Morphological and molecular analyses reveal two new species of Grifola (Polyporales) from Yunnan, China.

Species of Grifola are famous edible mushrooms and are deeply loved by consumers around the world. Most species of this genus have been described and recorded in Oceania, Europe and South America, with only Grifolafrondosa being recorded in Asia. In this study, two novel species of Grifola from southwestern China (Asia) are introduced. Macro and micromorphological characters are described. Grifolaedulissp. nov. present medium-size basidiomata with gray to gray-brown lobes upper surface, mostly tibiiform or narrowly clavate, rarely narrowly lageniform or ellipsoid chlamydospores, cuticle hyphae terminal segments slightly enlarged. Grifolasinensissp. nov. has white to grayish white lobes upper surface, mostly ellipsoid, rarely narrowly utriform chlamydospores, and broadly ellipsoid to ellipsoid basidiospores (4.6-7.9 × 3.0-5.9 µm). The two new species are supported by phylogenetic analyses of combined nuclear rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) and ß-tubulin (TUBB). Moreover, the genetic distance between TUBB sequences of those specimen from GenBank was 1.76-1.9%. Thus, the conspecificity relationship of our specimens remains uncertain, and further specimens are required to conclusively confirm its identity.

Visualizing and sorbing Hg(II) with a cellulose-based red fluorescence aerogel: Simultaneous detection and removal.

Both sensing and removal of Hg(II) are important to environment and human health in view of the high toxicity and wide applications of mercury in industry. This study aims to develop a cellulose-based fluorescent aerogel for simultaneous Hg(II) sensing and removal via conveniently cross-linking two nanomaterials cellulose nanocrystals and bovine serum albumin-functionalized gold nanoclusters (BSA-AuNCs) with epichlorohydrin. The aerogel exhibited strong homogeneous red fluorescence at the non-edged regions under UV light due to highly dispersed BSA-AuNCs in it, and its fluorescence could be quenched by Hg(II). Through taking pictures with a smartphone, Hg(II) in the range of 0-1000 µg/L could be quantified with a detection limit of 12.7 µg/L. The sorption isotherm of Hg(II) by the aerogel followed Freundlich model with an equation of Qe = 0.329*Ce1/0.971 and a coefficient of 0.999. The maximum sorption capacity can achieve 483.21 mg/g for Hg(II), much higher than many reported sorbents. The results further confirmed Hg(II) strong sorption and sensitive detection are due to its complexation and redox reaction with the chemical groups in aerogels and its strong fluorescence quenching effect. Due to extensive sources and low cost, cellulose is potential to be developed into aerogels with multiple functions for sophisticated applications.

Strategies on biosynthesis and production of bioactive compounds in medicinal plants.

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

Advancements and Challenges in High-Capacity Ni-Rich Cathode Materials for Lithium-Ion Batteries.

Nowadays, lithium-ion batteries are undoubtedly known as the most promising rechargeable batteries. However, these batteries face some big challenges, like not having enough energy and not lasting long enough, that should be addressed. Ternary Ni-rich Li[NixCoyMnz]O2 and Li[NixCoyAlz]O2 cathode materials stand as the ideal candidate for a cathode active material to achieve high capacity and energy density, low manufacturing cost, and high operating voltage. However, capacity gain from Ni enrichment is nullified by the concurrent fast capacity fading because of issues such as gas evolution, microcracks propagation and pulverization, phase transition, electrolyte decomposition, cation mixing, and dissolution of transition metals at high operating voltage, which hinders their commercialization. In order to tackle these problems, researchers conducted many strategies, including elemental doping, surface coating, and particle engineering. This review paper mainly talks about origins of problems and their mechanisms leading to electrochemical performance deterioration for Ni-rich cathode materials and modification approaches to address the problems.

Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

Fe-doping green fluorescent carbon dots via co-electrolysis of chrysoidine G and potassium ferrocyanide for sensitive Cr(VI) detection.

