Weakly Solvating Ether-Based Electrolyte Constructing Anion-Derived Solid Electrolyte Interface in Graphite Anode toward High-Stable Potassium-Ion Batteries.

Low-cost graphite has emerged as the most promising anode material for potassium-ion batteries (PIBs). Constructing the inorganic-rich solid electrolyte interface (SEI) on the surface of graphite anode is crucial for achieving superior electrochemical performance of PIBs. However, the compositions of SEI formed by conventional strongly solvating electrolytes are mainly organic, leading to the SEI structure being thick and causing the co-intercalation behavior of ions with the solvent. Herein, a weakly solvating electrolyte is applied to weaken the cation-solvent interaction and alter the cation solvation sheath structures, conducing to the inorganic composition derived from anions also participating in the formation of SEI, together with forming a uniformly shaped SEI with superior mechanical properties, and thus improving the overall performance of PIBs. The electrolyte solvation structure rich in aggregated ion pairs (AGGs) (69%) enables remarkable potassium-ion intercalation behavior at the graphite anode (reversible capacity of 269 mAh g-1) and highly stable plating/stripping of potassium metal anode (96.5%). As a practical device application, the assembled potassium-ion full-battery (PTCDA//Graphite) displays superior cycle stability. The optimizing strategy of cation solvation sheath structures offers a promising approach for developing high-performance electrolytes and beyond.

Molecular Engineering Chemical Pre-lithiation Reagent with Low Redox Potential for Graphite Anode Enables High Coulombic Efficiency.

Graphite (Gr) is a low-cost and high-stability anode for lithium-ion batteries (LIBs). However, Gr anode exhibits an obstinate drawback of low initial Coulombic efficiency (ICE), owing to the active lithium loss for the solid electrolyte interphase (SEI) layer. Herein, a straightforward and effective chemical pre-lithiation strategy is proposed to compensate for the lithium loss. A molecular engineering phenanthrene-based lithium-arene complex (Ph-based LAC) reagent is designed by density functional theory (DFT) calculations. The engineering Ph-based reagent enhances the stability of the π-electron system and the electron-donating capacity, resulting in a reduced redox potential to facilitate lithium transfer. The electrochemical distinct of the Ph-based reagent is illustrated, the prelithiation process in a low Li-insertion platform, and the lithiation degree is controllable with the dipping time (ICE = 102%, 3 min). Notably, a denser and homogeneous SEI layer has pre-formed to enhance the Li+ transport and interface stability. Moreover, the lithium-ion full batteries assemble with LiFePO4 and NCM811 cathode, which exhibits high ICE (96.5% and 90.3%) and energy density (310 and 333 Wh kg-1). These findings present a facile and controllable pre-lithiation strategy to compensate for the lithium of LIBs, providing new valuable insights into the design and optimization of battery manufacture.

Dihydrocelastrol induces cell death and suppresses angiogenesis through BCR/AP-1/junb signalling in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although treatment options have improved, a large proportion of patients show low survival rates, highlighting an urgent need for novel therapeutic strategies. The aim of this study was to investigate the efficacy of the new small-molecule compound dihydrocelastrol (DHCE), acquired through the structural modification of celastrol (CE), in the treatment of DLBCL. DHCE showed potent anti-lymphoma efficacy and synergistic effects with doxorubicin. DHCE triggered DLBCL cell apoptosis and G0/G1-phase blockade, thereby hindering angiogenesis. DHCE inhibited B-cell receptor cascade signalling and Jun B and p65 nuclear translocation, thereby suppressing pro-tumourigenic signalling. Finally, DHCE exerted lower toxicity than CE, which showed severe hepatic, renal, and reproductive toxicity in vivo. Our findings support further investigation of the clinical efficacy of DHCE against DLBCL.

A cubic perovskite fluoride anode with the surface conversion reactions dominated mechanism for advanced lithium-ion batteries.

