CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3' endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation of nontransformed immortalized control pancreatic cells. Mechanistically, JTE-607 induces transcriptional readthrough in replication-dependent histones, reduces core histone expression, destabilizes chromatin structure, and arrests cells in the S-phase of the cell cycle. Therefore, CPSF3 represents a potential therapeutic target for the treatment of PDAC.

Colloidal tubular microrobots for cargo transport and compression.

Microrobot swarms have seen increased interest in recent years due to their potentials for in vivo delivery and imaging with cooperative propulsion modes and enhanced imaging signals. Yet most swarms developed so far are limited to dense particle aggregates, far simpler than complicated three-dimensional assemblies of anisotropic particles. Here, we show via assembly path design that complex hollow tubular structures can be assembled from simple isotropic colloidal spheres and those complicated, metastable, microtubes can be formed from simple, energetically favorable colloidal membranes. The assembled microtubes can remain intact and roll under a precessing magnetic field, with propulsion directions and velocities precisely controlled by field components. The hollow spaces inside enable these tubular microrobots to grab, transport, and release cargos on command. We also demonstrate unique compressing and uncompressing capabilities with our tubular microrobots, making them effective microtweezers. Our work shows that complicated microrobots can be transformed from simple assemblies, providing an insight on building micromachines.

Disruption of MeCP2-TCF20 complex underlies distinct neurodevelopmental disorders.

MeCP2 is associated with Rett syndrome (RTT), MECP2 duplication syndrome, and a number of conditions with isolated features of these diseases, including autism, intellectual disability, and motor dysfunction. MeCP2 is known to broadly bind methylated DNA, but the precise molecular mechanism driving disease pathogenesis remains to be determined. Using proximity-dependent biotinylation (BioID), we identified a transcription factor 20 (TCF20) complex that interacts with MeCP2 at the chromatin interface. Importantly, RTT-causing mutations in MECP2 disrupt this interaction. TCF20 and MeCP2 are highly coexpressed in neurons and coregulate the expression of key neuronal genes. Reducing Tcf20 partially rescued the behavioral deficits caused by MECP2 overexpression, demonstrating a functional relationship between MeCP2 and TCF20 in MECP2 duplication syndrome pathogenesis. We identified a patient exhibiting RTT-like neurological features with a missense mutation in the PHF14 subunit of the TCF20 complex that abolishes the MeCP2-PHF14-TCF20 interaction. Our data demonstrate the critical role of the MeCP2-TCF20 complex for brain function.

Beyond Conventional Catalysts: Monoelemental Tellurium as a Game Changer for Piezo-Driven Hydrogen Evolution.

The increasing demand for clean hydrogen production over fossil fuels necessitates the development of sustainable piezoelectrochemical methods that can overcome the limitations of conventional electrocatalytic and photocatalytic approaches. In this regard, existing piezocatalysts face challenges related to their low piezoelectricity or active site coverage for hydrogen evolution reaction (HER). Driven by global environmental concerns, there is a compelling push to engineer practical materials for highly efficient HER. Herein, monoelemental 2D tellurium (Te) is presented as a class of layered chalcogenide with a non-centrosymmetric crystal structure (P3121 space group). The refined Te nanosheets demonstrate an unprecedented highly efficient H2 production rate ≈9000 µmol g-1 h-1 under ultrasonic mechanical vibration due to built-in piezo-potential in the system. The remarkable piezocatalytic performance of Te nanosheets arises from a synergistic interplay between their semi-metallic nature, favorable free energy landscape, enhanced electrical conductivity and outstanding piezoelectricity. As a proof of concept, the theoretical approach based on Density Functional Theory (DFT) validates the findings due to the gradual exposure of active sites on the Te nanosheets leading to a self-optimized catalytic performance for hydrogen generation. Therefore, mechanically driven Te emerges as a promising piezocatalyst with the potential to revolutionize highly efficient and sustainable technology for futuristic applications.

End-to-end sequence-structure-function meta-learning predicts genome-wide chemical-protein interactions for dark proteins.

