Effect of cross-linking density on the rheological behavior of ultra-soft chitosan microgels at the oil-water interface.

In this paper, microgels with uniform particle size were prepared by physically cross-linking the hydrophobically modified chitosan (h-CS) with sodium phytate (SP). The effects of cross-linking density on the interfacial adsorption kinetics, viscoelasticity, stress relaxation, and micorheological properties of the hydrophobically modified chitosan microgels (h-CSMs) at the oil-water interface were extensively investigated by the dilatational rheology, compressional rheology, and particle tracing microrheology. The results were correlated with the particle size, morphology, and elasticity of the microgels characterized by dynamic light scattering and atomic force microscopy. It was found that with the increase of cross-linking density, the h-CSMs changed from a polymer-like state to ultra-soft fussy spheres with higher elastic modulus. The compression isotherms demonstrated multi-stage increase caused by the interaction between the shells and that between the cores of the microgels successively. As the increase of cross-linking density, the h-CSMs diffused slower to the oil-water interface, but demonstrating faster permeation adsorption and rearrangement at the oil-water interface, finally forming interfacial layers of higher viscoelastic modulus due to the core-core interaction. Both the initial tension relaxation and the microgel rearrangement after interface expansion became faster as the microgel elasticity increased. The interfacial microrheology demonstrated dynamic caging effect caused by neighboring microgels. This article provides a more comprehensive understanding of the behaviors of polysaccharide microgels at the oil-water interface.

Multi-method computational evaluation of the inhibitors against leucine-rich repeat kinase 2 G2019S mutant for Parkinson's disease.

Leucine-rich repeat kinase 2 G2019S mutant (LRRK2 G2019S) is a potential target for Parkinson's disease therapy. In this work, the computational evaluation of the LRRK2 G2019S inhibitors was conducted via a combined approach which contains a preliminary screening of a large database of compounds via similarity and pharmacophore, a secondary selection via structure-based affinity prediction and molecular docking, and a rescoring treatment for the final selection. MD simulations and MM/GBSA calculations were performed to check the agreement between different prediction methods for these inhibitors. 331 experimental ligands were collected, and 170 were used to build the structure-activity relationship. Eight representative ligand structural models were employed in similarity searching and pharmacophore screening over 14 million compounds. The process for selecting proper molecular descriptors provides a successful sample which can be used as a general strategy in QSAR modelling. The rescoring used in this work presents an alternative useful treatment for ranking and selection.

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

Synergistic binding mechanisms of co-contaminants in soil profiles: Influence of iron-bearing minerals and microbial communities.

In contaminated soil sites, the coexistence of inorganic and organic contaminants poses a significant threat to both the surrounding ecosystem and public health. However, the migration characteristics of these co-contaminants within the soil and their interactions with key components, including Fe-bearing minerals, organic matter, and microorganisms, remain unclear. This study involved the collection of a 4.3-m-depth co-contaminated soil profile to investigate the vertical distribution patterns of co-contaminants (namely, arsenic, cadmium, and polychlorinated biphenyls (PCBs)) and their binding mechanisms with environmental factors. The results indicated a notable downward accumulation of inorganic contaminants with increasing soil depth, whereas PCBs were predominantly concentrated in the uppermost layer. Chemical extraction and synchrotron radiation analysis highlighted a positive correlation between the abundance of reactive iron (FeCBD) and both co-contaminants and microbial communities in the contaminated site. Furthermore, Mantel tests and structural equation modeling (SEM) demonstrated the direct impacts of FeCBD and microbial communities on co-contaminants within the soil profile. Overall, these results provided valuable insights into the migration and transformation characteristics of co-contaminants and their binding mechanisms mediated by minerals, organic matter, and microorganisms.

Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression.

