Hybrid Membrane-Camouflaged Biomimetic Immunomodulatory Nanoturrets with Sequential Multidrug Release for Potentiating T Cell-Mediated Anticancer Immunity.

Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel Escherichia coli (E. coli) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg2+. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.

Zonal interdependence in the temporomandibular joint cartilage.

The temporomandibular joint (TMJ) cartilage is biomechanical sensitive. Cells in TMJ cartilage are zonally arranged, earlier differentiated in the super zone and late differentiated in the deep zone. The purpose was to detect the zonal interdependence in TMJ cartilage under dental biomechanical stimulations. Here, we obtained the Sox9CreER ; Rosa26tdTomato and Col10CreER ; Rosa26tdTomato mice to label super zone Sox9-expressing (Sox9+ ) or deep zone Col10-expressing (Col10+ ) cells by tdTomato (TdT), and Sox9CreER ; Rosa26DTA and Col10CreER ; Rosa26DTA mice to ablate Sox9+ or Col10+ cells selectively. These mice were subjected to unilateral anterior crossbite (UAC) or bilateral anterior elevation (BAE) dental stimulation, which promoted terminal differentiation or proliferation of TMJ chondrocytes, respectively. In both UAC and BAE models, the Sox9-TdT+ cells performed as proliferation and mature differentiation, showing as expressing Ki67 and Col-X, respectively; while the Col10-TdT+ cells performed as terminal differentiation, showing as expressing osteocalcin (OCN). In both Sox9+ - and Col10+ -cells ablation groups, there were reductions in cell number, cartilage thickness and matrix amount, subchondral bone loss, and condylar deformation. The UAC-promoted terminal differentiation was enhanced, and the BAE-promoted cellular proliferation was ruined. Impressively, when Col10+ cells were ablated, the UAC-promoted DAP3 expression, an anoikis marker, was further increased, while the BAE-suppressed DAP3 expression was instead greatly increased. These findings demonstrated that the cartilage zones function interdependently. The super zone harbors the cells that undergo differentiation to deep zone cells, the deep zone contains load-bearing matrix which is structural essential for the cells located inside or superficial.

N-Indole-Substituted Imidazolylidene Pd-PEPPSI Precatalysts: Enhanced Performance with a 3,5-Diisopropyl-4-indolyl Moiety.

Pd-PEPPSI complexes of N-(4-indolyl)-N'-phenylimidazol-2-ylidene (IIn) ligands with a 5-isopropyl-4-indolyl moiety are synthesized and evaluated in heteroarene C-H arylation, Suzuki-Miyaura cross-coupling, and Buchwald-Hartwig amination reactions. The IIn-Pd complex bearing a 3,5-diisopropyl-4-indolyl substituent (C5) exhibits the best catalytic activity in this series and substantially outperforms commercial precatalyst PEPPSI-Pd-IPr. The results also suggest that the alkyl group at position 3 of the 4-indolyl moiety shows stronger impacts than that at position 5.

Discovery of 3-hydroxymethyl-azetidine derivatives as potent polymerase theta inhibitors.

Inhibition of the low fidelity DNA polymerase Theta (Polθ) is emerging as an attractive, synthetic-lethal antitumor strategy in BRCA-deficient tumors. Here we report the AI-enabled development of 3-hydroxymethyl-azetidine derivatives as a novel class of Polθ inhibitors featuring central scaffolding rings. Structure-based drug design first identified A7 as a lead compound, which was further optimized to the more potent derivative B3 and the metabolically stable deuterated compound C1. C1 exhibited significant antiproliferative properties in DNA repair-compromised cells and demonstrated favorable pharmacokinetics, showcasing that 3-hydroxymethyl-azetidine is an effective bio-isostere of pyrrolidin-3-ol and emphasizing the potential of AI in medicinal chemistry for precise molecular modifications.

Discovery of macrocyclic CDK2/4/6 inhibitors with improved potency and DMPK properties through a highly efficient macrocyclic drug design platform.

