Advancing the Understanding of Microplastic Weathering: Insights from a Novel Polarized Light Scattering Approach.

Weathering is a significant process that alters the properties of microplastics (MPs) and consequently affects their environmental behaviors. In this study, we introduced a novel approach based on polarized light scattering technique, which offers advantages in terms of rapid, high-throughput, and submicron-sized detection. This technique was successfully applied to characterize the weathered MPs after a 180-day laboratory simulation of coastal environments. By employing polarization measurements, we obtained a 46-dimensional matrix data set for the weathered MP fragments and subsequently processed them using a backpropagation neural network. The successful extraction of effective polarization pulses confirmed the presence of MP fragments within the size range of 0.2-60 µm, yielding total accuracies for size classification ranging from 78.9 to 86.9%. Furthermore, this technique achieved an overall accuracy of 93.8% in classifying MPs with different weathering degrees and polymer types, revealing polarization parameters associated with size and morphological changes play a dominant role in characterizing the weathering process of MPs. Compared with conventional approaches, the novel polarized light scattering approach holds great promise for rapid, high-throughput, and accurate characterization of MPs with small sizes. The findings of this study provided new insights into how MPs change after long-term weathering in aquatic environments.

Unveiling spatiotemporal distribution, partitioning, and transport mechanisms of tire additives and their transformation products in a highly urbanized estuarine region.

Numerous tire additives are high-production volume chemicals that are used extensively worldwide. However, their presence and partitioning behavior remain largely unknown, particularly in marine environments. This study is the first to reveal the spatiotemporal distribution, multimedia partitioning, and transport processing of 22 tire additives and their transformation products (TATPs) in a highly urbanized estuary (n = 166). Nineteen, 18, and 20 TATPs were detectable in water, suspended particulate matter (SPM), and sediments, respectively, with total levels of 59.7-2021 ng/L, 164-6935 ng/g, and 4.66-58.4 ng/g, respectively. The multimedia partitioning mechanisms of TATPs are governed by their molecular weight, hydrophobicity, and biodegradation rate. Mass inventories coupled with model simulations have revealed that substantial quantities of TATPs accumulate within estuarine environments, and these compounds can be continuously transported into the ocean, particularly during the wet season. According to the multi-criteria evaluation approach, four and three TATPs were identified as high-priority pollutants during the dry and wet seasons, respectively. Unexpectedly, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone was only listed as a medium-priority pollutant. This study underscores the importance of marine surveillance and advocates for particular attention to these ubiquitous but underexplored TATPs in future studies.

Unraveling the toxicity mechanisms of nanoplastics with various surface modifications on Skeletonema costatum: Cellular and molecular perspectives.

Nanoplastics are ubiquitous in marine environments, exhibiting high bioavailability and potential toxicity to marine organisms. However, the impacts of nanoplastics with various surface modifications on marine microalgae remain largely unexplored. This study explored the toxicity mechanisms of two nanoplastic types-polystyrene (PS) and polymethyl methacrylate (PMMA)-with distinct surface modifications on Skeletonema costatum at cellular and molecular levels. Results showed that nanoplastics significantly impaired the growth of microalgae, particularly PS-NH2, which caused the most pronounced growth inhibition, reaching 56.99 % after a 96-h exposure at 50 mg/L. Transcriptomic profiling revealed that nanoplastics disrupted the expression of genes predominantly involved in ribosome biogenesis, aminoacyl-tRNA biosynthesis, amino acid metabolism, and carbohydrate metabolism pathways. The integrated biochemical and transcriptomic evidence highlighted that PS-NH2 nanoplastics had the most adverse impact on microalgae, affecting fundamental pathways such as ribosome biogenesis, energy metabolism, photosynthesis, and oxidative stress. Our findings underscore the influence of surface-modified nanoplastics on algal growth and contribute new understanding to the toxicity mechanisms of these nanoplastics in marine microalgae, offering critical information for assessing the risks of emerging pollutants.

Million Microfiber Releases: Comparing Washable and Disposable Face Masks.

