Synergy Effect Research Articles

Water-promoted selective hydrogenation of cinnamaldehyde over hydrotalcite-derived Co catalysts

Non-noble metal-catalyzed selective CO hydrogenation of α,β-unsaturated aldehydes to corresponding alcohols is chemically atom economic and practically feasible. This work reports hydrotalcite-derived Co-based catalysts for catalyzing aqueous phase selective hydrogenation reaction of cinnamaldehyde to cinnamyl alcohol. The structure characterizations demonstrate the phase transition from hydrotalcite to co-existed CoOx and metallic Co0 in the optimal Co2Al-H2-400 catalyst. It exhibits superior catalytic activity and selectivity relative to other as-obtained Co catalysts, because of the synergy effect of Co2+ sites to promote the adsorptive activation of CO group and small-size Co0 sites to facilitate the activating dissociation of hydrogen. Furthermore, the catalytic role of water has also been explored. Adopting water as pure solvent and partially adding water into organic solvent can both effectively enhance the activity and selectivity. Such reaction environment may induce creation of more intermolecular hydrogen bonds for promoting the hydrogen transfer and thus boosting the hydrogenation reaction.

MAIN DIRECTIONS OF CREATION AND ADJUSTMENT OF AN INCENTIVE SYSTEM FOR SCIENTIFIC AND PEDAGOGICAL WORKERS IN AN EDUCATIONAL ORGANIZATION

The article is devoted to the formation of an incentive system at a university. The principle of binary indicators of publication and creative activity is formulated as the basis for ensuring the motivation of scientific and pedagogical workers. As a result of the research, a theoretical justification was formulated for the priority of using collective methods of work over individual ones in research work, collaboration of employees of related universities and obtaining a synergy effect when carrying out research in small scientific groups. The study takes into account the peculiarities of the work activity of university teachers and the influence of a rational incentive system on the results of publication activity. Priorities for the university have been identified, which include a strategic vision for the development of research activities, the flexibility of the points system without an unambiguous fixation and the need to revise points depending on intermediate results at the end of the calendar year. A direct and inverse relationship has been identified between the organization of research work at a university and the creative, publishing activity of its employees, short-term and long-term (cumulative) effects from the effective organization of scientific activity in an educational organization.

Heating efficiency of agarose samples doped with magnetic nanoparticles subjected to ultrasonic and magnetic field

Recently, magneto-ultrasound heating of tissue in the presence of magnetic nanoparticles (NPs) has been studied due to its high potential for use in oncological hyperthermia. It has been published that a synergistic effect, generation of additional heat caused by magneto-ultrasonic coupling, was observed in a tissue-mimicking material (TMM) enriched with magnetic NPs. The specific absorption rate (SAR) was determined from the temperature rise measurements in a focus of the ultrasound beam. It is important to use precise measurement methods when considering medical applications, for which there are limitations to the power of each field, resulting from the prevention of biological phenomena dangerous to the patient. This study demonstrates that in magneto-ultrasonic heating SAR can be measured much more accurately if the ultrasonic field is almost uniform. Measurements were performed on TMM containing Fe3O4 NPs with a diameter of approximately 8 nm and superparamagnetic properties. Both, the measurement and simulation results showed that the errors resulting from the inaccuracy of placing the temperature probe are smaller than in the case of the focused ultrasound. At the same time, the temperature increase caused by the ultrasonic field is almost linear and the influence of heat convection on the SAR determination is negligible. The measurements showed that magneto-ultrasonic hyperthermia can provide the desired thermal effect at lower ultrasound powers and magnetic fields compared to ultrasonic or magnetic hyperthermia used alone. No synergy effect was recorded.