Systematically discovering protein-ligand interactions across the entire human and pathogen genomes is critical in chemical genomics, protein function prediction, drug discovery, and many other areas. However, more than 90% of gene families remain "dark"-i.e., their small-molecule ligands are undiscovered due to experimental limitations or human/historical biases. Existing computational approaches typically fail when the dark protein differs from those with known ligands. To address this challenge, we have developed a deep learning framework, called PortalCG, which consists of four novel components: (i) a 3-dimensional ligand binding site enhanced sequence pre-training strategy to encode the evolutionary links between ligand-binding sites across gene families; (ii) an end-to-end pretraining-fine-tuning strategy to reduce the impact of inaccuracy of predicted structures on function predictions by recognizing the sequence-structure-function paradigm; (iii) a new out-of-cluster meta-learning algorithm that extracts and accumulates information learned from predicting ligands of distinct gene families (meta-data) and applies the meta-data to a dark gene family; and (iv) a stress model selection step, using different gene families in the test data from those in the training and development data sets to facilitate model deployment in a real-world scenario. In extensive and rigorous benchmark experiments, PortalCG considerably outperformed state-of-the-art techniques of machine learning and protein-ligand docking when applied to dark gene families, and demonstrated its generalization power for target identifications and compound screenings under out-of-distribution (OOD) scenarios. Furthermore, in an external validation for the multi-target compound screening, the performance of PortalCG surpassed the rational design from medicinal chemists. Our results also suggest that a differentiable sequence-structure-function deep learning framework, where protein structural information serves as an intermediate layer, could be superior to conventional methodology where predicted protein structures were used for the compound screening. We applied PortalCG to two case studies to exemplify its potential in drug discovery: designing selective dual-antagonists of dopamine receptors for the treatment of opioid use disorder (OUD), and illuminating the understudied human genome for target diseases that do not yet have effective and safe therapeutics. Our results suggested that PortalCG is a viable solution to the OOD problem in exploring understudied regions of protein functional space.

Liquid Crystals: Versatile Self-Organized Smart Soft Materials.

Smart soft materials are envisioned to be the building blocks of the next generation of advanced devices and digitally augmented technologies. In this context, liquid crystals (LCs) owing to their responsive and adaptive attributes could serve as promising smart soft materials. LCs played a critical role in revolutionizing the information display industry in the 20th century. However, in the turn of the 21st century, numerous beyond-display applications of LCs have been demonstrated, which elegantly exploit their controllable stimuli-responsive and adaptive characteristics. For these applications, new LC materials have been rationally designed and developed. In this Review, we present the recent developments in light driven chiral LCs, i.e., cholesteric and blue phases, LC based smart windows that control the entrance of heat and light from outdoor to the interior of buildings and built environments depending on the weather conditions, LC elastomers for bioinspired, biological, and actuator applications, LC based biosensors for detection of proteins, nucleic acids, and viruses, LC based porous membranes for the separation of ions, molecules, and microbes, living LCs, and LCs under macro- and nanoscopic confinement. The Review concludes with a summary and perspectives on the challenges and opportunities for LCs as smart soft materials. This Review is anticipated to stimulate eclectic ideas toward the implementation of the nature's delicate phase of matter in future generations of smart and augmented devices and beyond.

Isoptericola haloaureus sp. nov., a dimorphic actinobacterium isolated from mangrove sediments of southeast India, implicating biosaline agricultural significance through nitrogen fixation and salt tolerance genes.

Strain MP-1014T, an obligate halophilic actinobacterium, was isolated from the mangrove soil of Thandavarayancholanganpettai, Tamil Nadu, India. A polyphasic approach was utilized to explore its phylogenetic position completely. The isolate was Gram-positive, filamentous, non-motile, and coccoid in older cultures. Ideal growth conditions were seen at 30 °C and pH 7.0, with 5% NaCl (W/V), and the DNA G + C content was 73.3%. The phylogenic analysis of this strain based upon 16S rRNA gene sequence revealed 97-99.8% similarity to the recognized species of the genus Isoptericola. Strain MP-1014T exhibits the highest similarity to I. sediminis JC619T (99.7%), I. chiayiensis KCTC19740T (98.9%), and subsequently to I. halotolerans KCTC19646T (98.6%), when compared with other members within the Isoptericola genus (< 98%). ANI scores of strain MP-1014T are 86.4%, 84.2%, and 81.5% and dDDH values are 59.7%, 53.6%, and 34.8% with I. sediminis JC619T, I. chiayiensis KCTC19740T and I. halotolerans KCTC19646T respectively. The major polar lipids of the strain MP-1014T were phosphatidylinositol, phosphatidylglycerol, diphosphotidylglycerol, two unknown phospholipids, and glycolipids. The predominant respiratory menaquinones were MK9 (H4) and MK9 (H2). The major fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C14:0, C15:0, and C16:0. Also, initial genome analysis of the organism suggests it as a biostimulant for enhancing agriculture in saline environments. Based on phenotypic and genetic distinctiveness, the strain MP-1014 T represents the novel species of the genus Isoptericola assigned Isoptericola haloaureus sp. nov., is addressed by the strain MP-1014 T, given its phenotypic, phylogenetic, and hereditary uniqueness. The type strain is MP-1014T [(NCBI = OP672482.1 = GCA_036689775.1) ATCC = BAA 2646T; DSMZ = 29325T; MTCC = 13246T].

