VBP1 negatively regulates CHIP and selectively inhibits the activity of hypoxia-inducible factor (HIF)-1α but not HIF-2α.

Hypoxia-inducible factor-1 (HIF-1) is a critical transcription factor that regulates the expression of genes involved in cellular adaptation to low oxygen levels. Aberrant regulation of the HIF-1 signaling pathway is linked to various human diseases. Previous studies have established that HIF-1α is rapidly degraded in a von Hippel-Lindau protein (pVHL)-dependent manner under normoxic conditions. In this study, we find that pVHL binding protein 1 (VBP1) is a negative regulator of HIF-1α but not HIF-2α using zebrafish as an in vivo model and in vitro cell culture models. Deletion of vbp1 in zebrafish caused Hif-1α accumulation and upregulation of Hif target genes. Moreover, vbp1 was involved in the induction of hematopoietic stem cells (HSCs) under hypoxic conditions. However, VBP1 interacted with and promoted the degradation of HIF-1α in a pVHL-independent manner. Mechanistically, we identify the ubiquitin ligase CHIP and HSP70 as new VBP1 binding partners and demonstrate that VBP1 negatively regulated CHIP and facilitated CHIP-mediated degradation of HIF-1α. In patients with clear cell renal cell carcinoma (ccRCC), lower VBP1 expression was associated with worse survival outcomes. In conclusion, our results link VBP1 with CHIP stability and provide insights into underlying molecular mechanisms of HIF-1α-driven pathological processes.

HIVEP3 as a potential prognostic factor promotes the development of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common malignancy worldwide. Human immune deficiency virus type 1 enhancer-binding protein 3 (HIVEP3) was verified to play a vital role in types of cancers. However, the functional role of HIVEP3 in AML was rarely reported. In this study, CCK-8, colony formation assay, flow cytometry, and Trans-well chamber experiments were applied for detecting cell proliferation, apoptosis, and invasion in AML cells. The expression of proteins related to TGF-ß/Smad signaling pathway was determined by western blot. Our data showed that the expression level of HIVEP3 was closely related to the risk classification and prognosis of AML patients. Moreover, HIVEP3 was highly expressed in AML patients and cells. Knockdown of HIVEP3 significantly repressed cell proliferation invasion, and enhanced cell apoptosis in HL-60 and THP-1 cells. In addition, HIVEP3 donwreglation could inhibit the TGF-ß/Smad signaling pathway. TGF-ß overexpression could reverse the inhibition effects of HIVEP3 knockdown on AML development and the TGF-ß/Smad signaling pathway. These findings indicated that HIVEP3 contributed to the progression of AML via regulating the TGF-ß/Smad signaling pathway and had a prognostic value for AML.

A SIRT6 Inhibitor, Marine-Derived Pyrrole-Pyridinimidazole Derivative 8a, Suppresses Angiogenesis.

Angiogenesis refers to the process of growing new blood vessels from pre-existing capillaries or post-capillary veins. This process plays a critical role in promoting tumorigenesis and metastasis. As a result, developing antiangiogenic agents has become an attractive strategy for tumor treatment. Sirtuin6 (SIRT6), a member of nicotinamide adenine (NAD+)-dependent histone deacetylases, regulates various biological processes, including metabolism, oxidative stress, angiogenesis, and DNA damage and repair. Some SIRT6 inhibitors have been identified, but the effects of SIRT6 inhibitors on anti-angiogenesis have not been reported. We have identified a pyrrole-pyridinimidazole derivative 8a as a highly effective inhibitor of SIRT6 and clarified its anti-pancreatic-cancer roles. This study investigated the antiangiogenic roles of 8a. We found that 8a was able to inhibit the migration and tube formation of HUVECs and downregulate the expression of angiogenesis-related proteins, including VEGF, HIF-1α, p-VEGFR2, and N-cadherin, and suppress the activation of AKT and ERK pathways. Additionally, 8a significantly blocked angiogenesis in intersegmental vessels in zebrafish embryos. Notably, in a pancreatic cancer xenograft mouse model, 8a down-regulated the expression of CD31, a marker protein of angiogenesis. These findings suggest that 8a could be a promising antiangiogenic and cancer therapeutic agent.

