A novel dual near-infrared fluorescent probe for bioimaging and visualization of viscosity in acute alcoholic liver injury.

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

Safety and efficacy of adding postbiotics in infant formula: a systematic review and meta-analysis.

Postbiotics, as emerging products, were added to infant formula, but their safety and efficacy are unclear. To clarify this issue, we wrote this meta-analysis. We searched PubMed, Embase, Web of Science and ProQuest from its establishment to February 2023. The review was registered on PROSPERO database (CRD42022352405). The effects of infant formula with and without postbiotics were compared, and the incidence of serious adverse events (SAEs), digestive symptoms, concentration of stool secretory immunoglobulin A (SIgA), and growth and development indexes were analyzed. Nine randomized controlled trials with 2065 participants were included. The addition of postbiotics to infant formula was found to increase the concentration of stool SIgA (P < 0.05) with very low certainty of evidence, without significantly impacting the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain and gastrointestinal disorders, the daily weight gain, the total gain in body length and the daily head circumference gain (all P > 0.05). Adding postbiotics to the formula is safe for infants, which would not increase the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain, and gastrointestinal disorders, and could increase the concentration of stool SIgA. IMPACT: Our study provides evidence that the addition of postbiotics to infant formula is safe but not effective. This is the first systematic review and meta-analysis of postbiotics. This study provides strong evidence for the safety of postbiotics and lays a foundation for related clinical trials.

A mitochondria-targeted far-red AIE fluorescent probe for distinguishing between mitophagy and ferroptosis in cancer cells.

A mitochondria-targeted far-red fluorescent probe LY-1 with AIE character was formulated to track cell viscosity alterations with excellent sensitivity and selectivity, which was used to discriminate between mitophagy and ferroptosis in cancer cells. Probe LY-1 is expected to be an effective vehicle for the diagnosis of mitochondrial viscosity relevant diseases.

A bibliometric review on electric vehicle (EV) energy efficiency and emission effect research.

Electric vehicles have received extensive attention due to their unique energy efficiency and good emission reduction effects. While a large-scale of electric vehicles are gradually replacing traditional fuel vehicles, it is necessary to ensure the energy efficiency of electric vehicles and the effectiveness of their emission reduction effects. This study conducted a bibliometric analysis of scientific publications on energy efficiency and emission reduction effects of electric vehicles from 2003 to 2022, using a variety of bibliometric tools such as R Studio, biblioshiny and VOSviewer. The results showed the gradual elimination of traditional energy vehicles, where electric vehicles play an important role in connecting energy efficiency and emission control. The results also showed the top publication outlets, citations trackers, authors with thematic evaluation of energy efficiency and emission reduction effects of electric vehicles. The contribution of the study is manifold. The academic contribution of the present study is the bibliometric analysis which will help academicians to get a quick overview of the most popular journals, top collaborators, documents, authors, and scientific knowledge structure. Secondly, policy makers, environmentalists, researchers, and academician will definitely get a pathway how they should go for future research. Finally, this study suggests more researches trend to focus on the sales of electric vehicles, automobile exhaust emissions, sensitivity analysis of electric vehicles, energy storage analysis to improve the energy efficiency of electric vehicles, and V2G related to the energy efficiency of electric vehicle clusters.

A bibliometric analysis of acute myocardial infarction in women from 2000 to 2022.

Background: Plenty of publications had been written in the last several decades on acute myocardial infarction (AMI) in women. However, there are few bibliometric analyses in such field. In order to solve this problem, we attempted to examine the knowledge structure and development of research about AMI in women based on analysis of related publications. Method: The Web of Science Core Collection was used to extract all publications regarding AMI in women, ranging from January 2000 to August 2022. Bibliometric analysis was performed using VOSviewer, Cite Space, and an online bibliometric analysis platform. Results: A total of 14,853 publications related to AMI in women were identified from 2000 to 2022. Over the past 20 years, the United States had published the most articles in international research and participated in international cooperation the most frequently. The primary research institutions were Harvard University and University of Toronto. Circulation was the most cited journal and had an incontrovertible academic impact. 67,848 authors were identified, among which Harlan M Krumholz had the most significant number of articles and Thygesen K was co-cited most often. And the most common keywords included risk factors, disease, prognosis, mortality, criteria and algorithm. Conclusion: The research hotspots and trends of AMI in women were identified and explored using bibliometric and visual methods. Researches about AMI in women are flourishing. Criteria and algorithms might be the focus of research in the near future, which deserved great attentions.