The effect of Bacillus in the composition of the probiotic Natupro® against bacterial pathogenic strains in vitro

Relevance. The use of probiotics for health benefits is becoming popular because of the quest for safer products with protective and therapeutic effects against diseases and infectious agents. The emergence and spread of antimicrobial resistance among pathogens had prompted restrictions over the nontherapeutic use of antibiotics for prophylaxis and growth promotion, especially in animal husbandry. While single-strain probiotics are beneficial to health, multi-strain probiotics might be more helpful because of synergy and additive effects among the individual isolates.Methods. In this study, the effectiveness of the multi-strain probiotic Natupro on pathogenic bacterial strains (Escherichia coli 320, Salmonella typhimurium 415, Staphylococcus aureus 12600, Streptococcus uberis 700407, Klebsiella pneumoniae 13883, Listeria monocitogenes 766/20) in vitro was studied.Results. According to the results of the work carried out, it was found that the bacterial strains in Natupro® exhibit lytic activity against pathogenic strains of Salmonella typhimurium 415 and Klebsiella pneumoniae 13883 and have a bacteriostatic effect on Escherichia coli strain 320 and Salmonella typhimurium 415.

Pt-on-CoNi alloy nanoparticles supported on N and P co-doped graphene catalyst for highly efficient hydrogen evolution by acidic water electrolysis

The multimetallic catalysts with adjustable electronic structures and synergy effect between various metals compared to monometallic catalysts are widely applied in electrocatalysis. Herein, graphene is doped with N and P to prepare rGNP support, then a trimetallic PtCoNi/rGNP catalyst is prepared via simple impregnation and galvanic replacement reaction methods. Pt is highly dispersed on the CoNi alloy nanoparticles (NPs) on rGNP for PtCoNi/rGNP. Based on various characterization techniques and electrochemical testing results such as ICP-OES, XRD, XPS, TEM, HRTEM, STEM, STEM-EDX elemental mapping and line-scanning, it confirms the nanostructure of PtCoNi/rGNP (Pt-on-CoNi alloy). The overpotential of PtCoNi/rGNP for hydrogen evolution (HER) via acidic water electrolysis at 100 mA cm−2 is 15 mV, lower than commercial Pt/C (Pt/C) (66 mV). The Tafel slope of PtCoNi/rGNP is 6.46 mV dec−1, smaller than that of Pt/C (17.15 mV dec−1). The overpotential at 10 mA cm−2 only increases with 3.2 mV (reaching 13.2 mV) after a long time stability testing of 72 h, still lower than Pt/C (20 mV), indicating that it has high catalytic activity and stability. This work not only reveals the synergistic effect mechanism of noble metal-on-non-noble metal for the HER, but also provides a new strategy to develop efficient and highly stable catalysts for the HER.

Study of a high salt tolerant amphiphilic polymer and its salt thickening mechanism

Polymer flooding is the most reliable method for the petroleum industry to further enhance oil recovery from the developed oil field and to keep the total oil production. For the reservoirs with high salinity, traditional polymer fluids, for example partially hydrolyzed polyacrylamide (HPAM), are failed to improve oil recovery rate due to the molecular agglomeration caused by compression-diffusion electric double layer. By optimizing the copolymerization of cyclic structure monomer n-vinylpyrrolidone (NVP) and long-chain hydrophobic monomer cetyl dimethyl allyl ammonium chloride (C16DMAAC), a high salt tolerant amphiphilic polymer P(AM/NVP/C16DMAAC), abbreviated as PANC, is synthesized. The optimal polymerization conditions were determined depending on the apparent viscosity measured by the rheometer. The microstructure of the polymer was evaluated using Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and scanning electron microscopy. The viscosity of 2000 mg/L PANC increased to 42.7 mPa·s at the salinity of 11.6 × 104 mg/L and temperature of 40 °C, while the viscosity of HPAM was only 7.3 mPa·s under the same condition. The viscosity of PANC was 479 % higher than that of HPAM, indicating the remarkable salt tolerant property of PANC. The viscosity of PANC increased from 12 mPa·s to 42.7 mPa·s when the salinity increased from 1 × 104 mg/L to 11.6 × 104 mg/L. By comparing the salt resistance of polymer PANC and polymer P(AM/AA/C16), abbreviated as AP-C16, indicating that NVP enhanced the rigidity of the PANC molecular chain, and hindered the shrinkage and curling of the molecular chain after salt addition. The inclusion effect of β-cyclodextrin on the hydrophobic groups of PANC indicated that PANC increased viscosity through the hydrophobic association of C16DMAAC. Furthermore, PANC showed a salt thickening ability due to the synergy effect of C16DMAAC and NVP. As such, the salt tolerant amphiphilic polymer PANC offers a novel polymer flooding material for oil displacement, especially under a high-salinity condition.