Thermal Hydrolysis Pretreatment-Anaerobic Digestion Promotes Plant-Growth Biostimulants Production from Sewage Sludge by Upregulating Aromatic Amino Acids Transformation and Quinones Supply.

Micromolecular plant-growth biostimulants (micro-PBs) production from sewage sludge is attracting increasing interest, as it is expected to enhance the fertilizing effect of sludge for land application. This study attempted to promote effective micro-PBs production from sewage sludge through thermal hydrolysis pretreatment-anaerobic digestion (THP-AD) and explore the underpinning regulation mechanisms. Results showed that the highest effective micro-PB production in digested sludge was achieved in THP(160 °C)-AD by day 12, with 80.73 mg/kg volatile solid (VS) of phytohormones and 417.75 mg/kg VS of allelochemicals, and these effective micro-PBs all originated from aromatic amino acids (AAAs). The metabolomic and metagenomic results revealed that, as compared with THP(120 °C)-AD and AD without THP, THP(160°C)-AD uniquely upregulated AAAs biosynthesis and consequently improved AAAs metabolism toward effective micro-PBs production. Further exploration of related microbial pathways and metabolites suggested that the upregulated AAAs biosynthesis in THP(160 °C)-AD in the early stage was partially attributed to the enhanced carbohydrate release. More importantly, the results showed that the amount of quinones, which probably facilitate energy generation via acting as electron-transfer mediators, was significantly positively correlated with the abundance of AAAs biosynthesis genes (R2 = 0.93). Hence, the improved initial release and biosynthesis of quinones are critical in enhancing the AAAs biosynthesis in THP(160 °C)-AD. Moreover, the enhanced quinones supply and the consequent active AAAs transformation in THP(160 °C)-AD reinforced the humification process, highly supporting effective micro-PBs stabilization. The important roles of quinones in effective micro-PBs production and stabilization in sludge anaerobic digestion should be considered in technology development for micro-PBs recovery.

Lower Platelet-to-Lymphocyte Ratio Was Associated with Poor Prognosis for Newborn Patients in NICU.

Background: Platelet-to-lymphocyte ratio (PLR) is reported to be related to the outcome of intensive care unit (ICU) patients. However, little is known about their associations with prognosis in newborn patients in neonatal ICU (NICU). The aim of the present study was to investigate the prognostic significance of the PLR for newborn patients in the NICU. Methods: Data on newborn patients in the NICU were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. The initial PLR value of blood examinations within 24 h was analyzed. Spearman's correlation was used to analyze the association of PLR with the length of hospital and ICU stays. The chi-square test was used to analyze the association of PLR with mortality rate. Multivariable logistic regression was used to determine whether the PLR was an independent prognostic factor of mortality. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive ability of models combining PLR with other variables. Results: In total, 5240 patients were enrolled. PLR was negatively associated with length of hospital stay and ICU stay (hospital stay: ρ = −0.416, p < 0.0001; ICU stay: ρ = −0.442, p < 0.0001). PLR was significantly correlated with hospital mortality (p < 0.0001). Lower PLR was associated with higher hospital mortality (OR = 0.85, 95% CI = 0.75−0.95, p = 0.005) and 90-day mortality (OR = 0.85, 95% CI = 0.76−0.96, p = 0.010). The prognostic predictive ability of models combining PLR with other variables for hospital mortality was good (AUC for Model 1 = 0.804, 95% CI = 0.73−0.88, p < 0.0001; AUC for Model 2 = 0.964, 95% CI = 0.95−0.98, p < 0.0001). Conclusion: PLR is a novel independent risk factor for newborn patients in the NICU.

Heptapeptide Isolated from Isochrysis zhanjiangensis Exhibited Anti-Photoaging Potential via MAPK/AP-1/MMP Pathway and Anti-Apoptosis in UVB-Irradiated HaCaT Cells.

