MiR-424-5p Inhibits Proliferation, Migration, Invasion and Angiogenesis of the HTR-8/SVneo Cells Through Targeting LRP6 Mediated ß-catenin.

The aim of this study was to investigate the effects of miR-424-5p on biological behaviors and angiogenesis of the HTR-8/SVneo Cells. Our study included 60 parturient women, which were divided into an PA group (placenta accreta, n = 30) and a normal group (normal placenta, n = 30). QPCR was used to measure the expression of miR-424-5p in placental tissues. The effects of the miR-424-5p mimic on proliferation, migration, and invasion of human HTR-8/SVneo cells and angiogenesis were analyzed. The potential modulated relationship between miR-424-5p and low-density lipoprotein receptor-related protein-6 (LRP6) was demonstrated by luciferase assay. The expression of LRP6, ß-catenin, matrix metalloproteinase-2 (MMP-2), placental growth factor (PGF) and vascular endothelial growth factor (VEGF) were measured by qPCR and Western blot assays. The expression of miR-424-5p in the PA group was significantly decreased than that in the normal group. The expression of miR-424-5p has negative correlation with blood loss. Upregulation of miR-424-5p significantly suppressed the cell proliferation, migration, and invasion of HTR-8/SVneo cells in vitro, as well as the tube formation of human umbilical vein endothelial cells (HUVECs). The luciferase assay demonstrated that LRP6 was a target of miR-424-5p. The expression of LRP6, ß-catenin, MMP-2, PGF and VEGF were also decreased with upregulation of miR-424-5p (p < 0.05). The inhibitory effects of miR-424-5p on HTR-8/SVneo cells and angiogenesis were enhanced by downregulation of LRP6, but were reversed by upregulation of LRP6. The present study suggests that downregulation of miR-424-5p is related to the occurrence of PA. Enhancing miR-424-5p inhibits proliferation, migration, invasion and angiogenesis of the HTR-8/SVneo cells through targeting LRP6 mediated ß-catenin, providing more insights about PA.

Development and validation of a novel prediction model for Carbapenem-resistant organism infection in a large-scale hospitalized patients.

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability.

Anthropogenic activity shapes the assemble and co-occurrence pattern of microbial communities in fishing harbors around the Bohai Economic Circle.

This study aimed to elucidate the effects of coastal environmental stress on the composition of sediment bacterial communities and their cooccurrence patterns in fishing harbors around the Bohai Economic Circle, China. Compared with the natural sea area, fishing harbors contained higher levels of organic pollution (organic pollution index = 0.12±0.026) and considerably reduced bacterial richness and evenness. The distributions of sediment microbial communities clustered along the pollutant concentration gradients across fishing harbors. Betaproteobacteria dominated (76%) organically polluted fishing harbors, which were mostly disturbed by anthropogenic activities. However, the harbors also revealed the absence of numerous pathogenic (Coxiella and Legionella) and photosynthetic (Synechococcus and Leptolyngbya) bacteria. Abundant genera, including Thiobacillus and Arenimonas, exhibited a positive correlation with total phosphorus and a negative correlation with total nitrogen in sediments. Meanwhile, Sulfurovum, Psychrobacter, and Woeseia showed the opposite trend. Pollutant accumulation and anthropogenic activities caused the decrease in the sediment microbial diversity and dispersal ability and promoted convergent evolution. Severely polluted harbors with simplified cooccurrence networks revealed the presence of destabilized microbial communities. In addition, the modularity of bacterial networks decreased with organic pollution. Our results provide important insights into the adjustment mechanism of microbial communities to community organization and functions under environmental pollution stress. Overall, this study enhanced our understanding of how microbial communities in coastal sediments adapted and survived amidst anthropogenic activities like oily effluent discharges from large ships, wash water, domestic sewage, garbage, and fisheries wastes. It also examined their resilience to future contamination.

Synergistic effect of protein foams and polysaccharide on the invisible hemostasis of acellular dermal matrix sponges.