Free fatty acids induce coronary microvascular dysfunction via inhibition of the AMPK/KLF2/eNOS signaling pathway.

Increased levels of serum free fatty acids (FFAs) are closely associated with microvascular dysfunction. In our previous study, a coronary microvascular dysfunction (CMD) model was successfully established via lipid infusion to increase the levels of serum FFAs in mice. However, the underlying mechanisms remained poorly understood. Therefore, the aim of the present study was to explore the mechanism underlying FFA­induced CMD. A CMD mouse model was established via lipid combined with heparin infusion for 6 h to increase the concentration of serum FFAs. Following the establishment of the model, the coronary flow reserve (CFR), extent of leukocyte activation and cardiac microvascular structures were assessed in the mice. Cardiac microvascular endothelial cells (CMECs) were treated with different concentrations of palmitic acid and cell viability was evaluated. Changes in the expression levels of AMP­activated protein kinase (AMPK), Krüppel­like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) were identified by immunohistochemical and western blot analyses. Experiments using AMPK activator, KLF2 overexpression plasmid, small interfering RNAs and nicorandil were subsequently designed to investigate the potential involvement of the AMPK/KLF2/eNOS signaling pathway. These experiments revealed that FFAs could induce CMD in mice, which was characterized by reduced CFR (1.89±0.37 vs. 2.74±0.30) and increased leukocyte adhesion (4,350±1,057.5 vs. 11.8±5.4 cells/mm2) compared with the control mice. CD11b expression and intracellular reactive oxygen species (ROS) levels were increased in CMD model mice compared with control mice. Serum TNF­α and IL­6 levels were higher in the model group than in the control group. Transmission electron microscopy revealed that CMECs in heart tissues of model mice were severely swollen. In addition, palmitic acid decreased CMEC viability and increased ROS production in a dose­dependent manner. Notably, the AMPK/KLF2/eNOS signaling pathway was demonstrated to be suppressed by FFAs both in vivo and in vitro. Activation of this axis with AMPK activator, KLF2 overexpression plasmid or nicorandil restored the CFR in CMD model mice, inhibited oxidative stress and increased CMEC viability. Taken together, the results of the present study demonstrated that FFAs could induce CMD via inhibition of the AMPK/KLF2/eNOS signaling pathway, whereas activation of this pathway led to the alleviation of FFA­induced CMD, which may be a therapeutic option for CMD.

Simultaneous quantitation of befotertinib (D-0316) and its metabolite D-0865 in human plasma by LC-MS/MS method.

A sensitive and reliable method was developed to determine befotertinib (D-0316) and its metabolite D-0865 from human plasma by LC-MS/MS. The samples were prepared by simple protein precipitation and 2 µL of the supernatant were chromatographed on a C18 analytical column (ACE Excel 2 Super C18, 50 × 2.1 mm). Elution was performed with mobile phase A (10 mM ammonium acetate in water containing 1 % formic acid) and mobile phase B (acetonitrile containing 1 % formic acid) under a gradient program in a total run time of 4 min. Triple Quadruple 5500 equipped with Turbo Ion Spray source and multiple reaction monitoring (MRM) were used for the analysis detection. The transitions were m/z 568.3 â†’ 72.1 m/z (befotertinib), m/z 554.2 â†’ 497.2 (D-0865), and m/z 455.2 â†’ 164.9 (verapamil, internal standard). According to the Chinese Pharmacopeia Commission and ICH Harmonised Guideline for Bioanalytical Method Validation, this method was validated within the spectrum of its accuracy, precision, selectivity, linearity, recovery, matrix effect, and stability. This LC-MS/MS method was successfully applied for the quantitation of befotertinib and its metabolite D-0865 in human plasma during the pharmacokinetics study of befotertinib in non-small cell lung cancer (NSCLC) patients.