The synergy effect of energy security and carbon-haze collaborative management: From the perspective of biased technological progress

It is important to ensure energy security and achieve carbon-haze collaborative management for sustainable development. Reducing imported energy dependence is necessary to maintain energy security, while its impact on environmental quality remains unclear. From the perspective of biased technological progress, this paper estimates the level of biased technological progress towards self-sufficient energy by a heterogeneous stochastic frontier analysis (SFA) function, and then empirically examines whether self-sufficient energy biased technological progress has a dampening effect on haze pollution and carbon emissions. It is found that: (1) Self-sufficient energy biased technological progress can effectively reduce haze pollution and carbon emissions, achieving a synergistic effect between energy security and carbon-haze collaborative management. (2) “Efficiency enhancement” and “quality improvement” are the essential mechanisms for the synergistic effect. (3) Environmental regulation, abundant resource and technology endowments can enhance the haze reduction effect. And the lower dependence on foreign trade and stable global economic policy environment are more conducive to achieving carbon-haze collaborative control. (4) In the Eastern and Western regions, self-sufficient energy biased technology can be sped up to alleviate haze pollution. The findings can enrich the research exploring pollution control from the perspective of biased technological progress, and provide policy recommendations for promoting high-quality development.

Abstract 6757: The anti-tumor efficacy of Th1-specific TROP2 vaccine (AST-07X) in a triple-negative breast cancer murine model

Abstract Background: The trophoblast cell-surface antigen 2 (TROP2) is associated with enhanced tumor proliferation and poor prognosis in breast cancer. TROP2 overexpresses on various epithelial cancer cell surfaces, and is commonly found in prostate, colon, pancreas, lung, and breast cancer. Therefore, anticancer strategy targeting TROP2 may be a potential treatment option for patients with metastatic triple-negative breast cancer (TNBC). Sacituzumab govitecan, a Trop-2-directed antibody drug conjugate (ADC), has shown significant benefits associated with progression-free and overall survival compared to standard chemotherapy for treating metastatic TNBC; however, its toxic effects were more frequent than that of chemotherapy (NCT02574455). In this study, we discovered TROP2 target peptides with T-helper 1 (Th1) polarization and anticancer efficacy. We then evaluated the anti-tumor efficacy of these epitopes and possibility of co-administration with ADC in a TNBC murine model. Materials and Methods: Th1 peptides were identified using the Th-Vac® platform and the predictive binding affinity ranking that indicates potential immunogenicity points of interest for HLA class II. Human peripheral blood mononuclear cell (PBMC) Th1-specific polarization-induced activity and in vivo immunogenicity (Module 2b) were evaluated using flow cytometry and ELISpot analysis. The anti-tumor efficacy of the selected Th1 peptide was evaluated against MDA-MB-23 inoculated athymic Balb/c mice. Each peptide was administered intradermally once weekly for a total of four times at a concentration of 100 μg/head. Sacituzumab govitecan (0.81 mg/kg) was administered intravenously once weekly, for a total of two times. Results: Ten peptides with high affinity for HLA class II were selected, and three epitopes that induce differentiation of T cells secreting TROP2-specific IFN-γ were subsequently selected. These epitopes (p1, p3 and p6) showed tumor growth inhibition efficacy of 52.4%, 38.5%, and 57.2%, respectively, compared to the control (vehicle) group in the TNBC tumor-bearing mice. The cocktail vaccine (AST-07X), which combined these epitopes, was the most dominant at 65.4%. The anti-tumor efficacy of the combination group of the cocktail vaccine and ADC was 77.4% compared with the control group, showing a potent synergistic effect compared to the 46.1% anti-tumor efficacy of the ADC-mono group. Conclusion: AST-07X that induce TROP2-specific Th1 anticancer immune responses, showed sufficient anti-tumor efficacy; these effects were evident under immunodeficient conditions, such as those of TNBC tumor-bearing athymic mice. Synergy effects were also induced via combined ADC administration. We are currently conducting further research on humanized mice to address the limitations of the immunodeficient murine model. Citation Format: Jinho Kang, Hyo-Hyun Park, Jin Kyeong Choi, Seong-Yong Jang, Min-Ah Kim, Myeong-Kyu Park, Ashley Youngmin Kim, Eunkyo Joung, Hun Jung. The anti-tumor efficacy of Th1-specific TROP2 vaccine (AST-07X) in a triple-negative breast cancer murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6757.

