High Lactate-Metabolizing Photosynthetic Bacteria Reprogram Tumor Immune Microenvironment.

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) has been considered a crucial step for boosted immunotherapy. In this work, we selectively screen a high-lactate-metabolizing photosynthetic bacteria (LAB-1) for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening was initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of anti-tumor immune therapy. Our approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency. This article is protected by copyright. All rights reserved.

Enhancing the microbial advanced oxidation of P-nitrophenol in sediment through accelerating extracellular respiration with electrical stimulation.

Microbial advanced oxidation, a fundamental process for pollutant degradation in nature, is limited in efficiency by the weak respiration of indigenous microorganisms. In this study, an electric field was employed to enhance microbial respiration and facilitate the microbial advanced oxidation of p-nitrophenol (PNP) in simulated wetlands with alternation of anaerobic and aerobic conditions. With intermittent air aeration, an electric field of 0.8 V promoted extracellular electron transfer to increase Fe2+ generation through dissimilatory iron reduction and the production of hydroxyl radicals (•OH) through Fenton-like reactions. As a result, the PNP removal rate of the electrically-stimulated group was higher than that of the control (72.15 % vs 46.88 %). Multiple lines of evidence demonstrated that the electrically-induced polarization of respiratory enzymes expedited proton-coupled electron transfer within the respiratory chain to accelerate microbial advanced oxidation of PNP. The polarization of respiratory enzymes with the electric field hastened proton outflow to increase cell membrane potential for adenosine triphosphate (ATP) generation, which enhanced intracellular electron transportation to benefit reactive oxygen species generation. This study provided a new method to enhance microelectrochemical remediation of the contaminant in wetlands via the combination of intermittent air aeration.

A class-imbalanced hybrid learning strategy based on Raman spectroscopy of serum samples for the diagnosis of hepatitis B, hepatitis A, and thyroid dysfunction.

Computer-aided vibrational spectroscopy detection technology has achieved promising results in the field of early disease diagnosis. Yet limited by factors such as the number of actual samples and the cost of spectral acquisition in clinical medicine, the data available for model training are insufficient, and the amount of data varies greatly between different diseases, which constrain the performance optimization and enhancement of the diagnostic model. In this study, vibrational spectroscopy data of three common diseases are selected as research objects, and experimental research is conducted around the class imbalance situation that exists in medical data. When dealing with the challenge of class imbalance in medical vibrational spectroscopy research, it no longer relies on some kind of independent and single method, but considers the combined effect of multiple strategies. SVM, K-Nearest Neighbor (KNN), and Decision Tree (DT) are used as baseline comparison models on Raman spectroscopy medical datasets with different imbalance rates. The performance of the three strategies, Ensemble Learning, Feature Extraction, and Resampling, is verified on the class imbalance dataset by G-mean and AUC metrics, respectively. The results show that all the above three methods mitigate the negative impact caused by unbalanced learning. Based on this, we propose a hybrid ensemble classifier (HEC) that integrates resampling, feature extraction, and ensemble learning to verify the effectiveness of the hybrid learning strategy in solving the class imbalance problem. The G-mean and AUC values of the HEC method are 82.7 % and 83.12 % for the HBV dataset, is 2.02 % and 1.98 % higher than the optimal strategy; 83.62 % and 83.76 % for the HCV dataset, is 9.79 % and 8.47 % higher than the optimal strategy; while for the thyroid dysfunction dataset are 77.56 % and 77.85 %, is 6.92 % and 6.36 % higher than that of the optimal strategy, respectively. The experimental results show that the G-mean and AUC metrics of the HEC method are higher than those of the baseline classifier as well as the optimal combination using separate strategies. It can be seen that the HEC method can effectively counteract the unfavorable effects of imbalance learning and is expected to be applied to a wider range of imbalance scenarios.

The G143S mutation in cytochrome b confers high resistance to pyraclostrobin in Fusarium pseudograminearum.