Perovskite fluorides are attractive anode materials for lithium-ion batteries (LIBs) because of their three-dimensional diffusion channels and robust structures, which are advantageous for the rapid transmission of lithium ions. Unfortunately, the wide band gap results in poor electronic conductivity, which limits their further development and application. Herein, the cubic perovskite iron fluoride (KFeF3, KFF) nanocrystals (∼100 nm) are synthesized by a one-step solvothermal strategy. Thanks to the good electrical conductivity of carbon nanotubes (CNTs), the overall electrochemical performance of composite anode material (KFF-CNTs) has been significantly improved. In particular, the KFF-CNTs deliver a high specific capacity (363.8 mAh g-1), good rate performance (131.6 mAh g-1at 3.2 A g-1), and superior cycle stability (500 cycles). Note that the surface conversion reactions play a dominant role in the electrochemical process of KFF-CNTs, together with the stable octahedral perovskite structure and nanoscale particle sizes achieving high ion diffusion coefficients. Furthermore, the specific lithium storage mechanism of KFF has been explored by the distribution of relaxation times technology. This work opens up a new way for developing cubic perovskite fluorides as high-capacity and robust anode materials for LIBs.

The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway.

BACKGROUND: Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and  the mechanism were further tested. METHODS: Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. RESULTS: We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. CONCLUSIONS: DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.

Molecular mechanism by which RRM2-inhibitor (cholagogue osalmid) plus bafilomycin A1 cause autophagic cell death in multiple myeloma.

Despite significant improvement in the prognosis of multiple myeloma (MM), the disease remains incurable; thus, more effective therapies are required. Ribonucleoside-diphosphate reductase subunit M2 (RRM2) is significantly associated with drug resistance, rapid relapse, and poor prognosis. Previously, we found that 4-hydroxysalicylanilide (osalmid), a specific inhibitor of RRM2, exhibits anti-MM activity in vitro, in vivo, and in human patients; however, the mechanism remains unclear. Osalmid inhibits the translocation of RRM2 to the nucleus and stimulates autophagosome synthesis but inhibits subsequent autophagosome-lysosome fusion. We confirm that RRM2 binds to receptor-interacting protein kinase 3 (RIPK3) and reduces RIPK3, inhibiting autophagosome-lysosome fusion. Interestingly, the combination of osalmid and bafilomycin A1 (an autophagy inhibitor) depletes RIPK3 and aggravates p62 and autophagosome accumulation, leading to autophagic cell death. Combination therapy demonstrates synergistic cytotoxicity both in vitro and in vivo. Therefore, we propose that combining osalmid and bafilomycin A1(BafA1) may have clinical benefits against MM.

Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma.

BACKGROUND: Aberrant DNA repair pathways contribute to malignant transformation or disease progression and the acquisition of drug resistance in multiple myeloma (MM); therefore, these pathways could be therapeutically exploited. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the biosynthesis of deoxyribonucleotides (dNTPs), which are essential for DNA replication and DNA damage repair. In this study, we explored the efficacy of the novel RNR inhibitor, 4-hydroxysalicylanilide (HDS), in myeloma cells and xenograft model. In addition, we assessed the clinical activity and safety of HDS in patients with MM. METHODS: We applied bioinformatic, genetic, and pharmacological approaches to demonstrate that HDS was an RNR inhibitor that directly bound to RNR subunit M2 (RRM2). The activity of HDS alone or in synergy with standard treatments was evaluated in vitro and in vivo. We also initiated a phase I clinical trial of single-agent HDS in MM patients (ClinicalTrials.gov: NCT03670173) to assess safety and efficacy. RESULTS: HDS inhibited the activity of RNR by directly targeting RRM2. HDS decreased the RNR-mediated dNTP synthesis and concomitantly inhibited DNA damage repair, resulting in the accumulation of endogenous unrepaired DNA double-strand breaks (DSBs), thus inhibiting MM cell proliferation and inducing apoptosis. Moreover, HDS overcame the protective effects of IL-6, IGF-1 and bone marrow stromal cells (BMSCs) on MM cells. HDS prolonged survival in a MM xenograft model and induced synergistic anti-myeloma activity in combination with melphalan and bortezomib. HDS also showed a favorable safety profile and demonstrated clinical activity against MM. CONCLUSIONS: Our study provides a rationale for the clinical evaluation of HDS as an anti-myeloma agent, either alone or in combination with standard treatments for MM. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03670173, Registered 12 September 2018.