The extensive use of single-use or disposable face masks has raised environmental concerns related to microfiber contamination. In contrast, research on the potential release and ecological impact of microfibers from washable masks (WMs), suggested as an eco-friendly alternative, is currently lacking. Here, we comprehensively investigated the release of microfibers from disposable and WMs of different types in simulated aquatic environments and real-life scenarios, including shaking, disinfection, hand washing, and machine washing. Using a combination of wide-field fluorescence microscopy, He-ion microscopy, and confocal µ-Raman spectroscopy, we revealed that disposable masks (DMs) released microfibers ranging from 18 to 3042 microfiber/piece, whereas WMs released 6.1 × 104-6.7 × 106 microfibers/piece depending on the simulated conditions above. Another noteworthy finding was the observed negative correlation between microfiber release and the proportion of reinforcement (embossing) on the DM surfaces. Microfibers from tested DMs primarily comprised polypropylene (PP), while WMs predominantly released poly(ethylene terephthalate) (PET) and cellulose microfibers. Furthermore, acute toxicological analyses unveiled that PP microfibers (0.01-50 mg/L) from DMs impacted zebrafish larval swimming behavior, while PET microfibers from WMs delayed early-stage zebrafish hatching. This study offers new insights into the source of microfiber contamination and raises concerns about the environmental implications linked to the use of washable face masks.

Anion Relay Chemistry Enables Stereoselective Carbonyl-Alkyne Metathesis Reactions.

Dithiane chemistry is increasingly advantageous in the development of novel anion relay chemistry (ARC) modes that harness their umpolung properties to address new chemical challenges. Herein, we report the use of an ARC strategy to promote the regioselective carbonyl alkyne metathesis (CAM) of various carbonyl compounds with alkynyl 1,3-dithianes. Notably, this ARC transformation provides a platform for obtaining stereodefined polysubstituted 1,3-dienes.

Fate and drivers of mariculture-derived microplastics from ponds to mangrove forests.

Due to the combined influences of marine and terrestrial disturbances, the sources of microplastics (MPs) in mangrove ecosystems are complex and diverse. Previous studies have inferred the possible involvement of mariculture activities as a potential source of mangrove MPs based on the characteristics of MPs. However, the direct contributions of mariculture-derived MPs to mangrove MPs remain largely unknown. In this study, we systematically investigated the fate of MPs in the discharge of mariculture wastewater by quantifying the source contributions of mariculture-derived MPs to rivers and mangroves. The majority of detected MPs were transparent fibers, with their composition primarily comprising materials commonly used in mariculture activities such as polyvinylpyrrolidone (PVP), polyethylene terephthalate (PET), and nylon. The partial least squares path model elucidated the relationships among the composition of MPs in ponds, rivers, and mangroves, indicating that ponds exert a substantial direct effect on mangroves, particularly significant in the sediments (63.68%). Water turbidity, sediment carbon content, and sediment particle size are key ecological factors influencing the abundance of mariculture-derived MPs. This study provides compelling evidence regarding the sources of mangrove MPs and novel insights into mitigating the dissemination of MPs.

Regioselective Synthesis of Multisubstituted 2,3-Dihydrooxazoles by 1,3-Dithiane Umpolung.

Herein, we report a novel strategy for the regioselective synthesis of aromatic and heteroaromatic 2,3-dihydrooxazoles from 2-alkynyl-1,3-dithianes and nitrones. This method exploits the 1,3-dithiane umpolung, nucleophilic cycloaddition, and rearrangement processes to achieve the rapid assembly of dihydrooxazole molecules. The regioselective method is extremely mild, achieving complete conversion within one min under air at 25 °C with high efficiency.

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

Metabolic activity of gut microbial enrichment cultures from different marine species and their transformation abilities to plastic additives.

The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.

Bio-based microplastic polylactic acid exerts the similar toxic effects to traditional petroleum-based microplastic polystyrene in mussels.

