Molecular characteristics and antibiotic resistance mechanisms of clindamycin-resistant Streptococcus agalactiae isolates in China.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal infections with high morbidity and mortality, and clindamycin is the main antibiotic used to treat GBS infections in patients allergic to penicillin. We aimed to analyse the antibiotic sensitivity, sequence types, serotypes, virulence factors, and antibiotic resistance mechanisms of clinically isolated clindamycin-resistant S. agalactiae and provide basic data for the treatment, prevention, and control of clinical infection of S. agalactiae. A total of 110 strains of clindamycin-resistant S. agalactiae were collected from two tertiary hospitals in Hebei, China. We performed antibiotic sensitivity tests for 11 antibiotics on these strains and whole-genome sequencing analysis. All the strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, tigecycline, and quinupristin-dalfopristin. Resistance to erythromycin, levofloxacin, tetracycline, and chloramphenicol were also observed. Genome sequence analysis revealed that all strains belonged to 12 sequence types (STs) related to six cloning complexes (CCs), namely CC10, CC19, CC23, CC651, CC1, and CC17. Five serotypes were identified, including IA, IB, II, III, and V. The most prominent resistance genes were mreA (100%) and ermB (81.8%). Furthermore, cfb, cylE, pavA and the gene cluster related to the pili were 100% present in all strains, followed by lmb (95.5%) and srr1 (67.2%). This study found that clindamycin-resistant S. agalactiae showed polymorphisms in molecular types and serotypes. Furthermore, multiple virulence factor genes have been identified in their genomes.

Knockdown of the long non­coding RNA MALAT1 ameliorates TNF­α­mediated endothelial cell pyroptosis via the miR­30c­5p/Cx43 axis.

Long noncoding RNAs (lncRNAs) are related to the development of atherosclerosis (AS). However, the role of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tumor necrosis factor­α (TNF­α)­induced rat aortic endothelial cell (RAOEC) pyroptosis, as well as the underlying mechanisms, remain unclear. RAOEC morphology was assessed using an inverted microscope. The mRNA and/or protein expression levels of MALAT1, microRNA(miR)­30c­5p and connexin 43 (Cx43) were assessed using reverse transcription­quantitative PCR (RT­qPCR) and/or western blotting, respectively. The relationships among these molecules were validated by dual­luciferase reporter assays. Biological functions, such as LDH release, pyroptosis­associated protein levels and the proportion of PI­positive cells, were evaluated using a LDH assay kit, western blotting and Hoechst 33342/PI staining, respectively. The present study demonstrated that compared with the control group, the mRNA expression levels of MALAT1 and protein expression levels of Cx43 were significantly up­regulated, whereas miR­30c­5p mRNA expressions levels were significantly decreased in TNF­α­treated RAOEC pyroptosis. Knockdown of MALAT1 or Cx43 significantly attenuated the increase in LDH release, pyroptosis­associated protein expression and PI­positive cell numbers among RAOEC treated using TNF­α, whereas an miR­30c­5p mimic exerted the opposite effect. Furthermore, miR­30c­5p was demonstrated to be a negative regulator of MALAT1 and could also target Cx43. Finally, co­transfection with siMALAT1 and miR­30c­5p inhibitor could attenuate the protective effect of MALAT1 knockdown against TNF­α­mediated RAOEC pyroptosis by upregulation of Cx43 expression. In conclusion, MALAT1 might serve an important role in TNF­α­mediated RAOEC pyroptosis by regulating the miR­30c­5p/Cx43 axis, which would provide a potential novel diagnostic and therapeutic target for AS.

Mesoporous Activated Biochar from Crab Shell with Enhanced Adsorption Performance for Tetracycline.

