PARVB deficiency alleviates cisplatin-induced tubular injury by inhibiting TAK1 signaling.

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.

Na3K6(CO3)3(NO3)2X·6H2O (X = NO3, Cl, Br): Exploring High-Performance UV Birefringent Crystals Induced by Coplanar π-Conjugated CO3 and NO3 Groups.

Planar π-conjugated groups, like CO3, NO3, and BO3 triangles, are ideal functional units for designing birefringent materials due to their large optical anisotropy and wide band gap. The key point for designing birefringent crystals is to select appropriate functional building blocks (FBBs) and the proper arrangement mode. It is well known that the substitution strategy has proven to be a promising and accessible approach. In this work, alkali metals were chosen to regulate and control two different π-conjugated groups, CO3 and NO3, to build new compounds with large birefringence. Subsequently, three new compounds, Na3K6(CO3)3(NO3)2X·6H2O (X = NO3, Cl, Br), were successfully synthesized using the hydrothermal method. The aliovalent substitution between the [NO3]- anionic group and halogen anions [Cl]-/[Br]- has been achieved in these compounds. Na3K6(CO3)3(NO3)2X·6H2O feature the well-coplanar CO3 and NO3 groups in their crystal structure. This coplanar arrangement mode may effectively enhance the anisotropic polarizability of Na3K6(CO3)3(NO3)2X·6H2O. And their experimental birefringence can reach 0.094-0.131 at 546 nm. Diffuse reflectance spectra demonstrate that these compounds exhibit short ultraviolet (UV) absorption edges of ∼235 nm. Meanwhile, Na3K6(CO3)3(NO3)2X·6H2O also have an easily grown capacity under facile conditions. This work not only reports three new potential UV birefringent crystals but also provides a strategy to make the π-conjugated MO3 group coplanar.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish.

During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.

Smarca5-mediated epigenetic programming facilitates fetal HSPC development in vertebrates.

Nascent hematopoietic stem and progenitor cells (HSPCs) acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.

m6A modulates haematopoietic stem and progenitor cell specification.

N6-methyladenosine (m6A) has been identified as the most abundant modification on eukaryote messenger RNA (mRNA). Although the rapid development of high-throughput sequencing technologies has enabled insight into the biological functions of m6A modification, the function of m6A during vertebrate embryogenesis remains poorly understood. Here we show that m6A determines cell fate during the endothelial-to-haematopoietic transition (EHT) to specify the earliest haematopoietic stem/progenitor cells (HSPCs) during zebrafish embryogenesis. m6A-specific methylated RNA immunoprecipitation combined with high-throughput sequencing (MeRIP-seq) and m6A individual-nucleotide-resolution cross-linking and immunoprecipitation with sequencing (miCLIP-seq) analyses reveal conserved features on zebrafish m6A methylome and preferential distribution of m6A peaks near the stop codon with a consensus RRACH motif. In mettl3-deficient embryos, levels of m6A are significantly decreased and emergence of HSPCs is blocked. Mechanistically, we identify that the delayed YTHDF2-mediated mRNA decay of the arterial endothelial genes notch1a and rhoca contributes to this deleterious effect. The continuous activation of Notch signalling in arterial endothelial cells of mettl3-deficient embryos blocks EHT, thereby repressing the generation of the earliest HSPCs. Furthermore, knockdown of Mettl3 in mice confers a similar phenotype. Collectively, our findings demonstrate the critical function of m6A modification in the fate determination of HSPCs during vertebrate embryogenesis.

CHILKBP protects against podocyte injury by preserving ZO-1 expression.

Glomerular diseases afflict millions of people and impose an enormous burden on public healthcare costs worldwide. Identification of potential therapeutic targets for preventing glomerular diseases is of considerable clinical importance. CHILKBP is a focal adhesion protein and modulates a wide array of biological functions. However, little is known about the role of CHILKBP in glomerular diseases. To investigate the function of CHILKBP in maintaining the structure and function of podocytes in a physiologic setting, a mouse model (CHILKBP cKO) was generated in which CHILKBP gene was conditionally deleted in podocytes using the Cre-LoxP system. Ablation of CHILKBP in podocytes resulted in massive proteinuria and kidney failure in mice. Histologically, typical podocyte injury including podocyte loss, foot process effacement, and glomerulosclerosis was observed in CHILKBP cKO mice. Mechanistically, we identified ZO-1 as a key junctional protein that interacted with CHILKBP. Loss of CHILKBP in podocytes exhibited a significant reduction of ZO-1 expression, leading to abnormal actin organization, aberrant slit diaphragm protein expression and compromised podocyte filtration capacity. Restoration of CHILKBP or ZO-1 in CHILKBP-deficient podocytes effectively alleviated podocyte injury induced by the loss of CHILKBP in vitro and in vivo. Finally, we showed the glomerular expression of CHILKBP and ZO-1 was decreased in patients with proteinuric kidney diseases. Our findings reveal a novel signaling pathway consisting of CHILKBP and ZO-1 that plays an essential role in maintaining podocyte homeostasis and suggest novel therapeutic approaches to alleviate glomerular diseases.