Microplastics (MPs) have accumulated in the oceans, causing adverse effects on marine organisms and the environment. Biodegradable polylactic acid (PLA) is considered as an excellent substitute for traditional petroleum-based plastics, but it is difficult to degrade completely and easily become MPs in the marine environment. To test the ecological risk of bio-based PLA, we exposed thick-shelled mussels (Mytilus coruscus) to bio-based PLA and petroleum-based polystyrene (PS) (at 102, 104, and 106 particles/L) for 14 days. The significant increase in enzyme activities related to oxidative stress and immune response showed that mussels were under physiological stress after MP ingestion. While enzyme activities of nerve conduction and energy metabolism were significantly disturbed after exposure. Meanwhile, normal physiological activities in respiration, ingestion and assimilation were also suppressed in association with enzyme changes. The negative effects of PS and PLA in mussels were not differentiated, and further integration analysis of integrated biomarker response (IBR) and principal component analysis (PCA) also showed that PLA would induce adverse effects in mussels and ecological risks as PS, especially at environmental concentrations. Therefore, it is necessary to pay more attention to the environmental and ecological risk of bio-based MP PLA accumulating in the marine environment.

TXNDC12 inhibits pancreatic tumor cells ferroptosis by regulating GSH/GGT7 and promotes its growth and metastasis.

Background: Thioredoxin domain-containing protein 12 (TXNDC12) is upregulated in a variety of tumours, including pancreatic cancer (PAAD), and its high expression is closely associated with poor prognosis. However, the regulatory mechanism of TXNDC12 in PAAD has not been reported. The aim of this study is to reveal the precise mechanism of TXNDC12 in regulating PAAD progression. Methods: The expression of TXNDC12 in pan-cancer as well as PAAD was verified by TCGA and GTEx databases, Western blot and RT-qPCR. CCK8 assay, clone formation assay and cell cycle assay were used to observe the effect of TXNDC12 on the proliferation of PAAD cells, the migration and invasion capacities were verified by wound healing assay and Transwell assay. The effect of TXNDC12 on apoptosis of MIA PaCa-2 and PANC-1 cells was detected using Hochest and flow cytometry. Finally, the interaction of TXNDC12 with GGT7 was predicted by STRING database and confirmed by CO-IP assay, the effect of TXNDC12 on ferroptosis through GGT7 was evaluated by GSH assay, MDA assay, ROS assay and Western blot. Results: TXNDC12 is upregulated in PAAD tissues, and patients with high TXNDC12 levels generally have shorter survival times. Knockdown of TXNDC12 significantly inhibited the proliferation, migration and invasion and promoted apoptosis of MIA PaCa-2 and PANC-1 cells. Mechanistically, knockdown of TXNDC12 resulted in a decrease in intracellular GSH content and an increase in GSSG content, as well as elevated levels of pro-ferroptosis factors, such as MDA and ROS. STRING database predicted that TXNDC12 interacts with GGT7, and CO-IP assay was used to validate this result. Finally, the effect of knocking down TXNDC12 on pancreatic cancer cell functions was able to be reversed by overexpression of GGT7. Conclusion: TXNDC12 inhibits ferroptosis in PAAD cells through the GSH/GGT7 axis thereby promoting their development.

Microplastics in Hong Kong's marine waters: Impact of rainfall and Pearl River discharge.

This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.

First Evidence of the Bioaccumulation and Trophic Transfer of Tire Additives and Their Transformation Products in an Estuarine Food Web.

The discovery of the significant lethal impacts of the tire additive transformation product N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) on coho salmon has garnered global attention. However, the bioaccumulation and trophic transfer of tire additives and their transformation products (TATPs) within food webs remain obscure. This study first characterized the levels and compositions of 15 TATPs in the Pearl River Estuary, estimated their bioaccumulation and trophic transfer potential in 21 estuarine species, and identified priority contaminants. Our observations indicated that TATPs were prevalent in the estuarine environment. Eight, six, seven, and 10 TATPs were first quantified in the shrimp, sea cucumber, snail, and fish samples, with total mean levels of 45, 56, 64, and 67 ng/g (wet weight), respectively. N,N'-Diphenyl-p-phenylenediamine (DPPD) and N,N'-bis(2-methylphenyl)-1,4-benzenediamine (DTPD) exhibited high bioaccumulation. Significant biodilution was only identified for benzothiazole, while DPPD and DTPD displayed biomagnification trends based on Monte Carlo simulations. The mechanisms of bioaccumulation and trophodynamics of TATPs could be explained by their chemical hydrophobicity, molecular mass, and metabolic rates. Based on a multicriteria scoring technique, DPPD, DTPD, and 6PPD-Q were characterized as priority contaminants. This work emphasizes the importance of biomonitoring, particularly for specific hydrophobic tire additives.

