Water source of Robinia pseudoacacia and Platycladus orientalis plantations under different soil moisture conditions in the Loess Plateau of Western Shanxi, China.

Water is a key factor limiting plant growth in loess regions. Studying water use by different afforestation species under different water conditions is crucial to understand the drought resistance mechanisms of plants in arid and semi-arid regions. We analyzed water use at different depths by the afforestation species Robinia pseudoacacia and Platycladus orientalis under the drought treatment (100% no throughfall, DT) and the natural rainfall (control, CK) by stable isotope (δ18O, δ2H) technique and explored their drought adaptability. The results showed that R. pseudoacacia mainly absorbed soil water at 0-40 cm soil layer in the wet months (June and September), with a contribution rate of 68.0%±2.4%, and at four layers (0-10, 10-40, 40-60, and 60-120 cm) evenly in the dry months (July and August) in the CK. In contrast, P. orientalis mainly absorbed soil water at 0-40 cm layer in both the wet and dry months, with the contribution rate being 77.0%±2.4% and 57.4%±3.0%, respectively. In the DT, the water-use depths of R. pseudoacacia and P. orientalis tended to move downward with the decreases of soil water content. The water-use depths of R. pseudoacacia changed from 0-40 cm to 60-120 cm, while that of P. orientalis changed from 0-40 cm to the four layers mentioned evenly. R. pseudoacacia and P. orientalis could adjust water-use depths under different water conditions and showed strong drought adaptability, a feature of great significance for evaluating the stress resistance and stability of local plantations.

JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis.

Long noncoding RNAs (lncRNAs) are a novel class of noncoding RNAs that have emerged as critical regulators and biomarkers in various cancers. Nevertheless, the expression profile and mechanistic function of lncRNAs in cholangiocarcinoma (CCA) remain unclear. Herein, we examined the expression levels of linc00976 in clinical specimens and cell lines using reverse transcription-quantitative PCR. In total, 50 patients with CCA were enrolled to analyze the correlation between linc00976 expression and clinical characteristics of CCA. Loss- and gain-of-function experiments were performed to investigate the biological effects of linc00976 on proliferation, ferroptosis, migration, and invasion of CCA cells in vitro and in vivo. In situ hybridization, RNA immunoprecipitation, bioinformatic databases, RNA pull-down assay, a dual-luciferase reporter assay, mRNA sequencing, chromatin immunoprecipitation-PCR, and rescue experiments were performed to elucidate the underlying mechanisms of linc00976-induced competitive endogenous RNA regulatory networks. We characterized a novel and abundant lncRNA, linc00976, that functions as a pro-oncogenic regulator of CCA progression. Compared with normal controls, linc00976 was dramatically upregulated in CCA tissue samples and cell lines. Patients with CCA exhibiting high linc00976 expression had a highly advanced clinical stage, substantial lymph node metastasis, and poor overall survival. Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. These findings suggest that targeting linc00976 may afford a promising therapeutic strategy for patients with CCA.

Design, synthesis and evaluation of the Brigatinib analogues as potent inhibitors against tertiary EGFR mutants (EGFRdel19/T790M/C797S and EGFRL858R/T790M/C797S).

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated encouraging clinical outcomes for patients with EGFR-mutated non-small cell lung cancer, a considerable number of patients will develop drug resistance and eventually undergo disease progression after taking EGFR-TKIs for a period of time. EGFRdel19/T790M/C797S and EGFRL858R/T790M/C797S are two most prevalent tertiary EGFR mutants identified in Osimertinib-resistant tumors and currently there is no therapy approved clinically targeting these mutants. In this study, we designed and synthesized a series of novel 4th generation EGFR inhibitors based on scaffold of Brigatinib. After extensive SAR studies, compound 23, the most promising candidate, exhibited strong biochemical potencies against EGFRdel19/T790M/C797S, EGFRL858R/T790M/C797S and other clinically relevant EGFR mutants while sparing wild type EGFR. In cellular assays, compound 23 potently inhibited proliferation of BaF3EGFR del19/T790M/C797S and PC-9EGFR del19/T790M/C797S. Moreover, compound 23 demonstrated good DMPK profile in mouse PK study.

Mechanism of aberrant long non-coding RNA expression in an adriamycin-resistant liver cancer cell strain.

BACKGROUND AND AIMS: Aberrant long non-coding RNA (lncRNA) expression in cancer can be used as a potential diagnostic biomarker and therapeutic target. In the present study we determined the potential pathogenic mechanism underlying significant aberrant expression of lncRNAs in HepG2-ADR. METHODS: First, we identified different levels of lncRNA expression in liver cancer and adjacent non-tumor tissues obtained from public data (GSE70880) in NCBI. Then, the results were verified in a sensitive liver cancer cell line (HepG2) and a adriamycin-resistant liver cancer cell line (HepG2-ADR). Then, the effects of lncRNAs on the phenotype and some biological characteristics were also determined in HepG2 and HepG2-ADR through overexpression and using siRNA interference methods. RESULTS: We showed that lncRNA ENST00000425005 is highly expressed in a liver cancer-resistant cell line when compared with adjacent non-tumor tissues based on bioinformatics analysis and qPCR verification. Compared with the control group, overexpression of lncRNA ENST00000425005 significantly promoted proliferation and adhesiveness, but inhibited apoptosis in HepG2-ADR cells. In contrast, interference of lncRNA in HepG2-ADR cells suppressed proliferation and adhesiveness, and induced apoptosis. CONCLUSION: In conclusion, lncRNA ENST00000425005 promotes cell proliferation and invasion in drug-resistant liver cancer cells by regulating epithelial-mesenchymal transition-related gene expression and participating in the regulation of EGF and FGF7.

Enantioselective sequential conjugate addition-allylation reactions: a concise total synthesis of (+)-podophyllotoxin.

A highly flexible and concise total synthesis of (+)-podophyllotoxin featured with an enantioselective sequential conjugate addition-allylation reaction was reported. Starting from commercially available 3,4,5-trimethoxycinnamic acid, this new route leads to (+)-podophyllotoxin 1 in only eight steps with 29% overall yield.

A new and efficient strategy for the synthesis of podophyllotoxin and its analogues.

[structure: see text]. An efficient and stereoselective strategy for the total synthesis of podophyllotoxin was developed. This route leads to podophyllotoxin 1 in only 12 steps with 29% overall yield. A notable feature of this synthetic strategy is the use of the cascade addition-alkylation to ensure the key C1-C2 stereochemistry that is pivotal for the synthesis of podophyllotoxin.