In this study, we aimed to synthesis of Fe-doping green fluorescent carbon dots (G-CDs) through the co-electrolysis of chrysoidine G and potassium ferrocyanide for Cr(VI) detection. The use of potassium ferrocyanide improves the quantum yield and sensing performance of G-CDs toward Cr(VI). The G-CDs have a maximum excitation wavelength of 308 nm and an emission wavelength of 510 nm. Comprehensive analyses including Raman, FT-IR, and XPS provided insights into the chemical structure and composition of the G-CDs. Under optimal conditions, G-CDs demonstrated concentration-dependent quenching upon interaction with Cr(VI). A linear relationship within the range of 0.25-100 µM was established with a calibration equation of ΔF/F0 = 0.005 + 0.015CCr(VI), yielding an R2 value of 0.996 and a limit of detection of 0.15 µM. The applicability of the G-CDs method was demonstrated by successful Cr(VI) detection in water samples with recovery rates ranging from 98.8 % to 100.1 % and relative standard deviation within 3.0 %. The fluorescence lifetime and Zeta potential measurements confirmed that the mechanism was via a static quenching process, while redox reaction, nanoparticle aggregation, and surface charge variation also played significant roles.

RNA-binding protein hnRNPU regulates multiple myeloma resistance to selinexor.

Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor.

Improving the Herbicide Resistance of Rice 4-Hydroxyphenylpyruvate Dioxygenase by DNA Shuffling Basis-Directed Evolution.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an ideal target for herbicide resistance genetic engineering. In this study, a mutant MFRR-2 with mesotrione resistance was screened from an Oryza sativa HPPD and mutant-Zea mays HPPD DNA shuffling library. The enzyme properties showed that although the stability of the mutant decreased in vitro, the enzyme activity of MFRR-2 at the optimum temperature of 25 °C was still equivalent to that of OsHPPD. Under 50 µM mesotrione treatment, MFRR-2 enzyme activity remained at approximately 90%, while the enzyme activity of OsHPPD decreased by approximately 50%. Surprisingly, Fe2+ was found to have an inhibitory effect on the enzyme activity. Then, the transgenic rice of the MFRR-2 gene showed approximately 1.5 times mesotrione resistance compared to OsHPPD transgenic rice. In conclusion, this study has conducted a beneficial exploration on the use of DNA shuffling for HPPD-directed evolution, and the mutant has potential application value for herbicide resistance genetic engineering.

Methylcrotonyl-CoA carboxylase subunit 1 (MCCA) regulates multidrug resistance in multiple myeloma.

AIMS: This study aimed to investigate the effect and mechanism of methylcrotonyl-CoA carboxylase subunit 1 (MCCA) on multidrug resistance in multiple myeloma (MM). MATERIALS AND METHODS: The apoptosis kit and CCK-8 reagent were used to detect drug-induced cell apoptosis and viability. Immunoprecipitation, immunofluorescence staining, and protein structural simulation were used to detect the interaction between MCCA and Bad. Immunodeficient mice were injected with ARD cells and treated with bortezomib. Changes in tumor burden were recorded by bioluminescence imaging, and κ light chain content in the blood of mice was detected by enzyme-linked immunoassay. KEY FINDINGS: Patients with high MCCA expression from a primary MM dataset had superior overall survival. After treatment with different anti-MM drugs, MCCA knockdown MM (MCCA-KD) cells had higher survival rates than control knockdown (CTR-KD) cells (p < 0.05). Mechanistic studies have revealed that MCCA-KD cells had dysfunctional mitochondria with decreased Bax and Bad levels and increased Bcl-xl and Mcl-1 levels. Furthermore, that MCCA and Bad demonstrated protein-protein interactions. The half-life of Bad in MCCA-KD cells is significantly shorter than that in CTR-KD cells (7.34 vs. 2.42 h, p < 0.05). In a human MM xenograft mouse model, we confirmed that MCCA-KD tumors had a poor response to anti-MM drugs in vivo. Finally, we showed that MCCA might contribute to multidrug resistance in different human cancers, particularly in solid tumors. SIGNIFICANCE: Our findings demonstrated a novel function of MCCA in multidrug resistance. The lack of MCCA expression promoted antiapoptotic cell signaling in MM cells.

Perilla frutescens: A traditional medicine and food homologous plant.