Receptor for activated C kinase 1 (RACK1) has been confirmed to take part in multiple biological events and the mechanism supporting abnormal RACK1 expression in ovarian cancer (OC) remains to be characterized. Here, we identified Smad ubiquitin regulatory factor 2 (SMURF2) as a bona fide E3 ligase of RACK1 in OC. SMURF2 effectively added the K6, K33 and K48 ubiquitin chains to the RACK1, resulting in polyubiquitination and instability of RACK1. PCAF promoted acetylation of RACK1 at K130, leading to SMURF2-mediated RACK1 ubiquitination inhibited and promote OC progression. The expression levels of SMURF2 and RACK1 were negatively correlated. SMURF2 was abnormal low expression in human ovarian cancer, resulting in decreased ubiquitination of RACK1 and increased stability, which promoted OC progression, and strongly associated with poor patients' prognosis. In general, our results demonstrated that SMURF2 plays a pivotal role in stabilizing RACK1, which in turn facilitates tumorigenesis in OC, suggesting that SMURF2-RACK1 axis may prove to be potential targets for the treatment of OC.

A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer.

Background and Objectives: Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer (OC) has yet to be fully understood. Therefore, this study systematically described the expression, mutation, and copy number variation of genes in the Notch signaling pathway in OC and evaluated the relationship between gene mutation and Overall Survival (OS) prognosis. Materials and Methods: Notch risk score (NTRS) was established by univariate Cox regression analysis combined with Lasso regression analysis, and the efficacy of NTRS in predicting prognosis and immunotherapy response in patients with OC was verified. We further assessed the correlations of NTRS with clinical features, immune infiltration level, immune checkpoint expression, and immune characteristics. Additionally, differential expression and functions of the fourteen signature genes were confirmed via vitro assays. Results: The results showed that Notch genes (NTGs) were markedly differentiated between tumor and normal tissues, which may help to explain the high heterogeneity in the biological characteristics and therapeutic outcomes of human OC. A Notch risk (NTR) prognostic model based on 11 key NTGs was successfully constructed. Tumors with high Notch risk scores (NTRS) were independently associated with shorter overall survival and poorer immunotherapy outcomes. We further assessed the correlations of NTRS with immune characteristics. The results showed that NTGs play a key role in regulating the tumor immune microenvironment. Additionally, we validated the baseline and induced expressions of 14 prognosis-related NTGs in our own OC samples. In vitro assays confirmed that the knockdown of NCOR2 and APH1B and overexpression of HEY2 and SKP2 could inhibit the proliferation, invasion, and migration of OC cells. Conclusions: These findings emphasize that Notch multilayer changes are associated with the prognosis of patients with OC and the characteristics of immune cell infiltration. Our predictive signature may predict the prognosis and immunotherapy response of OC patients in an independent manner. NCOR2, APH1B, HEY2, and SKP2 may more prominently represent important indicators to improve patient prognosis.

Organic carbon preservation in wetlands: Iron oxide protection vs. thermodynamic limitation.

The sequestration of organic carbon (OC) in wetland sediments is influenced by the presence of oxygen or lack thereof. The mechanisms of OC sequestration under redox fluctuations, particularly by the co-mediation of reactive iron (Fe) protection and thermodynamic limitation by the energetics of the OC itself, remain unclear. Over the past 26 years, a combination of field surveys and remote sensing images had revealed a strong decline in both natural and constructed wetland areas in Tianjin. This decline could be attributed to anthropogenic landfill practices and agricultural reclamation efforts, which may have significant impacts on the oxidation-reduction conditions for sedimentary OC. The Fe-bound OC (CBD extraction) decreased by 2 to 10-fold (from 8.3 to 10% to 0.7-4.5%) with increasing sediment depth at three sites with varying water depths (WD). The high-resolution spectro-microscopy analysis demonstrated that Fe (oxyhydr)oxides were colocalized with sedimentary OC. Corresponding to lower redox potential, the nominal oxidation state of C (NOSC), which corresponds to the energy content in OC, became more negative (energy content increased) with increasing sediment depth. Taken together, the preservation of sedimentary OC is contingent on the prevailing redox conditions: In environments where oxygen availability is high, reactive Fe provides protection for OC, while in anoxic environments, thermodynamic constraints (i.e., energetic constraints) limit the oxidation of OC.

