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DP303c is a HER2-targeted ADC with a cleavable linker-MMAE payload. Previous in vitro studies demonstrated that DP303c showed similar or better antitumor activity than T-DM1 in xenograft models. This was a multicenter, dose escalation and dose expansion phase 1 study in China. Eligible patients were 18-75 years old with HER2-positive advanced solid tumors who were unable to benefit from standard therapy. DP303c was administered intravenously every 3 weeks, with accelerated titration at lower dose of 0.5 mg/kg and 3 + 3 design with dose levels of 1.0, 2.0, 3.0 or 4.0 mg/kg at dose escalation part, followed by the selected dose level at dose expansion part. The primary endpoints were safety and tolerability, as well as identification of recommended phase 2 dose. As of Feb 28, 2023, 94 patients were enrolled and received DP303c (dose escalation: n = 22; dose expansion: n = 72), of whom 68 patients had breast cancer. One dose limiting toxicity (Grade 3 eye pain) was observed at 4.0 mg/kg dose, and the maximum tolerated dose was not reached. The most common treatment-related adverse events at grade 3 or higher were blurred vison (16.0%), dry eye (6.4%), and peripheral neuropathy (5.3%). No treatment-related death occurred. Overall, among 91 efficacy evaluable patients, 39 patients (42.9%) achieved an objective response. Disease control was observed in 62 patients (68.1%). In 66 efficacy evaluable patients with breast cancer, 34 patients achieved an objective response (51.5%). Disease control was achieved in 51 patients (77.3%). Median PFS was 6.4 months. On a molar basis, DP303c Cmax at 3.0 mg/kg doses was 132-folder higher than that for free MMAE. DP303c demonstrated promising anti-tumor activity with acceptable safety in patients with pre-treated advanced HER2 positive solid tumors, especially in breast cancer. Based on safety and efficacy results, 3.0 mg/kg Q3W was determined as recommended phase 2 dose for DP303c. (Trial registration: ClinicalTrials.gov Identifier: NCT04146610). [ABSTRACT FROM AUTHOR]

Summary: Hexavalent chromium resistance and reduction mechanisms of microorganism provide a critical guidance for Cr(VI) bioremediation. However, related researches are limited in mesophiles and deficient for thermophiles. In this work, a novel alkaline Cr(VI)‐reducing thermophile Anoxybacillus flavithermus ABF1 was isolated from geothermal region. The mechanisms of Cr(VI) resistance and reduction were investigated. The results demonstrated that A. flavithermus ABF1 could survive in a wide temperature range from 50°C to 70°C and in pH range of 7.0–9.0. Strain ABF1 showed excellent growth activity and Cr(VI) removal performance when initial Cr(VI) concentration was lower than 200 mg L−1. 93.71% of Cr(VI) was removed at initial concentration of 20 mg L−1 after 72 h. The majority of Cr(VI) was found to be reduced extracellularly by enzymes secreted by cells. XPS and Raman analysis further manifested that Cr2O3 was the product of Cr(VI) reduction. Moreover, the Cr(VI) transportation‐related gene cysP and Cr(VI) reduction‐related gene azoR of A. flavithermus ABF1 played key roles in inhibiting Cr(VI) entering cells and promoting extracellular Cr(VI) reduction respectively. This work provides novel insight into the mechanisms of Cr(VI) resistance and detoxication of thermophiles, which leads to a promising alternative strategy for heavy metal bioremediation in areas with elevated temperature. [ABSTRACT FROM AUTHOR]

Morchella sextelata is an edible and medicinal fungus with high nutritional, medicinal, and economic value. Recently, M. sextelata has been produced through artificial cultivation in China, but its stable production remains problematic because the details of its growth and development process are limitedly understood. Herein, to investigate the dynamic process of M. sextelata development, we integrated the transcriptomics and metabolomics data of M. sextelata from three developmental stages: the young mushroom period (YMP), marketable mature period (MMP), and physiological maturity period (PMP). The results showed that the transcriptome changed dynamically at different stages and demonstrated the significant enrichment of pathways that regulate plant growth and development, such as N-glycan biosynthesis and carbon and purine metabolism. Similarly, small-molecule metabolites, such as D-fructose-1,6-biphosphate, which was upregulated during the YMP, dihydromyricetin, which was upregulated during the MMP, and L-citrulline, which was upregulated during the PMP, also showed phase-dependent characteristics. Then, combined analysis of the transcriptome data and metabolome traits revealed that the transcriptome may affect metabolic molecules during different growth stages of M. sextelata via specific enzymes, such as α-glucosidase and glucanase, which were included in two opposite transcriptome modules. In summary, this integration of transcriptomics and metabolomics data for understanding the vegetative growth of M. sextelata during different developmental stages implicated several key genes, metabolites, and pathways involved in the vegetative growth. We believe that these findings will provide comprehensive insights into the dynamic process of growth and development in M. sextelata and new clues for optimizing the methods for its cultivation application. [ABSTRACT FROM AUTHOR]

Exiguobacterium is a versatile genus with potential in industry and agriculture. No bacteriophage that infects Exiguobacterium has been reported, despite its potential impacts on the utilization of Exiguobacterium. E. indicum EI9 was isolated from Dianchi Lake, a plateau eutrophic lake in China, which can significantly inhibit the growth of Microcystis aeruginosa. To isolate and characterize Exiguobacterium-infecting bacteriophage, a virulent bacteriophage, DCEIV-9 that specifically infects E. indicum EI9 was isolated from Dianchi lake water sample. DCEIV-9 produced tiny, round, and clear plaques with 0.5-1 mm in diameter. Electron microscopy showed that DCEIV-9 is a typical representative of the Siphoviridae, with an icosahedral head (56 nm in diameter) and a non-contractile tail (163 nm in length). Based on a one-step growth curve, latent period of 20 min and burst size of 51 PFU/infected cell were determined. DCEIV-9 was sensitive to temperature over 50 °C and prefers acid environment. DCEIV-9 was extremely sensitive to proteinase K, chloroform, ethanol, Triton X-100 but not sensitive to SDS. Restriction endonucleases analysis indicated that DCEIV-9 is a dsDNA virus. DCEIV-9 can only infect E. indicum, indicates that it has a narrow host range. DCEIV-9 is a potential new species., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)