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Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC. [ABSTRACT FROM AUTHOR]

The microstructural characterization of Basalt Fiber Reinforced Polymer (BFRP) bars under seawater deterioration (dry–wet cycles modes and immersion modes) was performed by scanning electron microscopy (SEM) and X-ray energy spectrum analyzer (EDS). Then, uniaxial compressive tests were carried out on the corroded BFRP bars to explore the effects of different corrosion periods, diameters, and slenderness ratios on the degradation of compressive performance and durability in seawater corrosion and constraint condition. The results showed that dry–wet cycles of seawater caused patchy pitting on the surfaces of BFRP bar, and white granular foams adhered to the bar surface after seawater immersion. The internal microstructure of BFRP bar was deteriorated, and the bonding force between the fiber and resin was reduced with the increase of dry–wet cycles. Five failure modes of BFRP bars occurred in uniaxial compressive tests, namely crushing failure, transverse cracking failure, shearing failure, splitting failure, and buckling failure. The increase of corrosion cycles significantly decreased the bearing capacity and compressive strength, but had little effect on the compressive elastic modulus of BFRP bars. The dry–wet cycles of seawater was more harmful to the mechanical properties of BFRP bars than immersion corrosion. Meanwhile, the mechanical properties of BFRP bars were affected by their diameters and slenderness ratios to some extent. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid, Diaphorina citri Kuwayama, is among the most important pests of citrus. It is the main vector of the Huanglongbing (HLB) pathogen Candidatus Liberibacter asiaticus (CLas), which causes severe losses in citrus crops. Control of D. citri is therefore of paramount importance to reduce the spread of HLB. In this regard, using RNA interference (RNAi) to silence target genes is a useful strategy to control psyllids. In this study, using RNAi, we examined the biological functions of the V‐ATPase subunit E (V‐ATP‐E) gene of D. citri, including its effect on acquisition of CLas. The amino acid sequence of V‐ATP‐E from D. citri had high homology with proteins from other insects. V‐ATP‐E was expressed at all D. citri life stages analyzed, and the expression level in mature adults was higher than that of teneral adults. Silencing of V‐ATP‐E resulted in a significant increase in mortality, reduced body weight, and induced cell apoptosis of the D. citri midgut. The reduced expression of V‐ATP‐E was indicated to inhibit CLas passing through the midgut and into the hemolymph, leading to a majority of CLas being confined to the midgut. In addition, double‐stranded RNA of D. citri V‐ATP‐E was safe to non‐target parasitic wasps. These results suggest that V‐ATP‐E is an effective RNAi target that can be used in D. citri control to block CLas infection. [ABSTRACT FROM AUTHOR]

A general and convenient method for the direct transition‐metal‐free intermolecular chlorodifluoromethylthiolation of a variety of unactivated alkenes and alkynes has been described. This methodology exhibits good functional group tolerance and is operationally simple. Mechanistic studies indicated an electrophilic substitution mechanism, and the strong electrophilic difluoromethylthiolating reagent HCF2SCl was generated in situ under standard reaction conditions. The developed protocol fulfils the requirements of sustainable and green chemistry. [ABSTRACT FROM AUTHOR]

Fivefold twin (FFT) and lamellar (LAM) structures are the primary configurations during the crystallization of alloys. However, the co-existence of these two structures in one system and the conversion mechanism are barely explored. In this study, we investigated the rapid solidification process of a Ti3Al alloy by using molecular dynamics simulation and discussed the evolution of the microstructure under two first-order phase transitions in detail. The first phase transition followed Ostwald's step rule, and the nucleation pathway in the system was supercooled liquid → BCC → FCC/HCP. A new phase transition pattern of FFTs transformed into a LAM structure leading to a second phase transition was found. The FFT atoms first transformed into other atoms as the partition interface, and then the LAM structure consumed Other atoms and grew further. The interconversions between different clusters were unstable and required complex intermediate states to reach stability. These findings provide a new understanding of the relationship between the FFT and LAM structures, especially for the metal that underwent two-phase transitions. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients. Methods: CTCs/CTECs and their subtypes were determined using SE‐iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression‐free survival (PFS), and overall survival (OS) were analyzed. Results: CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive‐stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC‐white blood cell (CTC‐WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC‐WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4–48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1–18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values. Conclusions: The presence of CTC‐WBC clusters at baseline and after two‐cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first‐line treatment. [ABSTRACT FROM AUTHOR]