Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

AI-based IsAb2.0 for antibody design.

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming. Computational approaches, while progressing, faced limitations due to insufficient structural data and the absence of a standardized protocol. To tackle these challenges, our lab previously developed IsAb1.0, an in silico antibody design protocol. Yet, IsAb1.0 lacked accuracy, had a complex procedure, and required extensive antibody bioinformation. Moreover, it overlooked nanobody and humanized antibody design, hindering therapeutic antibody development. Building upon IsAb1.0, we enhanced our design protocol with artificial intelligence methods to create IsAb2.0. IsAb2.0 utilized AlphaFold-Multimer (2.3/3.0) for accurate modeling and complex construction without templates and employed the precise FlexddG method for in silico antibody optimization. Validated through optimization of a humanized nanobody J3 (HuJ3) targeting HIV-1 gp120, IsAb2.0 predicted five mutations that can improve HuJ3-gp120 binding affinity. These predictions were confirmed by commercial software and validated through binding and neutralization assays. IsAb2.0 streamlined antibody design, offering insights into future techniques to accelerate immunotherapy development.

Suprathreshold Water Spray Stimulus Enhances Plant Defenses against Biotic Stresses in Tomato.

Mechanical stimuli can affect plant growth, development, and defenses. The role of water spray stimulation, as a prevalent mechanical stimulus in the environment, in crop growth and defense cannot be overlooked. In this study, the effects of water spray on tomato plant growth and defense against the chewing herbivore Helicoverpa armigera and necrotrophic fungus Botrytis cinerea were investigated. Suprathreshold water spray stimulus (LS) was found to enhance tomato plant defenses against pests and pathogens while concurrently modifying plant architecture. The results of the phytohormone and chemical metabolite analysis revealed that LS improved the plant defense response via jasmonic acid (JA) signaling. LS significantly elevated the level of a pivotal defensive metabolite, chlorogenic acid, and reduced the emissions of volatile organic compounds (VOCs) from tomato plants, thereby defending against pest and pathogen attacks. The most obvious finding to emerge from this study is that LS enhances tomato plant defenses against biotic stresses, which will pave the way for further work on the application of mechanical stimuli for pest management.

[Characteristics of Water-soluble Ion Pollution in PM2.5 and the Causes of High Acidity of PM2.5 in Dalian].

To gain a deeper understanding of the pollution status and influencing factors of fine particles （PM2.5） and their water-soluble ions （WSI） in Dalian and to implement precise control of pollution events such as haze and acid rain, PM2.5 samples were collected in Dalian from June 2021 to May 2022. Then, the mass concentrations of PM2.5 and WSI were determined using the weight method and ion chromatography, respectively, and the pollution characteristics and sources were analyzed. Furthermore, the causes of the high acidity of PM2.5 in spring were discussed. The results showed that the annual average mass concentrations of PM2.5 and WSI in Dalian during the sampling period were （33.24 ±28.87） µg·m-3 and （18.66 ±20.52） µg·m-3, respectively, and the secondary ions （SNA, including SO42-, NO3-, and NH4+） accounted for the highest proportion of WSI [（86.2 ±9.3）%]. The order of ion concentration levels from highest to lowest was： NO3->SO42->NH4+>Cl->K+>Ca2+>Na+>Mg2+>F-. Due to the influence of meteorological conditions and coal combustion emissions during the concentrated heating period from late autumn to early spring, the seasonal variation in PM2.5 and WSI was winter>spring>autumn>summer, whereas SNA was the highest in spring and the lowest in summer. The results of correlation and principal component analysis showed that WSI in PM2.5 was mainly from the secondary transformation of atmospheric SO2 and NO2 （contributing to the majority of SNA）, mixed sources of combustion and dust （characterized by K+, Mg2+, Cl-, and F-）, and sources of sand and sea salt （characterized by Na+, Ca2+, and Mg2+）. In summer, the main combustion source was biomass burning, whereas in autumn, winter, and spring, coal combustion emissions were predominant. The change in wind direction from autumn to winter brought by a shift from the source of sea salt to soil dust； additionally, the external pollution transported by northwest winds contributed to the complexity of the sources of WSI in PM2.5 during spring in Dalian. ISORROPIA-II model simulations suggested NH4NO3 as the most present solid aerosol form in PM2.5 in Dalian, followed by CaSO4 and （NH4）2SO4； compared to that in solid aerosols, more SNA existed in liquid aerosols. The annual average pH of PM2.5 in Dalian was 5.65 ±3.00, with pH values close to neutral in summer, autumn, and winter but significantly acidic in spring （2.03 ±3.18）. The high acidity observed in spring was attributed to the combination of low temperature, high humidity, and high SNA concentrations. These conditions resulted in higher aerosol water content and increased gas-to-particle conversion rates, ultimately leading to an ammonia-deficient environment. The backward trajectory and PSCF results indicated that the external transport of high acidity PM2.5 in spring mainly came from the northwest （45.0%） and southwest （40.8%） directions. Mobile source emissions made the most significant contribution to the transportation of pollutants in the former, forming high-pollution source areas in the Beijing-Tianjin-Hebei Region, which may have been mainly related to urban motor vehicle and port vessel emissions； the latter was influenced by relatively strong stationary sources and showed higher SO2 emissions in the southern part of Henan Province and the central part of Jiangsu Province.

Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

A Rhodamine-Spiropyran Conjugate Empowering Tunable Mechanochromism in Polymers under Multiple Stimuli.

Mechanochromic functionality realized via the force-responsive mechanophores in polymers has great potential for damage sensing and information storage. Mechanophores with the ability to recognize multiple stimuli for tunable chromic characteristics are highly sought after for versatile sensing ability and color programmability. Nevertheless, the majority of mechanophores are based on single-component chromophores with limited sensitivity, or require additional fabrication technology for multi-modal chromism. Here, we report a novel multifunctional mechanophore capable of vividly detectable and tunable mechanochromism in polymers. This synergistic optical coupling relies on strategically fusing rhodamine and spiropyran (Rh-SP), and tethering polymer chains on both subunits. The mechanochromic behaviors of the Rh-SP-linked polymers under sonication and compression are thoroughly evaluated in response to changes in force and the light-controlled relaxation process. Non-sequential ring-opening of the two subunits under force is identified, endowing high-contrast mechanochromism. Light-induced differential ring-closing reactions of the two subunits, together with the acidichromism of the SP moiety, are employed to engineer elastomers with programmable and wide-spectrum colors. Our work presents an effective strategy for highly appreciable and regulable mechanochromic functionality, and also provides new insights into the rupture mechanisms of π-fused mechanophores, as well as how the stimuli history controls stress accumulation in polymers.

Photoinduced Pd-Catalyzed Intramolecular 6-endo Heck Reaction of Alkyl Halides.

A novel photocatalytic palladium-induced 6-endo-selective alkyl Heck reaction of unactivated alkyl iodides and alkyl bromides has been described. This strategy facilitates the gentle and efficient synthesis of a variety of 5-phenyl-1,2,3,6-tetrahydropyridine derivatives. It demonstrates a broad substrate tolerance and excellent 6-endo selectivity. Unlike the high-temperature requirements of traditional alkyl Heck reactions, this transformation efficiently proceeds at room temperature and shows significant promise for industrial-scale applications. Mechanistic investigations reveal that this alkyl Heck reaction proceeds via a hybrid palladium-radical process.

Mechanism and Origins of Enantioselectivity in the Nickel-catalyzed Asymmetric Synthesis of Silicon-Stereogenic Benzosiloles.

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and ß-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C-H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

Latent space search based multimodal optimization with personalized edge-network biomarker for multi-purpose early disease prediction.