Hardware Schemes for Smarter Indoor Robotics to Prevent the Backing Crash Framework Using Field Programmable Gate Array-Based Multi-Robots.

The use of smart indoor robotics services is gradually increasing in real-time scenarios. This paper presents a versatile approach to multi-robot backing crash prevention in indoor environments, using hardware schemes to achieve greater competence. Here, sensor fusion was initially used to analyze the state of multi-robots and their orientation within a static or dynamic scenario. The proposed novel hardware scheme-based framework integrates both static and dynamic scenarios for the execution of backing crash prevention. A round-robin (RR) scheduling algorithm was composed for the static scenario. Dynamic backing crash prevention was deployed by embedding a first come, first served (FCFS) scheduling algorithm. The behavioral control mechanism of the distributed multi-robots was integrated with FCFS and adaptive cruise control (ACC) scheduling algorithms. The integration of multiple algorithms is a challenging task for smarter indoor robotics, and the Xilinx-based partial reconfiguration method was deployed to avoid computational issues with multiple algorithms during the run-time. These methods were coded with Verilog HDL and validated using an FPGA (Zynq)-based multi-robot system.

A Versatile Approach for Adaptive Grid Mapping and Grid Flex-Graph Exploration with a Field-Programmable Gate Array-Based Robot Using Hardware Schemes.

Robotic exploration in dynamic and complex environments requires advanced adaptive mapping strategies to ensure accurate representation of the environments. This paper introduces an innovative grid flex-graph exploration (GFGE) algorithm designed for single-robot mapping. This hardware-scheme-based algorithm leverages a combination of quad-grid and graph structures to enhance the efficiency of both local and global mapping implemented on a field-programmable gate array (FPGA). This novel research work involved using sensor fusion to analyze a robot's behavior and flexibility in the presence of static and dynamic objects. A behavior-based grid construction algorithm was proposed for the construction of a quad-grid that represents the occupancy of frontier cells. The selection of the next exploration target in a graph-like structure was proposed using partial reconfiguration-based frontier-graph exploration approaches. The complete exploration method handles the data when updating the local map to optimize the redundant exploration of previously explored nodes. Together, the exploration handles the quadtree-like structure efficiently under dynamic and uncertain conditions with a parallel processing architecture. Integrating several algorithms into indoor robotics was a complex process, and a Xilinx-based partial reconfiguration approach was used to prevent computing difficulties when running many algorithms simultaneously. These algorithms were developed, simulated, and synthesized using the Verilog hardware description language on Zynq SoC. Experiments were carried out utilizing a robot based on a field-programmable gate array (FPGA), and the resource utilization and power consumption of the device were analyzed.

Top Tips for Designing and Managing a Public Engagement Laboratory.

Public engagement with science is a core facet of the broader science ecosystem, in particular the science research and science education sectors. In this article we demarcate the benefits of dedicated laboratories along with practitioner advice pertaining to the design and running of a public engagement learning environment. A practicing public engagement laboratory and one that is currently being developed are used as illustrative cases to provide real-world insights to public engagement practitioners.

Hypoxia-Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors.

Developing safe and precise image-guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia-responsive photosensitizer, TPA-Azo. Introducing the azo group into the photosensitizer TPA-BN with aggregation-induced emission quenches its fluorescence. When the nonfluorescent TPA-Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA-BN with an amino group that exhibits fluorescence-activatable image-guided photodynamic therapy with dual-organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence-activatable photosensitizers.

Rheological Tunable Magnetic Fluids with Long-Term Stability.

