Resistance Ability Research Articles

Hierarchical 0D CuO Wrapped by Petal-like 2D ZnO: A Strategic Approach of Superhydrophobic Melamine Sponge toward Wastewater Treatment.

In addressing the pressing environmental challenges posed by frequent oil spills, this work presents a novel approach of synthesizing a superhydrophobic three-dimensional (3D) porous melamine sponge (MS). CuO and ZnO nanoparticles were grown on the MS via a hydrothermal method to create MS/CuO/ZnO with multiscale hierarchical nanostructures. The resulting material exhibited a stable water contact angle of 155° through various tests. MS/CuO/ZnO demonstrated exceptional oil absorption capacities (40-145 g/g and 0.83-0.99 mL.cm-3), surpassing 98% efficiency in oil separation, and retained reusability for 10 cycles. Impressively, the sponge achieved successful separation of oil/water emulsions with a permeation flux of 14870 L m-2 h-1. The composite sponge, distinguished by its high photodegradation ability, can degrade both water- and oil-targeted pollutants under visible light irradiation from light-emitting diode (LED). With its remarkable attributes including superior oil absorption, excellent oil/water separation, mechanical resistance, and excellent photocatalytic ability, it exhibits considerable potential for applications in both wastewater treatment and large-scale marine oil spill response. The easily prepared MS/CuO/ZnO emerges as a versatile solution capable of addressing pressing challenges and marking a significant leap toward sustainable and impactful environmental remediation.

Effects of heat treatment on the nano-indentation, corrosion and cavitation erosion behavior of 17-4PH stainless steel by laser surface melting

The effects of heat treatment on the microstructure, residual stresses, nano-indentation behavior, the resistance to the corrosion and cavitation erosion (CE) of 17-4PH stainless steel (17-4PH SS) by laser surface melting (LSM) were thoroughly investigated. Experimental results showed that the samples were mainly composed of martensite phase, and the NbC precipitations formed after heat treatment. The distribution of NbC precipitations was more uniform in the sample (S3) after solution treatment 3 h at 1040 °C + aging treatment 3 h at 480 °C. The grain size was increased for the samples after heat treatment. This heat treatment processing significantly reduced the residual stresses generated from the LSM process, and the nano-indentation behavior of the LSM samples after heat treatment was improved compared to that of the LSM sample without heat treatment. The S3 sample displayed the highest corrosion resistance as indicated by the low corrosion current density (icorr), high pitting potential (Epit) and high polarization resistance (Rp). The CE resistance of samples after heat treatment in 3.5 wt% NaCl solution was higher than that of the sample without heat treatment. Among them, the S3 sample exhibited the highest CE resistance, and its CE mass loss was only 59.5 % of the sample without heat treatment. The excellent CE resistance resulted from the appropriate combination of mechanical properties, corrosion resistance and self-recovery ability of the passivation film.

Failure behavior of SiC/SiC with BSAS-based EBC in gas combustion environment

To promote the application of SiC/SiC in hot-end components in aero-engines, the thermal shock behavior of SiC/SiC and SiC/SiC-EBC were investigated in gas combustion environment between 450 °C and 1200 °C. The tensile strength change, microstructure evolution and thermal cycling performance of samples after 200, 400, 1000 and 2000 cycles were studied respectively to reveal the damage and failure mechanism. Cracking damage induced by thermal stress was the main reason for performance degradation of SiC/SiC after initial thermal cycles, then oxidation/corrosion damage dominated with increasing cycles. The oxidation/corrosion damage to SiC/SiC was effectively inhibited by EBC with almost no reduction in strength. However, the poor crack resistance of SiC/SiC was the main factor affecting its thermal shock performance. Improving the crack resistance or self-healing ability of SiC/SiC and combining it with EBC is considered to be an effective strategy to increase its service lifetime.

Functional domains of Acinetobacter bacteriophage tail fibers.

A rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to its numerous intrinsic antibiotic resistance mechanisms and ability to quickly acquire new resistance determinants. Specialized phage enzymes, called depolymerases, degrade the bacterial capsule polysaccharide layer and show therapeutic potential by sensitizing the bacterium to phages, select antibiotics, and serum killing. The functional domains responsible for the capsule degradation activity are often found in the tail fibers of select A. baumannii phages. To further explore the functional domains associated with depolymerase activity, tail-associated proteins of 71 sequenced and fully characterized phages were identified from published literature and analyzed for functional domains using InterProScan. Multisequence alignments and phylogenetic analyses were conducted on the domain groups and assessed in the context of noted halo formation or depolymerase characterization. Proteins derived from phages noted to have halo formation or a functional depolymerase, but no functional domain hits, were modeled with AlphaFold2 Multimer, and compared to other protein models using the DALI server. The domains associated with depolymerase function were pectin lyase-like (SSF51126), tailspike binding (cd20481), (Trans)glycosidases (SSF51445), and potentially SGNH hydrolases. These findings expand our knowledge on phage depolymerases, enabling researchers to better exploit these enzymes for therapeutic use in combating the antimicrobial resistance crisis.

Effects of Progressive Drought Stress on the Growth, Ornamental Values, and Physiological Properties of Begonia semperflorens

Water is one of the most important elements affecting the growth of ornamental plants. To investigate the effects of drought stress on the growth, ornamental values, and physiological properties of Begonia semperflorens, watering treatments with 250 mL (control check, CK), 200 mL (extremely light drought, ELD), 150 mL (light drought, LD), 100 mL (moderate drought, MD), 50 mL (severe drought, SD), and 25 mL (extremely severe drought, ESD) on the B. semperflorens variety “Chao Ao” were performed in this study. As a result, compared to the control (CK), the number of flowers, leaves, and branches, leaf size, plant height, crown diameter, as well as water content, transpiration rate, net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and chlorophyll content in leaves decreased, followed by an increased amount of drought stress. The contents of the osmotic adjustment substances, such as soluble sugar, soluble protein, proline, and betaine, were increased under drought stress. Indicators related to antioxidant activities, such as SOD activity, increased and then decreased. The POD activity, CAT activity, MDA content, and plasma membrane permeability of B. semperflorens were higher under increased drought stress than in the control condition. The APX activity decreased and then increased under drought stress. In conclusion, B. semperflorens responds to drought stress by increasing osmotic adjustment substances and antioxidant activities and reducing the water loss, growth potential, and photosynthetic rate. The correlation analysis showed that, except for APX, the drought resistance coefficients of 23 other indexes were correlated in different degrees. Therefore, this study suggests that B. semperflorens has a strong drought resistance ability, retaining high ornamental values in conditions of moderate drought stress, and can still survive under extremely high drought stress.

A novel anti-corrosion and antibacterial integrated MAO/PCNZ composite coating on AZ31B Mg alloy

Magnesium and its alloys possess elastic modulus close to natural bone and degradable effects, making them widely applied in bone implantation. However, their rapid corrosion in a simulated body fluid restricts further application. This work firstly employs micro arc oxidation (MAO) technique to in situ grow a corrosion-resistant ceramic layer on the surface of AZ31B Mg alloy. Subsequently, nano ZnO particles are modified using a silane coupling agent and then incorporated into a poly(ε-caprolactone) coating with chitosan through a simple blending and micellar method to obtain the PCNZ composite coating. The chemical composition and micro structure are characterized by FTIR, XRD, SEM and AFM. Electrochemical tests and antibacterial experiments indicate that PCNZ composite coating exhibits excellent long-term corrosion resistance and certain antibacterial ability, demonstrating potential application in the field of bone implantation.

Heritability and predictive ability for the heterobothriosis resistance and growth performance in the tiger pufferfish Takifugu rubripes fed standard or low fishmeal diets