Marine microalgae can be used as sustainable protein sources in many fields with positive effects on human and animal health. DAPTMGY is a heptapeptide isolated from Isochrysis zhanjiangensis which is a microalga. In this study, we evaluated its anti-photoaging properties and mechanism of action in human immortalized keratinocytes cells (HaCaT). The results showed that DAPTMGY scavenged reactive oxygen species (ROS) and increase the level of endogenous antioxidants. In addition, through the exploration of its mechanism, it was determined that DAPIMGY exerted anti-photoaging effects. Specifically, the heptapeptide inhibits UVB-induced apoptosis through down-regulation of p53, caspase-8, caspase-3 and Bax and up-regulation of Bcl-2. Thus, DAPTMGY, isolated from I. zhanjiangensis, exhibits protective effects against UVB-induced damage.

Structure-Activity Relationships and Potent Cytotoxic Activities of Terphenyllin Derivatives from a Small Compound Library.

A small library of 120 compounds was established with seventy new alkylated derivatives of the natural product terphenyllin, together with 45 previous reported derivatives and four natural p-terphenyl analogs. The 70 new derivatives were semi-synthesized and evaluated for cytotoxic activities against four cancer cell lines. Interestingly, 2',4''-diethoxyterphenyllin, 2',4,4''-triisopropoxyterphenyllin, and 2',4''-bis(cyclopentyloxy)terphenyllin showed potent activities with IC50 values in a range from 0.13 to 5.51 µM, which were similar to those of the positive control, adriamycin. The preliminary structure-activity relationships indicated that the introduction of alkyl substituents including ethyl, allyl, propargyl, isopropyl, bromopropyl, isopentenyl, cyclopropylmethyl, and cyclopentylmethyl are important for improving the cytotoxicity.

Control of Stratification in Drying Particle Suspensions via Temperature Gradients.

A potential strategy for controlling stratification in a drying suspension of bidisperse particles is studied using molecular dynamics simulations. When the suspension is maintained at a constant temperature during fast drying, it can exhibit "small-on-top" stratification with an accumulation (depletion) of smaller (larger) particles in the top region of the drying film, consistent with the prediction of current theories based on diffusiophoresis. However, when only the region near the substrate is thermalized at a constant temperature, a negative temperature gradient develops in the suspension because of evaporative cooling at the liquid-vapor interface. Since the associated thermophoresis is stronger for larger nanoparticles, a higher fraction of larger nanoparticles migrate to the top of the drying film at fast evaporation rates. As a result, stratification is converted to "large-on-top". Very strong small-on-top stratification can be produced with a positive thermal gradient in the drying suspension. Here, we explore a way to produce a positive thermal gradient by thermalizing the vapor at a temperature higher than that of the solvent. Possible experimental approaches to realize various thermal gradients in a suspension undergoing solvent evaporation and thus to produce different stratification states in the drying film are suggested.

Stratification of drying particle suspensions: Comparison of implicit and explicit solvent simulations.

Large scale molecular dynamics simulations are used to study drying suspensions of a binary mixture of large and small particles in explicit and implicit solvents. The solvent is first modeled explicitly and then mapped to a uniform viscous medium by matching the diffusion coefficients and the pair correlation functions of the particles. "Small-on-top" stratification of the particles, with an enrichment of the smaller ones at the receding liquid-vapor interface during drying, is observed in both models under the same drying conditions. With the implicit solvent model, we are able to model much thicker films and study the effect of the initial film thickness on the final distribution of particles in the dry film. Our results show that the degree of stratification is controlled by the Péclet number defined using the initial film thickness as the characteristic length scale. When the Péclet numbers of large and small particles are much larger than 1, the degree of "small-on-top" stratification is first enhanced and then weakens as the Péclet numbers are increased.

Stratification in Drying Films Containing Bidisperse Mixtures of Nanoparticles.