Repurposing Salicylamides to Combat Phytopathogenic Bacteria and Induce Plant Defense Responses.

Based on the research strategy of "drug repurposing", a series of derivatives and marketed drugs that containing salicylic acid skeleton were tested for their antibacterial activities against phytopathogens. Salicylic acid can not only regulate some important growth metabolism of plants, but also induce plant disease resistance. The bioassay results showed that the salicylamides exhibited excellent antibacterial activity. Especially, oxyclozanide showed the best antibacterial effect against Xanthomonas oryzae, Xanthomonas axonopodis pv. citri and Pectobacterium atroseptica with MICs of 0.78, 3.12 and 12.5 µg.mL-1, respectively. In vivo experiments with rice bacterial leaf blight had further demonstrated that oxyclozanide exhibited stronger antibacterial activity than the commercial bactericide, thiodiazole copper. Oxyclozanide could induce plant defense responses through the determination of salicylic acid content and the activities of defense-related enzymes including CAT, POD, and SOD in rice. The preliminarily antibacterial mechanism study indicated that oxyclozanide exhibited the antibacterial activity by disrupting cell integrity and reducing bacterial pathogenicity. Additionally, oxyclozanide could induce plant defense responses through the determination of salicylic acid content.

Transcriptional and epigenetic control of hematopoietic stem cell fate decisions in vertebrates.

Hematopoietic stem cells (HSCs) are the foundation of adult hematopoiesis that produce all types of mature blood lineages. In vertebrates, HSC development is a stepwise process, coordinately regulated by chromatin architectures and a group of transcriptional and epigenetic regulators. A deeper understanding of the molecular mechanisms governing the generation, expansion, and function of HSCs holds great promise in the generation and expansion of engraftable HSCs in vitro for clinical applications. This study reviewed recent advances in transcriptional and epigenetic control of hematopoietic stem cell fate decisions in vertebrates.

Nephrotic-syndrome-associated mutation of KANK2 induces pathologic binding competition with physiological interactor KIF21A.

Nephrotic syndrome (NS) is a common kidney disorder caused by dysfunction of the glomerular filtration barrier. Some genetic mutations identified in NS patients cause amino acid substitutions of kidney ankyrin repeat-containing (KANK) proteins, which are scaffold proteins that regulate actin polymerization, microtubule targeting, and cell adhesion via binding to various molecules, including the kinesin motor protein KIF21A. However, the mechanisms by which these mutations lead to NS are unclear. Here, we unexpectedly found that the eukaryotic translation initiation factor 4A1 (eIF4A1) interacts with an NS-associated KANK2 mutant (S684F) but not the wild-type protein. Biochemical and structural analyses revealed that the pathological mutation induces abnormal binding of eIF4A1 to KANK2 at the physiological KIF21A-binding site. Competitive binding assays further indicated that eIF4A1 can compete with KIF21A to interact with the S684F mutant of KANK2. In cultured mouse podocytes, this S684F mutant interfered with the KANK2/KIF21A interaction by binding to eIF4A1, and failed to rescue the focal adhesion or cell adhesion that had been reduced or morphologically changed by KANK2 knockout. These structural, biochemical, and cellular results not only provide mechanistic explanations for the podocyte defects caused by the S684F mutation, but also show how a gain-of-binding mutation can lead to a loss-of-function effect.

Revealing the synergy between zinc and aluminum in Cu/ZnO/Al2O3 industrial catalyst.

