Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain. METHODS: SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients. RESULTS: We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimeras. CONCLUSION: Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for clinical management of SLE.

The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH-/- Mice.

The meat derived from mammals such as cows, sheep, and pigs is commonly referred to as red meat. Recent studies have shown that consuming red meat can activate the immune system, produce antibodies, and subsequently develop into tumors and cancer. This is due to the presence of a potential carcinogenic compound in red meat called N-ethanol neuraminic acid (Neu5Gc). Neu5Gc is a common sialic monosaccharide in mammals, synthesized from N-acetylneuraminic acid (Neu5Ac) in the body and typically present in most mammals. However, due to the lack of the CMAH gene encoding the cytidine 5'-monophosphate Neu5Ac hydroxylase, humans are unable to synthesize Neu5Gc. Compared to primates such as mice or chimpanzees, the specific loss of Neu5Gc expression in humans is attributed to fixed genome mutations in CMAH. Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. Further research has shown that early pregnancy factor (EPF) has the ability to regulate CD4+T cell-dependent immune responses. In this study, we established a simulated human animal model using C57/BL6 mice with CMAH gene knockout and analyzed the inhibitory effect of EPF on red meat Neu5Gc-induced CMAH-/- C57/BL6 mouse antibody production and chronic inflammation development. The results showed that the intervention of EPF reduced slow weight gain and shortened colon length in mice. In addition, EPF treatment significantly reduced the levels of anti Neu5Gc antibodies in the body, as well as the inflammatory factors IL-6 and IL-1ß, TNF-α and the activity of MPO. In addition, it also alleviated damage to liver and intestinal tissues and reduced the content of CD4 cells and the expression of B cell activation molecules CD80 and CD86 in mice. In summary, EPF effectively inhibited Neu5Gc-induced antibody production, reduced inflammation levels in mice, and alleviated Neu5Gc-induced inflammation. This will provide a new re-search concept and potential approach for developing immunosuppressants to address safety issues related to long-term consumption of red meat.

Characterization of an Aptamer Targeting Neu5Gc, as an Endogenous Pathogenic Factor Derived from Red Meat.

N-glycolylneuraminic acid (Neu5Gc), a sialic acid predominantly found in the non-neurohumoral fluids of hind-mouthed animals, is incapable of synthesizing Neu5Gc due to a deletion in the CMAH exon of the gene encoding human CMP-Neu5Gc hydroxylase. But consumption of animal-derived foods that contain Neu5Gc, such as red meat, can instigate an immune response in humans, as Neu5Gc is recognized as a foreign substance by the human immune system. This recognition leads to the production of anti-Neu5Gc antibodies, subsequently resulting in chronic inflammation. When Neu5Gc is consumed excessively or frequently, it may contribute to the development of heart disease and cancer. This makes Neu5Gc, an endogenous pathogenic factor derived from red meat, a new hot topic in red meat safety research. In this study, aptamers obtained by the magnetic bead SELEX technique were subjected to homology and secondary structure prediction analysis as well as affinity determination. The result indicated that the aptamer 2B.N2A9 exhibited a robust binding affinity, with an affinity constant (Ka) of 1.87 × 108 L/mol. This aptamer demonstrated optimal binding specificity within a pH range of 5.4 to 7.4. Molecular docking analysis further revealed that aptamer 2B.N2A9 formed stable binding interactions with the target Neu5Gc at specific sites, namely G-14, C-15, G-13, G-58, G-60, and C-59. An Enzyme-Linked Oligonucleotide Sorbent Assay (ELOSA) methodology was established to detect the endogenous pathogenic factor Neu5Gc present in red meat. This method demonstrated a limit of detection (LOD) of 0.71 ng/mL, along with an average recovery rate of 92.23%. The aptamer obtained in this study exhibited favorable binding properties to Neu5Gc. The assay was relatively convenient and demonstrated good sensitivity. Further investigation into the distribution of Neu5Gc in various red meats is of public health significance and scientific potential. A practical detection method should be provided to guide red meat diets and ensure the nutrition and safety of meat products.

Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke.

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12.

A novel blue emitting phosphor Ca1-ySryScBO4:Bi3+ with zero-thermal quenching for multi-scenario application.

In recent years, Bi3+ activated phosphors have received a lot of attention from researchers; however, the performance and application areas of phosphors are yet to be developed. In this work, a series of CaScBO4(CSBO):xBi3+ phosphors were successfully prepared using a high-temperature solid-state method. Under UV excitation, blue light emission was achieved at 430 nm with a quantum yield of 91%, and at 423 K, the emission intensity retained 82.8% of the original intensity at 298 K. By crystal field engineering, the substitution of Sr2+ at the Ca2+ site enhances the temperature stability of the material, and at 423 K, 473 K and 573 K, the samples maintain 104%, 103% and 85% of the emission intensity at room temperature, respectively. It indicates that the cation substitution causes the increase in the oxygen vacancy concentration, and the oxygen vacancy defect compensates the energy lost in electrons at high temperature, producing resistance to anti-TQ performance. Finally, a blue-violet LED was fabricated by using the phosphor and an ultraviolet LED chip, and white LEDs (CCT = 4683 K, Ra = 89.7) were obtained by co-packaging this phosphor with commercial phosphors and a UV chip. Importantly, the great potential of this phosphor in the field of plant lighting and biocontrol can be demonstrated.

Interface Engineering to Drive High-Performance MXene/PbS Quantum Dot NIR Photodiode.

The realization of a controllable transparent conducting system with selective light transparency is crucial for exploring many of the most intriguing effects in top-illuminated optoelectronic devices. However, the performance is limited by insufficient electrical conductivity, low work function, and vulnerable interface of traditional transparent conducting materials, such as tin-doped indium oxide. Here, it is reported that two-dimensional (2D) titanium carbide (Ti3 C2 Tx ) MXene film acts as an efficient transparent conducting electrode for the lead sulfide (PbS) colloidal quantum dots (CQDs) photodiode with controllable near infrared transmittance. The solution-processed interface engineering of MXene and PbS layers remarkably reduces the interface defects of MXene/PbS CQDs and the carrier concentration in the PbS layer. The stable Ti3 C2 Tx /PbS CQDs photodiodes give rise to a high specific detectivity of 5.51 × 1012  cm W-1  Hz1/2 , a large dynamic response range of 140 dB, and a large bandwidth of 0.76 MHz at 940 nm in the self-powered state, ranking among the most exceptional in terms of comprehensive performance among reported PbS CQDs photodiodes. In contrast with the traditional photodiode technologies, this efficient and stable approach opens a new horizon to construct widely used infrared photodiodes with CQDs and MXenes.

Cancer CD39 drives metabolic adaption and mal-differentiation of CD4+ T cells in patients with non-small-cell lung cancer.

While ectonucleotidase CD39 is a cancer therapeutic target in clinical trials, its direct effect on T-cell differentiation in human non-small-cell lung cancer (NSCLC) remains unclear. Herein, we demonstrate that human NSCLC cells, including tumor cell lines and primary tumor cells from clinical patients, efficiently drive the metabolic adaption of human CD4+ T cells, instructing differentiation of regulatory T cells while inhibiting effector T cells. Of importance, NSCLC-induced T-cell mal-differentiation primarily depends on cancer CD39, as this can be fundamentally blocked by genetic depletion of CD39 in NSCLC. Mechanistically, NSCLC cells package CD39 into their exosomes and transfer such CD39-containing exosomes into interacting T cells, resulting in ATP insufficiency and AMPK hyperactivation. Such CD39-dependent NSCLC-T cell interaction holds well in patients-derived primary tumor cells and patient-derived organoids (PDOs). Accordingly, genetic depletion of CD39 alone or in combination with the anti-PD-1 immunotherapy efficiently rescues effector T cell differentiation, instigates anti-tumor T cell immunity, and inhibits tumor growth of PDOs. Together, targeting cancer CD39 can correct the mal-differentiation of CD4+ T cells in human NSCLC, providing in-depth insight into therapeutic CD39 inhibitors.