BACKGROUND: Wheat crown rot (WCR), primarily caused by Fusarium pseudograminearum has become more and more prevalent in winter wheat areas in China. However, limited fungicides have been registered for the control of WCR in China so far. Pyraclostrobin is a representative quinone outside inhibitor (QoI) with excellent activity against Fusarium spp. There is currently limited research on the resistance risk and resistance mechanism of F. pseudograminearum to pyraclostrobin. RESULTS: Here, we determined the activity of pyraclostrobin against F. pseudograminearum. The EC50 values ranged from 0.022 to 0.172 µg mL-1 with an average EC50 value of 0.071 ± 0.030 µg mL-1. Four highly pyraclostrobin-resistant mutants were obtained from two sensitive strains by ultraviolet (UV) mutagenesis in the laboratory. The mutants showed decreased mycelial growth rate and virulence as compared with the corresponding wild-type strains, indicating that pyraclostrobin resistance suffered a fitness penalty in F. pseudograminearum. It was found that the high resistance of four mutants was caused by the G143S mutation in Cytb. Molecular docking analysis also further confirms that the G143S mutation in Cytb decreased the binding affinity between pyraclostrobin and Cytb. CONCLUSION: The resistance risk of F. pseudograminearum to pyraclostrobin could be low to medium. Although a mutation at the G143S position of Cytb could potentially occur, this mutation decreases the fitness of the mutant, which may reduce its survival in the environment. Therefore, the negative consequences of a possible mutation are lower. This makes pyraclostrobin a good candidate for controlling crown rot in wheat. © 2024 Society of Chemical Industry.

Genome-Wide Identification, Molecular Characterization, and Expression Analysis of the HSP70 and HSP90 Gene Families in Thamnaconus septentrionalis.

Heat shock proteins (HSPs) are a class of highly conserved proteins that play an important role in biological responses to various environmental stresses. The mariculture of Thamnaconus septentrionalis, a burgeoning aquaculture species in China, frequently encounters stressors such as extreme temperatures, salinity variations, and elevated ammonia levels. However, systematic identification and analysis of the HSP70 and HSP90 gene families in T. septentrionalis remain unexplored. This study conducted the first genome-wide identification of 12 HSP70 and 4 HSP90 genes in T. septentrionalis, followed by a comprehensive analysis including phylogenetics, gene structure, conserved domains, chromosomal localization, and expression profiling. Expression analysis from RNA-seq data across various tissues and developmental stages revealed predominant expression in muscle, spleen, and liver, with the highest expression found during the tailbud stage, followed by the gastrula, neurula, and juvenile stages. Under abiotic stress, most HSP70 and HSP90 genes were upregulated in response to high temperature, high salinity, and low salinity, notably hspa5 during thermal stress, hspa14 in high salinity, and hsp90ab1 under low salinity conditions. Ammonia stress led to a predominance of downregulated HSP genes in the liver, particularly hspa2, while upregulation was observed in the gills, especially for hsp90b1. Quantitative real-time PCR analysis corroborated the expression levels under environmental stresses, validating their involvement in stress responses. This investigation provides insights into the molecular mechanisms of HSP70 and HSP90 in T. septentrionalis under stress, offering valuable information for future functional studies of HSPs in teleost evolution, optimizing aquaculture techniques, and developing stress-resistant strains.

Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms.

Single-cell RNA sequencing (scRNA-seq) datasets contain true single cells, or singlets, in addition to cells that coalesce during the protocol, or doublets. Identifying singlets with high fidelity in scRNA-seq is necessary to avoid false negative and false positive discoveries. Although several methodologies have been proposed, they are typically tested on highly heterogeneous datasets and lack a priori knowledge of true singlets. Here, we leveraged datasets with synthetically introduced DNA barcodes for a hitherto unexplored application: to extract ground-truth singlets. We demonstrated the feasibility of our framework, "singletCode," to evaluate existing doublet detection methods across a range of contexts. We also leveraged our ground-truth singlets to train a proof-of-concept machine learning classifier, which outperformed other doublet detection algorithms. Our integrative framework can identify ground-truth singlets and enable robust doublet detection in non-barcoded datasets.

Enhancing frozen dough quality: Investigating the impact of soy hull polysaccharide (SHP) on rheological properties and microstructure.