Perilla frutescens, an annual herb of the Labiatae family, has been cultivated in China for more than 2000 years. P. frutescens is the one of the first medicinal and edible plant published by the Ministry of Health. Its leaves, stems and seeds can be used as medicine and edible food. Because of the abundant nutrients and bioactive components in this plant, P. frutescens has been studied extensively in medicine, food, health care and chemical fields with great prospects for development. This paper reviews the cultivation history, chemical compositions and pharmacological activities of P. frutescens, which provides a reference for the development and utilization of P. frutescens resources.

Carbon dots electrochemically prepared from dopamine and epigallocatechin gallate for hypochlorite detection with high selectivity via a dynamic quenching mechanism.

Monitoring hypochlorite levels in water is of great importance because of its high toxicity and wide applications as water disinfectants. In this manuscript, carbon dot (CD) was electrochemically prepared by using dopamine and epigallocatechin gallate (molar ratio 1:1) as the carbon source for efficient hypochlorite determination. By electrolyzing the solution at 10 V for 12 min with PBS as an electrolyte, dopamine would react with epigallocatechin at the anode, and through polymerization, dehydration, and carbonization, strong blue-fluorescent CDs were obtained. CDs were characterized by UV-Vis spectroscopy, fluorescence spectroscopy, high-resolution transmission electron microscopy, FT-IR, etc. These CDs have an excitation wavelength at 372 nm and an emission wavelength at 462 nm, owing an average particle size of 5.5 nm. The presence of hypochlorites can quench the fluorescence of CDs, and its reduction in intensity is linear with hypochlorite concentration over the range of 0.5-50 µM, ΔF/F0 = 0.0056 + 0.0194CClO-, R2=0.997. The detection limit achieved 0.23 µM (S/N = 3). The mechanism for fluorescence quenching is via a dynamic process. Different from many other fluorescence methods based on the strong oxidizing ability of hypochlorites, our method shows strong selectivity toward hypochlorites over other oxidizing agents such as H2O2. The assay was validated by the detection of hypochlorites in water samples, with recoveries between 98.2% and 104.3%.

Organic-Inorganic Hybrid Crystal-Assisted Etching of Nickel Foam for the Collectively Exhaustive Electrochemical Performance of Oxygen Evolution Reaction.

In this work, an organic-inorganic hybrid crystal, violet-crystal (VC), was used to etch the nickel foam (NF) to fabricate a self-standing electrode for the water oxidation reaction. The efficacy of VC-assisted etching manifests the promising electrochemical performance towards the oxygen evolution reaction (OER), requiring only ~356 and ~376 mV overpotentials to reach 50 and 100 mA cm-2 , respectively. The OER activity improvement is attributed to the collectively exhaustive effects arising from the incorporation of various elements in the NF, and the enhancement of active site density. Furthermore, the self-standing electrode is robust, exhibiting a stable OER activity after 4,000 cyclic voltammetry cycles, and ~50 h. The anodic transfer coefficients (αa ) show that the first electron transfer step is the rate-determining step on the surface of NF-VCs-1.0 (NF etched by 1 g of VCs) electrode, while the chemical step involving dissociation following the first electron transfer step is identified as the rate-limiting step in other electrodes. The lowest Tafel slope value observed in the NF-VCs-1.0 electrode indicates the high surface coverage of oxygen intermediates and more favorable OER reaction kinetics, as confirmed by high interfacial chemical capacitance and low charge transport/interfacial resistance. This work demonstrates the importance of VCs-assisted etching of NF to activate the OER, and the ability to predict reaction kinetics and rate-limiting step based on αa values, which will open new avenues to identify advanced electrocatalysts for the water oxidation reaction.

Role and therapeutic target of P2X2/3 receptors in visceral pain.

Visceral pain (VP) is caused by internal organ disease. VP is involved in nerve conduction and related signaling molecules, but its specific pathogenesis has not yet been fully elucidated. Currently, there are no effective methods for treating VP. The role of P2X2/3 in VP has progressed. After visceral organs are subjected to noxious stimulation, cells release ATP, activate P2X2/3, enhance the sensitivity of peripheral receptors and the plasticity of neurons, enhance sensory information transmission, sensitize the central nervous system, and play an important role in the development of VP. However, antagonists possess the pharmacological effect of relieving pain. Therefore, in this review, we summarize the biological functions of P2X2/3 and discuss the intrinsic link between P2X2/3 and VP. Moreover, we focus on the pharmacological effects of P2X2/3 antagonists on VP therapy and provide a theoretical basis for its targeted therapy.