A Combination of CPI-0610 and SAHA Induces Apoptosis through STAT3 and p38 Signalling Pathways in Diffuse Large B-cell Lymphoma Cells.

BACKGROUND: Although immunotherapies have greatly improved diffuse large B-cell lymphoma (DLBCL) prognosis, a proportion of patients remain to be relapsed or refractory. Therefore, the identification of novel therapeutic targets and drugs is urgently required. Inhibition of the bromodomain and extra-terminal (BET) proteins has been a promising therapeutic strategy for various haematologic cancers. CPI-0610 is a potent and selective BET inhibitor. The effects of CPI-0610 in DLBCL cells have not been reported yet. AIMS: The aim of this study was to assess the effects of CPI-0610 in DLBCL and its underlying mechanisms. METHODS: DLBCL cells were treated with CPI-0610, followed by measuring cell viability, cell cycle, apoptosis, autophagy, and specific cell signaling pathways. Moreover, immunodeficient mice were engrafted with SUDHL2 cells and then treated with CPI-0610 for analysis of tumor burden. We also analyzed the synergistic effect of CPI-0610 with histone deacetylase inhibitor suberoylanilide hydroxamic acid. RESULTS: The present study demonstrated that CPI-0610 displayed cell cytotoxicity by arresting the G1 cell cycle and inducing endogenous and exogenous apoptotic pathways. Additionally, CPI-0610 decreased BRD4 and c-Myc expressions and affected MAPK, JAK/STAT, and AKT signalling pathways in human DLBCL cells. An in vivo experiment exhibited that CPI-0610 decreased the primary tumour growth of the DLBCL xenograft model. Furthermore, the use of CPI-0610 in combination with suberoylanilide hydroxamic acid exhibited a specific synergistic effect in inducing apoptosis through the regulation of STAT3 and p38. CONCLUSION: Targeting BET may be an effective therapeutic strategy and potentiated by a combination with histone deacetylase inhibition in DLBCL.

[Simulation of land use and assessment of ecosystem service value in the eastern coastal cities of Zhejiang Province, China]. / 浙江东部沿海城市土地利用模拟及生态系统服务价值评估.

Simulating the change of ecosystem service values (ESV) caused by land use/cover change (LUCC) in the eastern coastal cities of Zhejiang Province is of great significance for regional sustainable development and ecological security. Based on remote sensing images of land use and Statistics Yearbook of 2000, 2010, and 2020, we analyzed the influence of LUCC on ESV in the study area during 2000-2020. We used the PLUS model to simulate land use change under three scenarios, including inertial development, ecological protection, and urban development in 2030, analyzed the spatial distribution and concentration degree of ESVs based on grid scale, and clarified the sensitivity characteristics of ESVs. The results showed that the construction land area showed an increasing trend during 2000-2020. The area of forest, cultivated land and water decreased significantly, resulting in a continuous downward trend of ESVs, which decreased by 160×108 yuan. Under the simulation of three scenarios of inertial development, ecological development, and urban development, the construction land area would increase by 93624, 54927, and 111966 hm2, respectively. The eastern plain would become the agglomeration area of construction land expansion. The ESVs of those three scenarios was 1693×108, 1729×108, and 1688×108 yuan, respectively, which were all lower than the ESVs of the study area in 2020. The decline rate of ESV in the ecological protection scenario slowed down. The spatial distribution of ESVs in the study area was high in the west and low in the east. Hot spots and cold spots of ESVs were distributed in a large range with strong agglomeration. Hot spots were mainly concentrated in the west, while cold spots were mainly distributed in the east and north.

A Meta-Analysis of Influencing Factors on the Activity of BiVO4-Based Photocatalysts.