TRIM64 promotes ox-LDL-induced foam cell formation, pyroptosis, and inflammation in THP-1-derived macrophages by activating a feedback loop with NF-κB via IκBα ubiquitination.

Atherosclerosis is a chronic inflammatory disease and the main pathology behind most cardiovascular diseases and the overactivation of macrophages initiates the development of atherosclerosis. However, the specific functions of oxidized low-density lipoprotein (ox-LDL) in macrophages remain elusive. Macrophages derived from monocyte (THP-1) were treated with ox-LDL and were used to generate atherosclerosis in an in vitro model. NLRP3 inflammasome markers were examined using quantitative RT-PCR and Western blotting. Cytokines were measured using ELISA. Chromatin immunoprecipitation (ChIP) was utilized to detect nuclear factor kappa B (NF-κB) and TRIM64 interactions. A fat-rich diet was applied to ApoE-/- mice for in vivo studies. ox-LDL promoted TRIM64 expression in a time-dependent manner. According to loss- and gain-of-function analyses, TRIM64 enhanced the activation of NLRP3 inflammasomes and the expression of downstream molecules. TRIM64 directly interacted with IκBα and promoted IκBα ubiquitination at K67 to activate NF-κB signaling. We detected direct binding between NF-κB and the TRIM64 promoter, as well as enhanced TRIM64 expression. Our study revealed an interaction between TRIM64 and NF-κB in the development of atherosclerosis. TRIM64 and NF-κB formed a positive feedback to activate NF-κB pathway. ox-LDL induces foam cell formation and TRIM64 expression TRIM64 regulates ox-LDL-induced foam cell formation, pyroptosis and inflammation via the NF-κB signaling TRIM64 activates NF-κB signaling by ubiquitination of IκBα NF-κB inhibition attenuates atherosclerosis in HFD-induced ApoE (-/-) mice.

Metachronous isolated penile metastasis from sigmoid colon adenocarcinoma: A case report.

BACKGROUND: Sigmoid colon adenocarcinoma has a high incidence among gastrointestinal tumors, and it very rarely metastasizes to the penis. The literature reports that the prognosis after penile metastasis is generally poor, with a median survival of about 9 mo. Metachronous isolated metastasis to the penis originating from sigmoid colon adenocarcinoma has not been reported so far. Here, we report a case of sigmoid colon adenocarcinoma with isolated penile metastasis occurring 2 years after surgery. The mass was pathologically confirmed as metastatic adenocarcinoma, and oral chemotherapy with capecitabine was given after surgery. The tumor did not recur during the 2-year follow-up period. CASE SUMMARY: A 79-year-old man presented to the urology department with "a mass located at the root of the penis since 1 mo". Enhanced computed tomography (CT) examination suggested a 12 mm × 10 mm × 9 mm nodule at the root of the right penile corpus cavernosum. Cranial, pulmonary, and abdominal CT; and bone scan did not show any tumorigenic lesions. The carcinoembryonic antigen (CEA) level was slightly elevated (6.01 ng/mL, reference value 0-5 ng/mL). The patient had undergone laparoscopic radical sigmoidectomy for sigmoid colon cancer 2 years ago. The postoperative pathology showed moderately differentiated adenocarcinoma of the sigmoid colon, and the stage was PT2N0M0. The penile mass was removed under general anesthesia. The postoperative pathology showed adenocarcinoma, and immunohistochemistry showed CDX2(+), CK20(+), and Villin(+). Based on the medical history, he was diagnosed with penile metastasis from sigmoid colon adenocarcinoma. The CEA level returned to normal (3.34 ng/mL) 4 d after surgery. Oral chemotherapy with capecitabine was given subsequently, and tumor recurrence was not found during the 2-year follow-up period. CONCLUSION: To our knowledge, this is a rare case of metachronous isolated penile metastasis from sigmoid colon adenocarcinoma. The penis is a potential site of metastasis of colon adenocarcinoma, and the possibility of metastasis should be considered in patients with a history of colon cancer who present with a penile mass. Solitary penile metastasis can be removed surgically, in combination with chemotherapy, and it may have good long-term outcomes.