Cyclin-dependent kinases (CDKs) are critical cell cycle regulators that are often overexpressed in tumors, making them promising targets for anti-cancer therapies. Despite substantial advancements in optimizing the selectivity and drug-like properties of CDK inhibitors, safety of multi-target inhibitors remains a significant challenge. Macrocyclization is a promising drug discovery strategy to improve the pharmacological properties of existing compounds. Here we report the development of a macrocyclization platform that enabled the highly efficient discovery of a novel, macrocyclic CDK2/4/6 inhibitor from an acyclic precursor (NUV422). Using dihedral angle scan and structure-based, computer-aided drug design to select an optimal ring-closing site and linker length for the macrocycle, we identified compound 8 as a potent new CDK2/4/6 inhibitor with optimized cellular potency and safety profile compared to NUV422. Our platform leverages both experimentally-solved as well as generative chemistry-derived macrocyclic structures and can be deployed to streamline the design of macrocyclic new drugs from acyclic starting compounds, yielding macrocyclic compounds with enhanced potency and improved drug-like properties.

Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells.

BACKGROUND: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent. RESULTS: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR. CONCLUSIONS: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

Plasma and milk metabolomics profiles in dairy cows with subclinical and clinical ketosis.

Ketosis, a commonly observed energy metabolism disorder in dairy cows during the peripartal period, is distinguished by increased concentrations of ß-hydroxybutyrate (BHB) in blood. This condition has a negative impact on milk production and quality, causing financial losses. An untargeted metabolomics approach was performed on plasma samples from cows between 5 and 7 DIM diagnosed as controls (CON, BHB <1.2 mM, n = 30), subclinically ketotic (SCK, 1.2 < BHB <3.0 mM, n = 30), or clinically ketotic (CK, BHB >3.0 mM, n = 30). Cows were selected from a commercial farm of 214 Holstein cows (average 305-d yield in the previous lactation of 35.42 ± 7.23 kg/d; parity, 2.41 ± 1.12; body condition score, 3.1 ± 0.45). All plasma and milk samples (n = 90) were subjected to Liquid Chromatography-Mass Spectrometry (LC-MS)-based metabolomic analysis. Statistical analyses was performed using the Graph Pad Prism 8.0, MetaboAnalyst 4.0 and R packages (version 4.1.3). Compared with the CON group, both SCK and CK groups had greater milk fat, freezing point, and fat-to-protein ratio and lower milk protein, lactose, solids-nonfat, and milk density. Within 21 d after calving, compared with CON, the SCK group experienced a reduction of 2.65 kg/d in milk yield, while the CK group experienced a decrease of 7.7 kg/d. Untargeted metabolomics analysis facilitated the annotation of a total of 5,259 and 8,423 metabolites in plasma and milk. Differentially affected metabolites were screened in CON vs. SCK, CON vs. CK, and SCK vs. CK (unpaired t-test, False discovery rate <0.05; and absolute value of log(2)-fold change >1.5). A total of 1,544 and 1,888 differentially affected metabolites were detected in plasma and milk. In plasma, glycerophospholipid metabolism, pyrimidine metabolism, tryptophan metabolism, sphingolipid metabolism, amino sugar and nucleotide sugar metabolism, phenylalanine metabolism, steroid hormone biosynthesis were identified as significant pathways. Weighted gene co-expression network analysis (WGCNA) indicated that tryptophan metabolism is a key pathway associated with the occurrence and development of ketosis. Increases in 5-Hydroxytryptophan and decreases in kynurenine and 3-indoleacetic acid in SCK and CK were suggestive of an impact at the gut level. The decrease of most glycerophospholipids indicated that ketosis is associated with disordered lipid metabolism. For milk, pyrimidine metabolism, purine metabolism, pantothenate and CoA biosynthesis, amino sugar and nucleotide sugar metabolism, nicotinate and nicotinamide metabolism, sphingolipid metabolism, fatty acid degradation were identified as significant pathways. The WGCNA indicated that purine and pyrimidine metabolism in plasma was highly correlated with milk yield during the peripartal period. Alterations in purine and pyrimidine metabolism characterized ketosis, with lower levels of these metabolites in both milk and blood underscoring reduced efficiency in nitrogen metabolism. Our results may help to establish a foundation for future research investigating mechanisms responsible for the occurrence and development of ketosis in peripartal cows.