With the continuous advancement of global industrialization, a large amount of organic and inorganic pollutants have been discharged into the environment, which is essential for human survival. Consequently, the issue of water environment pollution has become increasingly severe. Photocatalytic technology is widely used to degrade water pollutants due to its strong oxidizing performance and non-polluting characteristics, and BiVO4-based photocatalysts are one of the ideal raw materials for photocatalytic reactions. However, a comprehensive global analysis of the factors influencing the photocatalytic performance of BiVO4-based photocatalysts is currently lacking. Here, we performed a meta-analysis to investigate the differences in specific surface area, kinetic constants, and the pollutant degradation performance of BiVO4-based photocatalysts under different preparation and degradation conditions. It was found that under the loading condition, all the performances of the photocatalysts can be attributed to the single BiVO4 photocatalyst. Moreover, loading could lead to an increase in the specific surface area of the material, thereby providing more adsorption sites for photocatalysis and ultimately enhancing the photocatalytic performance. Overall, the construct heterojunction and loaded nanomaterials exhibit a superior performance for BiVO4-based photocatalysts with 136.4% and 90.1% improvement, respectively. Additionally, within a certain range, the photocatalytic performance increases with the reaction time and temperature.

Mitochondrial Control for Healthy and Autoimmune T Cells.

T cells are critical players in adaptive immunity, driving the tissue injury and organ damage of patients with autoimmune diseases. Consequently, investigations on T cell activation, differentiation, and function are valuable in uncovering the disease pathogenesis, thus exploring promising therapeutics for autoimmune diseases. In recent decades, accumulating studies have pinpointed immunometabolism as the fundamental determinant in controlling T cell fate. Specifically, mitochondria, as a hub of intracellular metabolism, connect glucose, lipid, and amino acid metabolic pathways. Herein, we summarize metabolic adaptations of mitochondrial oxidative phosphorylation and the relevant glucose, lipid, and amino acid metabolism during T cell activation, differentiation, and function. Further, we focused on current updates of the molecular bases for metabolic reprogramming in autoimmune T cells and advances in exploring metabolic-targeted therapeutics against autoimmune diseases. This might facilitate the in-depth understanding of autoimmune pathogeneses and the clinical management of autoimmune diseases.

Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study.

BACKGROUND: Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level. METHODS: The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. RESULTS: The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01-2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17-3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 µg/mL compared with the day workers. CONCLUSIONS: Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.

iEnhancer-SKNN: a stacking ensemble learning-based method for enhancer identification and classification using sequence information.

Enhancers, a class of distal cis-regulatory elements located in the non-coding region of DNA, play a key role in gene regulation. It is difficult to identify enhancers from DNA sequence data because enhancers are freely distributed in the non-coding region, with no specific sequence features, and having a long distance with the targeted promoters. Therefore, this study presents a stacking ensemble learning method to accurately identify enhancers and classify enhancers into strong and weak enhancers. Firstly, we obtain the fusion feature matrix by fusing the four features of Kmer, PseDNC, PCPseDNC and Z-Curve9. Secondly, five K-Nearest Neighbor (KNN) models with different parameters are trained as the base model, and the Logistic Regression algorithm is utilized as the meta-model. Thirdly, the stacking ensemble learning strategy is utilized to construct a two-layer model based on the base model and meta-model to train the preprocessed feature sets. The proposed method, named iEnhancer-SKNN, is a two-layer prediction model, in which the function of the first layer is to predict whether the given DNA sequences are enhancers or non-enhancers, and the function of the second layer is to distinguish whether the predicted enhancers are strong enhancers or weak enhancers. The performance of iEnhancer-SKNN is evaluated on the independent testing dataset and the results show that the proposed method has better performance in predicting enhancers and their strength. In enhancer identification, iEnhancer-SKNN achieves an accuracy of 81.75%, an improvement of 1.35% to 8.75% compared with other predictors, and in enhancer classification, iEnhancer-SKNN achieves an accuracy of 80.50%, an improvement of 5.5% to 25.5% compared with other predictors. Moreover, we identify key transcription factor binding site motifs in the enhancer regions and further explore the biological functions of the enhancers and these key motifs. Source code and data can be downloaded from https://github.com/HaoWuLab-Bioinformatics/iEnhancer-SKNN.

Wheat straw return can lead to biogenic toluene emissions.

