Promoting oxygen vacancies utility for tetracycline degradation via peroxymonosulfate activation by reduced Mg-doped Co3O4: Kinetics and key role of electron transfer pathway.

Developing cobalt-based catalysts with a high abundance of oxygen vacancies (Vo) and exceptional Vo utility efficiency for the prompt removal of stubborn contaminants through peroxymonosulfate (PMS) activation poses a significant challenge. Herein, we reported the synthesis of the reduced Mg-doped Co3O4 nanosheets, i.e. Mg-doped Co3O4-r, via Mg doping and followed by NaBH4 reduction, aiming to degrade tetracycline (TC). Various characterization results illustrated that NaBH4 reduction imparted higher Vo utility efficiency to Mg-doped Co3O4-r, along with an ample presence of reduced Co2+ species and an increased surface area, thereby substantially elevating PMS activation capability. Notably, Mg-doped Co3O4-r achieved more than 97.9% degradation of 20 mg/L TC within 10 min, showing an over 8-fold increase in reaction rate relative to the Mg-doped Co3O4 (kobs: 0.3285 min-1 vs 0.0399 min-1). The high removal efficiency of TC was sustained across a broad pH range of 3-11, even in the presence of common anions and humic acid. Radical quenching trials, EPR outcomes, and electrochemical analysis indicated that neither radicals nor 1O2 were the primary active species. Instead, electron transfer pathway played a dominant role in TC degradation. The Mg-doped Co3O4-r displayed excellent recyclability and versatility. Even after the fifth cycle, it maintained an impressive 83.0% removal of TC. Furthermore, it exhibited rapid degradation capabilities for various pollutants, including levofloxacin, pefloxacin, ciprofloxacin, malachite green, and rhodamine B. The TC degradation pathway was proposed based on LC-MS determination of its degradation intermediates. This study showcases an innovative strategy for the rational design of an efficient cobalt-based activator, leveraging electron transfer pathways through PMS activation to degrade antibiotics effectively.

Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway.

BACKGROUND: Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS: DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS: The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION: KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

UV-aged polystyrene nanoplastics aggravate intestinal barrier damage by overproduction of ROS.

UV irradiation significantly alters nanoplastics (NPs) physicochemical properties, thus affecting their biological toxicity. This study is the first to assess the influence of virgin and UV-aged polystyrene NPs (v-PS NPs, a-PS NPs) on the intestinal barrier of ICR mice. We found that a-PS NPs can cause more severe intestinal barrier damage compared with v-PS NPs. The reason may be attributed to that a-PS NPs produced more ROS in intestinal tissue. Moreover, the strong oxidizing property of hydroxyl radicals (·OH) generated from the a-PS NPs can damage cell membranes through lipid peroxidation, thereby leading to a low clearance rate of ·OH due to the impaired intestinal tissue function, in turn, causing more ROS to accumulate and inducing severe oxidative damage. This research underscores the crucial role of ·OH in mediating oxidative damage from UV-aged nanoparticles, emphasizing the need to consider environmental factors in assessing NPs toxicity.

Insight into the structural characteristics of self-assembled liposome with epigallocatechin gallate/alcohol dehydrogenase.

In this study, the encapsulation and structural characteristics of the self-assembled liposome formed by epigallocatechin gallate (EGCG) and alcohol dehydrogenase (ADH) were studied. According to the results, EGCG significantly increased the catalytic activity of ADH with a 33.33 % activation rate and the liposomes were able to entrap EGCG-ADH with an effectiveness of 88.94 %. The self-assembled monolayers had nanometer-sized particles, and the excellent self-assembled system was demonstrated by the low PDI value and high surface absolute potential. The scanning electron microscope showed that the self-assembled liposome was honeycomb, groove-shaped, and rough. The spectroscopic results showed that EGCG-ADH complex was formed through hydrogen bond, which changed the secondary structure of the liposome, and verified EGCG-ADH liposome system was successfully prepared. In vitro digestion experiments showed that the gastrointestinal tolerance and antioxidant activity of EGCG-ADH liposomes were significantly higher than those of free EGCG-ADH.