Heterobothriosis resistance and high growth performance are major concerns in the tiger pufferfish (Takifugu rubripes) farming. Our previous small-scale study suggested the feasibility of genomic selection (GS) for these traits but also identified an undesired genetic correlation between them, which could hamper simultaneous genetic improvement. Here, we sought to validate these initial findings through larger samples and crosses and also explore the potential of GS for the individuals fed a normal fishmeal diet and a low fishmeal (LFM) diet. We produced three populations: one was fed a normal diet (PopFM: 1100 individuals) and two were fed an LFM diet (PopLFM1: 993 individuals; PopLFM2: 1017 individuals); all three populations were artificially infected with Heterobothrium okamotoi, a monogenean parasite causing heterobothriosis. We recorded standard lengths of the fish after artificial infection (SLEAI) and the number of parasites on the gill cavity wall (HC) and genotyped genome-wide single nucleotide polymorphisms (SNPs) using genotyping by random amplicon sequencing, direct (GRAS-Di) technology for each sample: PopFM, 12 K SNPs; PopLFM1, 19 K SNPs; PopLFM2, 21 K SNPs. Heritability and prediction ability for each trait were estimated for each population using genomic best linear unbiased prediction (GBLUP), Bayes C, and Bayesian ridge regression methods. SNP effects on each trait were estimated by Bayes C, Bayesian ridge regression, and genome-wide association analyses (GWAS) using the same data sets. We observed moderate to high levels of heritability for HC (0.16–0.57) and SLEAI (0.50–0.77), with predictive ability of 0.25–0.55 for HC and of 0.51–0.73 for SLEAI. These values were slightly larger in LFM diet groups. As reported previously, a weak undesired genetic correlation was observed between the traits, and the correlation was more pronounced in the LFM groups. In conclusion, our results indicate that genetic gain in growth and parasite resistance traits can be expected for the tiger pufferfish through GS, especially for individuals reared on an LFM diet. However, close attention should be paid to the extent of the undesirable genetic correlation between the two traits that may be amplified in the populations fed an LFM diet.

Potential for Biofilm Formation and Antibiotic Resistance of Staphylococci Isolated from Bulk Tank Milk Samples

The prevalence of staphylococci in the environment of humans, including food, may lead to the production of toxins and food poisoning in consumers. Additionally, staphylococci constitute a reservoir of genes determining antibiotic resistance. The study aimed to compare the antibiotic resistance and biofilm-forming ability of staphylococci isolated from bulk tank milk and assess the occurrence of animal-associated methicillin-resistant Staphylococcus aureus. The study consisted of isolation of strains from cow milk, confirming their belonging to Staphylococcus sp. and S. aureus, investigation of the presence of a gene determining the production of coagulase, and genes determining resistance to β-lactams, tetracyclines, vancomycin, natural penicillins, and aminopenicillins, as well as virulence genes determining biofilm production. There were 56 bacterial strains isolated, which belong to Staphylococcus spp. All isolates showed resistance to amoxicillin, erythromycin, and tetracycline. The lowest resistance was demonstrated for vancomycin (48.2%). The mecA gene was not detected in any of the isolates and there was no positive reaction to the PB2 protein, which indicates that none of the isolated strains was methicillin resistant. Only 26.8% of isolated strains did not show the ability to produce biofilm. Special attention should be paid to the health of dairy cows and the supervision of the use of antibiotics in the dairy herd environment because, even in milk from healthy cows, there is a real risk of the occurrence of multi-drug resistant bacteria.

Diallel Analysis of Wheat Resistance to Fusarium Head Blight and Mycotoxin Accumulation under Conditions of Artificial Inoculation and Natural Infection.

Breeding resistant wheat cultivars to Fusarium head blight (FHB), caused by Fusarium spp., is the best method for controlling the disease. The aim of this study was to estimate general combining ability (GCA) and specific combining ability (SCA) for FHB resistance in a set of eight genetically diverse winter wheat cultivars to identify potential donors of FHB resistance for crossing. FHB resistance of parents and F1 crosses produced by the half diallel scheme was evaluated under the conditions of artificial inoculation with F. graminearum and natural infection. Four FHB related traits were assessed: visual rating index (VRI), Fusarium damaged kernels (FDK), and deoxynivalenol and zearalenone content in the harvested grain samples. Significant GCA effects for FHB resistance were observed for the parental cultivars with high FHB resistance for all studied FHB resistance related traits. The significant SCA and mid-parent heterosis effects for FHB resistance were rare under both artificial inoculation and natural infection conditions and involved crosses between parents with low FHB resistance. A significant negative correlation between grain yield under natural conditions and VRI (r = -0.43) and FDK (r = -0.47) under conditions of artificial inoculation was observed in the set of the studied F1 crosses. Some crosses showed high yield and high FHB resistance, indicating that breeding of FHB resistant genotypes could be performed without yield penalty. These crosses involved resistant cultivars with significant GCA effects for FHB resistance indicating that that they could be used as good donors of FHB resistance.