In this study, three mesoporous-activated crab shell biochars were prepared by carbonation and chemical activation with KOH (K-CSB), H3PO4 (P-CSB), and KMnO4 (M-CSB) to evaluate their tetracycline (TC) adsorption capacities. Characterization by SEM and a porosity analysis revealed that the K-CSB, P-CSB, and M-CSB possessed a puffy, mesoporous structure, with K-CSB exhibiting a larger specific surface area (1738 m2/g). FT-IR analysis revealed that abundant, surface ox-containing functional groups possessed by K-CSB, P-CSB, and M-CSB, such as -OH, C-O, and C=O, enhanced adsorption for TC, thereby enhancing their adsorption efficiency for TC. The maximum TC adsorption capacities of the K-CSB, P-CSB, and M-CSB were 380.92, 331.53, and 281.38 mg/g, respectively. The adsorption isotherms and kinetics data of the three TC adsorbents fit the Langmuir and pseudo-second-order model. The adsorption mechanism involved aperture filling, hydrogen bonding, electrostatic action, π-π EDA action, and complexation. As a low-cost and highly effective adsorbent for antibiotic wastewater treatment, activated crab shell biochar has enormous application potential.

A facile post-assembly approach for the fabrication of non-close-packed gold nanocrystal arrays from binary nanocrystal superlattices.

Here, we demonstrate a novel approach for fabricating non-close-packed gold nanocrystal arrays using facile one-step post-modification of a Cs4PbBr6-Au binary nanocrystal superlattice by electron beam etching of the perovskite phase. The proposed methodology can serve as a promising approach for the scalable preparation of a vast library of non-close-packed nanoparticulate superstructures with various morphologies composed of numerous colloidal nanocrystals.

Noncontact Charge Shielding Knife for Liquid Microfluidics.

Multibehavioral droplet manipulation in a precise and programmed manner is crucial for stoichiometry, biological virus detection, and intelligent lab-on-a-chip. Apart from fundamental navigation, merging, splitting, and dispensing of the droplets are required for being combined in a microfluidic chip as well. Yet, existing active manipulations including strategies from light to magnetism are arduous to use to split liquids on superwetting surfaces without mass loss and contamination, because of the high cohesion and Coanda effect. Here, we demonstrate a charge shielding mechanism (CSM) for platforms to integrate with a series of functions. In response to attachment of shielding layers from the bottom, the instantaneous and repeatable change of local potential on our platform achieves the desired loss-free manipulation of droplets, with a wide-ranging surface tension from 25.7 mN m-1 to 87.6 mN m-1, functioning as a noncontact air knife to cleave, guide, rotate, and collect reactive monomers on demand. With further refinement of the surface circuit, the droplets, just as the electron, can be programmed to be transported directionally at extremely high speeds of 100 mm s-1. This new generation of microfluidics is expected to be applied in the field of bioanalysis, chemical synthesis, and diagnostic kit.

PHOSPHATE STARVATION RESPONSE1 (PHR1) interacts with JASMONATE ZIM-DOMAIN (JAZ) and MYC2 to modulate phosphate deficiency-induced jasmonate signaling in Arabidopsis.

Phosphorus (P) is a macronutrient necessary for plant growth and development. Inorganic phosphate (Pi) deficiency modulates the signaling pathway of the phytohormone jasmonate in Arabidopsis thaliana, but the underlying molecular mechanism currently remains elusive. Here, we confirmed that jasmonate signaling was enhanced under low Pi conditions, and the CORONATINE INSENSITIVE1 (COI1)-mediated pathway is critical for this process. A mechanistic investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) repressors physically interacted with the Pi signaling-related core transcription factors PHOSPHATE STARVATION RESPONSE1 (PHR1), PHR1-LIKE2 (PHL2), and PHL3. Phenotypic analyses showed that PHR1 and its homologs positively regulated jasmonate-induced anthocyanin accumulation and root growth inhibition. PHR1 stimulated the expression of several jasmonate-responsive genes, whereas JAZ proteins interfered with its transcriptional function. Furthermore, PHR1 physically associated with the basic helix-loop-helix (bHLH) transcription factors MYC2, MYC3, and MYC4. Genetic analyses and biochemical assays indicated that PHR1 and MYC2 synergistically increased the transcription of downstream jasmonate-responsive genes and enhanced the responses to jasmonate. Collectively, our study reveals the crucial regulatory roles of PHR1 in modulating jasmonate responses, and provides a mechanistic understanding of how PHR1 functions together with JAZ and MYC2 to maintain the appropriate level of jasmonate signaling under conditions of Pi deficiency.

Effect of Percutaneous Kyphoplasty on the progression of intervertebral disc degeneration: a retrospective cohort study.