Risk assessment and binding mechanisms of potentially toxic metals in sediments from different water levels in a coastal wetland.

The excessive accumulation of potentially toxic metals (Pb and Cd) in coastal wetlands is among the main factors threatening wetland ecosystems. However, the effects of water table depth (WTD) on the risk and binding mechanisms of potentially toxic metals in sediments remain unclear. Here, sediments from different WTD obtained from a typical coastal wetland were evaluated using a newly developed strategy based on chemical extraction methods coupled with high-resolution spectroscopy. Our findings indicated that the WTD of the coastal wetland fluctuates frequently and the average enrichment factor for Pb was categorized as minor, whereas Cd enrichment was categorized as moderate. High-resolution spectroscopy techniques also demonstrated that organic functional groups and partly inorganic compounds (e.g., Fe-O/Si-O) played a vital role in the binding of Pb and Cd to surface sediments. Additionally, mineral components rather than organic groups were mainly bound to these metals in the bottom sediments. Collectively, our findings provide key insights into the potential health effects and binding characteristics of potentially toxic metals in sediments, as well as their dynamic behavior under varying sediment depths at a microscale.

Novel LncRNA ZFHX4-AS1 as a Potential Prognostic Biomarker That Affects the Immune Microenvironment in Ovarian Cancer.

Background: Ovarian cancer (OvCa) is a malignant disease of the female reproductive system with a high mortality rate. LncRNA has been confirmed to play a crucial role in the development and progression of various cancer types. Novel lncRNA ZFHX4-AS1 has been reported in several cancers, albeit its functional mechanisms in OvCa remain unclear. Methods: With reference to the public databases and based on integrating bioinformatics analyses, we explored the expression of ZFHX4-AS1 and its roles in the prognosis of OvCa. We employed the Kaplan-Meier curves to investigate the outcome of patients with different ZFHX4-AS1 expressions. Furthermore, its biological function and the related hallmark pathways were assessed through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Gene-set enrichment analysis (GSEA). We explored the correlation between lncRNA ZFHX4-AS1 and tumor-infiltrating immune cells through CIBERSORT. The immune checkpoints associated with lncRNA ZFHX4-AS1 and its related genes were investigated. The effect of lncRNA ZFHX4-AS1 on proliferation, invasion and migration of OvCa cells was verified through Cell Counting Kit (CCK)-8, colony formation, wound healing and transwell assays. Results: The expression of lncRNA ZFHX4-AS1 was upregulated in OvCa relative to that in normal tissues. Increased lncRNA ZFHX4-AS1 expression was associated with poor overall survival and progression-free survival in OvCa. The GO and KEGG pathway analyses revealed the role of lncRNA ZFHX4-AS1 in cell metabolism, protein synthesis, cell proliferation, and cell cycle. GSEA indicated the hallmark gene sets that were significantly enriched in the high and low expression groups. The CIBERSORT database revealed M2 macrophages, memory B-cells, naïve B cells, and activated NK cells were affected by lncRNA ZFHX4-AS1 expression (all P < 0.05). The expression of lncRNA ZFHX4-AS1 and its related differential genes MRPS11, NSA2, and MRPL13 were significantly correlated with the immune checkpoints. Knockdown of lncRNA ZFHX4-AS1 could inhibit the proliferation, invasion and migration of OvCa cells. Conclusions: The results suggested that lncRNA ZFHX4-AS1 is a novel prognostic biomarker associated with cell proliferation, metabolism, infiltration, and distribution of tumor-infiltrating immune cells in OvCa, indicating that lncRNA ZFHX4-AS1 can be used as a potential therapeutic target for OvCa in the future.

Design, semi-synthesis and bioactivity evaluation of novel podophyllotoxin derivatives as potent anti-tumor agents.