Salvianolic Acid B Alleviates Limb Ischemia in Mice via Promoting SIRT1/PI3K/AKT Pathway-Mediated M2 Macrophage Polarization.

Salvianolic acid B (Sal B) is an effective treatment agent for ischemic disease in China. However, Sal B's effects on peripheral arterial disease (PAD) and its mechanism remains poorly understood. Macrophage polarization plays a crucial role in PAD. Nevertheless, treatment modalities that increase the population of anti-inflammatory (M2) macrophages are limited. This study aimed to explore the protective effects of Sal B on limb perfusion and investigate the mechanism of Sal B-induced macrophage polarization. C57BL/6 male mice (6 weeks) were randomized into control, Model + NS, and Model + Sal B groups (n = 5). Then, we established a hind limb ischemia mouse model to assess the Sal B's role (15 mg/kg/d) in PAD. We quantified the blood perfusion via laser speckle contrast imaging (LSCI) and measured the capillary density and muscle edema with CD31 and H&E staining. The Sal B-induced macrophage polarization was confirmed by qPCR and ELISA. The results showed that the Sal B group exhibited a significant improvement in the blood perfusion, capillary density, muscle edema, and M2 markers gene expressions. Cell migration and tube formation were promoted in the endothelial cells stimulated with a culture supernatant from Sal B-treated macrophages. In contrast, endothelial functions improved by Sal B-treated macrophages were impaired in groups treated with SIRT1 and PI3K inhibitors. These findings provide evidence for Sal B's protective role in PAD and demonstrate the enhancement of macrophage polarization via the SIRT1/PI3K/AKT pathway.

Fetal Cerebral Hemodynamic Changes in Preeclampsia Patients by Ultrasonic Imaging under Intelligent Algorithm.

This study was aimed at evaluating the adoption value of ultrasound imaging features on fetal cerebral hemodynamics in preeclampsia patients based on the partial difference algorithm and the hybrid segmentation network (HSegNet) algorithm. Forty pregnant women with preeclampsia diagnosed by ultrasound examination were selected as the research objects, and another forty normal pregnant women were selected as the control. Then, by using the partial differential algorithm, the imaging of fetal cerebral hemodynamics in preeclampsia patients was enhanced and optimized, and the general clinical data and experimental results were collected. The results showed that the automatic labeling of fetal cerebral artery in fetal middle cerebral artery (MCA) hemodynamic images was realized by HSegNet algorithm model, and the final accuracy was 97.3%, which had a good consistency with the manual annotation of doctors. Education level was a protective factor for preeclampsia (odds ratio (OR) = 0.535). Body mass index (BMI) and family history of hypertension during pregnancy were independent risk factors for preeclampsia (OR = 1.286, and 2.774, respectively). MCA end-diastolic volume (EDV) of preeclampsia fetuses was higher than that of normal fetuses. The MCA systolic-diastolic ratio (S/D), the pulsatility index (PI), and the resistive index (RI) in the preeclampsia group were significantly lower than those in the normal pregnancy group. The results showed that MCA PI, MCA RI, and MCA S/D had certain predictive values for the occurrence of adverse pregnancy outcomes (P < 0.05). In summary, the intelligent algorithm-based fetal MCA hemodynamic ultrasound image in the study could effectively predict pregnancy outcomes of patients and provide certain theoretical support for the subsequent reduction of adverse pregnancy outcomes in patients with preeclampsia.

Proangiogenesis effects of compound danshen dripping pills in zebrafish.