Abstract 6015: Effect of antineoplastic drugs on cell-to-cell communication in the progression of colorectal cancer

Abstract Background: In the past few years, there has been notable progress in colorectal cancer research, resulting in novel development and delivery of drugs specifically designed for individual patient requirements. However, one of the major roadblocks in designing and treating colorectal cancer is the drug resistance found in advanced stages. Thus, there is a profound need to establish new methods to overcome this barrier. Previous work illustrated that cell-to-cell communications are dysfunctional for multitude of reasons in colorectal cancer cells. Restoration of cell-to-cell communication is a mean to deliver antineoplastic drugs via bystanding effect. Prior research has demonstrated that restoring gap junctions of cell-to-cell communication in breast cancer cells enhances the efficacy of cisplatin, a drug previously deemed resistant. Hence, this study seeks to assess the potency and efficacy of antineoplastic agents known to show resistance in colorectal cancer, with the intention to investigate how gap junctions can increase the efficacy of antineoplastic agents via restoration of cell-to-cell communication. Method: We assessed cell viability utilizing the RealTime Glo MT Cell Viability assay (Promega, Inc.). Four specific colorectal cancer cell lines, Caco2, HT-29, SW620, and SW480, were used. Four antineoplastic agents, doxorubicin, cediranib, nilotinib, and erlotinib, were selected for the study and subsequently in the combination study of gap junction enhancer. The lethal dose at 50% (LD50) was calculated for each antineoplastic agent in each cell line. Results: The results show significant variation of LD50. HT-29 cells dosed with doxorubicin showed LD50 of 8.9 µM, 1.6 µM, and 0.5 µM at 24 hours, 36 hours, and 48 hours of exposure, respectively. HT-29 cells dosed with erlotinib showed LD50 of 15.8 µM and 8.9 µM at 48 hours and 60 hours of exposure, respectively. SW620 dosed with doxorubicin showed LD50 is 0.5 µM at 36 hours of exposure. SW620 dosed with erlotinib showed LD50 of 15.8 µM and 0.5 µM at 48 hours and 60 hours of exposure, respectively. Caco2 cells dosed with cediranib showed LD50 of 2.8 µM and 1.6 µM at 36 hours and 48 hours of exposure, respectively. Conclusion: The findings from this study revealed varying LD50 values for these cell lines when treated with the four distinct drugs. This enabled us to determine a foundational effect of these drugs on these cell lines, which had not been previously identified. Discovering this foundational effect will allow us to investigate the synergy effect when combined with gap junction enhancer by setting a baseline effect using these results. Citation Format: Tomas Lugo, Annelise Nguyen. Effect of antineoplastic drugs on cell-to-cell communication in the progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6015.

Abstract 592: A novel pMEK inhibitor ABM-4095 for the treatment of pancreatic cancer

Abstract The MEK-ERK pathway is often activated in tumors by mutations of upstream BRAF- or RAS-proteins. The RAS is frequently mutated in several cancers, especially in pancreatic cancer with an about 95% rate. Pancreatic cancer has the highest mortality rate with a 5-year survival rate of 8% and a median survival of 6 months. Targeted therapies have been extensively evaluated in pancreatic cancer, however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The only currently approved targeted therapy is erlotinib in combination with the chemotherapy drug gemcitabine. To date, four MEK inhibitors that block RAF-activation have been approved by the FDA, but their ability to inhibit ERK signal activated by RAS-mutations is limited due to the induction of MEK phosphorylation by relief of ERK-dependent feedback inhibition of RAF. Here, we report a novel small molecule, ATP-uncompetitive, pMEK inhibitor ABM-4095 that potently prevents phosphorylation of MEK by RAF with moderate inhibition of MEK kinase activity. Most of MEK inhibitors approved by FDA or in clinical trials increase pMEK levels instead. ABM-4095 has a good cell permeability. Its anti-cancer efficacy has been demonstrated both in the in vitro cancer cell line proliferation assay and in vivo xenograft models. ABM-4095 showed a synergy effect with erlotinib in pancreatic cancer cells. In a Miapaca-2 xenograft model, ABM-4095 showed good dose-dependent tumor inhibition as a single agent or combining with the KRAS G12C inhibitor AMG-510, and tumor regressions were observed. In summary, ABM-4095 is a potent pMEK inhibitor with a high activity against the RAS-mutant pancreatic cancer in vitro and in vivo. Detailed preclinical results will be presented. Citation Format: Min Xu, Yong Hu, Lanjiao Zhao, Xiuquan Chen, Youqin Chen, Chen Yang, Jizhi Li, Chen Chen, Xiaobing Lv. A novel pMEK inhibitor ABM-4095 for the treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 592.