In this study, a series of potential candidate molecules with excellent antitumor activity targeting tubulin and PTEN/PI3K/Akt signaling pathway was synthesized by modifying the molecule structure of podophyllotoxin (PPT) at the C-4 position via a structure-guided drug design approach. MTT assay results indicated that compound 12c had stronger anti-proliferative activities against HGC-27, MCF-7 and H460 cell lines than etoposide (VP-16), especially for HGC-27 (12c: IC50 = 0.89 ± 0.023 µM; PPT: IC50 = 6.54 ± 0.69 µM, VP-16: IC50 = 2.66 ± 0.28 µM) with lower affect in healthy human cells (293 T and GES-1). Further pharmacological analysis exhibited that 12c could bind the tubulin at the colchicine site and disrupt the dynamic equilibrium of microtubules. Moreover, 12c also suppressed the expressions/activities of matrix metalloprotease (MMP)-2, vimentin and up-regulation E-cadherin suggesting that 12c could block the epithelial-mesenchymal transition (EMT). The increased cell survival and invasion/migration were associated with the inactivation of PTEN/PI3K/Akt, 12c could regulate this pathway and cascade influence on the mitochondrial pathway, eventually, leading to the cell apoptosis. Thus, 12c may have the potential to become a candidate molecule in gastric cancer clinical treatment.

Identification of a Recurrence Gene Signature for Ovarian Cancer Prognosis by Integrating Single-Cell RNA Sequencing and Bulk Expression Datasets.

Ovarian cancer is one of the most common gynecological malignancies in women, with a poor prognosis and high mortality. With the expansion of single-cell RNA sequencing technologies, the inner biological mechanism involved in tumor recurrence should be explored at the single-cell level, and novel prognostic signatures derived from recurrence events were urgently identified. In this study, we identified recurrence-related genes for ovarian cancer by integrating two Gene Expression Omnibus datasets, including an ovarian cancer single-cell RNA sequencing dataset (GSE146026) and a bulk expression dataset (GSE44104). Based on these recurrence genes, we further utilized the merged expression dataset containing a total of 524 ovarian cancer samples to identify prognostic signatures and constructed a 13-gene risk model, named RMGS (recurrence marker gene signature). Based on the RMGS score, the samples were stratified into high-risk and low-risk groups, and these two groups displayed significant survival difference in two independent validation cohorts including The Cancer Genome Atlas (TCGA). Also, the RMGS score remained significantly independent in multivariate analysis after adjusting for clinical factors, including the tumor grade and stage. Furthermore, there existed close associations between the RMGS score and immune characterizations, including checkpoint inhibition, EMT signature, and T-cell infiltration. Finally, the associations between RMGS scores and molecular subtypes revealed that samples with mesenchymal subtypes displayed higher RMGS scores. In the meanwhile, the genomics characterization from these two risk groups was also identified. In conclusion, the recurrence-related RMGS model we identified could provide a new understanding of ovarian cancer prognosis at the single-cell level and offer a reference for therapy decisions for patient treatment.

RRS1 knockdown inhibits the proliferation of neuroblastoma cell via PI3K/Akt/NF-κB pathway.

