An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Conventional chemotherapy for lung cancer exerts anti-tumor effects through cytotoxicity, and through immunologic regulation by reducing specific T cell subsets and inducing the expression of programmed death ligand 1 (PD-L1) on tumor cells. Even though pemetrexed has shown huge potential in combination with other targeted or immune therapies, there is still little information about the values of specific immune checkpoint markers for advanced lung adenocarcinoma treated with pemetrexed. In the present study, a total of 56 patients with advanced lung adenocarcinoma, who received pemetrexed-based chemotherapy, were included retrospectively. Immunohistochemistry was performed to assess PD-L1, programmed death 1 (PD-1), thymidylate synthase, and tumor infiltrating lymphocytes (TILs). In this cohort, the positive expression of PD-L1 and PD-1 were 26.8% and 33.9% respectively. PD-L1, PD-1, and thymidylate synthase expression were not significantly associated with any clinical features, while the expression of both PD-L1 and PD-1 were correlated with Ki-67 expression. Furthermore, the expression of PD-1 was significantly correlated with TILs. The progression-free survival (PFS) in patients with PD-L1+ specimens was significantly longer compared to PD-L1- specimens. Moreover, PD-L1 expression was an independent protective factor for PFS, and the smoking status was an independent risk factor. PD-L1 expression was significantly associated with better prognosis for patients with pemetrexed-based treatment. Our findings suggested that PD-L1 expression might be a favorable prognostic biomarker for pemetrexed-based regimen, which is a rationale for combining immunotherapy with chemotherapy for lung cancer.
The peritrophic matrix (PM) secreted by the midgut cells of insects is formed by the binding of PM proteins to chitin fibrils. The PM envelops the food bolus, serving as a barrier between the content of the midgut lumen and its epithelium, and plays a protective role for epithelial cells against mechanical damage, pathogens, toxins, and other harmful substances. However, few studies have investigated the characteristics and synthesis factors of the PM in the silkworm, Bombyx mori. Here, we examined the characteristics of the PM in the silkworms. The PM thickness of the silkworms increased gradually during growth, while there was no significant difference in thickness along the entire PM region. Permeability of the PM decreased gradually from the anterior to posterior PM. We also found that PM synthesis was affected by food ingestion and the gut microbiota. Our results are beneficial for future studies regarding the function of the PM in silkworms.
To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC).In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups.Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033).In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.
Abstract Background BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU‐sourced reference bevacizumab (EU‐bevacizumab) in patients with advanced nonsquamous non‐small cell lung cancer (NSCLC). Methods Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU‐bevacizumab plus paclitaxel and carboplatin (EU‐bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU‐bevacizumab. The primary endpoint was overall response rate at week 18 (ORR 18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU‐bevacizumab ORR 18 risk ratio was contained within the predefined equivalence margins of 0.75–1.33 (China National Medical Products Administration requirements), or 0.73–1.36 (US Food and Drug Administration), or if the 95% CI of the ORR 18 risk difference between treatments was contained within the predefined equivalence margin of −0.12 to 0.15 (EMA requirements). Results In total, 649 randomized patients (BAT1706, n = 325; EU‐bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR 18 was comparable between the BAT1706 and EU‐bevacizumab arms (48.0% and 44.5%, respectively). The ORR 18 risk ratio of 1.08 (90% CI: 0.94–1.24) and the ORR 18 risk difference of 0.03 (95% CI: −0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU‐bevacizumab. The safety profile of BAT1706 was consistent with that of EU‐bevacizumab and no new safety signals were observed. Conclusion In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU‐bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.
In this study, we developed a structure-based approach to identify Helitrons in four lepidopterans and systematically analysed Helitrons in the silkworm genome. We found that the content of Helitrons varied greatly among genomes. The silkworm genome harboured 67 555 Helitron-related sequences that could be classified into 21 families and accounted for ∼4.23% of the genome. Thirteen of the families were new. Three families were putatively autonomous and included the replication initiator motif and helicase domain. The silkworm Helitrons were widely and randomly distributed in the genome. Most Helitron families radiated within the past 2 million years and experienced a single burst of expansion. These Helitron families captured 3724 gene fragments and contributed to at least 1.4% of the silkworm full-length cDNAs, suggesting important roles of Helitrons in the evolution of the silkworm genes. In addition, we found that some new Helitrons were generated by combinations of other Helitrons. Overall, the results presented in this study provided insights into the generation and evolution of Helitron transposons and their contribution to transcripts.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
In the title compound, C7H8N2S, the C—N(imino) and C—N(amino) bond distances within the thiourea moiety are 1.3395 (18) and 1.321 (2) Å, respectively. This significant difference in magnitude is also observed for some halogen–phenylthiourea compounds.
The domesticated silkworm (Bombyx mori) was domesticated from wild silkworm (Bombyx mandarina) more than 5,000 years ago. During domestication, body color between B. mandarina and B. mori changed dramatically. However, the molecular mechanism of the silkworm body color transition is not known. In the present study, we examined within- and between-species nucleotide diversity for eight silkworm melanin synthesis pathway genes, which play a key role in cuticular pigmentation of insects. Our results showed that the genetic diversity of B. mori was significantly lower than that of B. mandarina and 40.7% of the genetic diversity of wild silkworm was lost in domesticated silkworm. We also examined whether position effect exists among melanin synthesis pathway genes in B. mandarina and B. mori. We found that the upstream genes have significantly lower levels of genetic diversity than the downstream genes, supporting a functional constraint hypothesis (FCH) of metabolic pathway, that is, upstream enzymes are under greater selective constraint than downstream enzymes because upstream enzymes participate in biosynthesis of a number of metabolites. We also investigated whether some of the melanin synthesis pathway genes experienced selection during domestication. Neutrality test, coalescent simulation, as well as network and phylogenetic analyses showed that tyrosine hydroxylase (TH) gene was a domestication locus. Sequence analysis further suggested that a putative expression enhancer (Abd-B-binding site) in the intron of TH gene might be disrupted during domestication. TH is the rate-limiting enzyme of melanin synthesis pathway in insects. Real-time polymerase chain reaction assay did show that the relative expression levels of TH gene in B. mori were significantly lower than that in B. mandarina at three different developmental stages, which is consistent with light body color of domesticated silkworm relative to wild silkworm. Therefore, we speculated that expression change of TH gene may contribute to the body color transition from B. mandarina to B. mori. Our results emphasize the exceptional role of gene expression regulation in morphological transition of domesticated animals.
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