Considering that cancer is resulting from the comutation of several essential genes of individual patients, researchers have begun to focus on identifying personalized edge-network biomarkers (PEBs) using personalized edge-network analysis for clinical practice. However, most of existing methods ignored the optimization of PEBs when multimodal biomarkers exist in multi-purpose early disease prediction (MPEDP). To solve this problem, this study proposes a novel model (MMPDENB-RBM) that combines personalized dynamic edge-network biomarkers (PDENB) theory, multimodal optimization strategy and latent space search scheme to identify biomarkers with different configurations of PDENB modules (i.e. to effectively identify multimodal PDENBs). The application to the three largest cancer omics datasets from The Cancer Genome Atlas database (i.e. breast invasive carcinoma, lung squamous cell carcinoma and lung adenocarcinoma) showed that the MMPDENB-RBM model could more effectively predict critical cancer state compared with other advanced methods. And, our model had better convergence, diversity and multimodal property as well as effective optimization ability compared with the other state-of-art methods. Particularly, multimodal PDENBs identified were more enriched with different functional biomarkers simultaneously, such as tissue-specific synthetic lethality edge-biomarkers including cancer driver genes and disease marker genes. Importantly, as our aim, these multimodal biomarkers can perform diverse biological and biomedical significances for drug target screen, survival risk assessment and novel biomedical sight as the expected multi-purpose of personalized early disease prediction. In summary, the present study provides multimodal property of PDENBs, especially the therapeutic biomarkers with more biological significances, which can help with MPEDP of individual cancer patients.

Catalytic Enantioselective Biltz Synthesis.

The Biltz synthesis establishes straightforward access to 5,5-disubstituted (thio)hydantoins by combining a 1,2-diketone and a (thio)urea. Its appealing features include inherent atom and step economy together with the potential to generate structurally diverse products. However, control of the stereochemistry of this reaction has proven to be a daunting challenge. Herein, we describe the first example of enantioselective catalytic Biltz synthesis which affords more than 40 thiohydantoins with high stereo- and regio-control, irrespective of the symmetry of thiourea structure. A one pot synthesis of corresponding hydantoins is also documented. Remarkably, experimental studies and DFT calculations establish the reaction pathway and origin of stereoselectivity.

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

Fabrication of bimetallic-doped materials derived from a Cu-based complex for enhanced dye adsorption and iodine capture.

In this work, we used Cu(II) ions, a bis-pyridyl-bis-amide ligand [N,N'-bis(4-pyridinecarboxamide)-1,2-cyclohexane (4-bpah)], and an aromatic dicarboxylic acid [1,4-cyclohexanedicarboxylic acid (H2CHDA)] to construct a 1D binuclear Cu-based complex, namely {[Cu3(4-bpah)(CHDA)3(H2O)]·2H2O}n (1). Moreover, we also developed a facile method to synthesize two monometallic/bimetallic-doped materials which were derived from the Cu complex (C-N-1 and C-V-1, which were doped with nitrogen and vanadium, respectively). The as-synthesized derived materials were fully characterized and the iodine sorption/release capabilities were investigated in detail. We performed iodine adsorption experiments on the two monometallic/bimetallic-doped materials and found that C-N-1 and C-V-1 possess highly efficient adsorption activities for the adsorption of iodine from solution. The C-N-1 and C-V-1 complexes exhibited remarkable adsorption capacities of 1141.60 and 1170.70 mg g-1, respectively, for iodine from a cyclohexane solution. Moreover, the dye adsorption properties of C-N-1 and C-V-1 were also investigated in detail. The obtained C-N-1 and C-V-1 exhibit effective dye uptake performances in water solution. The adsorption of Congo red (CR) on a single metal carbon material C-N-1 doped with heteroatoms reached equilibrium within 240 min and reached an adsorption capacity of 1357.00 mg g-1 and the adsorption capacities of C-V-1 for methylene blue (MB), gentian violet (GV), rhodamine B (RhB), and CR at room temperature were found to be 187.60, 190.60 and 108.10 and 1501.00 mg g-1 in 180 min, respectively. By comparison, we found that doping vanadium could play an important role in the adsorption processes. The adsorption capacity of C-V-1 (containing the vanadium in its structure) was relatively higher than that of C-N-1, which indicated that the introduction of non-noble metals may effectively tune the adsorption kinetics activity and the introduction of noble metals can change the surface electronegativity of porous carbon materials, thus leading to significantly improved adsorption capabilities.

Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis.

