugate vaccines and novel anti-tumour targeted drug carrier materials. It can maximise the pharmacological effects and reduce the toxicity risk caused by nonspecific off-target reactions of drug molecules. However, the number and types of natural phosphorylated saccharides are limited, and the complexity and heterogeneity of their structures after extraction and separation seriously restrict their applications in pharmaceutical development. The increasing demands for the research on these molecules have extensively promoted the development of carbohydrate synthesis. Numerous innovative synthetic methodologies have been reported regarding the continuous expansion of the potential building blocks, catalysts, and phosphorylation reagents. This review summarizes the latest methods for enzymatic and chemical synthesis of phosphorylated saccharides, emphasizing their breakthroughs in yield, reactivity, regioselectivity, and application scope. Additionally, the anti-bacterial, anti-tumour, immunoregulatory and other biological activities of some phosphorylated saccharides and their applications were also reviewed. Their structure-activity relationship and mechanism of action were discussed and the key phosphorylation characteristics, sites and extents responsible for observed biological activities were emphasised. This paper will provide a reference for the application of phosphorylated saccharide in the research of carbohydrate-based drugs in the future.