Abstract 3313: Discovery of a potent, selective, and orally available small molecule for disruption of the SOS1-RAS interaction

Abstract KRAS mutations represent one of the most common genetic alterations in many cancers including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC). While Sotorasib and Adagrasib, KRAS G12C inhibitors, have received approval, they exhibit limited responsiveness in clinical trials and are not applicable to various other KRAS mutation types. SOS1 (Son of Sevenless 1) functions as a guanine nucleotide exchange factor (GEF) on RAS, facilitating the transition of inactive GDP-bound RAS to its active GTP-bound state. In addition, SOS1 plays a pivotal role in negative feedback by actively contributing to the reactivation of ERK during treatment with inhibitors targeting the RTK/RAS/MAPK pathway. Inhibiting SOS1, which impedes the reactivation of ERK, has the potential to enhance the effectiveness of inhibitors targeting the RTK/RAS/MAPK signaling cascade and prevent the emergence of resistance mechanisms via H-RAS and N-RAS bypass pathways. Therefore, combining the inhibition of SOS1 with inhibitors targeting the RTK/RAS/MAPK pathway may enhance outcomes and mitigate relapse associated with observed resistances. Here, we present the discovery of a potent, selective, and orally bioavailable small molecule SOS1 inhibitor that effectively disrupts the interaction between SOS1 and RAS. It has demonstrated remarkable synergy effects with RTK/RAS/MAPK pathway inhibitors, significantly impeding the growth of tumors carrying KRAS or EGFR mutations in vivo. Overall, our development candidate has demonstrated significant therapeutic potential in combination with inhibitors targeting the RTK/RAS/MAPK pathway for cancers bearing activating mutations in this pathway. Citation Format: Dong Hyuk Ki, Hana Yu, Donggeon Kim, Yeejin Jeon, Seongin Jo, Joonwoo Nam, Eun-Jung Kim, Sungeun Kim, Hunmi Choi, Jieun Kim, Jihyun Yu, Sungpil Choi, Wooseok Han. Discovery of a potent, selective, and orally available small molecule for disruption of the SOS1-RAS interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3313.

Abstract 4454: Manipulation of the amino acid metabolism promotes therapeutic efficacy through targeting lysosome in glioblastoma

Abstract Nutrients are converted by the body to smaller molecules, which are utilized for both anabolic and catabolic reactions. Cooperative regulation of these metabolic processes is critical for maintaining tissue homeostasis. Based on these findings, our group has been focusing on how the regulation of nutrient-driven metabolism controls the malignancy of cancer cells. Metabolic regulation has been considered crucial for cellular adaptation to environmental changes and promoting survival and proliferation. Recent studies showed the successful applications of targeting specific nutrients for cancer therapy. In this study, we developed a new lysosome-targeting therapeutic strategy, centered around the manipulation of the amino acid metabolism for GBM. Using patient-derived GBM cells, we found that lysosomal proteolytic activity is a unique metabolic biomarker representing malignant phenotypes of GBM and that it is closely correlated with the efficacy of current conventional therapy for GBM patients. Furthermore, the MiT/TFE family members, TFEB and TFE3, which are the master regulators of lysosomal biogenesis, controlled malignant progression and therapeutic efficacy in vitro and vivo. Combinatory analyses with clinical patient samples and xenograft models demonstrated that the MiT/TFE family plays a crucial role as a regulator of malignant properties in GBM. Analysis of The Cancer Genome Atlas (TCGA) glioma dataset, which includes data from patients with Grade 2, 3, and 4 (GBM) gliomas, showed that higher expression of the MiT/TFE family was significantly associated with shorter survival. Interestingly, we discovered that an essential amino acid controls lysosomal biogenesis and membrane integrity by regulation of nitric oxide signaling pathway. Finally, we screened the potential anti-cancer drugs, including temozolomide, exhibiting the synergy effect in amino acid-restriction conditions by conducting a drug screening using a clinically available anti-cancer drug library. Our study demonstrated that lysosomal function, supported by amino acid metabolism, plays a critical role in the regulation of GBM malignant status and proposed precision nutrition as a promising therapeutic approach. Citation Format: Yongwei Jing, Masahiko Kobayashi, Atsushi Hirao. Manipulation of the amino acid metabolism promotes therapeutic efficacy through targeting lysosome in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4454.