Comparison of cement-augmented pedicle screw and conventional pedicle screw for the treatment of lumbar degenerative patients with osteoporosis.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To compare the safety and clinical efficacy between using cement-augmented pedicle screws (CAPS) and conventional pedicle screws (CPS) for the treatment of lumbar degenerative patients with osteoporosis. Management of lumbar degenerative patients with osteoporosis undergoing spine surgery is challenging. The clinical efficacy and potential complications of the mid-term performance of the CAPS technique in the treatment of lumbar degenerative patients with osteoporosis remain to be evaluated. PATIENTS AND METHODS: The data of 131 lumbar degenerative patients with osteoporosis who were treated with screw fixation from May 2016 to December 2019 were retrospectively analyzed in this study. The patients were divided into the following two groups according to the type of screw used: (I) the CAPS group (n = 85); and (II) the CPS group (n = 46). Relevant data were compared between two groups, including the demographics data, clinical results and complications. RESULTS: The difference in the VAS, ODI and JOA scores at three and 6 months after the operation between the two groups was statistically significant (P < 0.05). At 12 months after surgery and the final follow-up, a significant difference in the fusion rate was found between the two groups (P < 0.05). Four cemented screws loosening were observed in the CAPS group (loosening rate 4/384, 1.04%) and 15 screws loosening were observed in the CPS group (loosening rate 15/214, 7.01%). In the CAPS group, a total of 384 augmented screws were used, and cement leakage was observed in 25 screws (25/384, 6.51%), but no obvious clinical symptoms or serious complications were observed. Adjacent vertebral fractures occurred in six patients in the CAPS group and one in the CPS group. CONCLUSIONS: CAPS technique is an effective strategy for the treatment of lumbar degenerative patients with osteoporosis, with a higher fusion rate and lower screw loosening rate than CPS.

CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival.

OBJECTIVES: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. DESIGN: We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real-time bioenergetic profile analysis (Seahorse). RESULTS: Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction increases mitochondrial reactive oxygen species production leading to the premature death of neutrophilsthrough apoptosis, especially in oxidative environment. The decreased functional neutrophils in tissues might explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. CONCLUSION: These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.

Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases.

OBJECTIVE: The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway. DESIGN: Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition. RESULTS: In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models. CONCLUSION: Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4+ T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.

Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation.

Biodegradable polymers are expected to be an alternative to plastics. Because of its high biocompatibility, poly (lactic-co-glycolic acid) (PLGA) is widely used in medicine. It has been reported that micro-nano plastics can be accumulated in the circulatory system and cause tissue injury. With the increasing environmental exposure of degradable polymer nanoparticles (NPs), the impact of this risk factor on cardiovascular disease deserves attention. Thus, we aim to study the harmful effect of PLGA NPs on the process of vascular stenosis which is a typical pathological feature of cardiovascular diseases. We establish a mouse vascular stenosis model with intravenously injecting of PLGA NPs for 2 weeks. This model leads to a significant narrowing of the left common carotid artery which is characterized by the increasing intima area and focal stenosis. We observe that PLGA NPs accelerate stenosis progression by inducing inflammation and impairing vascular function. It promotes the proliferation of smooth muscle cells and causes abnormal collagen distribution. The combination of wall shear stress and PLGA NPs uptake speed up endothelial cell damage, decrease endothelial permeability and cell migration capacity. Our results suggest that PLGA NPs may pose a risk in cardiovascular stenosis which inspire us to concern the biodegradable polymeric materials in our living especially the clinic applications.

The need for digital health education among next-generation health workers in China: a cross-sectional survey on digital health education.

BACKGROUND: Digital health is important for sustainable health systems and universal health coverage. Since the outbreak of COVID-19, many countries, including China, have promoted the introduction of digital health in their medical services. Developing the next generation of physicians with digital health knowledge and skills is a prerequisite for maximizing the potential of digital health. OBJECTIVE: We aimed to understand the perception of digital health among Chinese medical students, the current implementation of digital health education in China, and the urgent need of medical students. METHODS: Our cross-sectional survey was conducted online and anonymously among current medical students in China. We used descriptive statistical analysis to examine participant demographic characteristics and the demand for digital health education. Additional analysis was conducted by grouping responses by current participation in a digital health course. RESULTS: A total of 2122 valid responses were received from 467 medical schools. Most medical students had positive expectations that digital health will change the future of medicine. Compared with wearable devices (85.53%), telemedicine (84.16%), and medical big data (86.38%), fewer respondents believed in the benefits of clinical decision support systems (CDSS) (63.81%). Most respondents said they urgently needed digital health knowledge and skills, and the teaching method of practical training and internship (78.02%) was more popular than the traditional lecture (10.54%). However, only 41.45% wanted to learn about the ethical and legal issues surrounding digital health. CONCLUSIONS: Our study shows that the current needs of Chinese medical students for digital health education remain unmet. A national initiative on digital health education, is necessary and attention should be paid to digital health equity and education globally, focusing on CDSS and artificial intelligence. Ethics knowledge must also be included in medical curriculum. Students as Partners (SAP) is a promising approach for designing digital health courses.

