Post-device Dimethylamine Treatment Enables Stable and Efficient Perovskite Solar Cells.

The incorporation of organic ligands via post-device treatment is an effective strategy to improve the stability of perovskite solar cells (PSCs). Although the active area is protected by metal electrode under post-treatment, the aggression of post-treatment ligands into active area cannot be avoided thoroughly. Unfortunately, the size of long-chain amines is too large, and the three-dimensional (3D) perovskite cannot maintain its 3D perovskite structure once the cation substitution occurs during the post-treatment. Despite that the low-dimensional (LD) perovskites are beneficial to stability, long-chain amines are harmful to carrier transport in PSCs. Here, we introduce dimethylamine (DMA), a slightly oversized cation that can be doped into 3D perovskite structure, for post-device treatment to improve the efficiency and stability of PSCs. After exposure to DMA gas, the inactive area of Cs/FA/MA mixed cation perovskite device that is not covered by metal electrode is converted into LD perovskite, passivating the defects of 3D perovskite in the active region, suppressing non-radiation recombination and ion migration. As a result, we achieved a power conversion efficiency (PCE) of 22.29 % with negligible hysteresis and better stability after DMA post-treatment, which is much higher than that (20.40 %) of the control device.

First detection of Tetraparvovirus ungulate 1 in diseased cattle (Chinese Simmental) from Hunan province, China.

Tetraparvovirus is an emerging parvovirus infecting a variety of mammals and humans, and associated with human diseases including severe acute respiratory infection and acute encephalitis syndrome. In the present study, a Tetraparvovirus ungulate 1 (formerly known as bovine hokovirus) strain HNU-CBY-2023 was identified and characterized from diseased Chinese Simmental from Hunan province, China. The nearly complete genome of HNU-CBY-2023 is 5346 nt in size and showed genomic identities of 85-95.5% to the known Tetraparvovirus ungulate 1 strains from GenBank, indicating a rather genetic variation. Phylogenetic and genetic divergence analyses indicated that Tetraparvovirus ungulate 1 could be divided into two genotypes (I and II), and HNU-CBY-2023 was clustered into genotype II. This study, for the first time, identified Tetraparvovirus ungulate 1 from domestic cattle from mainland China, which will be helpful to understand the prevalence and genetic diversity of Tetraparvovirus ungulate 1.

Film-Forming Capability and Antibacterial Activity of Surface-Deacetylated Chitin Nanocrystals: Role of Degree of Deacetylation.

Developing sustainable food-active packaging materials is a major issue in food preservation applications. Chitin nanocrystals (ChNCs) are regarded as unique bioderived nanomaterials due to their inherent nitrogen moiety. By tuning the chemical functionality of this nanomaterial, it is possible to affect its properties, such as film-forming capability and antibacterial activity. In this work, surface-deacetylated chitin nanocrystals (D-ChNCs) with different degrees of deacetylation (DDs) were prepared by partial deacetylation of native chitin and subsequent acid hydrolysis, and their film-forming capability and antibacterial activity were studied systematically. The D-ChNCs showed favorable film-forming ability and antibacterial activity, which are closely related to their DD. With the increase in DD (from 5.7% to 45.4%), the formed transparent films based on ChNCs showed gradually increased elongation at break (from 0.5% to 2.5%) and water contact angle (from 25.5° to 87.0°), but decreased break strength (from 3.13 to 0.89 MPa), Young's modulus (from 0.84 to 0.24 MPa), and water vapor permeability (from 4.7 × 10-10 to 4.1 × 10-10g/m s Pa). Moreover, the antibacterial activity of the D-ChNCs against E. coli and S. aureus also increased with the increase of DD. This study also found that the depolarization and potential dissipation of the bacterial cell membrane induced by the contact between amino-rich D-ChNCs and bacteria through electrostatic attraction are the possible mechanisms causing bacterial cell death. This study provides a basis for understanding the effects of DD on the film-forming capability and antibacterial activity of ChNCs, which is conducive to the design of novel active packaging films based on ChNCs.

The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.

MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.

Causal relationships between peripheral immune cells and Alzheimer's disease: a two-sample Mendelian randomization study.