Large scale molecular dynamics simulations for bidisperse nanoparticle suspensions with an explicit solvent are used to investigate the effects of evaporation rates and volume fractions on the nanoparticle distribution during drying. Our results show that "small-on-top" stratification can occur when Pe sϕ s ≳ c with c ∼ 1, where Pe s is the Péclet number and ϕ s is the volume fraction of the smaller particles. This threshold of Pe sϕ s for "small-on-top" is larger by a factor of ∼α2 than the prediction of the model treating solvent as an implicit viscous background, where α is the size ratio between the large and small particles. Our simulations further show that when the evaporation rate of the solvent is reduced, the "small-on-top" stratification can be enhanced, which is not predicted by existing theories. This unexpected behavior is explained with thermophoresis associated with a positive gradient of solvent density caused by evaporative cooling at the liquid/vapor interface. For ultrafast evaporation the gradient is large and drives the nanoparticles toward the liquid/vapor interface. This phoretic effect is stronger for larger nanoparticles, and consequently the "small-on-top" stratification becomes more distinct when the evaporation rate is slower (but not too slow such that a uniform distribution of nanoparticles in the drying film is produced), as thermophoresis that favors larger particles on the top is mitigated. A similar effect can lead to "large-on-top" stratification for Pe sϕ s above the threshold when Pe s is large but ϕ s is small. Our results reveal the importance of including the solvent explicitly when modeling evaporation-induced particle separation and organization and point to the important role of density gradients brought about by ultrafast evaporation.

Tracking of the conversion and transformation pathways of dissolved organic matter in sludge hydrothermal liquids during Cr(VI) reduction using FT-ICR MS.

In this study, the remediation effects of two types of sludge (ferric-based flocculant and non-ferric-based flocculant) on Cr(VI)-polluted wastewater were evaluated to clarify the key components in sludge hydrothermal solutions responsible for reducing Cr(VI) and understand the underlying molecular-level transformation mechanisms. The results revealed that the primary reactions during the hydrothermal processes were deamination and decarboxylation reactions. Correlation analysis highlighted proteins, reducing sugars, amino groups, and phenolic hydroxyl groups as the major contributors. In-depth analysis of the transformation process of functional groups within dissolved organic matter (DOM) and synergistic redox process between Cr(VI) and DOM in hydrothermal solutions demonstrated that phenolic hydroxyl and amino groups gradually underwent oxidation during reduction of Cr(VI) by DOM, forming aldehyde and carboxyl groups, among the others. Time-dependent density functional theory calculations revealed notable shift of reducing functional groups from ground state to excited state following iron complexation, ultimately facilitating reduction reaction. Subsequent investigations, including soil column leaching and seed germination rate tests, indicated that synergistic redox interaction between Cr(VI) and DOM significantly reduced waterborne heavy metal and toxic organic pollution. These findings carry substantial implications for sludge treatment and remediation of heavy metal pollution in wastewater, offering valuable insights into effective environmental remediation strategies.

Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.

OBJECTIVE: To characterize the phenotype spectrum, diagnosis, and response to growth-promoting therapy in patients with ACAN variants causing familial short stature. METHODS: Three families with ACAN variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed. RESULTS: Three novel heterozygous variants, c.757+1G>A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C>T, p.(Gln2227*) in the ACAN gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have ACAN variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25/105, 11/105, and 10/105, respectively). Some identical variants existing in different families could be hot variants, c.532A>T, p.(Asn178Tyr), c.1411C>T, p.(Gln471*), c.1608C>A, p.(Tyr536*), c.2026+1G>A, (splicing), and c.7276G>T, p.(Glu2426*). Short stature, early-onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (-2.18 ± 1.06 SD vs. -2.69 ± 0.95 SD, p < 0.001). The heights of children who received rhGH (and GnRHa) treatment were significantly improved compared with those of untreated adults (-2.20 ± 1.10 SD vs. -3.24 ± 1.14 SD, p < 0.001). CONCLUSION: Our study achieves a new understanding of the phenotypic spectrum, diagnosis, and management of individuals with ACAN variants. No clear genotype-phenotype relationship of patients with ACAN variants was found. Gene sequencing is necessary to diagnose ACAN variants that cause short stature. In general, appropriate rhGH and/or GnRHa therapy can improve the adult height of affected pediatric patients caused by ACAN variants.

MiR-196a-5p facilitates progression of estrogen-dependent endometrial cancer by regulating FOXO1.