BACKGROUND: RRS1 plays an important role in regulating ribosome biogenesis. Recently, RRS1 has emerged as an oncoprotein involved in tumorigenicity of some cancers. However its role in neuroblastoma remains unknown. METHODS: RRS1 expression was detected in pediatric neuroblastoma patients' tissues and cell lines. The effects of RRS1 knockdown on proliferation, apoptosis, and cell cycle were evaluated in neuroblastoma cell lines. RRS1-related survival pathway was analyzed by co-immunoprecipitation (Co-IP), mass spectrometry, reverse transcription-quantitative real-time PCR (RT-qPCR), and western blot. Protein-protein interaction (PPI) network was constructed using Cytoscape software and the STRING databases. RESULTS: Increased RRS1 level was found in neuroblastoma cases (35.6%) and cell lines. High RRS1 expression levels were associated with poor prognosis. RRS1 knockdown inhibited cell proliferation, induced apoptosis, and caused cell cycle arrest in SK-N-AS and SH-SY5Y cells. Co-IP and mass spectrometry analysis showed that RRS1 affects PI3K/Akt and nuclear factor κB (NF-κB) pathways. RT-qPCR and western blot results revealed that RRS1 knockdown inhibited the PI3K/Akt/NF-κB pathway through dephosphorylation of key proteins. In PPI network, AKT, PI3K, and P65 connected RRS1 with differentially expressed proteins more closely. CONCLUSIONS: This study suggests RRS1 knockdown may inhibit neuroblastoma cell proliferation by the PI3K/Akt/NF-κB pathway. Therefore, RRS1 may be a potential target for neuroblastoma treatment. IMPACT: RRS1 is involved in the progression of neuroblastoma. Knockdown of RRS1 contributes to inhibit the survival of neuroblastoma cells. RRS1 is associated with the PI3K/Akt/NF-κB signaling pathway in neuroblastoma cells. RRS1 may be a promising target for neuroblastoma therapy.

Hydrophobically modified chitosan microgels stabilize high internal phase emulsions with high compliance.

Food-grade microgel-stabilized emulsions have been attracting much attention due to their promising applications in food formulations. In this study, the use of hydrophobically modified chitosan microgels (h-CSMs) as particle emulsifiers to stabilize high internal phase emulsions (HIPEs) was demonstrated for the first time. Four hydrophobically modified chitosan (h-CS) were obtained by grafting deoxycholic acid (DA) with chitosan (CS) at grafting rates of 4.64%, 13.21%, 15.12% and 30.29%, respectively. The selected modified chitosan were further cross-linked with sodium tripolyphosphate (TPP) to form h-CSMs. It was found that, compared to pure CS and the modified h-CS, the h-CSMs have higher hydrophobicity, and can stabilize oil-in-water HIPEs effectively. The interfacial properties of the h-CSMs, and the formation, microstructure and rheological properties of HIPEs were characterized by dynamic interfacial adsorption, contact angle, visual observation, laser confocal microscopy and rheological measurements, respectively. The results show that stable HIPEs with oil concentration up to 90 wt% can be formed using very low h-CSM particle concentration (only 0.05 wt% for the HIPE with 90 wt% oil), and the HIPEs stabilized by h-CSMs displayed higher rheological compliance than other solid particle stabilized HIPEs at high oil volume fraction. The strong emulsification properties of the h-CSMs are attributed to their increased hydrophobicity, the enhanced exposure of hydrophobic groups during microgelation process, and the viscoelasticity of h-CSMs.

Sulfate concentrations affect sulfate reduction pathways and methane consumption in coastal wetlands.

Coastal wetlands are an important source of methane emissions, and understanding the mechanisms that control methane emissions from coastal wetlands is of great significance to global warming. Anaerobic oxidation of methane driven by sulfate is an important process to prevent methane emissions from coastal wetlands. The effects of environmental changes on this process and the function of the sulfate-methane transition zone (SMTZ) are poorly understood. In this study, spatiotemporal variations in pore-water geochemistry (concentrations of SO42-, CH4 and DIC as well as δ13C-DIC and δ13C-CH4) in the Beidagang wetland, Tianjin, China, were investigated to unravel factors controlling the role of anaerobic oxidation of methane in coastal wetlands. Results show that the geochemical profile of pore-water is characterized by significant spatial and temporal variability, which may be related to changes in sulfate concentration, temperature and dissolved oxygen. The carbon isotope fractionation factors (εC) during methane oxidation range from 8.9‰ to 12.5‰, indicating that the sulfate-driven anaerobic oxidation of methane (S-AOM) dominates the methane oxidation in the Beidagang coastal wetland in both winter and summer, in both high and low salinity wetlands, and in both open water and littoral areas. However, sulfate concentration has a strong influence on the sulfate reduction pathways and methane consumption. The consumption of methane and sulfate by S-AOM is more significant in coastal wetlands with high sulfate concentrations, with S-AOM consuming nearly all of the upward-diffusing methane (96%) and downward-diffusing sulfate (96%). In addition, the dissolved inorganic carbon (DIC) produced in the pore-water mainly comes from methanogenesis, accounting for more than 80% of the total DIC pool, but in the areas with high sulfate concentrations in water column, the contribution of S-AOM to the DIC pool is greater, although only a small fraction of the total DIC pool (9%). The depth and width of the SMTZ show a clear spatial and temporal pattern, with active methanogenesis activity and upward high methane flux shoaling the SMTZ and increasing the risk of high methane emissions from coastal wetlands with low sulfate concentrations. Our findings highlight the importance of sulfate-driven anaerobic oxidation of methane in coastal wetlands and the effect of sulfate concentration on it. It contributes to our understanding of the mechanism of methane production and emissions from the coastal wetland system, particularly in light of the increased demand for coastal wetland restoration under global warming.