OBJECTIVE: Previous research suggests that peripheral immune cells may play a role in the development of Alzheimer's disease (AD). Our study aims to determine if the composition of peripheral immune cells directly contributes to the occurrence of AD. METHODS: We utilized a two-sample Mendelian randomization (MR) approach to examine the association between peripheral immune cells and AD.The primary analysis method used was the inverse variance weighted (IVW) method, and we also conducted analyses using MR Egger, weighted median, simple mode, and weighted mode methods to ensure the accuracy of the results.Heterogeneity and horizontal pleiotropy were evaluated using Cochran's Q statistics and the MR Egger intercept, respectively. RESULTS: The study found a significant correlation between increased IgD + CD24- AC cells (Odds Ratio [OR] = 1.03, 95% Confidence Interval [CI] = 1.01-1.06, P = 0.0172), increased CD4 + %leukocyte (OR = 1.08, 95% CI = 1.02-1.14, P = 0.0086), and increased CD4 + CD8dim AC cells (OR = 1.06, 95% CI = 1.01-1.11, P = 0.0218), with an increased susceptibility to AD. Conversely, an increase in EM DN (CD4-CD8-) %T cells (OR = 0.95, 95% CI = 0.92-0.99, P = 0.0164) and an increase in DN (CD4-CD8-) AC cells (OR = 0.93, 95% CI = 0.88-0.99, P = 0.0145) were associated with a protective effect against AD. CONCLUSION: Our findings establish a causal link between peripheral immune cells and AD. This study is the first to examine the relationship between peripheral immune cells and AD using MR, offering valuable insights for early diagnosis and treatment decisions.

Toward a Medication Information Literacy Indicator System for Older Adults: A Delphi Study.

BACKGROUND: The safety of medication use among older adults is a growing concern, given the aging population. Despite widespread attention, the exploration of medication literacy in older adults, particularly from the perspective of information literacy, is in its nascent stages. METHODS: This study utilized the existing literature to define medication information literacy (MIL) as a theoretical framework. A two-round Delphi survey was conducted to identify the essential components of a MIL indicator system for older adults. The analytic hierarchy process (AHP) was then used to assign weights to each indicator. RESULTS: The study observed relatively high response rates in both rounds of the questionnaire, which, along with expert authority coefficients (Cr) of 0.86 and 0.89, underscores the credibility and expertise of the panellists. Additionally, Kendall's coefficient of concordance (Kendall's W) ranging from 0.157 to 0.33 (p < 0.05) indicates a consensus among experts on the identified indicators. Utilizing the Delphi process, a MIL indicator system for older adults was developed, comprising five primary and 23 secondary indicators. These indicators were weighted, with medication information cognition and acquisition emerging as pivotal factors in enhancing medication literacy among older adults. CONCLUSIONS: This study developed a MIL indicator system tailored for older adults using the Delphi approach. The findings can inform healthcare professionals in providing customized medication guidance and assist policymakers in crafting policies to enhance medication safety among older adults. PATIENT OR PUBLIC CONTRIBUTION: Patient and public engagement played a pivotal role in the development of our medication information literacy indicator system for older adults. Their involvement contributed to shaping research questions, facilitating study participation, and enriching evidence interpretation. Collaborations with experts in geriatric nursing, medicine, and public health, along with discussions with caregivers and individuals with lived experience, provided invaluable insights into medication management among older adults. Their input guided our research direction and ensured the relevance and comprehensiveness of our findings.

Comparison of minimal access and open breast surgery: a propensity score-matched study on postoperative immune function in breast cancer.

BACKGROUND: Minimal access breast surgery (MABS) is commonly employed in the management of breast cancer, but there is limited research on the postoperative immune function associated with MABS. OBJECTIVE: This study aimed to assess the postoperative immune function in breast patients who underwent MABS or conventional open breast surgery (COBS). METHODS: We retrospectively analyzed the medical records of 829 breast cancer patients treated with either MABS or COBS at a single hospital between January 2020 and June 2023. Among them, 116 matched pairs were obtained through 1:1 propensity score matching (PSM). Flow cytometry was used to measure the percentages of CD3+, CD4+, and CD8+ cells, as well as the CD4+/CD8+ ratio, on three different time points: preoperative day 1 (PreD1), postoperative day 1 (PostD1), and postoperative day 7 (PostD7). RESULTS: Both the MABS and COBS groups demonstrated a significant reduction in the percentages of CD3+, CD4+, and CD8+ cells, along with the CD4+/CD8+ ratio, from PreD1 to PostD1. Interestingly, the MABS group showed a reversal of these parameters, returning to preoperative levels by PostD7. Conversely, the COBS group showed an increase in these parameters from PostD1 to PostD7, but they still remained significantly lower than preoperative levels at PostD7. CONCLUSION: MABS treatment may result in reduced postoperative immune suppression and faster recovery of preoperative immune function compared to COBS in patients.