Efficient management of hemorrhage is vital for preventing hemorrhagic shock and safeguarding wounds against infection. Inspired by the traditional Chinese steamed bread-making process, which involves kneading, foaming, and steaming, we devised a hemostatic sponge by amalgamating an acellular dermal matrix gel, hydroxyethyl starch, and rice hydrolyzed protein. The integration of hydroxyethyl starch bolstered the sponge's mechanical and hemostatic attributes, while the inclusion of rice hydrolyzed protein, acting as a natural foaming agent, enhanced its porosity This augmentation facilitated rapid blood absorption, accelerated clot formation, and stimulated the clotting cascade. Experimental findings underscore the exceptional biocompatibility and physicochemical characteristics of the hemostatic sponge, positioning it on par with commercially available collagen hemostatic sponges for hemorrhage control. Mechanistically, the sponge fosters aggregation and activation of red blood cells and platelets, expediting coagulation kinetics both in vivo and in vitro. Notably, this hemostatic sponge activates the clotting cascade sans crosslinking agents, offering a premium yet cost-effective biomaterial with promising clinical applicability.

Disulfidptosis-related lncRNAs signature predicting prognosis and immunotherapy effect in lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma (LUAD) is a prevalent malignant tumor worldwide, with high incidence and mortality rates. However, there is still a lack of specific and sensitive biomarkers for its early diagnosis and targeted treatment. Disulfidptosis is a newly identified mode of cell death that is characteristic of disulfide stress. Therefore, exploring the correlation between disulfidptosis-related long non-coding RNAs (DRGs-lncRNAs) and patient prognosis can provide new molecular targets for LUAD patients. METHODS: The study analysed the transcriptome data and clinical data of LUAD patients in The Cancer Genome Atlas (TCGA) database, gene co-expression, and univariate Cox regression methods were used to screen for DRGs-lncRNAs related to prognosis. The risk score model of lncRNA was established by univariate and multivariate Cox regression models. TIMER, CIBERSORT, CIBERSORT-ABS, and other methods were used to analyze immune infiltration and further evaluate immune function analysis, immune checkpoints, and drug sensitivity. Real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of DRGs-lncRNAs in LUAD cell lines. RESULTS: A total of 108 lncRNAs significantly associated with disulfidptosis were identified. A prognostic model was constructed by screening 10 lncRNAs with independent prognostic significance through single-factor Cox regression analysis, LASSO regression analysis, and multiple-factor Cox regression analysis. Survival analysis of patients through the prognostic model showed that there were obvious survival differences between the high- and low-risk groups. The risk score of the prognostic model can be used as an independent prognostic factor independent of other clinical traits, and the risk score increases with stage. Further analysis showed that the prognostic model was also different from tumor immune cell infiltration, immune function, and immune checkpoint genes in the high- and low-risk groups. Chemotherapy drug susceptibility analysis showed that high-risk patients were more sensitive to Paclitaxel, 5-Fluorouracil, Gefitinib, Docetaxel, Cytarabine, and Cisplatin. Additionally, RT-PCR analysis demonstrated differential expression of DRGs-lncRNAs between LUAD cell lines and the human bronchial epithelial cell line. CONCLUSIONS: The prognostic model of DRGs-lncRNAs constructed in this study has certain accuracy and reliability in predicting the survival prognosis of LUAD patients, and provides clues for the interaction between disulfidptosis and LUAD immunotherapy.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway.

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells' viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells' viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

Minimally Invasive Aesthetic Suturing Technique for Anterior Aesthetic Crown Lengthening Surgery: A Case Series with 24- month Follow-Up.

BACKGROUND: A minimally invasive aesthetic suturing technique was employed in aesthetic crown lengthening surgery (ACLS). The objective of this report was to evaluate the clinical and patient- reported outcomes of this technique for ACLS. METHODS: Fifteen patients who underwent ACLS were treated utilizing the described suturing technique. Clinical parameters, including plaque index (PI), gingival index (GI), bleeding index (BI), papilla index score (PIS), early wound healing index (EHI), visual analogue scale (VAS), pink esthetic score and white esthetic score (PES/WES), were recorded at baseline, immediately post-surgery and during follow-up visits spanning 5 days to 24 months. The two-sample t-test was performed to evaluate statistical significance (α = 0.05). RESULT: 100% of the patients reported a high level of satisfaction, with a stable high postoperative VAS scores. From baseline to 5-day postoperation, there was no statistically significant increase in PI, although there was a slight deterioration observed in GI (0.13Å}0.23, P＜0.05) and BI (0.49Å}0.55, P＜ 0.05). Early wound healing (EHI 1) was achieved by all patients at 5 days post-surgery. Additionally, 3 patients exhibited changes in PIS within the initial 3 months following surgery, after which, all patients attained an optimal degree of papilla filling (degree III). CONCLUSION: The application of the minimally invasive aesthetic suturing technique in ACLS demonstrates favorable outcomes in terms of patient satisfaction and long-term stability. However, the assertion of its superiority over conventional suturing methods for ACLS necessitates substantiation through rigorous investigation via well-designed randomized controlled clinical trials.