Nonlinear dilatational rheology of different protein aggregates at the oil-water interface.

Proteins tend to self-assemble into different morphological aggregates such as nanoparticles or fibrils during heat treatment depending on the processing conditions. The protein aggregates exhibit excellent interfacial activity and even better ability to stabilize emulsions than native proteins. The interfacial rheological properties at the oil-water interface play a very important role in emulsion stability, among which the interfacial nonlinear rheology is closely related to their ability to resist large perturbation. However, there are very few studies reporting the nonlinear interfacial rheological behavior of protein aggregates at the oil-water interface. In this study, ß-lactoglobulin fibrous aggregates (F) and nanoparticle aggregates (NP) were prepared, and the adsorption kinetics and dilatational nonlinear rheological behavior of ß-lactoglobulin aggregates at the oil-water interface under large amplitude deformation were studied using a pendant drop tensiometer, and compared with those of native proteins. From the adsorption experiments, the adsorption of protein aggregates, especially fibrils, was faster than that of native proteins in the early stage, while in the late stage, the native proteins displayed a significantly higher degree of rearrangement than the fibrils. The surface hydrophobicity and the short fibrils present mainly determine the properties of the fibril interface, while the behavior of the nanoparticle interface was significantly influenced by the size and charge properties of the nanoparticles. From the dilatational experiment, the Lissajous plots revealed that the F interface at all pHs evaluated and the ßlg interface at pH 5.8 displayed strain softening in both expansion and compression processes, while the NP interface at all pHs and ßlg interface at pH 2 and pH 7 displayed strain softening in expansion and strain hardening in compression processes. The nonlinear response of the protein aggregates at the oil-water interface was more obvious at pH 5.8. The modulus change from frequency sweeps revealed that the fibril interface was strong but not very structured in contrast to that formed by the native proteins which displays high structuration although weak in strength, whereas the strength of the interface formed by protein nanoparticles is in between, but more sensitive to the surface charge.

Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway.

METHODS: All rats were randomly divided into four groups, namely, control, CUMS, CUMS + CUR, and CUMS + CUR + SR18292 (PGC-1α inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1α, estrogen-related receptor alpha (ERRα), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1α/FNDC5/BDNF pathway. The PGC-1α inhibitor SR18292 was used to explore the role of PGC-1α in the induction of BDNF by CUR. RESULTS: Daily gavage of 100 mg/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. CUR also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that CUR supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of CUR. CONCLUSION: Collectively, our data evaluating the neuroprotective action of CUR in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of CUR.

Molybdenum Bioavailability and Asymbiotic Nitrogen Fixation in Soils are Raised by Iron (Oxyhydr)oxide-Mediated Free Radical Production.