BACKGROUND AND PURPOSE: Estrogen-dependent endometrial cancer mainly occurs in younger pre-menopausal and post-menopausal women and threatens their health. Recently, microRNAs (miRNAs) have been considered as novel targets in endometrial cancer treatment. Therefore, we aimed to explore the effect of miRNA (miR)-196a-5p in estrogen-dependent endometrial cancer. METHODS: 17ß-estradiol (E2; 2.5, 5, 10 and 20 nM) was used to treat RL95-2, HEC-1B and ECC-1 cells followed by cell viability assessment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The level of miR-196a-5p was measured by reverse transcription-quantitative PCR (RT-qPCR). We then transfected miR-196a-5p mimic/inhibitor and Forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) into E2-treated cells. Apoptotic cells were measured by flow cytometry. Wound healing and Transwell assays were implemented to assess migration and invasion. Bioinformatics and luciferase reporter assays were applied to confirm the interaction between miR-196a-5p and FOXO1. Immunoblotting determined the levels of FOXO1, Bcl-2, Bax, Caspase 3. RESULTS: E2 promoted cell viability and miR-196a-5p expression in RL95-2 and ECC-1 cells. miR-196a-5p mimic enhanced cell viability, migration and invasion but suppressed apoptosis and FOXO1, whilst miR-196a-5p inhibitor blocked these processes. In addition, miR-196a-5p upregulated Bcl-2, but down regulated Bax and Caspase 3 expression, an effect that was reversed by miR-196a-5p inhibitor. We determined that miR-196a-5p targeted FOXO1, and that si-FOXO1 blocked the effects of miR-196a-5p inhibitor on viability, apoptosis, migration and invasion of E2-treated RL95-2 and ECC-1 cells. CONCLUSIONS: Our findings suggested potential diagnostic and therapeutic applications for miR-196a-5p and its FOXO1 target in patients suffering from estrogen-dependent endometrial cancer.

Citric acid treatment directly on anaerobic digestor sludge alleviates the inhibitory effect of in-situ generated humic acids by their deconstruction and redistribution.

Humic acids were known to inhibit sewage sludge anaerobic digestion (AD) and many studies have been investigated to deal with the inhibitory effect of humic acids (HA) in raw sludge feeding the digestor. However, HA could also be in-situ produced during the sludge AD process with a significant amount, but the relieving of the inhibitory effect posed by the in-situ produced HA has been historically ignored. Thus, this study attempted to use citric acid (CA), an easily biodegradable polyatomic acid, to directly treat sludge in the anaerobic digestor instead of the feeding sludge, for alleviating inhibition caused by the in-situ produced HA. Results showed that methane production of AD batches with CA pretreatment at 0.06∼0.10 g/g TS on digestor sludge were effectively enhanced, with the highest production being 2.89 times of that observed in control AD without CA treatment and 2.08 times of that achieved by contrast AD with CA pretreatment on raw sludge. However, the AD batches with CA treatment at low dosages of 0.02∼0.04 g/g TS had lower methane production, during which sludge solubilization and hydrolysis were enhanced initially associated with released HA surfactant and hydrolytic enzymes; then later inhibited since higher structurally sound HA in SP easily rebind proteinaceous substrates and enzymes again. Whilst CA treatment at 0.06∼0.10 g/g TS could promote sludge solubilization and hydrolysis throughout the sludge AD process. This dosage-dependent effect of CA treatment can be caused by its discriminating impact on HA structure and distribution. At low dosages, complexes of HA-proteins (including hydrolases) can be decrosslinked and transferred to the soluble phase (SP), thus enhancing solubilization and hydrolysis initially. However, the released HA in SP could rebind more organics and hydrolases during AD, resulting in augmented inhibition. While the dosage increased, HA were drastically deconstructed with aromatic cores in SP migrating to extracellular polymeric substances, preventing binding effects on organics and hydrolases. Accordingly, a smart mutex-switch operational strategy of CA treatment was proposed. The results suggested, to alleviate the inhibitory effect of HA on sludge AD, more attention should be given to HA produced and accumulated in AD rather than raw sludge so that the CA treatment directly on sludge in the digestor can be a promising method.

Modeling Solution Drying by Moving a Liquid-Vapor Interface: Method and Applications.