Organophosphate flame retardants and their metabolites in the Pearl River Estuary: Occurrence, influencing factors, and ecological risk control strategies based on a mass balance model.

Estuaries serve as crucial filters for land-based pollutants to the open sea, but there is a lack of information on the migration and fate of organophosphate flame retardants (OPFRs) within estuaries. This study focused on the Pearl River Estuary (PRE) by examining the co-occurrence of OPFRs and their metabolites and quantifying their transport fluxes using a mass balance model. The seawater concentrations of OPFRs and their metabolites exhibited significant seasonal variations (p < 0.01), while the sediment concentrations of OPFRs reflected the long-term distributional equilibrium in the PRE. The concentration of Σ9OPFRs in seawater showed a relentless dilution from the entrance to the offshore region in the normal and wet seasons, which was significantly in accordance with the gradients of pH, dissolved oxygen (DO), and salinity (p < 0.05). Furthermore, horizontal migration dominated the transport of OPFRs, and the inventory assessment revealed that both the water column and sediment were important reservoirs in the PRE. According to the estimated fluxes from the mass balance model, riverine input emerged as the principal pathway for OPFR entry into the PRE (1.55 × 105, 6.28 × 104, and 9.00 × 104 kg/yr in the normal, dry and wet seasons, respectively), whereas outflow to the open sea predominantly determined the main fates of the OPFRs. The risk quotient (RQ) results showed that EHDPHP (0.835) in water posed medium ecological risk, while other OPFRs and metabolites presented relatively lower risk (RQ < 0.1). The risk control effects were evaluated through scenario simulations of mathematical fitting between controllable source factors and the RQ of risky OPFR. The risk of EHDPHP in the PRE could be effectively reduced by restricting its concentrations in entrance region (<9.31, 8.67, and 12.7 ng/L in the normal, dry and wet seasons, respectively) of the PRE. This research offers foundational insights into environmental management and pollution control strategies for emerging pollutants in estuaries.

Giant Ulcer with Necrosis on Right Vulva, Groin, and Thigh-- A Case of Necrotizing Fasciitis Associated with Erythematous Pemphigus.

Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.

First insights into the bioaccumulation, biotransformation and trophic transfer of typical tetrabromobisphenol A (TBBPA) analogues along a simulated aquatic food chain.

Tetrabromobisphenol A (TBBPA) analogues have been investigated for their prevalent occurrence in environments and potential hazardous effects to humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. Using a developed toxicokinetic model framework, we quantified the bioaccumulation, biotransformation and trophic transfer of tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A di(allyl ether) (TBBPA-DAE) during trophic transfer from brine shrimp (Artemia salina) to zebrafish (Danio rerio). The results showed that the two TBBPA analogues could be readily accumulated by brine shrimp, and the estimated bioconcentration factor (BCF) value of TBBPS (5.68 L kg-1 ww) was higher than that of TBBPA-DAE (1.04 L kg-1 ww). The assimilation efficiency (AE) of TBBPA-DAE in zebrafish fed brine shrimp was calculated to be 16.3%, resulting in a low whole-body biomagnification factor (BMF) in fish (0.684 g g-1 ww). Based on the transformation products screened using ultra-high-performance liquid chromatograph-high resolution mass spectrometry (UPLC-HRMS), oxidative debromination and hydrolysis were identified as the major transformation pathways of TBBPS, while the biotransformation of TBBPA-DAE mainly took place through ether bond breaking and phase-II metabolism. Lower accumulation of TBBPA as a metabolite than its parent chemical was observed in both brine shrimp and zebrafish, with metabolite parent concentration factors (MPCFs) < 1. The investigated BCFs for shrimp of the two TBBPA analogues were only 3.77 × 10-10 - 5.59 × 10-3 times of the theoretical Kshrimp-water based on the polyparameter linear free energy relationships (pp-LFERs) model, and the BMF of TBBPA-DAE for fish was 0.299 times of the predicted Kshrimp-fish. Overall, these results indicated the potential of the trophic transfer in bioaccumulation of specific TBBPA analogues in higher trophic-level aquatic organisms and pointed out biotransformation as an important mechanism in regulating their bioaccumulation processes. ENVIRONMENTAL IMPLICATION: The internal concentration of a pollutant in the body determines its toxicity to organisms, while bioaccumulation and trophic transfer play important roles in elucidating its risks to ecosystems. Tetrabromobisphenol A (TBBPA) analogues have been extensively investigated for their adverse effects on humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. This study investigated the bioaccumulation, biotransformation and trophic transfer of TBBPS and TBBPA-DAE in a simulated di-trophic food chain. This state-of-art study will provide a reference for further research on this kind of emerging pollutant in aquatic environments.

