Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Sodium Tanshinone IIA Sulfonate alleviates vascular senescence in diabetic mice by modulating the A20-NFκB-NLRP3 inflammasome-catalase pathway.

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence ß-Galactosidase Staining (SA-ß-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-ß-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.

Cancer Cell Secreted Legumain Promotes Gastric Cancer Resistance to Anti-PD-1 Immunotherapy by Enhancing Macrophage M2 Polarization.

The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvß3, then activate Integrin αvß3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvß3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvß3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvß3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target.

Activation of pyramidal neurons in the infralimbic cortex alleviates LPS-induced depressive-like behavior in mice.

The infralimbic (IL) cortex dysfunction has been implicated in major depressive disorder (MDD), yet the precise cellular and molecular mechanisms remain poorly understood. In this study, we investigated the role of layer V pyramidal neurons in a mouse model of MDD induced by repeated lipopolysaccharide (LPS) administration. Our results demonstrate that three days of systemic LPS administration induced depressive-like behavior and upregulated mRNA levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß (TGF-ß) in the IL cortex. Electrophysiological recordings revealed a significant decrease in the intrinsic excitability of layer V pyramidal neurons in the IL following systemic LPS exposure. Importantly, chemogenetic activation of IL pyramidal neurons ameliorated LPS-induced depressive-like behavior. Additionally, LPS administration significantly increased microglial activity in the IL, as evidenced by a greater number of Ionized calcium binding adaptor molecule-1 (IBA-1)-positive cells. Morphometric analysis further unveiled enlarged soma, decreased branch numbers, and shorter branch lengths of microglial cells in the IL cortex following LPS exposure. Moreover, the activation of pyramidal neurons by clozapine-N-oxide increased the microglia branch length but did not change branch number or cytosolic area. These results collectively suggest that targeted activation of pyramidal neurons in the IL cortex mitigates microglial response and ameliorates depressive-like behaviors induced by systemic LPS administration. Therefore, our findings offer potential therapeutic targets for the development of interventions aimed at alleviating depressive symptoms by modulating IL cortical circuitry and microglial activity.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models.

BACKGROUND: Diffusion-weighted imaging (DWI) has been developed to stage liver fibrosis. However, its diagnostic performance is inconsistent among studies. Therefore, it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort. AIM: To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances. METHODS: This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants. All participants underwent multi-b value DWI. The main DWI-derived parameters included Mono-apparent diffusion coefficient (ADC) from mono-exponential DWI, intravoxel incoherent motion model-derived true diffusion coefficient (IVIM-D), diffusion kurtosis imaging-derived apparent diffusivity (DKI-MD), stretched exponential model-derived distributed diffusion coefficient (SEM-DDC), fractional order calculus (FROC) model-derived diffusion coefficient (FROC-D) and FROC model-derived microstructural quantity (FROC-µ), and continuous-time random-walk (CTRW) model-derived anomalous diffusion coefficient (CTRW-D) and CTRW model-derived temporal diffusion heterogeneity index (CTRW-α). The correlations between DWI-derived parameters and fibrosis stages and the parameters' diagnostic efficacy in detecting significant fibrosis (SF) were assessed and compared. RESULTS: CTRW-D (r = -0.356), CTRW-α (r = -0.297), DKI-MD (r = -0.297), FROC-D (r = -0.350), FROC-µ (r = -0.321), IVIM-D (r = -0.251), Mono-ADC (r = -0.362), and SEM-DDC (r = -0.263) were significantly correlated with fibrosis stages. The areas under the ROC curves (AUCs) of the combined index of the six models for distinguishing SF (0.697-0.747) were higher than each of the parameters alone (0.524-0.719). The DWI models' ability to detect SF was similar. The combined index of CTRW model parameters had the highest AUC (0.747). CONCLUSION: The DWI models were similarly valuable in distinguishing SF in patients with liver disease. The combined index of CTRW parameters had the highest AUC.

Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope?

Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising treatment regimen for cancer. Despite the striking response in patients with hematologic malignancies, most patients with solid tumors treated with CAR-T cells have a low response rate and experience major adverse effects, which indicates the need for biomarkers that can predict and improve clinical outcomes with future CAR-T cell treatments. Recently, the role of the gut microbiota in cancer therapy has been established, and growing evidence has suggested that gut microbiota signatures may be harnessed to personally predict therapeutic response or adverse effects in optimizing CAR-T cell therapy. In this review, we discuss current understanding of CAR-T cell therapy and the gut microbiota, and the interplay between the gut microbiota and CAR-T cell therapy. Above all, we highlight potential strategies and challenges in harnessing the gut microbiota as a predictor and modifier of CAR-T cell therapy efficacy while attenuating toxicity.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Assessing the Role of BN-Embedding Position in B2N2-Perylenes.

Incorporating heteroatoms can effectively modulate the molecular optoelectronic properties. However, the fundamental understanding of BN doping effects in BN-embedded polycyclic aromatic hydrocarbons (PAHs) is underexplored, lacking rational guidelines to modulate the electronic structures through BN units for advanced materials. Herein, a concise synthesis of novel B2N2-perylenes with BN doped at the bay area is achieved to systematically explore the doping effect of BN position on the photophysical properties of PAHs. The shift of BN position in B2N2-perylenes alters the π electron conjugation, aromaticity and molecular rigidness significantly, achieving substantially higher electron transition abilities than those with BN doped in the nodal plane. It is further clarified that BN position dominates the photophysical properties over BN orientation. The revealed guideline here may apply generally to novel BN-PAHs, and aid the advancement of BN-PAHs with highly-emissive performance.

The ecological suitability area of Cirsium lineare (Thunb.) Sch.-Bip. under future climate change in China based on MaxEnt modeling.

Many kinds of medicinal ingredients occur in Cirsium lineare that have good clinical efficacy, conferring on this species its high medicinal development value. However, with a rapidly changing global climate, it is increasingly imperative to study the factors affecting the habitat distribution and survival of species. We predicted the current and future distribution areas of suitable habitats for C. lineare, analyzed the importance of environmental variables in influencing habitat shifts, and described the alterations to suitable habitats of C. lineare in different periods (modern, 2050s, and 2070s) and scenarios (RCP2.6, RCP4.5, and RCP8.5). The results show that, under the current climate, the total suitable area of C. lineare is about 2,220,900 km2, of which the highly suitable portion amounts to ca. 292,600 km2. The minimum temperature of the coldest month, annual precipitation, and mean daily temperature range are the chief environmental variables affecting the distribution of habitat for C. lineare. In the same period, with rising greenhouse gas emission concentrations, the total suitable area will increase. In general, under future climate change, the suitable habitat for C. lineare will gradually migrate to the west and north, and its total suitable area will also expand. The results of this experiment can be used for the conservation and management of the wild resources of C. lineare. We can choose suitable growth areas to protect the medicinal resources of C. lineare through in situ conservation and artificial breeding.

Achieving Ideal and Environmentally Stable n-Type Charge Transport in Polymer Field-Effect Transistors.

Realizing ideal charge transport in field-effect transistors (FETs) of conjugated polymers is crucial for evaluating device performance, such as carrier mobility and practical applications of conjugated polymers. However, the current FETs using conjugated polymers as the active layers generally show certain non-ideal transport characteristics and poor stability. Here, ideal charge transport of n-type polymer FETs is achieved on flexible polyimide substrates by using an organic-inorganic hybrid double-layer dielectric. Deposited conjugated polymer films show highly ordered structures and low disorder, which are supported by grazing-incidence wide-angle X-ray scattering, near-edge X-ray absorption fine structure, and molecular dynamics simulations. Furthermore, the organic-inorganic hybrid double-layer dielectric provides low interfacial defects, leading to excellent charge transport in FETs with high electron mobility (1.49 ± 0.46 cm2 V-1 s-1) and ideal reliability factors (102 ± 7%). Fabricated polymer FETs show a self-encapsulation effect, resulting in high stability of the FET charge transport. The polymer FETs still work with high mobility above 1 cm2 V-1 s-1 after storage in air for more than 300 days. Compared with state-of-the-art conjugated polymer FETs, this work simultaneously achieves ideal charge transport and environmental stability in n-type polymer FETs, facilitating rapid device optimization of high-performance polymer electronics.

Nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: a cost-effectiveness analysis.

BACKGROUND: The aim of the study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy as first-line treatment for patients with advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma from the perspective of Chinese and US society. METHODS: To conduct the analysis, a state-transitioned Markov model, which included three mutually exclusive health states (progression-free survival (PFS), progressive disease (PD), and death), was developed. Cycle length was set at 3 weeks and lifetime horizon was set at 10 years. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated in the analysis. Willingness-to-pay (WTP) thresholds in the model were set at $37,653.00/QALY in China and $100,000.00/QALY in the US, respectively. Meanwhile, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the robustness of the model. RESULTS: Over a lifetime horizon, the ICERs of nivolumab plus chemotherapy versus chemotherapy alone were $430,185.04/QALY and $944,089.78/QALY in China and the US, respectively. Cost of nivolumab and utility for the PFS state had the most significant impact on ICERs both in the US and China based on the results of the one-way sensitivity analyses. In the probabilistic sensitivity analyses, the proportions of nivolumab plus chemotherapy being cost-effective compared with chemotherapy alone were 0%. CONCLUSIONS: In conclusion, nivolumab plus chemotherapy is unlikely to be a cost-effective treatment option compared with chemotherapy alone in the first-line setting of advanced gastric, GEJ, or esophageal adenocarcinoma.

Association between resting myocardial work indices and stress myocardial perfusion in patients with angina and non-obstructive coronary artery disease.

Background: Myocardial work (MW) indices and longitudinal strain (LS) are sensitive markers of early left ventricular systolic dysfunction. Stress computed tomography myocardial perfusion imaging (CT-MPI) can assess early myocardial ischemia. The association between resting MW indices and stress myocardial perfusion remains unclear. This study compares resting MW indices with LS to assess stress myocardial perfusion in angina patients with non-obstructive coronary artery disease (CAD). Methods: Eighty-four patients who underwent resting echocardiography, coronary computed tomography angiography, and stress CT-MPI were reviewed. Seventeen myocardial segments were divided into three regions according to the epicardial coronary arteries. Global indices included global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Regional indices included regional longitudinal strain (RLS), regional work index (RWI), and regional work efficiency (RWE). Reduced global perfusion was defined as an average stress myocardial blood flow (MBF) <116 mL/100 mL/min for the whole heart. Reduced regional perfusion was defined as an average stress MBF <116 mL/100 mL/min for the coronary territories. No patients demonstrated obstructions in the epicardial coronary arteries (stenosis diameter <50%). The MW indices and LS were compared. Receiver operating characteristic curves were constructed and logistic regression analyses were used to investigate the predictors of reduced myocardial perfusion. Results: Patients with reduced stress perfusion demonstrated reduced GLS, GWI, GCW, and GWE (P<0.05) and increased GWW (P<0.05). After adjustment for age and sex, GWE was still independently associated with reduced myocardial perfusion (odds ratio =0.386, 95% confidence interval: 0.214-0.697; P<0.05). Receiver operating characteristic curves reflected the good diagnostic ability of GWE and its superiority to GLS (area under the curve: 0.858 vs. 0.741). The optimal cutoff GWE value was 95% (sensitivity, 70%; specificity, 90%). Regions with lower stress perfusion showed lower RLS, RWI, and RWE (P<0.05). The optimal cutoff value of RWE for predicting reduced regional perfusion was 95%, with an area under the curve of 0.780, a sensitivity of 62%, and a specificity of 83%. Conclusions: Resting MW indices perform well in assessing global and regional stress myocardial perfusion in angina patients with non-obstructive CAD, and GWE is superior to GLS in the global evaluations.

Target versus sub-target dose of renin-angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis.