Transcriptome-based analysis reveals a crucial role of the 20E/HR3 pathway in the diapause of Pieris rapae.

Pieris rapae is among the most damaging pests globally, and diapause makes it highly resistant to environmental stresses, playing a crucial role in the survival and reproduction of P. rapae while exacerbating the challenges of pest management and control. However, the mechanisms of its diapause regulation remain poorly understood. This research used RNA sequencing to profile the transcriptomes of three diapause phases (induction and preparation, initiation, maintenance) and synchronous nondiapause phases in P. rapae. During each comparison phase, 759, 1045, and 4721 genes were found to be differentially expressed. Among these, seven clock genes and seven pivotal hormone synthesis and metabolism genes were identified as having differential expression patterns in diapause type and nondiapause type. The weighted gene co-expression network analysis (WGCNA) revealed the red and blue modules as pivotal for diapause initiation, while the grey module was identified to be crucial to diapause maintenance. Meanwhile, the hub genes HDAC11, METLL16D, Dyw-like, GST, and so on, were identified within these hub modules. Moreover, an ecdysone downstream nuclear receptor gene, HR3, was found to be a shared transcription factor across all three phases. RNA interference of HR3 resulted in delayed pupal development, indicating its involvement in regulating pupal dipause in P. rapae. The further hormone assays revealed that the 20-hydroxyecdysone (20E) titer in diapause type pupae was lower than that in nondiapause type pupae, which exhibited a similar trend to HR3. When 20E was injected into diapause pupae, the HR3 expression levels were improved, and the pupal diapause were broken. These results indicate that the 20E/HR3 pathway is a critical pathway for the diapause regulation of P. rapae, and perturbing this pathway by ecdysone treatment or RNAi would result in the disruption of diapause. These findings provide initial insights into the molecular mechanisms of P. rapae diapause and suggest the potential use of ecdysone analogs and HR3 RNAi pesticides, which specifically target to diapause, as a means of pest control in P. rapae.

The Automated Systematic Search Deduplicator (ASySD): a rapid, open-source, interoperable tool to remove duplicate citations in biomedical systematic reviews.

BACKGROUND: Researchers performing high-quality systematic reviews search across multiple databases to identify relevant evidence. However, the same publication is often retrieved from several databases. Identifying and removing such duplicates ("deduplication") can be extremely time-consuming, but failure to remove these citations can lead to the wrongful inclusion of duplicate data. Many existing tools are not sensitive enough, lack interoperability with other tools, are not freely accessible, or are difficult to use without programming knowledge. Here, we report the performance of our Automated Systematic Search Deduplicator (ASySD), a novel tool to perform automated deduplication of systematic searches for biomedical reviews. METHODS: We evaluated ASySD's performance on 5 unseen biomedical systematic search datasets of various sizes (1845-79,880 citations). We compared the performance of ASySD with EndNote's automated deduplication option and with the Systematic Review Assistant Deduplication Module (SRA-DM). RESULTS: ASySD identified more duplicates than either SRA-DM or EndNote, with a sensitivity in different datasets of 0.95 to 0.99. The false-positive rate was comparable to human performance, with a specificity of > 0.99. The tool took less than 1 h to identify and remove duplicates within each dataset. CONCLUSIONS: For duplicate removal in biomedical systematic reviews, ASySD is a highly sensitive, reliable, and time-saving tool. It is open source and freely available online as both an R package and a user-friendly web application.

Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy.

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study.