BACKGROUND: The effect of percutaneous kyphoplasty (PKP) or rather polymethylmethacrylate (PMMA) on adjacent intervertebral discs is still controversial. The evidence from experimental study to clinical study presents bipolar conclusions. In this study, we investigated the effect of PKP on adjacent intervertebral disc degeneration (IDD). METHODS: The experimental group included adjacent intervertebral discs of vertebrae treated with the PKP procedure, and the control group included adjacent intervertebral discs of non-traumatized vertebrae. All measurements were taken by magnetic resonance imaging or X-ray. The intervertebral disc height, the modified Pfirrmann grading system (MPGS), and its differences with Klezl Z and Patel S (ZK and SP) classifications were compared. RESULTS: A total of 264 intervertebral discs from 66 individuals were selected for the study. The comparison of intervertebral disc height between the two groups pre and post-operatively resulted in a p-value of > 0.05. No significant change was observed in the adjacent discs in the control groups post-operatively. Post-operatively, the mean Ridit increased significantly from 0.413 to 0.587 in the upper disc and from 0.404 to 0.595 in the lower disc in the experimental group. The comparison of MPGS differences showed that the predominant value was 0 in the Low-grade leaks group and 1 in the Medium and high-grade leaks group. CONCLUSIONS: The PKP procedure can accelerate adjacent IDD, but it does not cause disc height changes in the early stage. The quantity of cement leaking into the disc space positively correlated with the rate of disc degeneration progression.

Generic Methods for Simultaneous Analysis of Four Direct Oral Anticoagulants in Human Plasma and Urine by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

The new direct oral anticoagulants (DOACs) are increasingly used to treat and prevent thromboembolic disorders, and monitoring concentrations may be valuable in some special scenarios to prevent clinical adverse events. This study aimed to develop generic methods for the rapid and simultaneous analysis of four DOACs in human plasma and urine. Protein precipitation and one-step dilution were used to prepare the plasma and urine; the extracts were injected to ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. Chromatographic separation was performed on an Acquity™ UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) with gradient elution of 7 min. A triple quadrupole tandem mass spectrometer with an electrospray ionization source was employed to analyze DOACs in a positive ion mode. The methods showed great linearity in the plasma (1~500 ng/mL) and urine (10~10,000 ng/mL) for all analytes (R2 ≥ 0.99). The intra- and inter-day precision and accuracy were within acceptance criteria. The matrix effect and extraction recovery were 86.5~97.5% and 93.5~104.7% in the plasma, while 97.0~101.9% and 85.1~99.5% in the urine. The stability of samples during the routine preparation and storage were within the acceptance criteria of less than ±15%. The methods developed were accurate, reliable, and simple for the rapid and simultaneous measurement of four DOACs in human plasma and urine, and successfully applied to patients and subjects with DOACs therapy for anticoagulant activity assessment.

Shoot-root signal circuit: Phytoremediation of heavy metal contaminated soil.

High concentrations of heavy metals in the environment will cause serious harm to ecosystems and human health. It is urgent to develop effective methods to control soil heavy metal pollution. Phytoremediation has advantages and potential for soil heavy metal pollution control. However, the current hyperaccumulators have the disadvantages of poor environmental adaptability, single enrichment species and small biomass. Based on the concept of modularity, synthetic biology makes it possible to design a wide range of organisms. In this paper, a comprehensive strategy of "microbial biosensor detection - phytoremediation - heavy metal recovery" for soil heavy metal pollution control was proposed, and the required steps were modified by using synthetic biology methods. This paper summarizes the new experimental methods that promote the discovery of synthetic biological elements and the construction of circuits, and combs the methods of producing transgenic plants to facilitate the transformation of constructed synthetic biological vectors. Finally, the problems that should be paid more attention to in the remediation of soil heavy metal pollution based on synthetic biology were discussed.

1-Adamantanamine Hydrochloride Resists Environmental Corrosion to Obtain Highly Efficient and Stable Perovskite Solar Cells.