Characteristics of advanced anaerobic digestion sludge-based biochar and its application for sewage sludge conditioning.

The utilization of sludge-based biochar, characterized by abundant pore structures, proves advantageous in enhancing sludge dewatering performance. In this study, advanced anaerobic digestion sludge underwent pyrolysis to produce biochar, subsequently employed for sludge conditioning. Results revealed that biochar, obtained at 800 °C, exhibited the highest specific surface area (105.3 m2/g) and pore volume (0.17 cm3/g). As the pyrolysis temperature increased, the sludge's functional groups tended to aromatize. When used to condition sludge, particularly at a 20 % (dry solid) dosage, biochar significantly reduced sludge capillary suction time and floc size. The addition of biochar enhanced the conditioning effect of cationic polyacrylamide by absorbing extracellular polymeric substances, creating water molecule channels, and forming skeletons for sludge flocs. These findings introduce a novel approach to sludge reuse and provide valuable data supporting the use of biochar as a sludge conditioner.

CytoSIP: an annotated structural atlas for interactions involving cytokines or cytokine receptors.

Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top , facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids.

With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 µM. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.

Bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer via modulating HAT1 and increasing IL-9.

Bevacizumab is a recombinant humanized monoclonal immunoglobulin (Ig) G1 antibody of VEGF, and inhibits angiogenesis and tumor growth in hepatocellular carcinoma (HCC). Ferroptosis, a new form of regulated cell death function independently of the apoptotic machinery, has been accepted as an attractive target for pharmacological intervention; the ferroptosis pathway can enhance cell immune activity of anti-PD1 immunotherapy in HCC. In this study we investigated whether and how bevacizumab regulated ferroptosis and immune activity in liver cancer. Firstly, we performed RNA-sequencing in bevacizumab-treated human liver cancer cell line HepG2 cells, and found that bevacizumab significantly altered the expression of a number of genes including VEGF, PI3K, HAT1, SLC7A11 and IL-9 in liver cancer, bevacizumab upregulated 37 ferroptosis-related drivers, and downregulated 17 ferroptosis-related suppressors in particular. We demonstrated that bevacizumab triggered ferroptosis in liver cancer cells by driving VEGF/PI3K/HAT1/SLC7A11 axis. Clinical data confirmed that the expression levels of VEGF were positively associated with those of PI3K, HAT1 and SLC7A11 in HCC tissues. Meanwhile, we found that bevacizumab enhanced immune cell activity in tumor immune-microenvironment. We identified that HAT1 up-regulated miR-143 targeting IL-9 mRNA 3'UTR in liver cancer cells; bevacizumab treatment resulted in the increase of IL-9 levels and its secretion via VEGF/PI3K/HAT1/miR-143/IL-9 axis, which led to the inhibition of tumor growth in vivo through increasing the release of IL-2 and Granzyme B from activated CD8+ T cells. We conclude that in addition to inhibiting angiogenesis, bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer. This study provides new insight into the mechanisms by which bevacizumab synergistically modulates ferroptosis and CD8+ T cell immune activity in liver cancer.

Response of photosynthetic characteristics and antioxidant system in the leaves of safflower to NaCl and NaHCO3.