Abstract 591: Discovery of ZM-2322, a highly selective, potent inhibitor of membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (PKMYT1)

Abstract The genome DNA is consistently threatened by a variety of intrinsic and exogenous DNA damage factors. Cell cycle checkpoint is one important mechanism in response to DNA damage and maintaining genome stability. In tumor cells, gene alterations, such as CCNE1 amplification (encoding for Cyclin E1), result in G1/S checkpoint loss and replication stress, leading to high dependency on the G2/M checkpoint. PKMYT1 inhibits crucial checkpoint protein CDK1 activity by phosphorylating CDK1 at the residues of Thr-14 and Tyr-15 in the G2/M phase. In CCNE1 amplification cells, the inhibition of PKMYT1 leads to the reduction of pCDK1 and loss of G2/M checkpoint, consequently results in premature mitosis and the accumulation of DNA damage, then finally induces cell death. Here we identify a novel small molecular ZM-2322, which displays robust intracellular binding to PKMYT1 and inhibits the specific downstream phosphorylation of CDK1 Thr-14 with IC50 values of 14 nM and 29 nM, respectively. ZM-2322 strongly inhibits the proliferation of the HCC1569 cell line with CCNE1 high-level amplification and shows a >400 × selectivity folds over a CCNE1 wildtype cell line SKOV3. ZM-2322 also shows significant inhibition of tumor growth in a dose-dependent manner in the HCC1569 xenograft model, and the efficacy correlates well with PK and target inhibition. There is evidence showing that loss-of-function mutations of FBXW7, a cyclin E E3 ligase, lead to cyclin E accumulation and are synthetic-lethal with PKMYT1 inhibition. Consistently, a potent anti-proliferation of ZM-2322 is observed in DLD-1 FBXW7 -/- cells, but not DLD-1 parental cells. These data suggest a high potency of ZM-2322 on PKMYT1 inhibition and a potential good kinase selectivity which is further confirmed by using a kinase panel biochemical assay. As expected, when compared head-to-head with another clinical PKMYT1 inhibitor RP-6306 which shows inhibitory effect on 27 of 217 human kinases with inhibition rates >90% at 1 μM, ZM-2322 is found to be a much more PKMYT1-selective inhibitor and hits only several individual kinases under the same assay condition, suggesting a potentiality in better safety profile and higher dose tolerance. Furthermore, our data illustrates that in combination with gemcitabine, ZM-2322 elicits strong synergetic anti-proliferation activities on HCC1569 cells in vitro and results in tumor regression with a minor effect on body weight in vivo. Besides, a strong synergy effect is also observed in the combo of ZM-2322 and ATR inhibitor in HCC1569 in vitro. These data indicate that ZM-2322 has the potential of application expansion and good tolerance under continuous administration. Taken together, our data suggest that ZM-2322 is a potent and highly selective PKMYT1 inhibitor. Citation Format: Feng Zhou, Lu Liu, Lei Jiang, Baoying Cheng, Zhentao Li, Dongxing Zhu, Jianbin Xue, Liting Xue, Renhong Tang. Discovery of ZM-2322, a highly selective, potent inhibitor of membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (PKMYT1) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 591.