As a common practice in agricultural system, straw return has been reported to release a large number of trace gases and attracted much attention. However, the role of straw return in toluene emission remains poorly understood. In this study we measured the emissions of toluene as well as other 50 volatile organic compounds (VOCs) from wheat straw return for 66 days under flooded and non-flooded conditions, respectively. The results showed that substantial toluene was released from the returned wheat straw particularly under flooded condition, and primarily derived from the secondary product. Toluene emissions from the returned wheat straw were 36.8 and 8.45 mg C/kg, sharing 28.0% and 8.6% of total VOCs released, and over 90% of toluene emissions occurred between days 24-56 and 0-17 under flooded and non-flooded conditions, respectively. The emission rates of toluene were relatively high but decreased sharply at the beginning 2 days, and then was steady until 24 days under the two moisture conditions. After the initial decrease these rose again to form one "peak emission window" between days 24-56 under flooded condition, while these were still very low and steady until the end under non-flooded condition. The toluene emission rates significantly positively correlated with microbial biomass C under flooded condition, but negatively associated with bacteria and fungus number, microbial biomass C, and CO2 flux under non-flooded condition, suggesting that microorganism might play an important role in toluene emissions from wheat straw return. A rough estimate indicated that straw return might be important for biogenic toluene.

Screening and identification of miRNAs regulating Tbx4/5 genes of Pampus argenteus.

Background: Silver pomfret (Pampus argenteus) is one of the most widely distributed and economically important pelagic fish species. However, an unique morphological feature of P. argenteus is the loss of pelvic fins, which can increase the energy requirement during food capture to some extent and is therefore not conducive to artificial culture. Tbx4/5 genes are highly conserved regulatory factors that regulate limb development in vertebrates and are in turn regulated by microRNAs (miRNAs). However, the miRNAs that directly regulate the Tbx4/5 genes in P. argenteus remain to be elucidated. Methods: The Tbx4/5 genes of P. argenteus were first cloned, and the small RNA transcriptomes were sequenced by high-throughput sequencing during the critical period of the fin development at days 1, 7, and 13 of hatching. The miRNAs regulating the Tbx4/5 genes of P. argenteus were subsequently predicted by bioinformatics analysis, and the related miRNAs were verified in vitro using a dual fluorescence reporter system. Results: A total of 662 miRNAs were identified, of which 257 were known miRNAs and 405 were novel miRNAs were identified. Compared to day 1, 182 miRNAs were differentially expressed (DE) on day 7, of which 77 and 105 miRNAs were downregulated and upregulated, respectively, while 278 miRNAs were DE on day 13, of which 136 and 142 miRNAs were downregulated and upregulated, respectively. Compared to day 13, four miRNAs were DE on day 7, of which three miRNAs were downregulated and one miRNA was upregulated. The results of hierarchical clustering of the miRNAs revealed that the DE genes were inversely expressed between days 1 and 7, and between days 1 and 13 of larval development, indicating that the larvae were in the peak stage of differentiation. However, the number of DE genes between days 7 and 13 of larval development was relatively small, suggesting the initiation of development. The potential target genes of the DE miRNAs were subsequently predicted, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of target genes were performed. The results suggested that the DE miRNAs were involved in growth, development, and signal transduction pathways, of which the Wnt and Fgfs signaling pathways are known to play important roles in the growth and development of fins. The results of dual fluorescence reporter assays demonstrated that miR-102, miR-301c, and miR-589 had a significant negative regulatory effect on the 3'-UTR of the Tbx4 gene, while miR-187, miR-201, miR-219, and miR-460 had a significant negative regulatory effect on the 3'-UTR of the Tbx5 gene. Altogether, the findings indicated that miRNAs play an important role in regulating the growth and development of pelvic fins in P. argenteus. This study provides a reference for elucidating the interactions between the miRNAs and target genes of P. argenteus in future studies.

Structural Characterization of a Pleurotus sajor-caju Polysaccharide and Its Neuroprotection Related to the Inhibition of Oxidative Stress.