Combinations of ivermectin with proteasome inhibitors induce synergistic lethality in multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Ivermectin is a US Food and Drug Administration-approved drug for antiparasitic use. Here, we showed that ivermectin exerted anti-MM effects and significantly synergized with proteasome inhibitors in vitro and in vivo. Ivermectin alone exhibited mild anti-MM activity in vitro. Further investigation suggested that ivermectin inhibited proteasome activity in the nucleus by repressing the nuclear import of proteasome subunits, such as PSMB5-7 and PSMA3-4. Therefore, ivermectin treatment caused the accumulation of ubiquitylated proteins and the activation of the UPR pathway in MM cells. Furthermore, ivermectin treatment caused DNA damage and DNA damage response (DDR) signaling pathway activation in MM cells. Ivermectin and bortezomib exhibited synergized anti-MM activity in vitro. The dual-drug treatment resulted in synergistic inhibition of proteasome activity and increased DNA damage. An in vivo study using a human MM cell line xenograft mouse model showed that ivermectin and bortezomib efficiently repressed MM tumor growth in vivo, while the dual-drug treatment was well tolerated by experimental animals. Overall, our results demonstrated that ivermectin alone or cotreated with bortezomib might be promising in MM treatment.

Effects of Carbon Templates in Tetraethyl Orthosilicate-Derived Superhydrophobic Coatings.

Superhydrophobic coatings have garnered significant research interest due to their potential applications in areas such as ant-icing and windows. This study focuses on the development of superhydrophobic coatings using air-assisted electrospray and the effect of different carbon additives as templates in the coating. Carbon templates, with their unique topological varieties, offer a cost-effective alternative to other patterning technologies such as photolithography. By introducing dispersed carbon black, carbon nanotubes, and graphene additives in TEOS solution, silica is given the ability of localized secondary growth on or around the carbon surfaces as well as the building structure to provide adequate roughness on the substrate surface. The templated silica formations provide a thin coating with nano-scale roughness for heightened water resistance. As compared with the template-free coating that has small silica particles, a surface roughness of 135 nm, and a water contact angle (WCA) of 101.6° (non-superhydrophobic), the carbon templating effect allowed for increased silica particle size, a surface roughness as high as 845 nm, a WCA above 160°, and the ability to maintain superhydrophobicity over 30 abrasion cycles. The morphological characteristics that resulted from the templating effect correlate directly with heightened performance of the coatings. Herein, the carbon additives have been found to serve as cheap and effective templates for silica formation in thin TEOS-derived superhydrophobic coatings.

Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2.

Phosphoinositide-dependent protein kinase-1 (PDK1), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK1 knockout mice displayed no heart development; in this article, we deleted PDK1 in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK1 with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK1 with Mef2cSHF-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK1 with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK1-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt473, S6k421/424, and Gsk3α21 enhanced; however, Akt308, S6k389, and Gsk3ß9 decreased. In mechanism investigation, we found SHP2 membrane localization and phosphorylation level of SHP2542 elevated, which suggested SHP2 likely mediated the disruption.

Development and application of a new biological nano-selenium fermentation broth based on Bacillus subtilis SE201412.

In order to improve the functionality and additional value of agricultural products, this study developing nano-selenium fermentation broth and established a new application strategy of bio-nano-selenium by screening and identifying selenium-rich microorganisms. We isolated a new strain from tobacco waste and named it Bacillus subtilis SE201412 (GenBank accession no. OP854680), which could aerobically grow under the condition of 66,000 mg L-1 selenite concentration, and could convert 99.19% of selenite into biological nano-selenium (BioSeNPs) within 18 h. Using strain SE201412, we industrially produced the different concentrations of fermentation broth containing 5000-3000 mg L-1 pure selenium for commercial use. The synthesized selenium nanoparticles (SeNPs) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). TEM and SEM results showed that SeNPs were distributed outside cells. NTA assay of fermentation broth indicated that the nanoparticles were spherical with an average particle size of 126 ± 0.5 nm. Toxicity test revealed that the median lethal dose (LD50) of the fermentation broth to mice was 2710 mg kg-1, indicating its low toxicity and high safety. In addition, we applied BioSeNP fermentation broth to rice and wheat through field experiments. The results showed that the application of fermentation broth significantly increased the total selenium content and organic selenium percentage in rice and wheat grains. Our findings provide valuable reference for the development of BioSeNPs with extensive application prospects.