Anti-PD-1 antibody has shown certain effects in patients with newly diagnosed extranodal NK/T-cell lymphoma (ENKTL). Here, we evaluated the clinical efficacy and safety of first-line anti-PD-1 antibody for the treatment of patients with ENKTL and explored biomarkers for treatment response. The clinical data of 107 patients with newly diagnosed ENKTL were retrospectively analysed. Patients received either first-line anti-PD-1 antibody induction treatment or anti-PD-1 antibody combined with asparaginase-based chemotherapy (immunochemotherapy). We found that immunochemotherapy was an independent prognostic factor for longer PFS (p < 0.001). The overall response rate and complete remission rate of immunochemotherapy group was higher than immunotherapy induction group (86.11% vs. 62.86% and 72.22% vs. 52.29%, respectively, p = 0.013). We also observed pretreatment CD4/CD8 ratio >0.83 was significant associated with better response and longer PFS in ENKTL patients received first-line anti-PD1-antibody. Plasma copy number of EBV decreased more significantly in patients with CD4/CD8 ratio >0.83 after treatment. PD-L1 expression was associated with better response and PFS, while elevated plasma IL-6, IL-10 and IFN-γ were associated with poor prognosis. Anti-PD-1 antibody treatment showed promising results in newly diagnosed ENKTL patients. The assessment of pretreatment CD4/CD8 ratio in ENKTL seems feasible for identifying responders to anti-PD-1 antibody treatment.

Harnessing Hafnium-Based Nanomaterials for Cancer Diagnosis and Therapy.

With the rapid development of nanotechnology and nanomedicine, there are great interests in employing nanomaterials to improve the efficiency of disease diagnosis and treatment. The clinical translation of hafnium oxide (HfO2 ), commercially namedas NBTXR3, as a new kind of nanoradiosensitizer for radiotherapy (RT) of cancers has aroused extensive interest in researches on Hf-based nanomaterials for biomedical application. In the past 20 years, Hf-based nanomaterials have emerged as potential and important nanomedicine for computed tomography (CT)-involved bioimaging and RT-associated cancer treatment due to their excellent electronic structures and intrinsic physiochemical properties. In this review, a bibliometric analysis method is employed to summarize the progress on the synthesis technology of various Hf-based nanomaterials, including HfO2 , HfO2 -based compounds, and Hf-organic ligand coordination hybrids, such as metal-organic frameworks or nanoscaled coordination polymers. Moreover, current states in the application of Hf-based CT-involved contrasts for tissue imaging or cancer diagnosis are reviewed in detail. Importantly, the recent advances in Hf-based nanomaterials-mediated radiosensitization and synergistic RT with other current mainstream treatments are also generalized. Finally, current challenges and future perspectives of Hf-based nanomaterials with a view to maximize their great potential in the research of translational medicine are also discussed.

Aerobic exercises regulate the epididymal anion homeostasis of high-fat diet-induced obese rats through TRPA1-mediated Cl- and HCO3- secretion†.

Aerobic exercises could improve the sperm motility of obese individuals. However, the underlying mechanism has not been fully elucidated, especially the possible involvement of the epididymis in which sperm acquire their fertilizing capacity. This study aims to investigate the benefit effect of aerobic exercises on the epididymal luminal milieu of obese rats. Sprague-Dawley male rats were fed on a normal or high-fat diet (HFD) for 10 weeks and then subjected to aerobic exercises for 12 weeks. We verified that TRPA1 was located in the epididymal epithelium. Notably, aerobic exercises reversed the downregulated TRPA1 in the epididymis of HFD-induced obese rats, thus improving sperm fertilizing capacity and Cl- concentration in epididymal milieu. Ussing chamber experiments showed that cinnamaldehyd (CIN), agonist of TRPA1, stimulated an increase of the short-circuit current (ISC) in rat cauda epididymal epithelium, which was subsequently abolished by removing the ambient Cl- and HCO3-. In vivo data revealed that aerobic exercises increased the CIN-stimulated Cl- secretion rate of epididymal epithelium in obese rats. Pharmacological experiments revealed that blocking cystic fibrosis transmembrane regulator (CFTR) and Ca2+-activated Cl- channel (CaCC) suppressed the CIN-stimulated anion secretion. Moreover, CIN application in rat cauda epididymal epithelial cells elevated intracellular Ca2+ level, and thus activate CACC. Interfering with the PGHS2-PGE2-EP2/EP4-cAMP pathway suppressed CFTR-mediated anion secretion. This study demonstrates that TRPA1 activation can stimulate anion secretion via CFTR and CaCC, which potentially forming an appropriate microenvironment essential for sperm maturation, and aerobic exercises can reverse the downregulation of TRPA1 in the epididymal epithelium of obese rats.