Magnetic fluids have advantages such as flow ability and solid-like property in strong magnetic fields, but have to suffer from the tradeoff between suspension stability and flow resistance. In this work, a thermal/photo/magnetorheological water-based magnetic fluid is fabricated by using oleic acid-coated Fe3 O4 (Fe3 O4 @OA) nanoparticles as the magnetic particles and the amphiphilic penta block copolymer (PTMC-F127-PTMC)-based aqueous solution as the carrier fluid. Due to the hydrophobic self-assembly between Fe3 O4 @OA and PTMC-F127-PTMC, the Newtonian-like magnetic fluid has outstanding long-term stability and reversible rheological changes between the low-viscosity flow state and the 3D gel structure. In the linear viscoelastic region, the viscosity exhibits an abrupt increase from below 0.10 Pa s at 20 °C to ≈1.3 × 104  Pa s at 40 °C. Benefitting from the photothermal and magnetocaloric effects of the Fe3 O4 @OA nanoparticles, the rheological change process also can be controlled by near infrared light and alternating magnetic field, which endows the magnetic fluid with the applications in the fields of mobile valves, moveable switches, buffer or damping materials in sealed devices, etc.

The genome of Symbiodiniaceae-associated Stutzerimonas frequens CAM01 reveals a broad spectrum of antibiotic resistance genes indicating anthropogenic drift in the Palk Bay coral reef of south-eastern India.

An increase in antibiotic pollution in reef areas will lead to the emergence of antibiotic-resistant bacteria, leading to ecological disturbances in the sensitive coral holobiont. This study provides insights into the genome of antibiotics-resistant Stutzerimonas frequens CAM01, isolated from Favites-associated Symbiodiniaceae of a near-shore polluted reef of Palk Bay, India. The draft genome contains 4.67 Mbp in size with 52 contigs. Further genome analysis revealed the presence of four antibiotic-resistant genes, namely, adeF, rsmA, APH (3")-Ib, and APH (6)-Id that provide resistance by encoding resistance-nodulation-cell division (RND) antibiotic efflux pump and aminoglycoside phosphotransferase. The isolate showed resistance against 73% of the antibiotics tested, concurrent with the predicted AMR genes. Four secondary metabolites, namely Aryl polyene, NRPS-independent-siderophore, terpenes, and ectoine were detected in the isolate, which may play a role in virulence and pathogenicity adaptation in microbes. This study provides key insights into the genome of Stutzerimonas frequens CAM01 and highlights the emergence of antibiotic-resistant bacteria in coral reef ecosystems.

NUDT21 alters glioma migration through differential alternative polyadenylation of LAMC1.

PURPOSE: Gliomas and their surrounding microenvironment constantly interact to promote tumorigenicity, yet the underlying posttranscriptional regulatory mechanisms that govern this interplay are poorly understood. METHODS: Utilizing our established PAC-seq approach and PolyAMiner bioinformatic analysis pipeline, we deciphered the NUDT21-mediated differential APA dynamics in glioma cells. RESULTS: We identified LAMC1 as a critical NUDT21 alternative polyadenylation (APA) target, common in several core glioma-driving signaling pathways. qRT-PCR analysis confirmed that NUDT21-knockdown in glioma cells results in the preferred usage of the proximal polyA signal (PAS) of LAMC1. Functional studies revealed that NUDT21-knockdown-induced 3'UTR shortening of LAMC1 is sufficient to cause translational gain, as LAMC1 protein is upregulated in these cells compared to their respective controls. We demonstrate that 3'UTR shortening of LAMC1 after NUDT21 knockdown removes binding sites for miR-124/506, thereby relieving potent miRNA-based repression of LAMC1 expression. Remarkably, we report that the knockdown of NUDT21 significantly promoted glioma cell migration and that co-depletion of LAMC1 with NUDT21 abolished this effect. Lastly, we observed that LAMC1 3'UTR shortening predicts poor prognosis of low-grade glioma patients from The Cancer Genome Atlas. CONCLUSION: This study identifies NUDT21 as a core alternative polyadenylation factor that regulates the tumor microenvironment through differential APA and loss of miR-124/506 inhibition of LAMC1. Knockdown of NUDT21 in GBM cells mediates 3'UTR shortening of LAMC1, contributing to an increase in LAMC1, increased glioma cell migration/invasion, and a poor prognosis.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

Food and drug industry applications of microalgae Spirulina platensis: A review.