The active sites in Cu/ZnO/Al2O3 industrial catalyst for CO2 hydrogenation to methanol need to be fully clarified. In this work, we reveal two types of active sites at the nano-sized Cu/ZnO interface, of which only one type is efficient. The efficient active site is characterized by isolated and under-coordinated Zn atoms located at the vertices of the supported ZnO island, thus the density of which is so limited. To anchor such Zn atoms onto other islands on Cu with high density is the key to enhancing the catalytic activity. To replace ZnO with Al2O3 islands on Cu is not favored energetically. However, under reduction condition, Zn single atoms can stably decorate the edges of the Al2O3 islands, resulting in the enhancement of the efficient active sites at the Cu/oxide interface. This could be the mechanism of the synergy effects taking place in the Cu/ZnO/Al2O3 catalyst.

Membrane fouling performance of Fe-based coagulation-ultrafiltration process: Effect of sedimentation time.

Pre-coagulation is commonly used with ultrafiltration (UF) to alleviate the membrane fouling. Compared to conventional coagulation-sedimentation-UF (CSUF) processes, the direct coagulation-UF (CUF) processes are widely believed to perform better due to the formation of a looser cake layer. It is however shown in this study that not only the density of a cake layer, but also its thickness as well, can affect the membrane fouling behavior, which therefore are influenced by both the sedimentation time and flocs characteristics. Herein, the membrane fouling performance of Fe-based coagulation-UF process was systematically investigated with different sedimentation times. A critical threshold of 30 min was observed at the lab-scale: if shorter than that, the membrane fouling depended mainly on the cake layer density, and thus CUF outperformed CSUF; but when the sedimentation time was over 30 min, the cake layer thickness turned to be the dominant factor, thereby resulting in CSUF performing better. Furthermore, it was shown that the critical sedimentation time was decided by flocs characteristics. A lower water temperature induced the formation of irregular flocs with a lower fractal dimension, and the corresponding cake layer exhibited an almost identical density with increasing sedimentation time. In this regard, CSUF processes were constantly superior to CUF as the cake layer thickness decreased. On the other hand, a critical sedimentation time reappeared because of the higher floc fractal dimension under acidic conditions. This work showed for the first time that the membrane fouling of CSUF was up to the sedimentation time, and it was possible to outperform CUF if the sedimentation time exceeded a critical threshold. Such a finding is crucial to the future development of coagulation integrated UF processes.

A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome.

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.

Protection and Prevention of Age-Related Hearing Loss.

Presbycusis is a sensorineural hearing loss caused by hearing system aging and degeneration. The clinical manifestations are progressive bilateral symmetrical hearing loss, and the hearing curve is mostly slope-shaped with high-frequency reduction, sometimes flat. The results of the second national sample survey of disabled persons (2006) showed that the total number of hearing and speech disability in China was 27.8 million, accounting for 34% of the total number of disabled people in China. Among them are people over 60 years old. There are 20.4541 million people with hearing disabilities. There are 9.49 million senile deaf patients, accounting for 34.1% of the total number of hearing disabilities. As society gradually becomes aging, the incidence of presbycusis is getting higher and higher. The study of its pathogenesis is of great significance for the diagnosis, treatment, and prevention of presbycusis. The rapid progress of molecular biology experimental technology has provided us with a new opportunity to fully understand and reveal the presbycusis. In the near future, early diagnosis of presbycusis-related genes and early prevention or delay of the occurrence and development of presbycusis will become a reality.

Effects of protein properties on ultrafiltration membrane fouling performance in water treatment.

Protein-like substances always induce severe ultrafiltration (UF) membrane fouling. To systematically understand the effect of proteins, regenerated cellulose UF membrane (commonly used for protein separation) performance was investigated in the presence of bovine serum albumin (BSA) under various water conditions. Results showed that although trypsin enhanced the membrane flux via proteolysis, catalysis took a long time. Membrane fouling was alleviated at high solution pH and low water temperature owing to the strong electrostatic repulsion force among BSA molecules. Both Na+ and Ca2+ could increase membrane flux. However, Ca2+ played a bridging role between adjacent BSA molecules, whereas membrane fouling was alleviated via a hydration repulsion force with Na+. The order of influence on membrane fouling was as follows: Ca2+ concentration > Na+ concentration > pH > temperature > trypsin concentration. Furthermore, a polyvinylidene fluoride UF membrane experiment showed that Ca2+ could reduce the fouling induced by BSA. Thus, the differences in UF membrane performance will have application potential for alleviating UF membrane fouling induced by proteins during water treatment.

Removal characteristics of microplastics by Fe-based coagulants during drinking water treatment.