Screening for in vitro systematic reviews: a comparison of screening methods and training of a machine learning classifier.

OBJECTIVE: Existing strategies to identify relevant studies for systematic review may not perform equally well across research domains. We compare four approaches based on either human or automated screening of either title and abstract or full text, and report the training of a machine learning algorithm to identify in vitro studies from bibliographic records. METHODS: We used a systematic review of oxygen-glucose deprivation (OGD) in PC-12 cells to compare approaches. For human screening, two reviewers independently screened studies based on title and abstract or full text, with disagreements reconciled by a third. For automated screening, we applied text mining to either title and abstract or full text. We trained a machine learning algorithm with decisions from 2000 randomly selected PubMed Central records enriched with a dataset of known in vitro studies. RESULTS: Full-text approaches performed best, with human (sensitivity: 0.990, specificity: 1.000 and precision: 0.994) outperforming text mining (sensitivity: 0.972, specificity: 0.980 and precision: 0.764). For title and abstract, text mining (sensitivity: 0.890, specificity: 0.995 and precision: 0.922) outperformed human screening (sensitivity: 0.862, specificity: 0.998 and precision: 0.975). At our target sensitivity of 95% the algorithm performed with specificity of 0.850 and precision of 0.700. CONCLUSION: In this in vitro systematic review, human screening based on title and abstract erroneously excluded 14% of relevant studies, perhaps because title and abstract provide an incomplete description of methods used. Our algorithm might be used as a first selection phase in in vitro systematic reviews to limit the extent of full text screening required.

Identification and characterization of a novel avian nephritis virus variant in chickens with enteritis in Hunan province, China.

Avian nephritis virus (ANV) infection is associated with diarrhea, uricosis, stunting, tubulonephrosis, interstitial nephritis, and mortality of chicken flocks, leading to economic losses in the poultry industry. In this study, an ANV strain designated as HNU-ANV-ML-2020 was identified in tissue samples collected from chickens with severe enteritis on a poultry farm in Hunan province, China, and analyzed. The genome of HNU-ANV-ML-2020 is 6943 nucleotides in length. It showed the highest sequence identity (88.1%) to ANV strain CHN/GXJL815/2017 (MN732559) from Guangxi province, China, while it showed less than 86% identity to other astrovirus (AstV) genome sequences available in the GenBank database. The capsid protein of this virus showed the highest sequence identity to ANV strains HQ330482 and HQ330498 from the UK (81.2% and 81.06%, respectively), while it showed only 73.9% identity to MN732559 and less than 80% identity to the capsid proteins of other AstVs available in GenBank. Further phylogenetic analysis demonstrated that HNU-ANV-ML-2020 belongs to group 4, together with ANV strains identified in Australia, Brazil, the UK, and the Netherlands. Furthermore, ANV strains identified in chickens in China were found to be separated into four distinct groups/genotypes, indicating substantial genetic divergence and a complex circulation pattern in China. The virus characterized in the present study is a novel ANV variant identified for the first time in Hunan province, China.

Synthesis and SAR study of novel diimide skeleton compounds with the anti-inflammatory activities in vitro and in vivo.

Amide bonds widely exist in the structure of natural products and drugs, and play an important role in biological activities. However, due to the limitation of synthesis conditions, there are few studies on biscarbonyl diimides. In this paper, a series of new compounds with diimide skeleton were synthesized by using CDI and NaH as condensation agents. The anti-inflammatory activity and cytotoxicity of the compound in RAW264.7 macrophages were evaluated by ELISA and MTT experiments. The results showed that these compounds had good anti-inflammatory activity in vitro, and the IC50 of compound 4d on inflammatory factors IL-6 and TNF-α reached 1.59 µM and 15.30 µM, respectively. Further structure-activity relationship showed that biscarbonyl diimide and unsaturated double bond played a major role in the anti-inflammatory activity. In addition, compound 4d can alleviate acute lung injury (ALI) induced by LPS in vivo, reduce alveolar cell infiltration, and decrease the expression of ALI inflammatory factors. At the same time, compound 4d can significantly improve the survival rate of LPS-induced sepsis in mice. In short, the design and synthesis of the diimide skeleton provides a potential lead compound for the treatment of inflammatory diseases, and also provides a new idea for the design of amide compounds.