A method of simulating the drying process of a soft matter solution with an implicit solvent model by moving the liquid-vapor interface is applied to various solution films and droplets. For a solution of a polymer and nanoparticles, we observe "polymer-on-top" stratification, similar to that found previously with an explicit solvent model. Furthermore, "polymer-on-top" is found even when the nanoparticle size is smaller than the radius of gyration of the polymer chains. For a suspension droplet of a bidisperse mixture of nanoparticles, we show that core-shell clusters of nanoparticles can be obtained via the "small-on-outside" stratification mechanism at fast evaporation rates. "Large-on-outside" stratification and uniform particle distribution are also observed when the evaporation rate is reduced. Polymeric particles with various morphologies, including Janus spheres, core-shell particles, and patchy particles, are produced from drying droplets of polymer solutions by combining fast evaporation with a controlled interaction between the polymers and the liquid-vapor interface. Our results validate the applicability of the moving interface method to a wide range of drying systems. The limitations of the method are pointed out and cautions are provided to potential practitioners on cases where the method might fail.

Untargeted Metabolomics Reveals the Effect of Selective Breeding on the Quality of Chicken Meat.

The selection for improved body weight is an effective approach in animal breeding. Guangxi Partridge chickens have differentiated into two lines under selective breeding, which include line S and line D that have shown statistically significant differences in body weight. However, the meat quality analysis in our study indicated that the quality of breast and thigh muscles in line S chickens changed, which included increased values of L*, b*, and drip loss and decreased a* value, pH, and shear force in skeletal muscles. To illuminate the effect of selection on skeletal muscles, LC-MS/MS metabolomics was performed to explore differentiated metabolites in divergent tissues from the two chicken lines. The results of principal component analysis and orthogonal projection to latent structures discriminant analysis suggested that metabolites of different groups were separated, which suggested that selective breeding certainly affected metabolism of skeletal muscles. KEGG analysis identified that valine, leucine, and isoleucine biosynthesis, glycerophospholipid metabolism, and glutathione metabolism noteworthily changed in breast muscle. Amino sugars and nucleotide sugar metabolism, ascorbate and aldarate metabolism, the pentose phosphate pathway, pentose and glucuronate interconversions, fructose and mannose metabolism, and glycerophospholipid metabolism were remarkedly identified in thigh muscle. These screened pathways suggested oxidative stress in breast and thigh muscles, which corresponded with our previous results. Therefore, this study determined that glycerophospholipid metabolism conservatively functioned in muscle flavor and development but exhibited different anti-oxidative patterns in different skeletal muscles. Overall, the present study identified several differentiated metabolites and pathways for exploring differences in meat quality between different broiler populations.

A novel green composite conductive material enhancing anaerobic digestion of waste activated sludge via improving electron transfer and metabolic activity.

Anaerobic digestion (AD) of waste activated sludge (WAS) is usually limited by the low generation efficiency of methane. The addition of composite conductive materials (CMs) is a promising strategy to enhance AD performance. In this study, a new green magnetic-straw-based biochar (MSBC) was synthesised by a simple ball-milling/carbonisation method, and its effects on AD performance of sludge were investigated. Experimental results showed that the as-synthesised MSBC had an intrinsic graphene-oxide-like structure, with Fe species serving as electroactive sites; these characteristics translate into a high electron transfer (ET) capability. After adding MSBC, the volatile fatty acid production and methane yield were significantly increased by 14.13% and 45.36%, respectively. Analysis of the changes in the ET system activities, hydrogenase activities, Cyt-C concentrations and the electron transfer capacity of the sludge sample with and without the MSBC revealed that the MSBC enhanced intracellular ET and changed the extracellular ET pathway from indirect interspecies hydrogen transfer to direct interspecies electron transfer (DIET), which would be responsible for increasing methane production and proportion in the biogas. However, further analyses of key enzyme activities and the microbial community indicated that the MSBC reinforces the methanogenesis pathway by creating a favourable environment (i.e., by enhancing hydrolysis-acidification and DIET-based CO2 reduction) for acetoclastic methanogens. These findings, however, are expected to provide an important reference for developing CMs application in AD.

Alkaline thermal hydrolysis of sewage sludge to produce high-quality liquid fertilizer rich in nitrogen-containing plant-growth-promoting nutrients and biostimulants.