Intimately coupled photocatalysis and functional bacterial system enhance degradation of 1,2,3- and 1,3,5-trichlorobenzene.

Intimate coupling of photocatalysis and biodegradation (ICPB) is considered a promising approach for the degradation of recalcitrant organic compounds. In this work, using Trichoderma with benzene degradation ability coupled with activated sludge as a biological source and sugarcane bagasse cellulose composite as a carrier, the ICPB system showed excellent degradation and mineralization of trichlorobenzene under visible light induction. The biofilm inside the ICPB carrier can degrade and mineralize the photocatalytic products. ICPB increased the degradation efficiency of 1,2,3-TCB and 1,3,5-TCB by 12.43% and 4.67%, respectively, compared to photocatalysis alone. The biofilms inside the ICPB carriers can mineralize photocatalytic products, which increases the mineralization efficiency by 18.74%. According to the analysis of intermediates, the degradation of 1,2,3-TCB in this coupled system involved stepwise dechlorination and ring opening. The biofilm in ICPB carrier evolved to be enriched in Cutaneotrichosporon, Trichoderma, Apiotrichum, Zoogloea, Dechloromonas, Flavihumibacter and Cupriavidus, which are known for biodegradable aromatic hydrocarbon and halogenate. Novel microbial seeds supplemented with Trichoderma-based ICPB seem to provide a new potential strategy for effective degradation and mineralization of TCB.

Coupling of photocatalysis and biological treatment for elemental chlorine free bleaching wastewater: Application of factorial design methodology.

In this study, the visible-light-induced intimately coupled photocatalysis and biodegradation (ICPB) technology was fabricated using the TiO2/bagasse cellulose composite as the carrier and Phanerochaete mixed activated sludge as the biological source. The ICPB degradation effect of elemental chlorine free (ECF) bleaching wastewater was evaluated via the response surface design. Then, the wastewater was characterized, including absorbable organic halogen (AOX), dissolved organic carbon (DOC), chemical oxygen demand (COD), chroma, pH, suspended solids, and the organic compound changes in wastewater were analyzed by fourier transform infrared spectroscopy (FT-IR). Under the optimal conditions of pH 7, carrier filling rate of 5%, aeration rate of 2 L/min, and reaction time of 7 h, the degradation efficiencies of AOX, COD, and DOC were 95%, 91%, and 82%, respectively. The X-ray photoelectron spectroscopy (XPS) results of the ICPB carrier after the reaction were almost identical to those before the reaction. The biomass and its activity on the ICPB system were analyzed by the dominant bacteria during degradation (Curaneotrichosporon, Paenibacillus, Cellulonas, Phanerochaete, Dechlorobacter, Rhodotorula, Sphingobacterium, and Ruminiclostridium), which had a good degradation effect on wastewater. This study affords a novel method for the degradation of ECF bleaching wastewater and a new idea for ICPB technology optimization.

Biofilm response and removal via the coupling of visible-light-driven photocatalysis and biodegradation in an environment of sulfamethoxazole and Cr(VI).

The widespread contamination of water systems with antibiotics and heavy metals has gained much attention. Intimately coupled visible -light-responsive photocatalysis and biodegradation (ICPB) provides a novel approach for removing such mixed pollutants. In ICPB, the photocatalysis products are biodegraded by a protected biofilm, leading to the mineralization of refractory organics. In the present study, the ICPB approach exhibited excellent photocatalytic activity and biodegradation, providing up to ∼1.27 times the degradation rate of sulfamethoxazole (SMX) and 1.16 times the Cr(VI) reduction rate of visible-light-induced photocatalysis . Three-dimensional fluorescence analysis demonstrated the synergistic ICPB effects of photocatalysis and biodegradation for removing SMX and reducing Cr(VI). In addition, the toxicity of the SMX intermediates and Cr(VI) in the ICPB process significantly decreased. The use of MoS2/CoS2 photocatalyst accelerated the separation of electrons and holes, with•O2- and h+ attacking SMX and e- reducing Cr(VI), providing an effective means for enhancing the removal and mineralization of these mixed pollutants via the ICPB technique. The microbial community results demonstrate that bacteria that are conducive to pollutant removal are were enriched by the acclimation and ICPB operation processes, thus significantly improving the performance of the ICPB system.