NFKBIZ regulates NFκB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates. NFKBIZ, a member of the nuclear factor kappa B inhibitory family, is closely related to tumor progression. However, the precise role of NFKBIZ in HCC remains unclear. To explore this, we conducted a series of experiments from clinic to cells. Western blot and qPCR revealed a significant downregulation of NFKBIZ in human HCC tissues. Clinical character analysis showed that the patients with lower NFKBIZ expression had poorer prognosis and higher clinical stage. By using CCK-8, wound healing, transwell invasion and migration assay, we discovered that NFKBIZ expression was reversely associated with the proliferation, invasion, and migration ability of HCC cells in vitro. Additionally, the results obtained from xenograft assay and lung metastasis models showed that NFKBIZ overexpression inhibited the growth and metastasis of HCC cells in vivo. Western blot and immunofluorescence assay further revealed that NFKBIZ mediated HCC cell growth and migration by regulating NFκB signaling transduction. Finally, flow cytometry, protein degradation assay and Co-immunoprecipitation indicated that TRIM16 can enhance NFKBIZ ubiquitination by direct interactions at its K48 site, which may thereby alleviate HCC cell apoptosis to induce the insensitivity to sorafenib. In conclusion, our study demonstrated that NFKBIZ regulated HCC tumorigenesis and metastasis by mediating NFκB signal transduction and TRIM16/NFKBIZ/NFκB axis may be the underlying mechanism of sorafenib insensitivity in HCC.

Cyy-287, a novel pyrimidine-2,4-diamine derivative, efficiently mitigates inflammatory responses, fibrosis, and lipid synthesis in obesity-induced cardiac and hepatic dysfunction.

Background: Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). Methods: The mice were randomly separated into four groups (n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks. After a 10-week administration, ALT and AST enzymes, echocardiography, immunohistochemical (IHC), Western blot (WB), Masson and Sirius Red staining were used to evaluate functional and morphological changes to the heart and liver. Microsomes from the mouse liver were extracted to quantify the total amount of CYP450 enzymes after drug treatment. Results: Cyy-287 decreased the levels of serum glucose, LDL, TC, ALT, and AST activities in HFD-treated mice. However, Cyy-287 administration increased ejection fraction (EF) and fractional shortening (FS) index of the heart. Cyy-287 inhibited histopathological changes in the heart and liver; decreased inflammatory activity; significantly diminished p38 mitogen-activated protein kinase (MAPK), the nuclear factor-kappa B (NF-κB) axis, and sterol regulatory element-binding protein-1c (SREBP-1c); and upregulated the AMP-activated protein kinase (AMPK) pathway in HFD-treated mice. Cyy-287 restored the content of hepatic CYP450 enzymes. Conclusion: These findings demonstrated that Cyy-287 protected heart and liver cells from obesity-induced damage by inhibiting inflammation, fibrosis, and lipid synthesis.

Changes in cargoes of platelet derived extracellular vesicles heterogeneous subpopulations induced by PM0.1--Undisclosed cardiovascular injury communication mechanism.

Epidemiological evidence has indicated a closely link between PM0.1 exposure and the incidence rate of cardiovascular diseases. This study explores the underlying communication roles of platelet-derived extracellular vesicles (PEVs) heterogeneous subpopulations in cardiovascular injury. PEVs and PMEVs which were extracted from platelet-rich plasma (PRP) un-exposure or exposure to PM0.1 by TIM4 affinity beads. By optimizing separation conditions, replacing pipelines, and resetting injection procedures, Asymmetric flow field-flow fractionation (AF4) was employed to separate, purify, characterize, and enrich PEVs and PMEVs heterogeneous subpopulations (small PEVs, PEVs-S/PMEVs-S: <100 nm; medium PEVs, PEVs-M/PMEVs-M: 100-200 nm; and large PEVs, PEVs-L/PMEVs-L: >200 nm). The results showed that the cargoes of PMEVs heterogeneous subpopulations which were released by PRP stimulated by PM0.1 were changed obviously. Moreover, compared with PEVs, PMEVs can lead to a decrease in the survival rate of Human Umbilical Vein Endothelial Cells (HUVECs). In PMEVs-S subpopulations, the alterations of lipids associated with membrane fusion and cell signaling transport (such as PC, Cer), as well as miRNAs related to inflammation, angiogenesis, and migration (miR-223, miR-22, miR-126, and miR-150), are similar to those in PMEVs-M subpopulations but distinct from PMEVs-L subpopulations. This study revealed the diverse communication mechanisms underlying PM0.1-induced cardiovascular injury, thereby offering potential avenues for the development of new biomarkers and therapeutic targets.

Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Cross-subject EEG-based emotion recognition through dynamic optimization of random forest with sparrow search algorithm.

The objective of EEG-based emotion recognition is to classify emotions by decoding signals, with potential applications in the fields of artificial intelligence and bioinformatics. Cross-subject emotion recognition is more difficult than intra-subject emotion recognition. The poor adaptability of classification model parameters is a significant factor of low accuracy in cross-subject emotion recognition. We propose a model of a dynamically optimized Random Forest based on the Sparrow Search Algorithm (SSA-RF). The decision trees number (DTN) and the leave minimum number (LMN) of the RF are dynamically optimized by the SSA. 12 features are used to construct feature combinations for selecting the optimal feature combination. DEAP and SEED datasets are employed for testing the performance of SSA-RF. The experimental results show that the accuracy of binary classification is 76.81% on DEAP, and the accuracy of triple classification is 75.96% on SEED based on SSA-RF, which are both higher than that of traditional RF. This study provides new insights for the development of cross-subject emotion recognition, and has significant theoretical value.

Analysis of the effects of ß-mannanase on immune function and intestinal flora in broilers fed the low energy diet based on 16S rRNA sequencing and metagenomic sequencing.

As an enzyme, ß-mannanase (BM) can be widely used as feed additive to improve the growth performance of animals. This experiment aimed to determine the effect of the addition of BM to low-energy diet on the immune function and intestinal microflora of broiler chickens. In this study, 384 one-day-old Arbor Acres broilers were randomly divided into 3 groups (8 replicates per group): positive control (PC, received a corn-soybean meal basal diet), negative control (NC, received a low-energy diet with Metabolizable Energy (ME) reduced by 50 kcal/kg) and NC + BM group (NC birds + 100 mg/kg BM). All birds were raised for 42 d. The results showed that BM mitigated the damage of immune function in peripheral blood of broilers caused by the decrease of dietary energy level by increasing the Concanavalin A (Con A) index of stimulation (SI) and macrophages phagocytic activity in the peripheral blood of broilers at 42 d (P < 0.05). The analysis of cecum flora showed that the low-energy diet significantly reduced the observed_species index (P < 0.01), Chao1 index and ACE index (P < 0.05), which reduced the abundance and evenness of species in the cecum of broilers at 21 d. It also significantly reduced the relative abundance of Candidatus_Arthromitus and significantly increased the relative abundance of Pseudomonas in the cecum of broilers at 21 d, while also significantly increasing the relative abundance of Monoglobus at 42 d. BM significantly increased the relative abundance of Lachnospiraceae_UCG-001 and Lachnospiraceae_bacterium_615 in the cecum of broilers at 21 d. In addition, BM inhibited microbial Fatty acid degradation by decreasing the activity of glutaryl-CoA dehydrogenase. Collectively, BM could improve intestinal health by enhancing the immune function of broilers, promoting the proliferation of beneficial bacteria and reducing the number of harmful bacteria, regulating intestinal flora, thereby alleviating the adverse effects of lower dietary energy levels.

Comparison of Efficacy and Adherence of Patient-Preferred (1 Unit Daily) and ADA/EASD Guideline-Recommended (2 Units Every 3 Days) Basal Insulin Titration Algorithms: Multicenter, Randomized, Clinical Study.