BACKGROUND: The compound Danshen Dripping Pill (CDDP), which is a mixture of extracts from Radix Salviae and Panax notoginseng, is a patented traditional Chinese medicine that is widely used in multiple countries for relieving coronary heart disease (CHD), but its pharmacological mechanism has not been fully elucidated. In this study, we screened the key pharmacological pathways and targets of CDDP that act on CHD using a network pharmacology-based strategy, and the angiogenic activity of CDDP was directly visually investigated in zebrafish embryos in vivo. METHODS: The potential therapeutic targets and pathways were predicted through a bioinformatics analysis. The proangiogenic effects of CDDP were examined using vascular sprouting assays on subintestinal vessels (SIVs) and optic arteries (OAs) as well as injury assays on intersegmental vessels (ISVs). Pharmacological experiments were applied to confirm the pathway involved. RESULTS: Sixty-five potential therapeutic targets of CDDP on CHD were identified and enriched in the PI3K/AKT and VEGF/VEGFR pathways. An in vivo study revealed that CDDP promoted angiogenesis in SIVs and OAs in a dose-dependent manner and relieved the impairments in ISVs induced by lenvatinib, a VEGF receptor kinase inhibitor (VRI). In addition, Vegfaa and Kdrl expression were significantly upregulated after CDDP treatment. Furthermore, the proangiogenic effect of CDDP could be abolished by PI3K/AKT pathway inhibitors. CONCLUSIONS: CDDP has a proangiogenic effect, the mechanism of which involves the VEGF/VEGFR and PI3K/AKT signaling pathways. These results suggest a new insight into the cardiovascular protective effect of CDDP.

Profiling of Protein Adducts of Estrogen Quinones in 5-Year Survivors of Breast Cancer Without Recurrence.

AIMS: The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17ß-estradiol-2,3-quinone (E2-2,3-Q) and 17ß-estradiol-3,4-quinone (E2-3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts. SETTINGS AND DESIGN: CohortMethods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E2-3,4-Q and E2-2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment. STATISTICAL ANALYSIS: All data are expressed as mean ± standard deviation of three determinations. We used Student's t-test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0. RESULTS: Result confirmed that logged levels of E2-2,3-Q-derived adducts correlated significantly with those of E2-3,4-Q-derived adducts (correlation coefficient r=.336-.624). Mean levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001). CONCLUSIONS: Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

Three New Aglain Derivatives from Aglaia odorata Lour. and Their Cytotoxic Activities.

Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03-8.40 µM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.

Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

BACKGROUND: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS: In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS: Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS: SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

Infectivity and antigenicity of pseudoviruses with high-frequency mutations of SARS-CoV-2 identified in Portugal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.

Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells.

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved in endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, have not been completely elucidated. In the present study, we identified orphan nuclear receptor Nur77 as a novel regulator in controlling inflammasome activation in vascular endothelial cells (ECs). We demonstrated that LPS-induced inflammasome activation was significantly inhibited by ectopic overexpression of Nur77, predominantly through transcriptional suppression of caspase-1 expression in vascular ECs. Consistent with this observation, we found that LPS-induced inflammasome activation was significantly augmented in lung ECs isolated from Nur77-knockout mice. Mechanistically, we showed that Nur77-induced inhibition of caspase-1 expression was due to an inhibition of IRF1 (IFN regulatory factor 1) expression and its subsequent binding to the caspase-1 promoter. Importantly, in a mouse model of LPS-induced ALI, Nur77 knockout led to a marked activation of caspase-1 in the lung, increased alveolar and circulating IL-1ß levels, and exacerbated ALI, all of which were substantially inhibited by administration of caspase-1 inhibitor. Together, our results support the presence of an important role for Nur77 in controlling inflammasome activation in vascular ECs and suggest that Nur77 could be a novel therapeutic target for the treatment of human diseases associated with aberrant inflammasome activation, such as ALI and atherosclerosis.