Passivating the defective surface of perovskite film is a promising strategy to improve the stability and efficiency of perovskite solar cells (PSCs). Herein, 1-adamantanamine hydrochloride (ATH) is introduced to the upper surface of the perovskite film to heal the defects of the perovskite surface. The best-performance ATH-modified device has a higher efficiency (23.45%) than the champion control device (21.53%). The defects are passivated, interfacial nonradiative recombination is suppressed, and interface stress is released by the ATH deposited on the perovskite film, leading to longer carrier lifetimes and enhancement in open-circuit voltage (VOC) and fill factor (FF) of the PSCs. With obvious improvement, VOC and FF of 1.159 V and 0.796 for the control device are raised to 1.178 V and 0.826 for the ATH-modified device, respectively. Finally, during an operational stability measurement of more than 1000 h, the ATH-treated PSC exhibited better moisture resistance, thermal persistence, and light stability.

Spinel-Derived Formation and Amorphization of Bimetallic Oxyhydroxides for Efficient Electrocatalytic Biomass Oxidation.

Replacing the oxygen evolution reaction (OER) with water-assisted oxidation of organic molecules represents a promising approach for achieving sustainable electrochemical biomass utilization. Among numerous OER catalysts, spinels have received substantial attention due to their manifold compositions and valence states, yet their application in biomass conversions remains rare. Herein, a series of spinels were investigated for the selective electrooxidation of furfural and 5-hydroxymethylfurfural, two model substrates for versatile value-added chemical products. Spinel sulfides universally exhibit superior catalytic performance compared to that of spinel oxides, and further investigations show that the replacement of oxygen with sulfur led to the complete phase transition of spinel sulfides into amorphous bimetallic oxyhydroxides during electrochemical activation, serving as the active species. Excellent values of conversion rate (100%), selectivity (100%), faradaic efficiency (>95%), and stability were achieved via sulfide-derived amorphous CuCo-oxyhydroxide. Furthermore, a volcano-like correlation was established between their BEOR and OER activities based on an OER-assisted organic oxidation mechanism.

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the YPEL gene family that is evolutionarily conserved in the eukaryotic species. To date, the physiological function of YPEL5 has not been yet assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are also dysregulated in ypel5-/- mutant as revealed by metabolomic and transcriptomic analysis. Mechanistically, Hnf4a is identified as a crucial downstream mediator and positively regulated by Ypel5. Hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Further, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of Hnf4a gene. Herein, this work demonstrates an essential role for Ypel5 in hepatocyte proliferation and function, and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrate.

Active compounds and potential targets of Shuganning injection in the treatment of hepatocellular carcinoma by network pharmacology and in vitro validation.

Shuganning injection (SGNI), a TCM (traditional Chinese medicine) injection with good hepatoprotective effects, exerted therapeutic effects on hepatocellular carcinoma (HCC). However, the active compounds and effects of SGNI on HCC remain unclear. The objective of this study was to investigate the active compounds and potential targets of SGNI in the treatment of HCC, and explore the molecular mechanisms of main compounds. Network pharmacology was applied to predict the active compounds and targets of SGNI on cancer. The interactions between active compounds and target proteins were validated by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and pull-down assay. The in vitro test of the effects and mechanism of vanillin and baicalein was elucidated by MTT, western blot, immunofluorescence, and apoptosis analysis. According to compound characteristics, targets, etc., two typical active ingredients (vanillin and baicalein) were selected as representatives to explore the effects on HCC. Vanillin (an important food additive) bound to NF-κB1 and baicalein (a bioactive flavonoid) bound to FLT3 (FMS-like tyrosine kinase 3) were confirmed in this study. Vanillin and baicalein both inhibited cell viability and promoted apoptosis of Hep3B and Huh7 cells. In addition, both vanillin and baicalein could enhance the activation of the p38/MAPK (mitogen-activated protein kinase) signaling pathway, which may partially explain the anti-apoptosis effects of the two compounds. In conclusion, two active compounds of SGNI, vanillin and baicalein, promoted apoptosis of HCC cells via binding with NF-κB1 or FLT3, and regulating the p38/MAPK pathway. Baicalein and vanillin may be good candidates for HCC treatment on drug development.

A Bifunctional BiOBr/ZIF-8/ZnO Photocatalyst with Rich Oxygen Vacancy for Enhanced Wastewater Treatment and H2O2 Generation.