Aim: Insulin titration often faces inertia, hindering glycemic control. A patient-centered approach empowers patients to overcome this inertia. This study aims to compare the effectiveness of patient-preferred and guideline-recommended self-titration algorithms in achieving glycemic targets and improving adherence. Methods: Outpatients with type 2 diabetes (T2D) who did not respond to oral antihyperglycemic drugs (OAD) were assessed. They were randomly assigned to patient-preferred and guideline-recommended groups. In the patient-preferred group, individuals selected an algorithm to self-adjust their insulin glargine dosage by 2 units every 3 days if the mean fasting blood glucose (FBG) over the past 3 consecutive days was ≥7.0 mmol/L, or by 1 unit daily if the FBG on the same day was ≥7.0 mmol/L. In the guideline-recommended group, insulin glargine was titrated by 2 units every 3 days if the mean FBG over the past 3 consecutive days was ≥7.0 mmol/L. The FBG target was set below <7.0 mmol/L. Results: Thirty-nine participants in the patient-preferred group and 42 in the guideline-recommended group completed the study. The cumulative rates of achieving the FBG target in the patient-preferred group compared to the guideline-recommended group were 69.2% vs 54.8% (χ²=1.792, p=0.181) in week 1, 89.7% vs 73.8% (χ²=3.403, p = 0.065) in week 2, 94.9% vs 76.2% (χ²=17.638, p=0.000) in week 3, and 100.0% vs 88.1% (χ²=4.405, p=0.036) in week 4. Adherence rates were significantly higher in the patient-preferred group (97.4%, 37/38) compared to the guideline-recommended group (66.7%, 28/42) (χ²=12.688, p=0.000). Insulin glargine dosage at FBG target achievement was 21.2±4.3 U in the patient-preferred group and 18.8±6.7 U in the guideline-recommended group (t=1.888, p=0.063). Hypoglycemia was reported in 1 patient in the guideline-recommended group, with no instances in the patient-preferred group. Conclusion: The patient-preferred self-titration algorithm demonstrates a higher rate of reaching glucose targets and improved adherence. Trial Registration Number: ChiCTR2100050805.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

pathMap: a path-based mapping tool for long noisy reads with high sensitivity.

With the rapid development of single-molecule sequencing (SMS) technologies, the output read length is continuously increasing. Mapping such reads onto a reference genome is one of the most fundamental tasks in sequence analysis. Mapping sensitivity is becoming a major concern since high sensitivity can detect more aligned regions on the reference and obtain more aligned bases, which are useful for downstream analysis. In this study, we present pathMap, a novel k-mer graph-based mapper that is specifically designed for mapping SMS reads with high sensitivity. By viewing the alignment chain as a path containing as many anchors as possible in the matched k-mer graph, pathMap treats chaining as a path selection problem in the directed graph. pathMap iteratively searches the longest path in the remaining nodes; more candidate chains with high quality can be effectively detected and aligned. Compared to other state-of-the-art mapping methods such as minimap2 and Winnowmap2, experiment results on simulated and real-life datasets demonstrate that pathMap obtains the number of mapped chains at least 11.50% more than its closest competitor and increases the mapping sensitivity by 17.28% and 13.84% of bases over the next-best mapper for Pacific Biosciences and Oxford Nanopore sequencing data, respectively. In addition, pathMap is more robust to sequence errors and more sensitive to species- and strain-specific identification of pathogens using MinION reads.

Enhancing Ultraviolet Stability and Performance of Wide Bandgap Perovskite Solar Cells Through Ultraviolet Light-Absorbing Passivator.

Ultraviolet light (UV) has caused tremendous damage to perovskite solar cells (PSCs), degrading the perovskite and shortening their lifetime. Defects act as non-radiative recombination sites, accelerate the degradation process, reduce the efficiency of the device and weaken the stability of solar cell. In this work, to realize efficient and stable p-i-n wide bandgap solar cells under UV, a synergetic strategy utilizing UV light-absorbing passivator, (Trifluoroacetyl) benzotriazole (TFABI), enhance UV photostability and regulate the defect passivation is proposed. By using TFABI, the degradation of the perovskite absorption layer under UV light is suppressed, spectral response is enhanced and the Pb vacancy defects are passivated. As a result, the target device achieves an efficiency of 21.54%, exhibiting excellent long-term stability under 365 nm UV irradiation. After 60 h of irradiation, it retains 85% of its initial value (60 mW cm-2 , RH 25-30%, 25 °C).

The accessible chromatin landscape of lipopolysaccharide-induced systemic inflammatory response identifying epigenome signatures and transcription regulatory networks in chickens.