BACKGROUND: The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI. RESULTS: Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I2 = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I2 = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I2 = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I2 = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I2 = 0) in a subgroup of very elderly patients > 75 years of age. CONCLUSIONS: Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.

Synthesis of (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-ones from (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oximes and iodobenzenes via a palladium-catalyzed dearomative arylation/oxidation reaction.

A new method has been successfully developed that offers a facile and reliable approach for synthesizing (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-one, providing 28 compounds. This optimized process enables efficient preparation of a wide range of compounds using readily available (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oxime and iodobenzene, and provides alternative ideas for the structural modification of benzofuran ketones.

Corrigendum: NanoSIMS analysis of water content in bridgmanite at the micron scale: an experimental approach to probe water in Earth's deep mantle.

[This corrects the article DOI: 10.3389/fchem.2023.1166593.].

Effects of modified triangular flap for third molar extraction on distal periodontal health of second molar: A randomized controlled study.

Objective: The aim of this study was to assess the effect of flap design for impacted mandibular third molar extraction on the distal periodontal tissue of their neighbors clinically, immunologically, and microbiologically. Study design: This randomized controlled study comprised 100 patients who were allocated randomly to receive either a triangular flap or a modified triangular flap. The distal periodontal pocket depth, plaque index, bleeding on probing, the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and the level of interleukin-1ß, interleukin-8 and matrix metalloproteinase-8 of adjacent second molars were measured at baseline, and 1, 4 and 8 weeks after surgery. Results: After 1 and 4 weeks, distal periodontal conditions of adjacent second molars deteriorated, along with an increase in subgingival microbiota and inflammatory factors in both groups. And compared to the modified triangular flap group, the triangular flap group significantly increased (p < 0.05). Prevotella intermedia, interleukin-1ß and probing depth were positively correlated in both groups. After 8 weeks, they returned to the preoperative level. Conclusions: In this study, both flap designs for impacted mandibular third molar extractions was associated with worse clinical periodontal indices, increased inflammatory biomarkers of gingival crevicular fluid, and more subgingival pathogenic microbiota within 4 weeks. But compared with the triangular flap, the modified triangular flap was better for distal periodontal health of adjacent second molars, which provides certain directions for clinical treatment.

Effects of elevated atmospheric ammonia concentration on photosynthetic characteristics and grain yield in wheat under different nitrogen rates.

To evaluate the effects of nitrogen (N) application rates on the growth, photosynthetic traits and yield of winter wheat under elevated atmospheric ammonia (NH3) concentrations could provide guidance for N management under high NH3 environment. We conducted a split-plot experiment for two consecutive years (2020-2021 and 2021-2022) with top-open chambers. The treatments included two NH3 concentrations [elevated ambient NH3 concentration at 0.30-0.60 mg·m-3 (EAM) and air NH3 concentration at 0.01-0.03 mg·m-3 (AM)] and two N application rates [recommended N dose (+N) and no N application (-N)]. We analyzed the effects of aforementioned treatments on net photosynthetic rate (Pn), stomatal conductance (gs), chlorophyll content (SPAD value), plant height, and grain yield. The results showed that averaged across the two years, EAM significantly increased Pn, gs, and SPAD values at the jointing and booting stages at the -N level by 24.6%, 16.3%, 21.9% and 20.9%, 37.1%, 5.7%, respectively, compared with AM. However, EAM significantly decreased Pn, gs, and SPAD values at jointing and booting stages at +N level by 10.8%, 5.9%, 3.6% and 6.8%, 18.9%, 9.3%, respectively, over AM treatment. There was a significant effect of NH3 treatment, N application rates and their interaction on plant height and grain yield. Compared with AM, EAM increased the average plant height and grain yield by 4.5% and 32.1% at -N level and decreased by 1.1% and 8.5% at +N level, respectively. In a nutshell, the eleva-ted ambient NH3 concentration had positive effect on photosynthetic characteristics, plant height, and grain yield under ambient N condition, but a inhibitory effect under N application.

[Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue].

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.