Nitrogen (N) fixation in soils is closely linked to microbially mediated molybdenum (Mo) cycling. Therefore, elucidating the mechanisms and factors that affect Mo bioavailability is crucial for understanding N fixation. Here, we demonstrate that long-term (26 years) manure fertilization increased microbial diversity and content of short-range ordered iron (oxyhydr)oxides that raised Mo bioavailability (by 2.8 times) and storage (by ∼30%) and increased the abundance of nifH genes (by ∼14%) and nitrogenase activity (by ∼60%). Nanosized iron (oxyhydr)oxides (ferrihydrite, goethite, and hematite nanoparticles) play a dual role in soil Mo cycling: (i) in concert with microorganisms, they raise Mo bioavailability by catalyzing hydroxyl radical (HO•) production via the Fenton reactions and (ii) they increase Mo retention by association with the nanosized iron (oxyhydr)oxides. In summary, long-term manure fertilization raised the stock and bioavailability of Mo (and probably also of other micronutrients) by increasing iron (oxyhydr)oxide reactivity and intensified asymbiotic N fixation through an increased abundance of nifH genes and nitrogenase activity. This work provides a strategy for increasing biological N fixation in agricultural ecosystems.

New Xanthones with Antiagricultural Fungal Pathogen Activities from the Endophytic Fungus Diaporthe goulteri L17.

Six new xanthone dimers, diaporxanthones A-F (1-6), and an unusual xanthone monomer diaporxanthone G (7), in addition to seven known analogues (8-14), were isolated and identified from endophytic Diaporthe goulteri L17 harbored in the fruits of the salt-tolerant plant Vitex trifolia. The chemical structures of these metabolites were elucidated on the basis of nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and reported data in the literature. Their absolute configurations were established by single-crystal X-ray diffraction analysis together with time-dependent density functional theory electronic circular dichroism calculations. Among these compounds, compounds 1 and 6 exhibited moderate antifungal activities against Nectria sp. and Colletotrichum musae and compound 4 showed significant cytotoxicity against all selected five cancer cell lines.

Aducanumab: The first targeted Alzheimer's therapy.

Alzheimer's disease (AD) is an irreversible brain disorder associated with severe progressive dementia and is characterized by deposits of amyloid plaques in the brain. Over the past 20 years, the mortality of strokes and heart disease has decreased, but deaths from AD have increased. The four drugs used clinically to treat AD can only relieve symptoms but cannot slow the progression of the disease. Aducanumab, a human monoclonal antibody that preferentially binds to aggregated amyloid-ß to reduce the number of amyloid plaques and slow disease progression, was approved to treat AD by the US Food and Drug Administration on June 7, 2021. It is the first disease-modifying therapy for AD, but there is considerable controversy regarding the drug's approval. Aducanumab offers hope for millions of patients.

TaASR1-D confers abiotic stress resistance by affecting ROS accumulation and ABA signalling in transgenic wheat.

Cultivating new crop cultivars with multiple abiotic stress tolerances is important for crop production. The abscisic acid-stress-ripening (ASR) protein has been shown to confer abiotic stress tolerance in plants. However, the mechanisms of ASR function under stress condition remain largely unclear. In this study, we characterized all ASR family members in common wheat and constitutively overexpressed TaASR1-D in a commercial hexaploid wheat cultivar Zhengmai 9023. The transgenic wheat plants exhibited increased tolerance to multiple abiotic stresses and increased grain yields under salt stress condition. Overexpression of TaASR1-D conferred enhanced antioxidant capacity and ABA sensitivity in transgenic wheat plants. Further, RNA in situ hybridization results showed that TaASR1-D had higher expression levels in the vascular tissues of leaves and the parenchyma cells around the vascular tissues of roots and stems. Yeast one-hybrid and electrophoretic mobility shift assays revealed that TaASR1-D could directly bind the specific cis-elements in the promoters of TaNCED1 and TaGPx1-D. In conclusion, our findings suggest that TaASR1-D can be used to breed new wheat cultivars with increased multiple abiotic stress tolerances, and TaASR1-D enhances abiotic stress tolerances by reinforcing antioxidant capacity and ABA signalling.