A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway.

BACKGROUND: Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. METHODS: We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. RESULTS: The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. CONCLUSION: The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

DCZ0801, a novel compound, induces cell apoptosis and cell cycle arrest via MAPK pathway in multiple myeloma.

Multiple myeloma (MM) is a refractory malignant hematological malignancy, and many therapeutic strategies have been developed to cure patients with MM. DCZ0801 is a compound that consists of oxophenamide and pterostilbene. The role of these compounds in hematological cancers such as MM has yet to be studied. In this study, we explored the potential mechanism of DCZ0801 action, its anti-tumor activity both in vitro and in vivo on MM. This study was carried out via cell cycle proliferation assay, apoptotic analysis, western blot analysis, and examination of xenotransplantation model of tumors. The in vitro studies revealed that DCZ0801 could inhibit cell proliferation and induce apoptosis by regulating both caspase-dependent and mitogen-activated protein kinase signaling pathways, inducing S-phase arrest of the cell cycle related to downregulation of CDK2, cyclin-A2, and CDC25A protein expression. The in vivo studies showed that DCZ0801 could significantly reduce the size of the tumors in nude mice. Our results demonstrated that DCZ0801 may emerge as the new therapeutic option for the patient with MM.

Experimental study on a comprehensive particle swarm optimization method for locating contaminant sources in dynamic indoor environments with mechanical ventilation.

Source localization is critical to ensuring indoor air quality and environmental safety. Although considerable research has been conducted on source localization in steady-state indoor environments, very few studies have dealt with the more challenging source localization problems in dynamic indoor environments. This paper presents a comprehensive particle swarm optimization (CPSO) method to locate a contaminant source in dynamic indoor environments with mechanical ventilation and develops a multi-robot source localization system to experimentally validate the method. Three robots were used to test the presented method in a typical dynamic indoor environment with periodic swinging of the air supply louvers of a cabinet air conditioner. The presented method was validated with two typical source locations, DS (in the downwind zone) and RS (in the recirculation zone). For DS and RS, 15 and 14 experiments out of 15 experiments were successful, with success rates of 100% and 93.3%, and each robot moved an average of 24.4 and 23.6 steps, respectively. The presented method was also compared with the standard particle swarm optimization (SPSO) and wind utilization II (WUII) methods for locating the source at DS. For the SPSO and WUII methods, only 3 and 6 experiments out of 15 experiments were successful, with success rates of 20% and 40% and averages of 33.0 and 38.0 steps, respectively. The experimental results show that the presented method not only has a much higher success rate than the SPSO and WUII methods but also has higher source localization efficiency.

An improved particle swarm optimization method for locating time-varying indoor particle sources.

The indoor transmission of airborne particles can spread disease and have health-related and even life-threatening effects on occupants, thus necessitating effective ways to locate indoor particle sources. The identification of particle sources from concentration distributions is a difficult task because particles are often released at a time-varying rate, and particle transport mechanisms are more complex than those of gas. This study proposes an improved multi-robot olfactory search method for locating two types of time-varying indoor particle sources: 1) periodic sources such as occupants' respiratory activities and 2) decaying sources such as laboratory leaky containers with hazardous chemicals. The method considers both particle concentrations and indoor air velocities by including an upwind term in the standard particle swarm optimization (PSO) algorithm, preventing robots from becoming trapped into a local optimum, which occurs when using other algorithms. We also considered two ventilation types (mixing ventilation and displacement ventilation) when particles are emitted from different source types, comprising four scenarios. For each scenario, particle concentration and air velocity were simulated using computational fluid dynamics (CFD) and then fed to the PSO algorithm for source localization. In addition, we validated the CFD approach for one scenario by comparing experimental data (e.g., velocities and particle concentrations) under laboratory settings. The results showed that the proposed method can locate the two types of particle sources within approximately 55 s, and the success rates of source localization exceeding 96%, which is a much higher level than levels achieved from the standard PSO and wind utilization II algorithms.