BACKGROUND: Formyl peptide receptor 2 (Fpr2) is an important receptor in host resistance to bacterial infections. In previous studies, we found that the liver of Fpr2-/- mice is the most severely damaged target organ in bloodstream infections, although the reason for this is unclear. AIM: To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections. METHODS: Transcriptome sequencing was performed on the livers of Fpr2-/- and wild-type (WT) mice. Differentially expressed genes (DEGs) were identified in the Fpr2-/- and WT mice, and the biological functions of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) en-richment analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) and western blot (WB) analyses were used to further validate the expression levels of differential genes. Cell counting kit-8 assay was employed to investigate cell survival. The cell cycle detection kit was used to measure the distribution of cell cycles. The Luminex assay was used to analyze cytokine levels in the liver. The serum biochemical indices and the number of neutrophils in the liver were measured, and hepatic histopathological analysis was performed. RESULTS: Compared with the WT group, 445 DEGs, including 325 upregulated genes and 120 downregulated genes, were identified in the liver of Fpr2-/- mice. The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle. The qRT-PCR analysis confirmed that several key genes (CycA, CycB1, Cdc20, Cdc25c, and Cdk1) involved in the cell cycle had significant changes. The WB analysis confirmed a decrease in the expression of CDK1 protein. WRW4 (an antagonist of Fpr2) could inhibit the proliferation of HepG2 cells in a concentration dependent manner, with an increase in the number of cells in the G0/G1 phase, and a decrease in the number of cells in the S phase. Serum alanine aminotransferase levels increased in Fpr2-/- mice. The Luminex assay measurements showed that interleukin (IL)-10 and chemokine (C-X-C motif) ligand (CXCL)-1 levels were significantly reduced in the liver of Fpr2-/- mice. There was no difference in the number of neutrophils, serum C-reactive protein levels, and liver pathology between WT and Fpr2-/- mice. CONCLUSION: Fpr2 participates in the regulation of cell cycle and cell proliferation, and affects the expression of IL-10 and CXCL-1, thus playing an important protective role in maintaining liver homeostasis.

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine.

Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set's 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as.predictors of post-KTx DGF and graft loss,targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, andreferences for personalized immunotherapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00320-w.

Anti-hyperuricemia effect of hesperetin is mediated by inhibiting the activity of xanthine oxidase and promoting excretion of uric acid.

Hesperetin is a natural flavonoid with many biological activities. In view of hyperuricemia treatment, the effects of hesperetin in vivo and in vitro, and the underlying mechanisms, were explored. Hyperuricemia models induced by yeast extract (YE) or potassium oxonate (PO) in mice were created, as were models based on hypoxanthine and xanthine oxidase (XOD) in L-O2 cells and sodium urate in HEK293T cells. Serum level of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) were reduced significantly after hesperetin treatment in vivo. Hesperetin provided hepatoprotective effects and inhibited xanthine oxidase activity markedly, altered the level of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and catalase (CAT), downregulated the XOD protein expression, toll-like receptor (TLR)4, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, interleukin-18 (IL-18), upregulated forkhead box O3a (FOXO3a), manganese superoxide dismutase (MnSOD) in a uric acid-synthesis model in mice. Protein expression of organic anion transporter 1 (OAT1), OAT3, organic cationic transporter 1 (OCT1), and OCT2 was upregulated by hesperetin intervention in a uric acid excretion model in mice. Our results proposal that hesperetin exerts a uric acid-lowering effect through inhibiting xanthine oxidase activity and protein expression, intervening in the TLR4-NLRP3 inflammasome signaling pathway, and up-regulating expression of FOXO3a, MnSOD, OAT1, OAT3, OCT1, and OCT2 proteins. Thus, hesperetin could be a promising therapeutic agent against hyperuricemia.

Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), peculiarly nonalcoholic steatohepatitis (NASH), has become the main cause of liver transplantation and liver-related death. However, the US Food and Drug Administration has not approved a specific medication for treating NASH. Neferine (NEF), a natural bisbenzylisoquinoline alkaloid separated from the traditional Chinese medicine Nelumbinis plumula, has a variety of pharmacological properties, especially on metabolic diseases. Nevertheless, the anti-NASH effect and mechanisms of NEF remain unclear. PURPOSE: This study aimed to investigate the amelioration of NEF on NASH and the potential mechanisms. STUDY DESIGN: HepG2 cells, hepatic stellate cells (HSCs) and high-fat diet (HFD)+carbon tetrachloride (CCl4) induced C57BL/6 mice were used to observe the effect of NEF against NASH and investigate the engaged mechanism. METHODS: HSCs and HepG2 cells stimulated by oleic acid (OA) were treated with NEF. C57BL/6 mice were fed with HFD+CCl4 to induce NASH mouse model and treated with or without NEF (5 mg/kg or 10 mg/kg, once daily, i.p) for 4 weeks. RESULTS: NEF significantly attenuated the accumulation of lipid droplets, intracellular triglyceride (TG) levels and hepatocytes apoptosis in OA-exposed HepG2 cells. NEF not only enhanced the AMPK and ACC phosphorylation in OA-stimulated HepG2 cells, but also reduced inflammatory response and fibrosis in lipopolysaccharide (LPS)-stimulated HepG2 and in LX-2, respectively. In HFD+CCl4-induced NASH mice, pathological staining confirmed NEF treatment mitigated hepatic lipid deposition, inflammatory cell infiltration as well as hepatic fibrosis. Furthermore, the liver weight, serum and hepatic TG and total cholesterol (TC) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were decreased compared with the model group. HFD+CCl4 also induced the upregulation of specific proteins and genes associated to inflammation (ILs, TNF-α, NLRP3, ASC, CCL2 and CXCL10) and hepatic fibrosis (collagens, α-SMA, TGF-ß and TIPM1), which were also suppressed by NEF treatment. CONCLUSION: Our results demonstrated that NEF played a protective role in hepatic steatosis via the regulation of AMPK pathways, which may serve as an attractive candidate for a potential novel strategy on prevention and treatment of NASH.

Evaluation of BDE-47-induced neurodevelopmental toxicity in zebrafish embryos.

There are growing concerns about the neurodevelopmental toxicity of polybrominated diphenyl ethers (PBDEs), but the toxicological phenotypes and mechanisms are not well elucidated. Here, zebrafish (Danio rerio) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from 4 to 72 h post-fertilization (hpf). The results showed that BDE-47 stimulated the production of dopamine and 5-hydroxytryptamine, but inhibited expression of Nestin, GFAP, Gap43, and PSD95 in 24 hpf embryos. Importantly, we unraveled the inhibitory effects of BDE-47 on neural crest-derived melanocyte differentiation and melanin syntheses process, evidenced by disrupted expression of wnt1, wnt3, sox10, mitfa, tyrp1a, tyrp1b, tryp2, and oca2 gene in 72 hpf embryos and decreased tyrosinase activities in embryos at 48 and 72 hpf. The transcriptional activities of myosin VAa, kif5ba, rab27a, mlpha, and cdc42 genes, which are associated with intracellular transport process, were also disturbed during zebrafish development. Ultimately, these alterations led to fast spontaneous movement and melanin accumulation deficit in zebrafish embryos upon BDE-47 exposure. Our results provide an important extension for understanding the neurodevelopmental effects of PBDEs and facilitate the comprehensive evaluation of neurotoxicity in embryos.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results: The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions: This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

A Novel Azo-Linked Polymer Bearing Trifluoromethyl Groups for I2 Capture.

In this work, a novel three nitro-group-bearing monomer 3,6-dinitro-9-(2-trifluoromethyl-4-nitrophenyl)-carbazole (Car-3NO2 -CF3 ) via a CN coupling reaction between 3,6-dinitro-9H-carbazole (Car-2NO2 ) and 2-chloro-5-nitrobenzotrifluoride is synthesized, and obtained single crystal and single crystal analysis data for this compound. The crystal system of Car-3NO2 -CF3 is monoclinic and it has a P 21/c space group. This new monomer (Car-3NO2 -CF3 ) is also utilized to synthesize a novel azo-linked polymer (Azo-Car-CF3 ). The trifluoromethyl group has polar CF bonds, and thus it is an effective functional group for the capture of iodine. Azo-Car-CF3 has great thermal stability with a mass loss of only 10% at 414 °C, as well as good chemical stability as is demonstrated by its low solubility in common organic solvents such as tetrahydrofuran (THF), acetone, methanol, ethanol, and N,N-dimethylformamide (DMF). The specific surface area of Azo-Car-CF3 can reach as high as 335 m2  g-1 . Azo-Car-CF3 exhibits an excellent capacity for iodine adsorption and can reach up to 1198 mg g-1 in cyclohexane solution, and its adsorption capacity for iodine vapor can get to 2100 mg g-1 . In addition, ethanol can be used to trigger the release of the captured iodine to be easily released from Azo-Car-CF3 .