Sodium-Glucose CoTransporter-2 Inhibitor Empagliflozin Ameliorates Sunitinib-Induced Cardiac Dysfunction via Regulation of AMPK-mTOR Signaling Pathway-Mediated Autophagy.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to decrease the adverse cardiac events and risks of cardiovascular mortality among patients with or without diabetes, which has made these drugs promising treatment options for patients with chronic heart failure. Cardiac dysfunction is a common and severe side effect induced by cancer chemotherapies, which seriously affects the prognosis and life quality of tumor patients. However, it is not clear whether SGLT2 inhibitors have cardiovascular benefits in patients with cancer chemotherapy-related cardiac dysfunction. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role against sunitinib (SNT)-induced cardiac dysfunction in a mouse model. Methods: Male C57BL/6J mice were randomized into control (control, n = 8), empagliflozin (EMPA, n = 8), sunitinib (SNT, n = 12), or sunitinib and empagliflozin coadministration (SNT + EMPA, n = 12) groups. EMPA, SNT, or SNT-combined EMPA was given via oral gavage for consecutive 28 days. Cardiovascular functions and pathological changes were examined, and the underlying mechanisms of EMPA's effects were investigated in H9c2 cardiomyocytes. Results: Mice in the SNT group exhibited dramatically elevated blood pressure (systolic blood pressure [SBP] 134.30 ± 6.455 mmHg vs. 114.85 ± 6.30 mmHg) and impaired left ventricular function (left ventricular ejection fraction [LVEF] 50.24 ± 3.06% vs. 84.92 ± 2.02%), as compared with those of the control group. However, EMPA could ameliorate SNT-induced cardiotoxicity, both in terms of SBP (117.51 ± 5.28 mmHg vs. 134.30 ± 6.455 mmHg) and LVEF (76.18 ± 5.16% vs. 50.24 ± 3.06 %). In H9c2 cardiomyocytes, SNT-induced cardiomyocyte death and cell viability loss as well as dysfunction of adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling-mediated autophagy were restored by EMPA. However, these favorable effects mediated by EMPA were blocked by the inhibition of AMPK or autophagy. Conclusion: EMPA could ameliorate SNT-induced cardiac dysfunction via regulating cardiomyocyte autophagy, which was mediated by the AMPK-mTOR signaling pathway. These findings supported that SGLT2 inhibitor therapy could be a potential cardioprotective approach for cardiovascular complications among patients receiving SNT. However, these favorable effects still need to be validated in clinical trials.

The novel target：exosoms derived from M2 macrophage.

More and more exosome-based therapeutics are being developed with advances in nanotechnology and precision medicine. Exosome is a kind of tiny vesicles with a bilayer of phospholipids, which can transfer biological macromolecules to recipients to influence the biological process. M2 macrophages are closely related to the occurrence and development of serious diseases such as tumor. In addition to the traditional concept of macrophage functions such as opsonization, secretion of cytokines and other soluble factors, some studies have found that the exosome derived from M2 macrophages can influence the development of disease by carrying microRNA, long noncodingRNA and functional proteins to regulate target gene expression as well as related proteins synthesis recently. Here, we outlined the biogenesis of the exosome and its biological functions in disease. Then we focused on elucidating the effects of the exosome derived from M2 macrophages on several diseases and its mechanisms. Finally, we discussed the appropriateness and inappropriateness in existing potential applications based on exosomes and macrophages.

Novel cryogenic dual-emission mechanism of lead-free double perovskite Cs2AgInCl6 and using SiO2 to enhance their photoluminescence and photostability.

Lead halide perovskite have attracted world-wide attention regarding their serious hazards on ecological environment and human health. To improve both the emission intensity and stability of Cs2AgInCl6, this study explores using SiO2 to structurally adjust Cs2AgInCl6. Note that including SiO2 changed the growth style and crystal morphology of Cs2AgInCl6 from an octahedron to a truncated octahedron. After structural adjustment, the unit cells scattered, and the absorption limit broke. Moreover, SiO2 was demonstrated to passivate the material's surface to form an anti-oxidation protective layer. Consequently, the photoluminescence emission intensity increased by 181.5% and the stability of Cs2AgInCl6 improved by 83.11%. This work provides a methodology and reference for future improvements to the luminescence of Cs2AgInCl6. Furthermore, a novel double-emission phenomenon (λex = 365 nm: λem ≈ 580 nm; λex = 325 nm: λem ≈ 505 nm) of Cs2AgInCl6 at cryogenic temperatures (20 K) was discovered; this phenomenon explains the shoulder emission problem of 400-450 nm at room temperature and clarifies the luminescence mechanism of Cs2AgInCl6.