A novel pterostilbene compound DCZ0825 induces macrophage M1 differentiation and Th1 polarization to exert anti-myeloma and immunomodulatory.

Multiple myeloma (MM) is an incurable and recurrent malignancy characterized by abnormal plasma cell proliferation. There is an urgent need to develop effective drugs in MM. DCZ0825 is a small molecule compound derived from pterostilbene with direct anti-myeloma activity and indirect immune-killing effects though reversal of the immunosuppression. DCZ0825 inhibits the activity and proliferation of MM cells causing no significant toxicity to normal cells. Using flow cytometry, this study found that DCZ0825 induced caspase-dependent apoptosis in MM cells and arrested the cell cycle in the G2/M phase by down-regulating CyclinB1, CDK1 and CDC25. Moreover, DCZ0825 up-regulated IRF3 and IRF7 to increase IFN-γ, promoting M2 macrophages to transform into M1 macrophages, releasing the immunosuppression of CD4T cells and stimulated M1 macrophages and Th1 cells to secrete more INF-γ to form immune killing effect on MM cells. Treatment with DCZ0825 resulted in an increased proportion of positive regulatory cells such as CD4T, memory T cells, CD8T, and NK cells, with downregulation of the proportion of negative regulatory cells such as Treg cells and MDSCs. In conclusion, DCZ0825 is a novel compound with both antitumor and immunomodulatory activity.

Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells.

The most common neoplasm among adult lymphomas is diffuse large B-cell lymphoma (DLBCL), typically characterized by pain-free and progressive lymph node enlargement. Due to high heterogeneity of DLBCL, 30-40 % of patients are resistant to R-CHOP standard chemoimmunotherapy. DCZ0358 is a new compound designed and synthesized from berberine by our group and the molecular mechanism by which it inhibited DLBCL growth has attracted our widespread attention. In this study, we employed the CCK8 assay to reveal that DCZ0358 inhibited proliferation in a dependent manner of time and dosage of DLBCL cells. Moreover, flowcytometry and western blot results showed that DCZ0358 downregulated the expression of CDK4, CDK6 and CyclinD1 to block cell cycle progression in G0/G1 phase. Furthermore, DCZ0358 enhanced mitochondrial membrane potential depolarization, promoted mitochondrial permeability transport pore openness, increased cytoplastic Ca2+ levels and decreased intracellular adenosine triphosphate production, which led to mitochondrial dysfunction. In particular, DCZ0358 treatment triggered cell apoptosis and elevated intracellular reactive oxygen species (ROS) levels, which subsequently mediated JNK pathway activation. Further research indicated the pre-treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358. Most importantly, DCZ0358 exhibited synergistic anti-tumor effects when combined with etoposide, a common clinical anti-DLBCL drug, both in vitro and certainly in vivo. Above results demonstrated anti-tumor molecular mechanism of DCZ0358 in DLBCL cells and highlighted the ROS/JNK/DNA damage pathway as a potential target in therapies, which have implications for the development of more effective clinical treatments for DLBCL.

A Cellulose-Type Carrier for Intimate Coupling Photocatalysis and Biodegradation.

Intimate coupling photocatalysis and biodegradation treatment technology is an emerging technology in the treatment of refractory organic matter, and the carrier plays an important role in this technology. In this paper, sugarcane cellulose was used as the basic skeleton, absorbent cotton was used as a reinforcing agent, anhydrous sodium sulfate was used as a pore-forming agent to prepare a cellulose porous support with good photocatalytic performance, and nano-TiO2 was loaded onto it by a low-temperature bonding method. The results showed that the optimal preparation conditions of cellulose carriers were: cellulose mass fraction 1.0%; absorbent cotton 0.6 g; and Na2SO4 60 g. The SEM, EDS and XPS characterization further indicated that the nano-TiO2 was uniformly loaded onto the cellulose support. The degradation experiments of Rhodamine B showed that the nano-TiO2-loaded composite supports had good photocatalytic performance. The degradation rate of 1,2,4-trichlorobenzene was more than 92% after 6 cycles, and the experiment of adhering a large number of microorganisms on the carriers before and after the reaction showed that the cellulose-based carriers obtained the required photocatalytic performance and stability, which is a good cellulose porous carrier.