Stereoselective Synthesis of Highly Substituted 1,3-Dienes through Dual 1,3-Sulfur Rearrangement of Dithianes with Alkynylsilanes.

Herein, we report a C3 and C1 coupling approach between vinyl 1,3-dithiane derivatives and alkynylsilanes for the construction of highly substituted conjugated dienes. Through the regioselective dual 1,3-sulfur migration process, this method enabled the synthesis of a wide range of highly substituted (E)-1,3-dienes stereoselectively in moderate to high yields, which provided one alternative way to synthesize the corresponding conjugated dienones.

New insight into the bioaccumulation and trophic transfer of free and conjugated antibiotics in an estuarine food web based on multimedia fate and model simulation.

The substantial utilization of antibiotics causes their "pseudo-persistence" in offshore environments. Published studies on antibiotic surveillance in food webs have primarily emphasized on parent forms; however, the compositions and concentrations of conjugated antibiotics in aquatic organisms remain largely unexplored. This study systematically examined the distribution characteristics and trophodynamics of free antibiotics and their conjugated forms in an estuarine food web. Total antibiotic levels differed insignificantly between the surface and bottom waters. The total mean values of free antibiotics in crabs, fish, shrimps, sea cucumbers, and snails varied from 0.77 to 1.4 ng/g (wet weight). The numbers and values of antibiotics rose in these biological samples after enzymatic hydrolysis. Conjugated antibiotics accounted for 23.8-76.9% of the total antibiotics in the biological samples, revealing that conjugated forms play a non-negligible role in aquatic organisms. More number of antibiotics exhibited bioaccumulation capabilities after enzymatic hydrolysis. In the food web, the free forms of anhydroerythromycin and conjugated forms of trimethoprim and ciprofloxacin underwent trophic dilution, whereas the free forms of trimethoprim and conjugated forms of ofloxacin underwent trophic amplification. The present work provides new insights into the bioaccumulation and trophic transfer of free and conjugated antibiotics in food webs.

Recent advances in the development of Rho kinase inhibitors (2015-2021).

Rho-associated coiled-coil kinases (ROCKs) are key downstream effectors of small GTPases. ROCK plays a central role in diverse cellular events with accumulating evidence supporting the concept that ROCK is important in tumor development and progression. Numerous ROCK inhibitors have been investigated for their therapeutic potential in the treatment of cancers. In this article, we review recent research progress on ROCK inhibitors, especially those with potential for the treatment of cancers, reported in the literature from 2015 to 2021. Most ROCK inhibitors show potent in vitro and in vivo antitumor activities and have potential in the treatment of cancers.

HECW2 promotes the progression and chemoresistance of colorectal cancer via AKT/mTOR signaling activation by mediating the ubiquitin-proteasome degradation of lamin B1.

Colorectal cancer (CRC) is among the most common malignancies worldwide. Although a recent study has shown that E3 ubiquitin ligases play a major role in regulating the occurrence and development of CRC, there are few reports on the role of the E3 ubiquitin ligase HECW2(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) in CRC progression and chemoresistance. We found that HECW2 is highly expressed in CRC tissues. HECW2 knockdown inhibits CRC progression and chemoresistance, whereas HECW2 overexpression has the opposite effect. Mechanistically, HECW2 activates the AKT/mTOR signaling pathway by mediating the ubiquitin-proteasome degradation of lamin B1, thereby promoting CRC progression and chemoresistance. Our findings suggest that HECW2 may be a promising novel therapeutic target for CRC treatment.