KEY MESSAGE: Compared with NaCl, NaHCO3 caused more serious oxidative damage and photosynthesis inhibition in safflower by down-regulating the expression of related genes. Salt-alkali stress is one of the important factors that limit plant growth. NaCl and sodium bicarbonate (NaHCO3) are neutral and alkaline salts, respectively. This study investigated the physiological characteristics and molecular responses of safflower (Carthamus tinctorius L.) leaves treated with 200 mmol L-1 of NaCl or NaHCO3. The plants treated with NaCl treatment were less effective at inhibiting the growth of safflower, but increased the content of malondialdehyde (MDA) in leaves. Meanwhile, safflower alleviated stress damage by increasing proline (Pro), soluble protein (SP), and soluble sugar (SS). Both fresh weight and dry weight of safflower was severely decreased when it was subjected to NaHCO3 stress, and there was a significant increase in the permeability of cell membranes and the contents of osmotic regulatory substances. An enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes identified significant enrichment of photosynthesis and pathways related to oxidative stress. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the darkgreen module had the highest correlation with photosynthesis and oxidative stress traits. Large numbers of transcription factors, primarily from the MYB, GRAS, WRKY, and C2H2 families, were predicted from the genes within the darkgreen module. An analysis of physiological indicators and DEGs, it was found that under saline-alkali stress, genes related to chlorophyll synthesis enzymes were downregulated, while those related to degradation were upregulated, resulting in inhibited chlorophyll biosynthesis and decreased chlorophyll content. Additionally, NaCl and NaHCO3 stress downregulated the expression of genes related to the Calvin cycle, photosynthetic antenna proteins, and the activity of photosynthetic reaction centers to varying degrees, hindering the photosynthetic electron transfer process, suppressing photosynthesis, with NaHCO3 stress causing more pronounced adverse effects. In terms of oxidative stress, the level of reactive oxygen species (ROS) did not change significantly under the NaCl treatment, but the contents of hydrogen peroxide and the rate of production of superoxide anions increased significantly under NaHCO3 stress. In addition, treatment with NaCl upregulated the levels of expression of the key genes for superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate-glutathione cycle, and the thioredoxin-peroxiredoxin pathway, and increased the activity of these enzymes, thus, reducing oxidative damage. Similarly, NaHCO3 stress increased the activities of SOD, CAT, and POD and the content of ascorbic acid and initiated the glutathione-S-transferase pathway to remove excess ROS but suppressed the regeneration of glutathione and the activity of peroxiredoxin. Overall, both neutral and alkaline salts inhibited the photosynthetic process of safflower, although alkaline salt caused a higher level of stress than neutral salt. Safflower alleviated the oxidative damage induced by stress by regulating its antioxidant system.

Overexpression of phosphatidylserine synthase IbPSS1 enhances salt tolerance by stimulating ethylene signaling-dependent lignin synthesis in sweetpotato roots.

Phosphatidylserine (PS) is an important lipid signaling required for plant growth regulation and salt stress adaptation. However, how PS positively regulate plant salt tolerance is still largely unknown. In this study, IbPSS1-overexpressed sweetpotato plants that exhibited overproduction of PS was employed to explore the mechanisms underlying the PS stimulation of plant salt tolerance. The results revealed that the IbPSS1-overexpressed sweetpotato accumulated less Na+ in the stem and leaf tissues compared with the wild type plants. Proteomic profile of roots showed that lignin synthesis-related proteins over-accumulated in IbPSS1-overexpressed sweetpotato. Correspondingly, the lignin content was enhanced but the influx of Na + into the stele was significantly blocked in IbPSS1-overexpressed sweetpotato. The results further revealed that ethylene synthesis and signaling related genes were upregulated in IbPSS1-overexpressed sweetpotato. Ethylene imaging experiment revealed the enhancement of ethylene mainly localized in the root stele. Inhibition of ethylene synthesis completely reversed the PS-overproduction induced lignin synthesis and Na+ influx pattern in stele tissues. Taken together, our findings demonstrate a mechanism by which PS regulates ethylene signaling and lignin synthesis in the root stele, thus helping sweetpotato plants to block the loading of Na+ into the xylem and to minimize the accumulation of Na+ in the shoots.

Logic-Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment.

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1ß levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.

Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Antidepressant effect of teriflunomide via oligodendrocyte protection in a mouse model.

Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both invivo and invitro. Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

Variation in the Floral Scent Chemistry of Nymphaea 'Eldorado', a Valuable Water Lily, with Different Flowering Stages and Flower Parts.