The impact of digital finance on regional economic resilience

This paper introduces an innovative Urban Economic Resilience Index and uses data from 276 cities in the period from 2011 to 2021 to investigate the impact of digital finance on economic resilience. The empirical results reveal that digital finance significantly improves economic resilience and has a pronounced effect on various dimensions of resilience such as resistance and resilience ability, adaption and adjustment ability, and innovation and transformation ability. Furthermore, these findings demonstrate the robustness including the incorporation of a diverse sample of municipalities, alternative measures for digital finance and economic resilience, the inclusion of supplementary control variables, and the application of the instrumental variable methodology. Furthermore, digital finance improves economic resilience by injecting vitality into innovation and entrepreneurship, accelerating industrial structure upgrading and enhancing financial efficiency. Analyses also show that compared to eastern regions and regions with high levels of network coverage as well as economic development, digital finance is more likely to improve economic resilience. Overall, this study provides new insights into digital finance and economic resilience.

Effects of Klebsiella michiganensis LDS17 on Codonopsis pilosula growth, rhizosphere soil enzyme activities, and microflora, and genome-wide analysis of plant growth-promoting genes.

We comprehensively evaluated the plant growth-promoting characteristics and heavy metal (HM) resistance ability of the LDS17 strain, as well as the effects of strain LDS17 inoculation on the Codonopsis pilosula seedling growth and the soil qualities in the Codonopsis pilosula rhizosphere. We conducted whole-genome analysis and identified lots of genes and gene clusters contributing to plant-beneficial functions and HM resistance, which is critical for further elucidating the plant growth-promoting mechanism of strain LDS17 and expanding its application in the development of plant growth-promoting agents used in the environment under HM stress.

Molecular Detection of Psts Antibiotic-Resistant Gene in Pseudomonas aeruginosa Isolates

Abstract Background: Otitis media is a very common infection among people of different age groups. Objective: The goal of the current work was to determine the existence of PstS gene among Pseudomonas aeruginosa isolates recovered from otitis media cases in Iraqi patients. Materials and Methods: A total of 100 ear swabs were collected from patients suffering from otitis media attending the ENT outpatient clinic at Baghdad Teaching Hospital from July 2022 to the end of December 2022. The age range was 18-75 years. Detection of morphology and biochemical testing by Vitek 2 system. The antibiotic sensitivity test of the bacteria spp. was the detection of 18 antibiotics for different types using Vitek2 system. Identify the genes for antibiotic resistance mechanisms. DNA was extracted from samples, and resistance genes PstS were amplified using polymerase chain reaction (PCR). Results: This study showed 80 out of 100 swabs revealed Pseudomonas aeruginosa isolates, and 71 (89%) isolates out of these 80 exhibited PstS genes. Age groups of the patients were 38-47, 48-57, and 58-67 years with percentages of 22.5%, 25%, and 25%, respectively. The highest resistance percentages of strains to tested antibiotics were for Ceftoriaxone, Cefpodoxime (100%), and the lowest resistant percentage was 22.5% for colistin, which determined the relationship between the presence of Psts and resistance to 18 antibiotics for different types. Colistin was the most effective antibiotic and can be considered as the drug of choice against Pseudomonas aeruginosa. Conclusions: Pseudomonas aeruginosa isolates recovered from patients suffering otitis media show the prevalence rate appears to be higher among the elderly and high virulence and antibiotic resistance due to the presence of PstS antibiotic resistance gene and ability to form biofilms, thus aggressive antimicrobial therapy is highly recommended in such conditions.

Molecular Detection, Antibiotic Resistance, and Biofilm Formation of Clinical Pseudomonas aeruginosa Isolates from Patients in Al-Hillah, Babylon Province, Iraq

Abstract Background: Pseudomonas aeruginosa is known as one of the main causes of nosocomial infections and is repeatedly related to opportunistic infections among hospitalized patients worldwide. Antibiotic resistance (AR) and biofilm-forming ability (BFA) are two major virulence factors of P. aeruginosa isolates that are involved in the continuation of infections. Objectives: This study aimed to isolate and identify P. aeruginosa isolates from patients and to elucidate the correlation between AR and BFA among isolates. Materials and Methods: A total of 130 clinical P. aeruginosa isolates were obtained from Al-Hillah Al-Sadiq Hospital in Babylon province, Iraq during the period from March to July 2022. AR profile and BFA of P. aeruginosa isolates were proceeded by Kirby-Bauer and Congo red agar (CRA) methods, respectively. Polymerase chain reaction (PCR) screening, targeting the ecfX gene, was conducted to identify species-specific ecfX genes in P. aeruginosa. Results: Multidrug-resistant (MDR) P. aeruginosa accounted for 96.1% (125/130) and 85.4% (111/130) of isolates showed BFA. Statistical analyses showed a nonsignificant correlation between AR and BFA in P. aeruginosa isolates. The ecfX PCR product analyses affirmed their allocation to P. aeruginosa isolates. Conclusion: The high incidence of MDR and BFA among P. aeruginosa isolates might require a plan for regular evaluation and controlling policy programs.