A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling.

Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of clonal plasma cells. Based on the organic drug osalmid, the novel small molecule compound DCZ0858 was designed and synthesized for treating MM. DCZ0858 inhibited the proliferation and activity of MM cells and reduced colony formation. It also promoted the apoptosis of primary cells from patients with MM and cultured MM cell lines but had little effect on peripheral blood mononuclear cells in healthy people. Simultaneously, DCZ0858 activated caspase family proteins, blocked MM cells in G0/G1 phase, and reduced the expression of related cyclins CDK4/6 and CyclinD1. Moreover, DCZ0858 overcame the protective effect of the bone marrow microenvironment and effectively inhibited the activity of mTORC1 and mTORC2. Further, xenograft model experiments in mice showed that DCZ0858 significantly inhibited the proliferation and growth of tumors, with low drug toxicity. These results indicate that DCZ0858 has marked anti-MM activity and little effect on normal cells and tissues, making it a new candidate clinical drug for the treatment of MM.

Glycolysis is suppressed by DCZ0801-induced inactivation of the Akt/mTOR pathway in Multiple Myeloma.

Multiple myeloma (MM) is a highly invasive and incurable plasma cell malignant disease with frequent recurrence. DCZ0801 is a natural compound synthesized from osalmide and pterostilbene and has few adverse effects. Here, we aimed to observe the therapeutic effects of DCZ0801 on myeloma cells and clarify the specific molecular mechanism underlying its anti-tumor activity. The Cell Counting Kit-8 assay, apoptosis detection, cell cycle analysis, western blot analysis, and tumor xenograft models were used to determine the effect of DCZ0801 treatment both in vivo and in vitro. We revealed that DCZ0801 treatment suppressed MM cell survival by inducing apoptosis and blocking the cell cycle at S phase. Deranged glycolysis and downregulated Akt/mTOR pathway may also be responsible for cell proliferation inhibition. Moreover, DCZ0801 treatment could remarkably reduce the tumor size in the xenograft mouse model. Therefore these findings indicate that DCZ0801 can be used as a novel therapeutic drug for patients suffering from multiple myeloma.

Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive lymphoid malignancies, which remains incurable, thus warranting the development of new therapies. Our previous study determined that rafoxanide is very effective in treating multiple myeloma (MM). In the present study, we tried to evaluate the effects of rafoxanide on DLBCL, as well as the potential underlying molecular mechanisms. MAIN METHODS: We used CCK-8 assay and flow cytometry to assess cell viability and apoptosis. The proteins and pathways associated with apoptosis and proliferation were evaluated through western blot, and xenograft mice were used as the experimental animal model. We also used the TUNEL assay and immunofluorescence for further analyses. KEY FINDINGS: Treatment with different doses of rafoxanide significantly inhibited cell viability and apoptosis. Additionally, the compound induced cell cycle arrest, reduced mitochondrial membrane potential (Δψm), and stimulated reactive oxygen species (ROS) generation without the influence of normal peripheral blood monocytes (PBMCs). As expected, rafoxanide played a role in regulating these proteins and the PTEN/PI3K/AKT and JNK/c-Jun pathways. Furthermore, immunofluorescence and western blot results showed that rafoxanide upregulated H2AX phosphorylation and then inhibited DNA repair in DLBCL. In the xenograft mouse model, tumor volumes were reduced after intraperitoneal injection with rafoxanide. We also observed that TUNEL positive cells were remarkably increased in rafoxanide-treated tumor tissues. SIGNIFICANCE: These results collectively provide a novel choice to regular treatment for DLBCL patients with poor prognosis.