Engineered Macrophage-Membrane-Coated Nanoparticles with Enhanced PD-1 Expression Induce Immunomodulation for a Synergistic and Targeted Antiglioblastoma Activity.

Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood-brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression (PD-1-MM@PLGA/RAPA). Using both in vitro and in vivo GBM models, we demonstrate that PD-1-MM@PLGA/RAPA can efficiently traverse across the BBB in response to the tumor microenvironment (TME) recruitment with nanoparticles accumulating at the tumor site. Furthermore, we show a boosted immune response as a result of enhancing CD8+ cytotoxic T-lymphocyte (CTL) infiltration. Together we provide a new nanoplatform for enhancing ICB in combination with conventional chemotherapy for GBM and many other cancers.

The Pharmacological Efficacy of Baicalin in Inflammatory Diseases.

Baicalin is one of the most abundant flavonoids found in the dried roots of Scutellaria baicalensis Georgi (SBG) belonging to the genus Scutellaria. While baicalin is demonstrated to have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity and lipophilicity limit the bioavailability and pharmacological functions. Therefore, an in-depth study of baicalin's bioavailability and pharmacokinetics contributes to laying the theoretical foundation for applied research in disease treatment. In this view, the physicochemical properties and anti-inflammatory activity of baicalin are summarized in terms of bioavailability, drug interaction, and inflammatory conditions.

Competitive adsorption of heavy metals between Ca-P and Mg-P products from wastewater during struvite crystallization.

Wastewater usually contains high concentration of calcium (Ca), posing a competitive reaction with magnesium (Mg) on phosphorus (P) recovery during the struvite crystallization. The differences in the adsorption of heavy metals by Ca-P and Mg-P (struvite) generated are still unclear. Herein, we analyzed the residues of four kinds of common heavy metals (Cu, Zn, Cd, Pb) in Ca-P and Mg-P (struvite) under varying conditions (solution pH, N/P ratio, Mg/Ca ratio) in the swine wastewater and explored their possible competitive adsorption mechanisms. The experiments using synthetic wastewater and real wastewater have similar experimental patterns. However, under the same conditions, the metal (Pb) content of struvite recovered from the synthetic wastewater (16.58 mg/g) was higher than that of the real wastewater (11.02 mg/g), as predicted by the Box-Behnken Design of Response Surface Methodology (BBD-RSM). The results demonstrated that Cu was the least abundant in the precipitates compared to Zn, Cd, and Pb of almost all experimental groups with an N/P ratio greater than or equal to 10. The fact might be mainly attributed to the its stronger binding capacity of Cu ion with NH3 and other ligands. Compared with struvite, the Ca-P product had a higher adsorption capacity for heavy metals and a lower P recovery rate. In addition, the higher solution pH and N/P ratio were favorable to obtain qualified struvite with lower heavy metal content. It can be applied to reduce the incorporation of heavy metals by modulating pH and N/P ratio through RSM, which is suitable for different Mg/Ca ratios. It is anticipated that the results obtained would offer support for the safe utility of struvite from wastewater containing Ca and heavy metals.

Baicalin Relieves LPS-Induced Lung Inflammation via the NF-κB and MAPK Pathways.