Spirulina platensis is a photosynthetic, blue-green, spiral- or bulb-shaped microalgae. Due to the presence of minerals, vitamins, pigments (carotenes, phycocyanin and chlorophyll) proteins (55%-70%), carbohydrates (15%-25%), and essential fatty acids (5%-8%), it has been used as a nutritional supplement for decades. NASA successfully employed it as a nutritional supplement for astronauts on space missions then its popularity was increased. The chemical composition of Spirulina, which is rich in vitamins, minerals, phenolics, vital fatty acids, amino acids, and pigments, can be beneficial to human health when incorporated into meals. The pharmacological effects include antibacterial, anticancer, metalloprotective, immune-stimulating, and antioxidant. It modulates immunological activities and possesses anti-inflammatory qualities by preventing mast cells from releasing histamine. Due to its high quantity of protein, carbohydrate, lipid, vital amino and fatty acids, dietary minerals and vitamins, Spirulina exerts the abovementioned benefits. In this review, up-to-date and possible biological aspects, patents applied on Spirulina and heights of confirmation are addressed, and the extent of current and future exploration is also explored.

A Versatile Approach to Polygonal Object Avoidance in Indoor Environments with Hardware Schemes Using an FPGA-Based Multi-Robot.

Service robots perform versatile functions in indoor environments. This study focuses on obstacle avoidance using flock-type indoor-based multi-robots. Each robot was developed with rendezvous behavior and distributed intelligence to perform obstacle avoidance. The hardware scheme-based obstacle-avoidance algorithm was developed using a bio-inspired flock approach, which was developed with three stages. Initially, the algorithm estimates polygonal obstacles and their orientations. The second stage involves performing avoidance at different orientations of obstacles using a heuristic based Bug2 algorithm. The final stage involves performing a flock rendezvous with distributed approaches and linear movements using a behavioral control mechanism. VLSI architectures were developed for multi-robot obstacle avoidance algorithms and were coded using Verilog HDL. The novel design of this article integrates the multi-robot's obstacle approaches with behavioral control and hardware scheme-based partial reconfiguration (PR) flow. The experiments were validated using FPGA-based multi-robots.

A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics.

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2's molecular role. Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonstrate a methodology to analyze all modern public data. We obtained relevant raw public transcriptomic data from GEO and ENA, then homogeneously processed it (QC, alignment to reference, differential expression analysis). We present a web portal to interactively access the mouse data, and we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found functionally distinct, consistently up- and downregulated subsets within these genes and some bias to their location. We present this common core of genes as well as focused cores for up, down, cell fraction models, and some tissues. We observed enrichment for this mouse core in other species MeCP2 models and observed overlap with ASD models. By integrating and examining transcriptomic data at scale, we have uncovered the true picture of this dysregulation. The vast scale of these data enables us to analyze signal-to-noise, evaluate a molecular signature in an unbiased manner, and demonstrate a framework for future disease focused informatics work.

Emerging roles of alternative cleavage and polyadenylation (APA) in human disease.

In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to APA are largely investigated in human diseases. However, the functions of the core APA machinery and related factors during disease conditions remain largely unknown. In this review, we discuss the roles of polyadenylation machinery in relation to brain disease, cardiac failure, pulmonary fibrosis, cancer, infectious conditions, and other human diseases. Collectively, we believe this review will be a useful avenue for understanding the emerging role of APA in the pathobiology of various human diseases.

Cleavage stimulating factor 64 depletion mitigates cardiac fibrosis through alternative polyadenylation.

Alternative polyadenylation (APA) regulates gene expression by cleavage and addition of poly(A) sequence at different polyadenylation sites (PAS) in 3'UTR, thus, generating transcript isoforms with different lengths. Cleavage stimulating factor 64 (CstF64) is an APA regulator which plays a role in PAS selection and determines the length of 3'UTR. CstF64 favors the use of proximal PAS, resulting in 3'UTR shortening, which enhances the protein expression by increasing the stability of the target genes. The aim of this study is to investigate the role of CstF64 in cardiac fibrosis, a key event leading to heart failure (HF). We determined the expression of CstF64, key profibrotic genes, and their 3'UTR changes by calculating distal PAS (dPAS) usage in left ventricular (LV) tissues and cardiac fibroblasts from HF patients. CstF64 was upregulated in HF LV tissues and cardiac fibroblasts along with increased deposition of fibrosis genes such as COL1A and FN1 and significant shortening in their 3'UTR. In addition, HF cardiac fibroblasts showed increased transforming growth factor receptor ß1 (TGFßR1) expression consistent with significant shortening in 3'UTR of TGFßR1. Upon knockdown of CstF64 from HF fibroblasts, downregulation in pro-fibrotic genes corresponding to lengthening in their 3'UTR was observed. Our finding suggests an important role of CstF64 in myofibroblast activation and promotion of cardiac fibrosis during HF through APA. Therefore, targeting CstF64 mediated RNA processing approach in human HF could provide a new therapeutic treatment strategy for limiting fibrotic remodeling.