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa.

Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations-namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam-have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam.

Navigating the climate challenges in Africa: Exploring the synergy and threshold effects of renewable energy and foreign direct investment on climate risk

Renewable energy is widely acknowledged as an essential response to climate change, which poses a severe threat to humanity and natural ecosystems. Drawing from the greenhouse theory of climate change and the pollution haven hypothesis, this study contributes to the literature by addressing three critical issues. First, we examine the effect of renewable energy on climate risk. Second, we explore the intervening role of foreign direct investment (FDI) on the renewable energy-climate risk nexus. Third, we determine the minimum threshold required for renewable energy to minimise climate risk. The analysis was based on 47 African countries and estimated using the generalised method of moments (GMM) and dynamic panel threshold regression techniques. The GMM technique is essential due to its ability to address endogeneity issues in the model. Also, the dynamic panel threshold technique is employed because it is built on the principles of GMM and provides an estimate of the threshold level and nonlinearities in the model. The empirical evidence presents a significant negative relationship, suggesting that renewable energy minimises the surge in climate risk in Africa. Second, the findings reveal that the weakening effect of renewable energy on climate risk is contingent on FDI. Third, the dynamic panel threshold results demonstrate that the minimum threshold required for renewable energy to reduce climate risk is 56%. Beyond this level, renewable energy presents a significant negative impact, implying that high renewable energy consumption lessens climate risk. Policy recommendations for boosting renewable energy consumption to alleviate climate risk have been provided.

Ag2CO3 phases in nanocomposites with palygorskite and their effects on photocatalytic and antibacterial activities

Various nanocomposites based on Ag2CO3 loaded onto natural fibrous palygorskite (Pal) were elaborated by a simple precipitation route. Their composition ranged from metastable hexagonal β-Ag2CO3 nanoparticles immobilized on the surface of Pal microfibers to a mixture with stable monoclinic m-Ag2CO3 particles trapped in the tangle of Pal fibers. The choice of elaboration parameters enables to control the relative content of each phases phase ratio “metastable β-hexagonal / (stable monoclinic + metastable β-hexagonal)” of Ag2CO3 and thus to tune the resulting multifunctional properties (mainly photocatalytic and biocidal activities) of the nanocomposites.Optical studies interestingly revealed, for all Ag2CO3-Pal nanocomposites, a noticeable absorption in the visible light range. Accordingly, all the Ag2CO3 based Pal nanocomposites were found to be photoactive under visible light for the removal of Orange G (OG) dye but biphasic (β + m)-Ag2CO3-Pal nanocomposite was more photoactive than those in which Ag2CO3 was monophasic (either β-hexagonal or monoclinic phases). This could be due to synergy effects between the two Ag2CO3 phases. Besides, all the developed Pal based nanocomposites remained active upon several reusability cycling tests. Likewise, both the nanocomposites materials and the starting Pal clay mineral were found antibacterial against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria.

Donor-Acceptor Assembly of Amphiphilic Molecules Based on 9,10-Distyrylanthracene Derivatives with Terminal Naphthalene Groups.

Amphiphilic rod-coil compounds have excellent photophysical properties and can be assembled into supramolecular nanostructures of different sizes in water or polar solvents. Herein, we synthesized the amphiphilic compounds 2N-DSA, 4N-DSA, and 6N-DSA with 9,10-distyrylanthracene (DSA) as the core and a naphthalene unit as the terminal group that connected DSA through a tetraethylene glycol chain. These compounds have excellent aggregation-induced emission (AIE) properties in aqueous solution and are assembled into worm-like fragments or different sizes of spherical assemblies, defending the volume ratio of the rod to coil segments. Notably, the donor-acceptor interaction between DSA and electron- deficient compounds 2,4,6-trinitrophenol (TNP), 2,4,5,7-tetranitrofluorenone (TNF), and tetraethylene glycol dinitrobenzoate (TGDNB) forms a charge transfer complex, which can be used as a nanoreactor to improve the yield of the Suzuki coupling reaction about 8-10 times. The experimental results reveal that the synergy effect of the donor-acceptor, intermolecular π-π stacking, and hydrophobic-hydrophilic interactions significantly influences the morphology of aggregates and the efficiency of the nanoreactor.