Photocatalytic technology is considered an ideal approach for clean energy conversion and environmental pollution applications. In this work, a bifunctional BiOBr/ZIF-8/ZnO photocatalyst was proposed for removing phenols in wastewater and generating hydrogen peroxide. Insights from scanning electron microscopy measurements revealed the well-dispersion of ZIF-8/ZnO was on the BiOBr layer, which could effectively prevent agglomeration of ZIF-8 and facilitate the separation of carriers. In addition, the optimal H2O2 yield of the BiOBr/ZIF-8/ZnO sample could reach 116 mmol·L-1·g-1 within 2 h, much higher than that of pure BiOBr (with the value of 82 mmol·L-1·g-1). The optimal BiOBr/ZIF-8/ZnO sample could also remove 90% of the phenol or bisphenol A in 2 h, and its kinetic constants were 3.8 times and 2.3 times that of pure BiOBr, respectively. Based on the analysis of the various experimental characterizations, the photocatalytic mechanism of the S-scheme BiOBr/ZIF-8/ZnO composite for the degradation of phenolic pollutants and generation of H2O2 was proposed. The formation of the heterojunction and the oxygen vacancy work together to significantly improve its photocatalytic efficiency. In addition, the BiOBr/ZIF-8/ZnO catalyst has a certain impact on the degradation of phenol in actual wastewater, providing a way to effectively remove refractory pollutants and generate H2O2 in actual water.

Co-Immobilization of GOD & HRP on Y-Shaped DNA Scaffold and the Regulation of Inter-Enzyme Distance.

In multienzymes cascade reaction, the inter-enzyme spacing is supposed to be a factor affecting the cascade activity. Here, a simple and efficient Y-shaped DNA scaffold is assembled using two partially complementary DNA single strands on magnetic microspheres, which is used to coimmobilize glucose oxidase (GOD) and horseradish peroxidase (HRP). As a result, on poly(vinyl acetate) magnetic microspheres (PVAC), GOD/HRP-DNA@PVAC multienzyme system is obtained, which can locate GOD and HRP accurately and control the inter-enzyme distance precisely. The distance between GOD and HRP is regulated by changing the length of DNA strand. It showed that the cascade activity is significantly distance-dependent. Moreover, the inter-enzyme spacing is not the closer the better, and too short distance would generate steric hindrance between enzymes. The cascade activity reached the maximum value of 967 U mg-1 at 13.6 nm, which is 3.5 times higher than that of free enzymes. This is ascribed to the formation of substrate channeling.

Antibacterial properties of antimicrobial peptide HHC36 modified polyetheretherketone.

Introduction: Polyetheretherketone (PEEK) is considered to be a new type of orthopedic implant material due to its mechanical properties and biocompatibility. It is becoming a replacement for titanium (Ti) due to its near-human-cortical transmission and modulus of elasticity. However, its clinical application is limited because of its biological inertia and susceptibility to bacterial infection during implantation. To solve this problem, there is an urgent need to improve the antibacterial properties of PEEK implants. Methods: In this work, we fixed antimicrobial peptide HHC36 on the 3D porous structure of sulfonated PEEK (SPEEK) by a simple solvent evaporation method (HSPEEK), and carried out characterization tests. We evaluated the antibacterial properties and cytocompatibility of the samples in vitro. In addition, we evaluated the anti-infection property and biocompatibility of the samples in vivo by establishing a rat subcutaneous infection model. Results: The characterization test results showed that HHC36 was successfully fixed on the surface of SPEEK and released slowly for 10 days. The results of antibacterial experiments in vitro showed that HSPEEK could reduce the survival rate of free bacteria, inhibit the growth of bacteria around the sample, and inhibit the formation of biofilm on the sample surface. The cytocompatibility test in vitro showed that the sample had no significant effect on the proliferation and viability of L929 cells and had no hemolytic activity on rabbit erythrocytes. In vivo experiments, HSPEEK can significantly reduce the bacterial survival rate on the sample surface and the inflammatory reaction in the soft tissue around the sample. Discussion: We successfully loaded HHC36 onto the surface of SPEEK through a simple solvent evaporation method. The sample has excellent antibacterial properties and good cell compatibility, which can significantly reduce the bacterial survival rate and inflammatory reaction in vivo. The above results indicated that we successfully improved the antibacterial property of PEEK by a simple modification strategy, making it a promising material for anti-infection orthopedic implants.