Improvement of Mg alloy corrosion resistance and apatite formation ability via PEO/Alginate/Akermanite hybrid coatings for biomedical purposes

The rapid degradation of Mg alloys in biodegradable orthopedic applications is a significant concern to be investigated. In this study, a bilayer composite coating based on alginate/akermanite and plasma electrolytic oxidation (PEO/ALG-AK) on the AZ31 Mg alloy was intended to enhance its corrosion resistance. For this purpose, akermanite nanopowder was synthesized using the sol-gel method and characterized by TEM and XRD. The influence of the PEO/ALG-AK coating layer on the physicochemical properties, electrochemical, and immersion behaviors in simulated body fluid (SBF) was compared to that of uncoated and PEO-coated samples. The AFM images revealed that the bilayer coating exhibited the highest average roughness (Ra = 781 ± 49.3 nm) among the other samples. The EIS test was conducted after 2, 72, and 168 h of immersion in SBF. The bilayer coatings on Mg alloy consistently demonstrated the highest corrosion resistance due to the ALG/Ak layer covering the PEO coating pores. The results of the polarization test also confirmed the achieved results. Furthermore, the implementation of the coatings, particularly the PEO/ALG-AK coating, illustrated a significant reduction in the release of Mg2+ ions and hydrogen bubbles, resulting in corrosion resistance improvement. Finally, the ability of samples to induce apatite formation was also assessed. The results displayed that the deposits on the bare Mg alloy, PEO, and PEO/ALG-AK coatings exhibited Ca/P ratios of 0.83, 1.11, and 1.57, respectively, which closely resembled the natural bone in the PEO/ALG-AK sample. Hence, this developed bilayer coating can be a suitable candidate for enhanced corrosion resistance and bioactivity (apatite formation ability) in the field of Mg biodegradable implants.

Screening of tropical maize inbred lines for disease resistance in Bangladesh

The cultivation of maize in Bangladesh has been boosted over the last decade. Concurrently, diseases are also becoming a major threat to its higher production because of lacking disease-resistant cultivars. The study screened 29 maize inbred lines against southern corn leaf blight, northern corn leaf blight, downy mildew, rust, stalk rot, anthracnose, and maize leaf streak in field conditions. Among the inbred lines, Ag-0296, Ag-0305, Ag-0309, Ag-0312, Ag-0314, Ag-0318 and Ag-0321 showed resistance to various diseases. Twenty-one inbred lines belonged to cluster I demonstrated highest plant height (154.75 cm), ear height (61.19 cm) and yield (4.41 t/h), intermediate days to pollen shedding (108.43), days to silking (109.90) and days to maturity (157.14). Finally, cluster analysis revealed Ag-0296, Ag-0298, Ag-0300, Ag-0301, Ag-0303, Ag-0304, Ag-0305, Ag-0306, Ag-0307, Ag-0309, Ag-0310, Ag-0311, Ag-0313, Ag-0315, Ag-0318, Ag-0319, Ag-0321 and Ag-0324 belongs to Cluster I as they showed both disease resistance ability with good agronomic attributes.

Urban transportation system toughness assessment under New Crown epidemics.