Nanozyme's catalytic activity at neutral pH: reaction substrates and application in sensing.

Nanozymes exhibit their great potential as alternatives to natural enzymes. In addition to catalytic activity, nanozymes also need to have biologically relevant catalytic reactions at physiological pH to fit in the definition of an enzyme and to achieve efficient analytical applications. Previous reviews in the nanozyme field mainly focused on the catalytic mechanisms, activity regulation, and types of catalytic reactions. In this paper, we discuss efforts made on the substrate-dependent catalytic activity of nanozymes at neutral pH. First, the discrepant catalytic activities for different substrates are compared, where the key differences are the characteristics of substrates and the adsorption of substrates by nanozymes at different pH. We then reviewed efforts to enhance reaction activity for model chromogenic substrates and strategies to engineer nanomaterials to accelerate reaction rates for other substrates at physiological pH. Finally, we also discussed methods to achieve efficient sensing applications at neutral pH using nanozymes. We believe that the nanozyme is catching up with enzymes rapidly in terms of reaction rates and reaction conditions. Designing nanozymes with specific catalysis for efficient sensing remains a challenge.

Bicyclol Alleviates Streptozotocin-induced Diabetic Cardiomyopathy By Inhibiting Chronic Inflammation And Oxidative Stress.

PURPOSE: Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. METHODS: A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. RESULTS: We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. CONCLUSION: Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.

Design and synthesis optimization of novel diimide indoles derivatives for ameliorating acute lung injury through modulation of NF-κB signaling pathway.

Acute lung injury (ALI) is a common respiratory disease caused by local or systemic inflammatory reaction. Based on the natural 7-chain diaryl anti-inflammatory framework, a series of diimide indoles derivatives were designed by combining curcumin and indole in this study. The synthesis of diimide compounds was extended using dichloromethane (DCM) as solvent and 1,1'-carbonyldiimidazole (CDI) and sodium hydride (NaH) as double activators, and a total of 40 diimide-indole derivatives were obtained. The results of in vitro anti-inflammatory activity showed that most compounds could inhibit the production of interleukin-6 (IL-6) better than curcumin and indomethacin. Among the compounds, the IC50 of compound 11f on IL-6 reached 1.05 µM with no obvious cytotoxic side effects. Mechanistically, compound 11f could block the expression of NF-κB P65 phosphorylation, and nuclear translocation of P65. The acute toxicity tests in-vivo also showed no obvious toxicity in mice after the intragastric administration of 1000 mg/kg. In addition, the compound 11f could significantly inhibit the LPS-induced inflammatory response in mice and reduce the number of neutrophils and wet/dry lung weight ratio, thereby alleviating ALI. These results indicated that the novel diimide indoles were promising anti-inflammatory agents for the treatment of ALI.

Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma.

Macrophages constitute a major component in human hepatocellular carcinoma (HCC) and perform various functions to facilitate disease progression. Reprogramming or reconstituting the tumor surveillance phenotypes of macrophages represents an attractive immunotherapeutic strategy in cancer treatments. The current study identified CD169 as a potential target for macrophage repolarization since it signified a population of macrophages positively correlated with an activated immune signature and better prognosis of patients with HCC. In vitro experiments revealed that a low dose of type I interferon (IFN) could effectively reprogram human monocyte-derived macrophages to upregulate CD169 expression, and such induced CD169+ macrophages exhibited significantly enhanced phagocytotic and CD8+ T cell-activating capacities compared to controls. A low dose of IFNα also inhibited hepatoma growth in mice in vivo, presumably through polarizing the CD169+ macrophage population and enhancing CD8+ T cell activities. Notably, IFNα also induced substantial PD-L1 expression on macrophages in vivo, and thus blockade of PD-L1 could further increase the anti-tumor efficacy of IFNα in the treatment of HCC. We propose a low dose of IFNα in combination with a PD-L1 blocking agent as a potential anti-tumor therapeutic strategy via its effects on macrophage polarization.