Lipopolysaccharide (LPS) can induce systemic inflammatory response (SIR) in animals. Understanding the regulatory mechanism of SIR and therapies to ensure healthy growth is urgently needed. Chromatin remodeling plays a crucial role in the expression of genes involved in immune diseases. In the present study, the ATAC-seq analysis revealed 3491 differential open chromatin sites in the spleen of chicks with SIR induced by LPS challenge, and we presented the motifs on these sites and the associated transcription factors. The regulatory network was presented by combining the differential open chromatin data with the mRNAs and exploded cytokines. Interestingly, the LPS challenge could regulate the mRNA expression of 202 genes through chromatin reprogramming, including critical genes such as TLE1 and JUN, which regulate signaling pathways such as I-κB kinase/NF-κB, Toll-like receptor, and downstream cytokine genes. Furthermore, dietary daidzein could inhibit DNA topoisomerase II, which reprograms the spatial conformation of chromatin in the inflammatory response and attenuates SIR. In conclusion, we successfully identified key genes directly regulated by chromatin reprogramming in SIR and demonstrated the chromatin epigenome signatures and transcriptional regulatory network, which provides an important reference for further research on avian epigenetics. There is great potential for alleviating SIR using dietary daidzein.

Sasanquasaponin from Camellia oleifera Abel Exerts an Anti-Inflammatory Effect in RAW 264.7 Cells via Inhibition of the NF-κB/MAPK Signaling Pathways.

Sasanquasaponin (SQS), a secondary metabolite that is derived from Camellia seeds, reportedly possesses notable biological properties. However, the anti-inflammatory effects of SQS and its underlying mechanisms remain poorly explored. Herein, we aimed to investigate the anti-inflammatory properties of SQS against lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells, focusing on the nuclear factor-κB (NF-κB) and MAPK signaling pathways. SQS was isolated using a deep eutectic solvent and D101 macroporous adsorption resin and analyzed using high-performance liquid chromatography. The viability of LPS-stimulated RAW264.7 was assessed using the CCK-8 assay. The presence of reactive oxygen species (ROS) was evaluated using 2',7'-dichlorofluorescein-diacetate. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using reverse transcription-quantitative PCR and ELISA. Western blot was performed to analyze the protein expression of LPS-induced RAW264.7 cells. Herein, SQS exhibited anti-inflammatory activity: 30 µg/mL of SQS significantly reduced ROS generation, inhibited the LPS-induced expression of iNOS and COX-2, and attenuated the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. The anti-inflammatory activity was potentially mediated by inhibiting the phosphorylation of IκBα and p65 in the NF-κB signaling pathway and the phosphorylation of ERK and JNK in the MAPK signaling pathway. Accordingly, SQS could inhibit inflammation in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPK signaling pathways. This study demonstrated the potential application of SQS as an anti-inflammatory agent.

Nanoscale Local Contacts Enable Inverted Inorganic Perovskite Solar Cells with 20.8 % Efficiency.

Inorganic perovskite solar cells (IPSCs) have gained significant attention due to their excellent thermal stability and suitable band gap (~1.7 eV) for tandem solar cell applications. However, the defect-induced non-radiative recombination losses, low charge extraction efficiency, energy level mismatches, and so on render the fabrication of high-efficiency inverted IPSCs remains challenging. Here, the use of 3-amino-5-bromopyridine-2-formamide (ABF) in methanol was dynamically spin-coated on the surface of CsPbI2.85Br0.15 film, which facilitates the limited etching of defect-rich subsurface layer, resulting in the formation of vertical PbI2 nanosheet structures. This enabled localized contacts between the perovskite film and the electron transport layer, suppress the recombination of electron-hole and beneficial to electron extraction. Additionally, the C=O and C=N groups in ABF effectively passivated the undercoordinated Pb2+ at grain boundaries and on the surface of CsPbI2.85Br0.15 film. Eventually, we achieved a champion efficiency of 20.80 % (certified efficiency of 20.02 %) for inverted IPSCs with enhanced stability, which is the highest value ever reported to date. Furthermore, we successfully prepared p-i-n type monolithic inorganic perovskite/silicon tandem solar cells (IPSTSCs) with an efficiency of 26.26 %. This strategy provided both fast extraction and efficient passivation at the electron-selective interface.