Since the concept of toughness was introduced to transportation systems, transportation system toughness has received extensive attention from researchers in the field of transportation worldwide. In this paper, a methodology for quantifying and assessing the toughness of urban transportation systems is proposed in the context of the New Crown epidemic. Firstly, the definition of urban transportation system toughness in this context is clarified, and the entropy evaluation method is applied to construct the performance curve of urban transportation systems over time. Then, it is proposed to quantify the system's resistance, recovery, and adaptive ability in terms of the change in the cumulative amount of system performance. Finally, the three characteristic abilities of system toughness are organically combined to obtain a comprehensive assessment of system toughness. Example calculations and analyses are carried out in four Chinese cities with different levels of development, and the results show that the performance of urban transportation systems is positively correlated with their levels of development, and all of them fluctuate greatly under the influence of the epidemic, but Wuhan has the strongest resistance and recovery ability of the transportation system, and shows the highest toughness, followed by Lanzhou, Changchun, and Shanghai. The system toughness quantification and assessment methods proposed in this paper provide a reference for research on improving the ability of urban transportation systems to deal with multiple uncertainty disturbances.

Listeria monocytogenes from Marine Fish and the Seafood Market Environment in Northern Greece: Prevalence, Molecular Characterization, and Antibiotic Resistance

The occurrence of Listeria monocytogenes in marine fish and fish market areas was investigated. Two hundred and eighty-eight samples (123 environmental samples—siphons, knives, cutting boards, floor, sinks, water, and ice—and 165 marine fish samples) were examined. Twenty-four isolates were characterized as Listeria monocytogenes (five from environmental samples (4.0%) and 19 from fish samples (11.5%)). The strains were further characterized according to their antibiotic resistance, pathogenicity, and biofilm formation ability. They were molecularly serotyped as IIc (n = 22) and IVb (n = 2) and possessed all the virulence genes tested (inlA, inlB, inlC, inlJ, actA, hlyA, iap, plcA, and prfA), except for two strains lacking the hlyA and iap genes, respectively. All strains showed strong (41.7%) or moderate biofilm-producing ability (58.3%) and almost all showed resistance to at least one antibiotic, with the highest rates being observed against clindamycin and vancomycin. The proteomic analysis by MALDI-TOF revealed two distinct clusters that involved strains from fish only and those from both fish and the environment. The presence of Listeria monocytogenes in the fish-market environment and marine fish, along with the pathogenicity and persistence characteristics of the seafood-related strains, emphasize the need for vigilance concerning the spread of this notorious foodborne pathogen.

Deciphering core microbiota in rhizosphere soil and roots of healthy and Rhizoctonia solani-infected potato plants from various locations.

Black scurf caused by Rhizoctonia solani severely affects potato production. Through amplification of V3-V4 and ITS1-5f variable regions of 16S and internal transcribed spacer (ITS) rRNA, the study was based on the location (Kunming, Qujing, and Zhaotong), plant components (rhizosphere soil and roots), and sample types (healthy and diseased) to assess the diversity of bacterial and fungal communities. We found plant components significantly influence microbial diversity, with rhizosphere soil being more diverse than roots, and the microbial community in the root is mainly derived from the rhizosphere soil. Moreover, the rhizosphere soil and roots of healthy potato plants exhibit greater microbial diversity compared to those of potato plants infected by Rhizoctonia solani. Bacterial phyla Actinobacteriota and Acidobacteriota were enriched in rhizosphere soil compared to that of roots, whereas Proteobacteria and Cyanobacteria showed the opposite trend. Fungal phylum Ascomycota was found in low relative abundance in rhizosphere soil than in roots, whereas Basidiomycota showed the opposite trend. Bacterial genera including Streptomyces, Lysobacter, Bacillus, Pseudomonas, Ensifer, Enterobacter, and the Rhizobium group (Allorhizobium, Neorhizobium, Pararhizobium, Rhizobium), along with fungal genera such as Aspergillus, Penicillium, Purpureocillium, and Gibberella moniliformis, have the potential ability of plant growth promotion and disease resistance. However, most fungal species and some bacterial species are pathogenic to potato and could provide a conducive environment for black scurf infection. Interaction within the bacterial network increased in healthy plants, contrasting with the trend in the fungal network. Our findings indicate that R. solani significantly alters potato plant microbial diversity, underscoring the complexity and potential interactions between bacterial and fungal communities for promoting potato plant health and resistance against black scurf.