A novel polysaccharide PSP2-1 was isolated and purified from Pleurotus sajor-caju. The structural characterization data displayed that the molecular weight of PSP2-1 was 44.9 kDa, and PSP2-1 consisted of fucose, galactose, glucose, and mannose. The methylation results showed that the glycosidic bonds of PSP2-1 included T-Fuc, 1,6-Gal, T-Glc, 1,6-Glc, 1,3,6-Glc, 1,3-Man, 1,2,6-Man, and T-Man. Neuroprotective studies indicated that PSP2-1 significantly improved the cell viability of the H2O2-induced oxidatively damaged neuronal cell HT22, reduced the release of LDH, inhibited apoptosis and release of cytochrome c, and alleviated the decline of mitochondrial membrane potential and ROS accumulation. Furthermore, PSP2-1 decreased the phosphorylation levels of cleaved PARP and cleaved caspase-3, and increased the ratio of bcl-2/bax. Additionally, PSP2-1 could inhibit the phosphorylation of MAPK family members including JNK, p38, and Erk. Finally, animal experiments showed that PSP2-1 could improve the oxidative stress injury and the learning and memory ability of mice with aging induced by D-galactose. Our results confirmed that PSP2-1 significantly ameliorated the oxidative stress injury, inhibited the apoptosis in H2O2-induced neuronal cells via MAPK pathway, and also improved cognition in mice with aging induced by D-galactose. Our research gives the foundation for the functional food application of P. sajor-caju polysaccharides in the future.

Genomewide identification and analysis of the OSCA gene family in barley (Hordeum vulgare L.).

The hyperosmolality-gated calcium-permeable channels (OSCA) are considered to be osmotic sensors that play an important role in the early stages of hyperosmotic stress response. We analysed the physicochemical properties, chromosome distribution, phylogeny, gene structure and expression pattern of the OSCA gene family in barley, and investigated the expression of HvOSCA genes in barley under drought stress by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, 14 members of the OSCA gene family were identified from barley, all containing the RSN1_7TM domain and often accompanied by the RSN1_TM and PHM7_cyt domains. According to the phylogenetic relationship, they were divided into four subgroups, and each with similar gene structures. Two types of duplicate events in the HvOSCA genes family evolved under the effect of purification selection. By analysing the cis-acting elements in the HvOSCA promoter, it was speculated that the barley OSCA gene family is involved in the regulation of multiple signalling pathways. The expression of HvOSCA genes in barley tissues and their relative expression under drought stress revealed that the gene family plays a role in plant organ differentiation, growth and development and coping with abiotic stress. These results provide new valuable information for the functional analysis of HvOSCA genes and the genetic improvement of barley, and provide an important reference for follow-up research.

Dl-3-n-Butylphthalide Reduced Neuroinflammation by Inhibiting Inflammasome in Microglia in Mice after Middle Cerebral Artery Occlusion.

The inflammatory response is one of the key events in cerebral ischemia, causing secondary brain injury and neuronal death. Studies have shown that the NLRP3 inflammasome is a key factor in initiating the inflammatory response and that Dl-3-n-butylphthalide (NBP) can attenuate the inflammatory response and improve neuronal repair during ischemic stroke. However, whether NBP attenuates the inflammatory response via inhibition of NLRP3 remains unclear. A 90 min middle cerebral artery occlusion was induced in 62 2-month-old adult male ICR mice, and NBP was administered by gavage zero, one, or two days after ischemia. Brain infarct volume, neurological deficits, NLRP3, microglia, and neuronal death were examined in sacrificed mice to explore the correction between NBP effects and NLRP3 expression. NBP significantly reduced infarct volume and attenuated neurological deficits after ischemic stroke compared to controls (p < 0.05). Moreover, it inhibited ASC+ microglia activation and NLRP3 and CASP1 expression in ischemic mice. In addition, neuronal apoptosis was reduced in NBP-treated microglia cultures (p < 0.05). Our results indicate that NBP attenuates the inflammatory response in ischemic mouse brains, suggesting that NBP protects against microglia activation via the NLRP3 inflammasome.