To produce liquid fertilizer containing nitrogen-containing plant-growth-promoting nutrients (N-PGPN) and plant-growth-promoting biostimulants (N-PGPB) from sewage sludge is attracting increasing interest recently, due to its superb fertilizing effect and the ease of application. Thus, this study aims to investigate the feasibility of producing high-quality liquid fertilizer with N-PGPN and N-PGPB recovery through alkaline thermal hydrolysis (ATH) using Ca(OH)2. Results suggested that ATH treatment was superior in N solubilization (TSN/TN > 54%) and organic N maintenance in sludge liquor (> 80%) when compared to single thermal hydrolysis (TH). More surprisingly, ATH also promoted the production of N-PGPN and N-PGPB. As for N-PGPN, the maximum free amino acids (FAAs) accumulation in ATH liquor was 56.82 g/L at 120 °C while soluble protein (SPN) and soluble humic acid (SHA) reached 8.30-8.88 g/L and 1.88-2.05 g/L at 140-160 °C. The greatest N-PGPB produced by ATH treatment was achieved at 160 °C, with the detection of 1.156 mg/L phytohormones (indole-3-acetic acid and hydroxyphenyl acetic acids) and 4.95 mg/L allelochemicals (indolic derivatives and aromatic carboxylic acids). The 2D correlation FTIR maps analyses suggested, compared with TH, ATH could achieve protein hydrolysis before polysaccharides solubilization and denaturation with the temperature increased, thus avoiding Maillard reaction and benefiting N-PGPB production. Moreover, the laboratory investigation and field study indicated the usage of ATH liquor improved the growth of plants without inducing heavy metal contamination and soil salinization. Hence, ATH is a promising technology to produce high-quality liquid fertilizer rich with N-PGPN and N-PGPB from sewage sludge, especially suitable for such sludge with a low VS/TS ratio where biological treatment is inapplicable.

Mechanism analysis of octapeptide from microalgae, Isochrysis zhanjiangensis for suppressing vascular injury and angiogenesis in human umbilical vein endothelial cell.

Incorporating microalgae active peptides into functional foods is one of the hottest topics in algae research. Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) is a novel octapeptide isolated from the microalgae, Isochrysis Zhanjiangensis that inhibits the vascular injury, angiogenesis and has a protective effect on cardiovascular diseases. In this study, IEC can suppress ROS production and inhibit pro-inflammatory factors through the Nrf2/SOD/HO-1 and NF-κB signaling pathways. Additionally, IEC inhibits angiogenesis by reducing the expression of MMP2 and MMP9 via the PI3K/AKT, NF-κB, and MAPK pathways. Molecular docking also demonstrated that IEC possesses an excellent docking effect with SOD, Bcl-2 and VEGFR-2. In conclusion, this study not only provides a new idea for the prevention of cardiovascular diseases, but also proves the possibility of octapeptide (IEC) in functional food and drugs, and further improves the use value of microalgae (Isochrysis Zhanjiangensis).

Pentapeptide AYP from Isochrysis Zhanjiangensis Exhibits Antiangiogenic Activity in HT1080 Cells and HUVECs by Suppressing Migration and Invasion In Vitro.

Microalgae are important biological sources of marine active peptides and renewable biological resources. Isochrysis zhanjiangensis has been widely used in biological ultrafiltration membranes and aquaculture. However, there are relatively few studies on its component structure and diverse activities. In this study, the mechanism of action of previously isolated pentapeptides (AYP, Ala-Tyr-Ala-Pro-Glu) on inflammation and tumor angiogenesis was evaluated. The results showed that AYP could effectively inhibit the invasion and migration of human umbilical vein endothelial cells (HUVECs) and HT1080 cells by downregulating the expression of MMP-2/-9, independent of cytotoxicity. Especially after 100 µM AYP treatment, the ability to inhibit migration was about 67.7% ± 1.9 for HT1080 cells and 63.6% ± 1.3 for HUVECs, respectively. In addition, the activity of iNOS and COX-2 was decreased by inhibiting the oversecretion of VEGF in HT1080 cells induced by CoCl2 and the activation of VEGFR-2 in HUVECs and by regulating PI3K/AKT and Ras/MAPK signaling pathways. It can prevent inflammation and block tumor angiogenesis. Therefore, AYP is expected to become a drug or functional food to prevent and treat tumor angiogenesis.