Nymphaea 'Eldorado', a valuable water lily, is a well-known fragrant plant in China. Studying the temporal and spatial characteristics of the floral components of this plant can provide a reference for the further development and utilization of water lily germplasm resources. In this study, headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) was used to explore the types and relative contents of floral components at different flowering stages (S1: bud stage; S2: initial-flowering stage; S3: full-flowering stage; S4: end-flowering stage) and in different floral organs of N. 'Elidorado', combined with the observation of the microscopic structure of petals. A total of 60 volatile organic compounds (VOCs) were detected at different flowering stages, and there were significant differences in floral VOCs at different flowering stages and in different flower organs. The volatile compounds of N. 'Eldorado' can be divided into seven chemical classes,, namely, alkenes, alcohols, esters, aldehydes, ketones, alkanes, and others; the most common were alkenes and alkanes. A total of 39, 44, 47, and 42 volatile compounds were detected at S1, S2, S3, and S4. The VOCs present in high concentrations include benzaldehyde, benzyl alcohol, benzyl acetate, trans-α-bergamotene, α-curcumene, cis-α-farnesene, and so on. The types and total contents of volatiles at the full-flowering stage were higher than at other flowering stages. Comparing the VOCs in different parts of flower organs, it was found that the contents of alcohols, esters, and aldehydes were greatest in the petals, the alkenes in stamens were abundant with a relative content of up to 54.93%, and alkanes in the pistil were higher than in other parts. The types and total contents of volatiles in the stamens of N. 'Eldorado' were higher than those in other flower organs; they were the main part releasing fragrance. The observation of petal microstructure revealed that the size and quantity of the papillae on the epidermises of petals, the number of intracellular plastids, and the aggregates of floral components (osmophilic matrix granules) were significantly higher at the full-flowering stage than at the other flowering stages. This study suggested the main flowering stage and location at which the floral VOCs are released by N. 'Eldorado' and provided a reference for guiding the breeding of this water lily, exploring genetic patterns and developing related products.

The application of chitosan quaternary ammonium salt to replace polymeric aluminum ferric chloride for sewage sludge dewatering.

Inorganic coagulants such as poly aluminum ferric chloride (Al/Fe) are applied conventionally to sewage sludge dewatering and can be retained in the sludge cake, causing its conductivity to increase and generate secondary pollution. To reduce these disadvantages, there is a need to develop alternative, more sustainable chemicals as substitutes for conventional inorganic coagulants. In the present investigation, the application of a polymeric chitosan quaternary ammonium salt (CQAS) is explored as a complete, or partial, replacement for Al/Fe in the context of sludge dewatering processes. Laboratory experiments using digested sewage sludge showed that CQAS could effectively substitute for over 80 % of the Al/Fe inorganic coagulant in the sludge dewatering process. This substitution resulted in a reduction of sludge cake conductivity by more than 50 %. Simulation of sludge dewatering curves and imaging of the sludge surface indicated that the addition of CQAS led to an increase in nanosized pores, and a decrease in the specific resistance of the sludge filter cake as the dosage of Al/Fe decreased to around 30 %. The variations of fluorescence emission, quantum yield and carboxylic and amino groups, suggested that the chelating of Al/Fe decreased due to the bridging effects of CQAS. The CQAS had different flocculation bridging effects on various EPS fractions, which varied the amount of protein chelated with Al/Fe in each fraction. This study provides new information about the benefits of replacing conventional inorganic coagulants with natural organic polymers for sewage sludge dewatering, in terms of reduced sludge cake conductivity and greater dry solids content.

Mechanisms of photoprotection in overwintering evergreen conifers: Sustained quenching of chlorophyll fluorescence.

Evergreen conifers growing in high-latitude regions must endure prolonged winters that are characterized by sub-zero temperatures combined with light, conditions that can cause significant photooxidative stress. Understanding overwintering mechanisms is crucial for addressing winter adversity in temperate forest ecosystems and enhancing the ability of conifers to adapt to climate change. This review synthesizes the current understanding of the photoprotective mechanisms that conifers employ to mitigate photooxidative stress, particularly non-photochemical "sustained quenching", the mechanism of which is hypothesized to be a recombination or deformation of the original mechanism employed by conifers in response to short-term low temperature and intense light stress in the past. Based on this hypothesis, scattered studies in this field are assembled and integrated into a complete mechanism of sustained quenching embedded in the adaptation process of plant physiology. It also reveals which parts of the whole system have been verified in conifers and which have only been verified in non-conifers, and proposes specific directions for future research. The functional implications of studies of non-coniferous plant species for the study of coniferous trees are also considered, as a wide range of plant responses lead to sustained quenching, even among different conifer species. In addition, the review highlights the challenges of measuring sustained quenching and discusses the application of ultrafast-time-resolved fluorescence and decay-associated spectra for the elucidation of photosynthetic principles.