Abstract 4648: Metabolic vulnerabilities of drug-resistant melanoma with therapeutic potential

Abstract Melanoma has been at the center of revolutions in both targeted BRAF therapy and immune therapy. However, the resistance to current therapeutic drugs has been a formidable obstacle to continuing benefit to patients. Overcoming resistance and new therapeutic agents and strategies are the primary goals of current cancer research. We currently found that metabolic pathways altered significantly in BRAFi-resistant melanoma. We hypothesized that BRAFi-resistant melanoma rewires its metabolic routes to reach its needs in energy and biosynthetic precursors, both essential for escaping the BRAFi attack. We found that five amino acids transporters and metabolic enzymes (ASNS, slc7a11, slc7a5, slc3a2, slc4a7) were the significant increase in resistant melanoma. Knockdown by shRNA or knockout by crispr/cas9 of these amino acids transporters or/and metabolic enzymes enhanced the sensitivity of BRAFi resistant melanoma to BRAFi. In contrast, overexpression of these amino acid transporters or/and metabolic enzymes promoted the ability of resistance of BRAFi in parent melanoma cells. Moreover, the inhibition of these amino acid transporters and metabolic enzymes by small molecular inhibitors significantly attenuated the resistance of the BRAFi-resistant melanoma whereas less affected the parent melanoma. Notably, we confirmed that blocking these amino acid transporters and metabolic enzymes by shRNA and/or small molecular inhibitors could rescue the sensitivity of resistant melanoma cells and inhibit resistant-melanoma cell growth in the preclinical mouse model in vivo. Importantly, we found that overexpression of slc7a11, slc7a5 and slc3a2 correlated with worse survival in melanoma in SK-TCGA data. Our findings uncovered the mechanism of how metabolic reprogramming fueled melanoma cell growth and proliferation for escaping drug attacks and offered a rational strategy to guide clinical treatment. The identified novel molecular proteins represented a promising therapeutic target for BRAF mutant melanoma patients with resistance to current therapy. Citation Format: Yanlin Yu, Lei Huang, Weiping Chen, Glenn Merlino. Metabolic vulnerabilities of drug-resistant melanoma with therapeutic potential [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 4648.

Abstract 1493: Secretory function of neuroendocrine-like prostate cancer cell enhances therapy resistance and metastatic potential of adjacent adenocarcinoma

Abstract Background: Castration-resistant prostate cancer (CRPC) is advanced non curable disease associated with poor prognosis and survival n patients. Androgen receptor pathway inhibitors (ARSIs) are used to treat advanced prostate cancer, but in majority of patients it progresses by developing resistance to AR-directed therapies and is referred to as CRPC. Adenocarcinoma cells in CRPC tumor often undergoes lineage switch and become neuroendocrine-like cancer cells (NEPC) with small-cell histology, characterized by the loss of Tp53 and Rb1 genes. NEPC cells are frequently present as scattered foci along with prostatic adenocarcinomas and are secretory in nature. Objective: The primary objective is to determine how these NEPC cells influence surrounding adenocarcinoma and aids in disease progression. Methods: We performed Mass spec and cytokine array experiments from NEPC conditioned media to determine its secretory phenotype. We orthotopically implanted NEPC and adeno cells in the nude mice and performed colony formation assay on flow sorted adeno cells from the tumor. We also checked the effect of NEPC on the adeno cells and TME components. Results: Our analysis of the RNA-seq data from SU2C-PCF cohort and NE-like cells revealed that functions related to secretion were significantly enriched in NE-like PCa. NE-like cells gain the ability to secrete neuropeptides, growth factors, and cytokines to establish cell-cell communication. This secretory function is tightly regulated by the Neuropilin2 (NRP2) axis. We studied for the effect of NE-like cells on the adenocarcinoma cells in the mice tumor model and found that the presence of NE-like cells facilitated the adenocarcinoma cells to acquire aggressive characteristics. This could be due to both direct and/or through the modulation of the tumor microenvironment (TME). The direct effect could be by enhancing the therapy resistant ability of the surrounding adenocarcinoma, and the indirect effect is through the tumor microenvironment especially through neurons and macrophages that promote metastatic potential. Conclusions: Overall, our results prove that NE-like cancer cells influence the adjacent adenocarcinoma cells directly by making them resistant to treatment and indirectly make them more metastatic by utilizing macrophage-neuron axis. Citation Format: Juhi Mishra, Sanika Bodas, Sreyashi Bhattacharya, Dipanwita Das, Sheeraz UnNazir, Samikshan Dutta, Kaustubh Datta. Secretory function of neuroendocrine-like prostate cancer cell enhances therapy resistance and metastatic potential of adjacent adenocarcinoma [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 1493.