Baicalin is an active ingredient extracted from the Chinese medicine Scutellaria and has many beneficial effects. Pulmonary interstitial and alveolar edema are common symptoms of an acute lung injury (ALI). We investigated the effects of baicalin on LPS-induced inflammation and the underlying mechanisms in mice and cells. The protein contents and mRNA expression of TNF-α, IL-1ß, and IL-6 in RAW264.7 cells and mice were detected using ELISA and qRT-PCR. Baicalin significantly suppressed TNF-α, IL-1ß, and IL-6 levels and expression, both in vitro and in vivo, compared with the LPS group. Baicalin inhibits the expression of TLR4 and MyD88, resulting in significant decreases in p-p65, p-p38, p-ERK, and p-JNK, as measured by the Western blotting of RAW264.7 cells. A baicalin treatment for 12 h resulted in a rapid increasing of the white blood cell number and significantly improved the pathological changes in the lung. We also found that the baicalin pretreatment for 12 h could decrease the MPO content and wet/dry (W/D) weight ratio, which indicates that baicalin can significantly reduce pulmonary edema. Furthermore, the baicalin pretreatment also resulted in the recovery of TGF-ß protein levels and decreased iNOS. Baicalin inhibits ALI inflammation in mice and cells and is a potential candidate for the treatment of ALI.

Organic Electrochemical Transistor Based on Hydrophobic Polymer Tuned by Ionic Gels.

Hydrophobic conjugated polymers have poor ionic transport property, so hydrophilic side chains are often grafted for their application as organic electrochemical transistors (OECTs). However, this modification lowers their charge transport ability. Here, an ionic gel interfacial layer is applied to improve the ionic transport while retaining the charge transport ability of the polymers. By using the ionic gels comprising gel matrix and ionic liquids as the interfacial layers, the hydrophobic polymer achieves the OECT feature with high transconductance, low threshold voltage, high current on/off ratio, short switching time, and high operational stability. The working mechanism is also revealed. Moreover, the OECT performance can be tuned by varying the types and ratios of ionic gels. With the proposed ionic gel strategy, OECTs can be effectively realized with hydrophobic conjugated polymers.

Temperature-Dependent Group Delay of Photonic-Bandgap Hollow-Core Fiber Tuned by Surface-Mode Coupling.

Surface modes (SM) are highly spatially localized modes existing at the core-cladding interface of photonic-bandgap hollow-core fiber (PBG-HCF). When coupling with SM, the air modes (AM) in the core would suffer a higher confinement loss despite being spectrally within the cladding photonic bandgap, and would be highly dispersive around the avoided crossing (anti-crossing) wavelength. In this paper, we numerically explored how such avoided crossings can play an important role in the tuning of the temperature dependence of group delay of AM of PBG-HCF. At higher temperatures, both the thermo-optic effect and thermal expansion contribute to the redshift of avoided crossing wavelength, giving rise to a temperature dependence of the AM dispersion. Numerical simulations show that the redshift of avoided crossing can significantly tune the thermal coefficient of delay (TCD) of PBG-HCF from -400 ps/km/K to 400 ps/km/K, approximately -120 ppm/K to 120 ppm/K. In comparison with the known tuning mechanism by thermal-induced redshift of photonic bandgap [Fokoua et al., Optica 4, 659, 2017], the tuning of TCD by SM coupling presents a much broader tuning range and higher efficiency. Our finding may provide a new route to design PBG-HCF for propagation time sensitive applications.

Realization of broadband truly rainbow trapping in gradient-index metamaterials.

Unidirectionally propagating wave (UPW) such as surface magnetoplasmon (SMP) has been a research hotspot in the last decades. In the study of the UPW, metals are usually treated as perfect electric conductors (PECs). However, it was reported that the transverse resonance condition induced by the PEC wall(s) may significantly narrow up the complete one-way propagation (COWP) band. In this paper, ultra-broadband one-way waveguides are built by utilizing the epsilon-negative (ENG) metamaterial (MM) and/or the perfect magnetic conductor (PMC) boundary. In both cases, the total bandwidth of the COWP bands are efficiently enlarged by more than three times than the one in the original metal-dielectric-semiconductor-metal structure. Moreover, the one-way waveguides consisting of gradient-index metamaterial are proposed to achieve broadband truly rainbow trapping (TRT). In the full-wave simulations, clear broadband TRT without back reflection is observed in terahertz regime. Besides, giant electric field enhancement is achieved in a PMC-based one-way structure, and the amplitude of the electric field is enormously enhanced by five orders of magnitude. Our findings are beneficial for researches on broadband terahertz communication, energy harvesting and strong-field devices.