The effects of SHP on the texture, rheological properties, starch crystallinity and microstructure of frozen dough were investigated. The efficacy of SHP in enhancing dough quality is concentration-dependent, with frozen dough containing 1.5% SHP exhibiting hardness comparable to fresh dough without SHP (221.31 vs. 221.42 g). Even at 0.5% SHP, there is a noticeable improvement in frozen dough quality. The rheological results showed that the viscoelasticity of dough increased with higher SHP concentration. What's more, XRD and SEM results indicated that the SHP's hydrophilicity reduces the degree of starch hydrolysis, slows down the damage of starch particles during freezing, and consequently lowers the crystallinity of starch. Additionally, CLSM observations revealed that SHP enhances the gluten network structure, diminishing the appearance of holes. Therefore, the physical, chemical properties, and microstructure of frozen dough with SHP demonstrate significant enhancement, suggesting SHP's promising antifreeze properties and potential as a food antifreeze agent.

Mid1 promotes synovitis in rheumatoid arthritis via ubiquitin-dependent post-translational modification.

INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.

A Study on the Borehole Wall Stability Analysis and Slurry Ratio Optimization for Construction of Pile in Complex Marine Strata.

In order to address the issue of hole collapse, which frequently arises when boring piles are being constructed in intricate marine strata, this paper discusses the influence of the slurry ratio on the slurry performance as well as the mechanism of slurry wall protection. It performs this by means of theoretical analysis, laboratory ratio testing, engineering analogies, numerical simulation, and field testing. Our findings demonstrate that adding sodium polyacrylate and sodium carboxymethyl cellulose can enhance mud's viscosity, contribute to flocculation, and improve the connection between mud and soil layers. Refering similar engineering cases, three optimization schemes are proposed for achieving a mud ratio that offers wall protection in complex marine strata. Furthermore, the particle flow model of slurry viscous fluid is established. The collapse of holes in the sand layer is reflected in the uneven radial displacement of hole walls and the invasion of mud particles. Increasing the viscosity of mud gradually transforms the uneven radial deformation of pore walls in the sand layer into a uniform radial deformation, whereas increasing the proportion of mud significantly decreases the radial displacement of hole walls. Additionally, when the mud pressure in the hole is 300 kPa and 600 kPa, the wall protection effect is better, and there is no particle penetration by substances such as sand. It is found that a high mud pressure can promote the diffusion of mud particles into the sand layer, while low mud pressure cannot balance the pressure on deep soil. The results of the field tests show that the ratio of water-clay-bentonite-CMC-Na-sodium carbonate = 700:110:90:1.5:0.5 used (where the mass percentage of each material is 77.8% water, 12.2% clay, 10% bentonite, 0.16% CMC-Na, and 0.05% sodium carbonate) can effectively prevent hole collapse and reduce the thickness of the sand layer at the bottom of the hole by 50%.

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

Liquiritin Alleviates Inflammation in Lipopolysaccharide-Induced Human Corneal Epithelial Cells.

PURPOSE: This research was designed to elucidate the anti-inflammatory impacts of liquiritin on lipopolysaccharide (LPS)-activated human corneal epithelial cells (HCECs). METHODS: The Cell Counting kit-8 (CCK-8) assay was adopted to assess cell viability. The enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α. Transcriptome analysis was conducted to identify the genes that exhibited differential expression between different treatment. The model group included cells treated with LPS (10 µg/mL), the treatment group comprised cells treated with liquiritin (80 µM) and LPS (10 µg/mL), and the control group consisted of untreated cells. To further validate the expression levels of the selected genes, including CSF2, CXCL1, CXCL2, CXCL8, IL1A, IL1B, IL24, IL6, and LTB, quantitative real-time PCR was performed. The expression of proteins related to the Akt/NF-κB signaling pathway was assessed through western blot analysis. NF-κB nuclear translocation was evaluated through immunofluorescence staining. RESULTS: The secretion of IL-6, IL-8, and TNF-α in LPS-induced HCECs was significantly downregulated by liquiritin. Based on the transcriptome analysis, the mRNA expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-1ß, IL-24, TNF-α, and IL-1α was overproduced by LPS stimulation, and suppressed after liquiritin treatment. Furthermore, the Western blot results revealed a remarkable reduction in the phosphorylation degrees of NF-κB p65, IκB, and Akt upon treatment with liquiritin. Additionally, immunofluorescence analysis confirmed liquiritin's inhibition of LPS-induced p65 nuclear translocation. CONCLUSIONS: Collectively, these findings imply that liquiritin suppresses the expression of proinflammatory cytokines, and the anti-inflammatory impacts of liquiritin may be caused by its repression of the Akt/NF-κB signaling pathway in LPS-induced HCECs. These data indicate that liquiritin could provide a potential therapeutic application for inflammation-associated corneal diseases.

