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Multiple myeloma (MM) is a cancer of terminally differentiated plasma cells. MM remains incurable, but overall survival of patients has progressively increased over the past two decades largely due to novel agents such as proteasome inhibitors (PI) and the immunomodulatory agents. While these therapies are highly effective, MM patients can be de novo resistant and acquired resistance with prolonged treatment is inevitable. There is growing interest in early, accurate identification of responsive versus non-responsive patients; however, limited sample availability and need for rapid assays are limiting factors. Here, we test dry mass and volume as label-free biomarkers to monitor early response of MM cells to treatment with bortezomib, doxorubicin, and ultraviolet light. For the dry mass measurement, we use two types of phase-sensitive optical microscopy techniques: digital holographic tomography and computationally enhanced quantitative phase microscopy. We show that human MM cell lines (RPMI8226, MM.1S, KMS20, and AMO1) increase dry mass upon bortezomib treatment. This dry mass increase after bortezomib treatment occurs as early as 1 h for sensitive cells and 4 h for all tested cells. We further confirm this observation using primary multiple myeloma cells derived from patients and show that a correlation exists between increase in dry mass and sensitivity to bortezomib, supporting the use of dry mass as a biomarker. The volume measurement using Coulter counter shows a more complex behavior; RPMI8226 cells increase the volume at an early stage of apoptosis, but MM.1S cells show the volume decrease typically observed with apoptotic cells. Altogether, this cell study presents complex kinetics of dry mass and volume at an early stage of apoptosis, which may serve as a basis for the detection and treatment of MM cells.

Seed coating with fungicides is a common practice in controlling seed-borne diseases, but conventional methods often result in high toxicity to plants and soil. In this study, a nanoparticle formulation was successfully developed using the metal–organic framework UiO-66 as a carrier of the fungicide ipconazole (IPC), with a tannic acid (TA)-ZnII coating serving as a protective layer. The IPC@UiO-66-TA-ZnII nanoparticles provided a controlled release, triggered and regulated by environmental factors such as pH and temperature. This formulation efficiently controlled the proliferation of Fusarium fujikuroi spores, with high penetration into both rice roots and fungal mycelia. The product exhibited high antifungal activity, achieving control efficacy rates of 84.09% to 93.10%, low biotoxicity, and promoted rice growth. Compared to the IPC flowable suspension formula, IPC@UiO-66-TA-ZnII improved the physicochemical properties and enzymatic activities in soil. Importantly, it showed potential for mitigating damage to beneficial soil bacteria. This study provides a promising approach for managing plant diseases using nanoscale fungicides in seed treatment. Highlights: IPC-loaded UiO-66 with tannic acid-ZnII shells for precision management of rice seedling disease through intelligent, responsive release. A pH- and temperature-sensitive, controlled-release nanoparticle system was developed. Tannic acid-ZnII-modified nanoparticles penetrate into rice roots and fungal mycelium. Nanoparticles provide better control of Fusarium fujikuroi and promote seedling growth. Nanoparticles reduce the pollution of soil environment by conventional seed coatings. [ABSTRACT FROM AUTHOR]

Reasonable design of an economical and efficient versatile oxygen electrocatalyst for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is urgently needed in metal-air batteries and fuel cells. Herein, a Ce-doped Fe-NC/Fe3C (Ce/Fe-NC/Fe3C-P) porous nanosheet catalyst was prepared from the pyrolysis of a two-dimensional ZIF assisted with NaCl molten salt. Under alkaline media, the ORR half-wave potential (E1/2) is 0.87 V, and the OER overpotential is 389 mV. The Zn-air batteries (ZABs) assembled with the Ce/Fe-NC/Fe3C-P catalyst demonstrate a maximum power density (PM) of 184 mW cm–2. Under acidic media, the E1/2 of the ORR is 0.78 V, and the PM is 347 mW cm–2 in the proton exchange membrane fuel cell (PEMFC) cathode. The enhanced catalytic activity and stability benefit from the abundant catalytic active sites (Fe3C, Fe–NX, Ce–N) by Fe and Ce doping, hierarchical porous structure, and relatively higher graphitization originating from the molten NaCl assisting pyrolysis. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A), a vital post-transcriptional regulator, is among the most prevalent RNA modifications in eukaryotes. Nevertheless, the biological functions of m6A in oomycetes remain poorly understood. Here, we showed that the PsMTA1 and PsMTA2 genes are orthologs of human METTL4, while the PsMET16 gene is an ortholog of human METTL16. These genes are implicated in m6A modification and play a critical role in the production of sporangia and oospores, the release of zoospores, and the virulence of Phytophthora sojae. In P. sojae, m6A modifications are predominantly enriched in the coding sequence and the 3' untranslated region. Notably, the PsMTA1 knockout mutant exhibited reduced virulence, attributed to impaired tolerance to host defense-generated ROS stress. Mechanistically, PsMTA1-mediated m6A modification positively regulates the mRNA lifespan of DNA damage response (DDR) genes in reaction to plant ROS stress during infection. Consequently, the mRNA abundance of the DDR gene PsRCC1 was reduced in the single m6A site mutant ΔRCC1/RCC1A2961C, resulting in compromised DNA damage repair and reduced ROS adaptation-associated virulence in P. sojae. Overall, these results indicate that m6A-mediated RNA metabolism is associated with the development and pathogenicity of P. sojae, underscoring the roles of epigenetic markers in the adaptive flexibility of Phytophthora during infection. Author summary: In this investigation, we embarked on delineating the m6A modification landscape in oomycetes, shedding light on the pivotal involvement of PsMTA1, PsMTA2, and PsMET16 in orchestrating m6A modification critical for the developmental processes and infection dynamics of Phytophthora sojae. Notably, our study underscores the significant impact of PsMTA1-mediated m6A modification on the virulence of P. sojae, particularly in its regulation of the expression of DNA damage response genes prompted by the ROS stress induced by host defenses during infection. This underscores the role of epigenetic variation as a mechanism facilitating adaptive infection strategies in plant pathogens, thus providing a conceptual framework for the design of innovative oomycete inhibitors rooted in epigenetic regulation. We firmly believe that these pioneering insights hold substantial interest for the broader scientific community. [ABSTRACT FROM AUTHOR]