Microplastics have caused great concern worldwide recently due to their ubiquitous presence within the marine environment. Up to now, most attention has been paid to their sources, distributions, measurement methods, and especially their eco-toxicological effects. With microplastics being increasingly detected in freshwater, it is urgently necessary to evaluate their behaviors during coagulation and ultrafiltration (UF) processes. Herein, the removal behavior of polyethylene (PE), which is easily suspended in water and is the main component of microplastics, was investigated with commonly used Fe-based salts. Results showed that although higher removal efficiency was induced for smaller PE particles, low PE removal efficiency (below 15%) was observed using the traditional coagulation process, and was little influenced by water characteristics. In comparison to solution pH, PAM addition played a more important role in increasing the removal efficiency, especially anionic PAM at high dosage (with efficiency up to 90.9%). The main reason was ascribed to the dense floc formation and high adsorption ability because of the positively charged Fe-based flocs under neutral conditions. For ultrafiltration, although PE particles could be completely rejected, slight membrane fouling was caused owing to their large particle size. The membrane flux decreased after coagulation; however, the membrane fouling was less severe than that induced by flocs alone due to the heterogeneous nature of the cake layer caused by PE, even at high dosages of Fe-based salts. Based on the behavior exhibited during coagulation and ultrafiltration, we believe these findings will have potential application in drinking water treatment.

Cultivation of phosphate-accumulating biofilm: Study of the effects of acyl-homoserine lactones (AHLs) and cyclic dimeric guanosine monophosphate (c-di-GMP) on the formation of biofilm and the enhancement of phosphate metabolism capacity.

This study investigated the mechanisms of microbial growth and metabolism during biofilm cultivation in the biofilm sequencing batch reactor (BSBR) process for phosphate (P) enrichment. The results showed that the sludge discharge was key to biofilm growth, as it terminated the competition for carbon (C) source between the nascent biofilm and the activated sludge. For the tested reactor, after the sludge discharge on 18 d, P metabolism and C source utilization improved significantly, and the biofilm grew rapidly. The P concentration of the recovery liquid reached up to 157.08 mg/L, which was sufficient for further P recovery via mineralization. Meta-omics methods were used to analyze metabolic pathways and functional genes in microbial growth during biofilm cultivation. It appeared that the sludge discharge activated the key genes of P metabolism and inhibited the key genes of C metabolism, which strengthened the polyphosphate-accumulating metabolism (PAM) as a result. The sludge discharge not only changed the types of polyphosphate-accumulating organisms (PAOs) but also promoted the growth of dominant PAOs. Before the sludge discharge, the necessary metabolic abilities that were spread among different microorganisms gradually concentrated into a small number of PAOs, and after the sludge discharge, they further concentrated into Candidatus_Contendobacter (P3) and Candidatus_Accumulibacter (P17). The messenger molecule C-di-GMP, produced mostly by P3 and P17, facilitated P enrichment by regulating cellular P and C metabolism. The glycogen-accumulating organism (GAO) Candidatus_Competibacter secreted N-Acyl homoserine lactones (AHLs), which stimulated the secretion of protein in extracellular polymeric substances (EPS), thus promoting the adhesion of microorganisms to biofilm and improving P metabolism via EPS-based P adsorption. Under the combined action of the dominant GAOs and PAOs, AHLs and C-di-GMP mediated QS to promote biofilm development and P enrichment. The research provides theoretical support for the cultivation of biofilm and its wider application.

Formation mechanism of high biofilm phosphorus storage capacity and its effect on phosphorus uptake-release and carbon source consumption.

Phosphorus recovery from wastewater is an effective method to alleviate the shortage of phosphorus resources. The biofilm phosphorus recovery process can realize simultaneous removal and enrichment of phosphorus in wastewater. In this study, a sequencing batch biofilm reactor was constructed to study the rapid phosphorus release and slow phosphorus release stages in the phosphorus recovery cycle. The relationship between high biofilm phosphorus storage capacity (Pbiofilm), phosphorus recovery solution concentration, phosphorus uptake-release behavior and carbon source consumption were explored. The increase in phosphorus recovery solution concentration promotes the elevation of Pbiofilm, which, conversely promotes phosphorus release in the next recovery cycle. In addition, the distinct phosphorus uptake-release characteristics of extracellular polymeric substances and cells were illustrated. This study provides a theoretical foundation to elevate the phosphorus recovery efficiency and reduce carbon source consumption in biofilm phosphorus recovery process.

Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.