Down-regulation of long noncoding RNA HOXA11-AS nullifies the impact of microRNA-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis.

OBJECTIVES: This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis (OA). METHODS: The articular cartilages were provided by OA patients who received total knee arthroplasty, and Human Chondrocyte (HC)-OA (HCOA) was also attained. The miR-506-3p and HOXA11-AS expressions in articular cartilages from OA patients and HCOA cells were analyzed via qPCR. After gain- and loss-of-function assays in HCOA cells, MTT assay and flow cytometry (FC) were used for assessing cell viability and apoptosis, accordingly. The levels of PIK3CA, AKT, and mTOR as well as AKT and mTOR phosphorylation levels assessed using western blotting (WB). The targeting correlation of HOXA11-AS and miR-506-3p as well as miR-506-3p and PIK3CA was assessed through Dual-Luciferase Reporter gene Assay (DLRA). RESULT: The articular cartilages from OA patients and Human Chondrocyte (HC)-OA (HCOA) cells showed increased HOXA11-AS and decreased miR-506-3p. Mechanistically, HOXA11-AS was capable of binding to miR-506-3p to increase PIK3CA, the target gene of miR-506-3p. miR-506-3p suppression facilitated HCOA cell proliferation and reduced their apoptosis, which was nullified by further silencing HOXA11-AS or silencing PIK3CA. The down-regulation of HOXA11-AS disrupted the PI3K/AKT/mTOR pathway, which was counteracted by further miR-506-3p inhibition. CONCLUSION: The silencing of HOXA11-AS might block the PI3K/AKT/mTOR pathway through miR-506-3p up-regulation, thereby restricting HCOA cell proliferation and provoking apoptosis.

Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Understanding the removal of heavy metals from stormwater runoff in permeable pavement system.

Understanding the removal of heavy metals (HMs) in permeable pavement systems is of great significance for controlling urban runoff pollution and optimizing structural design. However, few studies have systematically investigated the mechanism of permeable pavement systems in removing HMs from stormwater runoff. In this study, we adopted a hierarchical strategy to understand the efficiency of individual structural layers on HMs removal in a permeable interlocking concrete pavement (PICP) system. Experimental results illuminated that the surface layer exhibited the highest uptakes of HMs, which can remove up to 64 % of Pb2+, 50 % of Cu2+, 28 % of Cd2+ and 13 % of Zn2+. Meanwhile, as the rainfall return period increased, the removal rates of HMs in PICP was gradually decreased. In addition, batch experiments were conducted and the adsorption results were in accordance with the rainfall filtration experiments. More importantly, X-ray Photoelectron Spectroscopy (XPS) and leaching results were investigated to understand the HMs removal mechanism, which found that the ion exchange is the main mechanism in the surface layer to remove HMs, whereas the chemical adsorption play a crucial role in the base and sub-base layers. Overall, these findings provided new insights into the transport patterns of HMs in the internal structural layers of the PICP.

Simultaneous removal of phenanthrene and Pb using novel PPG-CNTs-nZVI beads.

PPG-CNTs-nZVI bead was synthesized by polyvinyl alcohol, pumice, carbon nanotube, and guar gum-nanoscale zero-valent iron to be applied on simultaneously removal of polycyclic aromatic hydrocarbons (PAHs; phenanthrene) and heavy metals (Pb2+) via adsorption. The individual and simultaneous removal efficiency of phenanthrene and Pb2+ using the PPG-CNTs-nZVI beads was evaluated with a range of initial concentrations of these two pollutants. The kinetics and isotherms of phenanthrene and Pb2+ adsorption by the PPG-CNTs-nZVI beads were also determined. The PPG-CNTs-nZVI beads show reasonably high phenanthrene adsorption capacities (up to 0.16 mg/g), and they absorbed 85% of the phenanthrene (initial concentration 0.5 mg/L) in 30 min. High Pb2+ adsorption capabilities were also demonstrated by the PPG-CNTs-nZVI beads (up to 11.6 mg/g). The adsorption fits the Langmuir model better than the Freundlich model. The adsorption still remained stable with various ionic strength circumstances and a wide pH range (2-5). Additionally, the co-adsorption of phenanthrene and Pb2+ by the PPG-CNTs-nZVI beads resulted in synergistic effects. Particularly, phenanthrene-Pb2+ complex formation via π-cation interactions demonstrated a greater affinity than phenanthrene or Pb2+ alone. The present findings suggest that PPG-CNTs-nZVI beads may be effective sorbents for the simultaneous removal of PAHs and heavy metals from contaminated waters.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling.