PDK1 regulates the progression of esophageal squamous cell carcinoma through metabolic reprogramming.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest human malignancies characterized by late-stage diagnosis, drug resistance, and poor prognosis. Pyruvate dehydrogenase kinase 1 (PDK1) plays an important role in regulating the metabolic reprogramming of cancer cells. However, its expression, function, and regulatory mechanisms of PDK1 in ESCC have not been reported. In this study, we found that PDK1 silence and dichloroacetic acid (DCA) significantly inhibited the growth of ESCC cells and induced cell apoptosis. Interestingly, PDK1 is a direct target of miR-6516-5p, and miR-6516-5p/PDK1 axis suppressed the growth of ESCC cell by inhibiting glycolysis. Moreover, DCA and cisplatin (cis-diammine-dichloroplatinum, DDP) synergistically inhibited the progression and glycolysis ability of ESCC cells both in vitro and in vivo by increasing oxidative stress via the inhibition of the Keap1/Nrf2 signaling pathway. And, Tert-butylhydroquinone (TBHQ), a specific activator of the Keap1/Nrf2 signaling, could diminish the synergic antitumor effects of DCA and DDP on ESCC cells. Collectively, our findings indicate that PDK1 may regulate the progression of ESCC by metabolic reprogramming, which provides new strategy for the treatment of ESCC.

Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung Inflammation following PM2.5 and Indeno[1,2,3-cd]pyrene Exposure.

BACKGROUND: Ambient particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) is suggested to act as an adjuvant for allergen-mediated sensitization and recent evidence suggests the importance of T follicular helper (Tfh) cells in allergic diseases. However, the impact of PM2.5 exposure and its absorbed polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains unknown. OBJECTIVES: We aimed to explore the impact of environmental PM2.5 and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. METHODS: PM2.5- or IP-mediated remodeling of cellular composition in lung lymph nodes (LNs) was determined by mass cytometry in a house dust mite (HDM)-induced mouse allergic lung inflammation model. The differentiation and function of Tfh cells in vitro were analyzed by flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, immunoprecipitation, and western blot analyses. RESULTS: Mice exposed to PM2.5 during the HDM sensitization period demonstrated immune cell population shifts in lung LNs as compared with those sensitized with HDM alone, with a greater number of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) response and pulmonary inflammation. Similarly enhanced phenotypes were also found in mice exposed to IP and sensitized with HDM. Further, IP administration was found to induce interleukin-21 (Il21) and Il4 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 cells. DISCUSSION: These findings suggest that the PM2.5 (IP)-AhR-c-Maf axis in Tfh2 cells was important in allergen sensitization and lung inflammation, thus adding a new dimension in the understanding of Tfh2 cell differentiation and function and providing a basis for establishing the environment-disease causal relationship. https://doi.org/10.1289/EHP11580.

Design, synthesis, cytotoxic activity, and molecular docking studies of indol and indazole-based stilbenes.

To develop new highly effective anticancer agents derived from naturally occurring stilbene scaffold, in total of 25 indol and indazole-based stilbenes including 18 new compounds were designed according to molecular hybridization strategy and synthesized via Witting reaction. The synthesized derivatives were assayed for cytotoxic activities against human tumor cell lines (K562 cells and MDA-MB-231 cells) and normal cell line (L-02 cells). The biological screening results showed that indol and indazole-based stilbenes are of great interest for developing anticancer agents as eight derivatives possessed strong antiproliferative activities with IC50 values less than 10 µM. In particular, indol-based stilbene IS1l bearing piperidine exhibited the most potent cytotoxicity against both K562 and MDA-MB-231 cells with IC50 values 2.4 µM and 2.18 µM, respectively, along with a remarkable selectivity towards human normal L-02 cells. Moreover, molecular docking was exploited to elucidate the binding model of IS1l with biochemical target tryptophan 2,3-dioxygenase (TDO). Together, the results suggested that compound IS1l is a promising anticancer agent worthy of further investigation.