Heterogeneous engineering and carbon confinement strategy to synergistically boost the sodium storage performance of transition metal selenides

Transition metal selenides (TMSs) stand out as a promising anode material for sodium-ion batteries (SIBs) owing to their natural resources and exceptional sodium storage capacity. Despite these advantages, their practical application faces challenges, such as poor electronic conductivity, sluggish reaction kinetics and severe agglomeration during electrochemical reactions, hindering their effective utilization. Herein, the dual-carbon-confined CoSe2/FeSe2@NC@C nanocubes with heterogeneous structure are synthesized using ZIF-67 as the template by ion exchange, resorcin-formaldehyde (RF) coating, and subsequent in situ carbonization and selenidation. The N-doped porous carbon promotes rapid electrolyte penetration and minimizes the agglomeration of active materials during charging and discharging, while the RF-derived carbon framework reduces the cycling stress and keeps the integrity of the material structure. More importantly, the built-in electric field at the heterogeneous boundary layer drives electron redistribution, optimizing the electronic structure and enhancing the reaction kinetics of the anode material. Based on this, the nanocubes of CoSe2/FeSe2@NC@C exhibits superb sodium storage performance, delivering a high discharge capacity of 512.6 mA h g−1 at 0.5 A g−1 after 150 cycles and giving a discharge capacity of 298.2 mA h g−1 at 10 A g−1 with a CE close to 100.0 % even after 1000 cycles. This study proposes a viable method to synthesize advanced anodes for SIBs by a synergy effect of heterogeneous interfacial engineering and a carbon confinement strategy.

The fishing industry and the growing food insecurity in Africa: an empirical analysis with an instrumented quantile approach

ABSTRACT Sustainable fishing and inclusive aquatic food systems improve livelihoods sustainability of millions of individuals in developing countries, particularly in Africa. This paper presents a comprehensive assessment of the role of the African fishing industry in ensuring food security in 40 African countries between 2001 and 2018, using the smoothed instrumental-variables quantile regression strategy. The findings reveal a positive effect of the fishing industry on food security in Africa, consistent in both the landlocked and coastal, low and middle-income African countries, irrespective of whether they adopt the English common law, the Portuguese or the French civil law systems to govern their institutions. Similarly, the results reveal that fisheries production interacts with increased nitrate-oxide emission to produce positive synergy effects on prevalence of undernourishment. Addressing the concern of environmental degradation in the quest for ensuring food security, we established a net impact of fish production-environmental degradation nexus on the prevalence of undernourishment which still reveals a negative effect. Practical policy implications should be formulated with immediate action to ensure sustainable fisheries management in preserving aquatic organisms for sustainable food security.

Internal revenue sharing methodology for virtual power plant clusters considering carbon incentive and penalty mechanisms

With the rapid development of renewable energy and the urgent need for global carbon emission reduction, virtual power plants have become a high-profile energy management model that can integrate multiple energy resources. How to effectively integrate renewable energy to reduce carbon emissions, how to optimize the use of different energy resources, and how to fairly distribute economic benefits within virtual power plant clusters while encouraging the reduction of carbon emissions are issues that need to be addressed in research. The study first established a virtual power plant model and conducted in-depth optimization for its economic and environmental indicators. Subsequently, the study constructed a game model within the virtual power plant cluster, aiming to solve the problem of income distribution in this diversified energy system. The research results found that commercial users have the highest carbon emissions, followed by industrial users, while residential users have the lowest carbon emissions. In terms of optimized user electricity consumption behavior, the peak-to-valley difference rate of industrial users has been reduced by 17%, and the daily load rate has increased by 6%; the peak-to-valley difference rate of commercial users has been reduced by 12%, and the daily load rate has increased by 6%; The peak-to-trough difference rate for residential users decreased by 8%, and the daily load rate increased by 4%. In addition, the research also proposes a method of internal revenue distribution of virtual power plant clusters based on a carbon reward and punishment mechanism, which provides a new way for the synergy effects and economic benefit distribution of virtual power plants. Research is of positive significance in solving pressing issues in the field of energy management and provides strong support for the development of future sustainable energy systems.