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Structural characterization of the polysaccharide from the black crystal region of Inonotus obliquus and its effect on AsPC-1 and SW1990 pancreatic cancer cell apoptosis.

In this study, one water soluble polysaccharide (IOP1-1) with a weight average molecular weight of 6886 Da was obtained from the black crystal region of Inonotus obliquus by hot water extraction, DEAE-52 cellulose extraction and Sephadex-100 column chromatography purification. Structural analysis indicated that IOP1-1 was a glucan with a main chain composed of α-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 4)-ß-Glcp-(1 â†’ 4)-ß-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 6)-ß-Glcp-(1 â†’ 4)-α-Glcp-(1 â†’ 3)-ß-Glcp-(1→. The CCK-8 assay results showed that IOP1-1 inhibited AsPC-1 and SW1990 pancreatic cancer cell proliferation in a concentration-dependent manner. Flow cytometric analysis revealed that IOP1-1 induced cell cycle arrest in AsPC-1 and SW1990 cells. Hoechst 33342 staining and Annexin V-FITC/PI double staining analysis showed that IOP1-1 could induce apoptosis in AsPC-1 and SW1990 cells. Furthermore, western blot analysis confirmed that IOP1-1 could induce apoptosis in AsPC-1 and SW1990 pancreatic cancer cells through three pathways: the mitochondrial pathway, the death receptor pathway, and endoplasmic reticulum stress. According to these research data, IOP1-1 may be utilized as an adjuvant treatment to anticancer medications, opening up new application prospects and opportunities.

Enhancing X-Ray Sensitization with Multifunctional Nanoparticles.

In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

EO nonlinear function generator.

An electro-optical programmable nonlinear function generator (PNFG) is developed on a multimode waveguide with four parallel thermal electrodes. The current on one electrode is chosen as the input, while the rest serve as function-defining units to modulate the multimode interference. The electro-thermo-optical effects are analyzed step by step and the impact on the eigenmode properties is derived. It shows that the optical output power variation by altered interference, in response to the input current, manifests as a complex ensemble of functions in general. The PNFG aims to find the special setting under which such relation can be simplified into some basic functions. Through an optimization program, a variety of such functions are found, including Sigmoid, SiLU, and Gaussian. Furthermore, the shape of these functions can be adjusted by finetuning the defining units. This device may be integrated in a large-scale photonic computing network that can tackle complex problems with nonlinear function adaptability.

Prenatal diesel exhaust exposure alters hippocampal synaptic plasticity in offspring.

Diesel exhaust particles (DEPs) are major air pollutants emitted from automobile engines. Prenatal exposure to DEPs has been linked to neurodevelopmental and neurodegenerative diseases associated with aging. However, the specific mechanism by DEPs impair the hippocampal synaptic plasticity in the offspring remains unclear. Pregnant C57BL/6 mice were administered DEPs solution via the tail vein every other day for a total of 10 injections, then the male offsprings were studied to assess learning and memory by the Morris water maze. Additionally, protein expression in the hippocampus, including CPEB3, NMDAR (NR1, NR2A, NR2B), PKA, SYP, PSD95, and p-CREB was analyzed using Western blotting and immunohistochemistry. The alterations in the histomorphology of the hippocampus were observed in male offspring on postnatal day 7 following prenatal exposure to DEPs. Furthermore, 8-week-old male offspring exposed to DEPs during prenatal development exhibited impairments in the Morris water maze test, indicating deficits in learning and memory. Mechanistically, the findings from our study indicate that exposure to DEPs during pregnancy may alter the expression of CPEB3, SYP, PSD95, NMDAR (NR1, NR2A, and NR2B), PKA, and p-CREB in the hippocampus of both immature and mature male offspring. The results offer evidence for the role of the NMDAR/PKA/CREB and CPEB3 signaling pathway in mediating the learning and memory toxicity of DEPs in male offspring mice. The alterations in signaling pathways may contribute to the observed damage to synaptic structure and transmission function plasticity caused by DEPs. The findings hold potential for informing future safety assessments of DEPs.