Physiological and molecular mechanisms of medicinal plants in response to cadmium stress: Current status and future perspective.

Medicinal plants have a wide range of uses worldwide. However, the quality of medicinal plants is affected by severe cadmium pollution. Cadmium can reduce photosynthetic capacity, lead to plant growth retardation and oxidative stress, and affect secondary metabolism. Medicinal plants have complex mechanisms to cope with cadmium stress. On the one hand, an antioxidant system can effectively scavenge excess reactive oxygen species produced by cadmium stress. On the other hand, cadmium chelates are formed by chelating peptides and then sequestered through vacuolar compartmentalization. Cadmium has no specific transporter in plants and is generally transferred to plant tissues through competition for the transporters of divalent metal ions, such as zinc, iron, and manganese. In recent years, progress has been achieved in exploring the physiological mechanisms by which medicinal plants responding to cadmium stress. The exogenous regulation of cadmium accumulation in medicinal plants has been studied, and the aim is reducing the toxicity of cadmium. However, research into molecular mechanisms is still lagging. In this paper, we review the physiological and molecular mechanisms and regulatory networks of medicinal plants exposed to cadmium, providing a reference for the study on the responses of medicinal plants to cadmium stress.

A chromosome-scale genome assembly of Artemisia argyi reveals unbiased subgenome evolution and key contributions of gene duplication to volatile terpenoid diversity.

Artemisia argyi Lévl. et Vant., a perennial Artemisia herb with an intense fragrance, is widely used in traditional medicine in China and many other Asian countries. Here, we present a chromosome-scale genome assembly of A. argyi comprising 3.89 Gb assembled into 17 pseudochromosomes. Phylogenetic and comparative genomic analyses revealed that A. argyi underwent a recent lineage-specific whole-genome duplication (WGD) event after divergence from Artemisia annua, resulting in two subgenomes. We deciphered the diploid ancestral genome of A. argyi, and unbiased subgenome evolution was observed. The recent WGD led to a large number of duplicated genes in the A. argyi genome. Expansion of the terpene synthase (TPS) gene family through various types of gene duplication may have greatly contributed to the diversity of volatile terpenoids in A. argyi. In particular, we identified a typical germacrene D synthase gene cluster within the expanded TPS gene family. The entire biosynthetic pathways of germacrenes, (+)-borneol, and (+)-camphor were elucidated in A. argyi. In addition, partial deletion of the amorpha-4,11-diene synthase (ADS) gene and loss of function of ADS homologs may have resulted in the lack of artemisinin production in A. argyi. Our study provides new insights into the genome evolution of Artemisia and lays a foundation for further improvement of the quality of this important medicinal plant.

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity.

Multiple myeloma (MM), a plasma cell cancer in bone marrow, remains an incurable disease. Melphalan, an alkylating agent, is a conventional anticancer drug that is still widely used for MM treatment in clinics. However, melphalan-induced organ toxicity and side effects are common. In this study, we loaded melphalan into a liposomal capsule and constituted liposomal melphalan (liposomal MEL). Liposomal MEL particles were approximately 120 nm in size and stable in vitro. The liposomal particles could be effectively taken up by MM cells. In vitro cytotoxicity assays using MM cell lines and primary MM cells showed that liposomal MEL exhibited similar anti-MM activity compared to an equivalent amount of free melphalan (free MEL) compound. In animal models, liposomal particles had bone marrow enrichment and prolonged half-life in vivo. Liposomal MEL exposure resulted in less liver and colon organ toxicity than exposure to an equivalent amount of free MEL-treated mice. Importantly, liposomal MEL had potent anti-MM activity in vivo in a human MM xenograft mouse model. Overall, our findings suggested that liposome-encapsulated melphalan was an effective drug modification of the melphalan compound and showed promise in MM treatment.