A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis.

Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3' UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development.

Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation.

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.

Immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma: A systemic review and meta-analysis.

BACKGROUND: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC). MATERIALS AND METHODS: A meta-analysis was conducted, and the efficacy and safety of CPI were assessed. RESULTS: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%. CONCLUSIONS: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.

Management of Cutaneous Angiosarcoma: an Update Review.

OPINION STATEMENT: Cutaneous angiosarcoma is a rare and invasive malignant tumor. For localized cAS patients, wide-margin excision was recommended. Due to the latent local invasion characteristic of cAS, we suggest preoperative and postoperative radiotherapy to nearly all patients. Recently, there is growing interest in using neoadjuvant chemotherapy and/or radiotherapy as part of a combination therapy regimen, which may allow some patients to undergo potentially less disabling surgery. For metastatic cAS patients with unresectable tumors and who refuse surgery, radical radiotherapy or chemoradiotherapy may be an option. Paclitaxel was recognized as the first-line treatment. For tumors resistant to taxanes, emerging medications such as targeted agents and immunotherapy are also under investigation.

A Novel Thunderbolt Z-Epicanthoplasty for Asians.

BACKGROUND: Although many epicanthoplasty techniques have been proposed, prominent hypertrophic scarring in the medial canthal region remains a problem. The aim of this study was to develop a novel design that has a less prominent scar with minimal tension. METHODS: A total of 489 patients underwent thunderbolt Z-epicanthoplasty from July 2015 to April 2019, with or without blepharoplasty. A triangular myocutaneous flap was lifted from the upper part of the epicanthal fold. The surrounding area was dissected to remove the rigid connective tissue between the orbicularis muscle and the skin, which creates skin tension. A Z-shaped flap toward the inferomedial canthal portion was added to create space for the triangular flap to be transposed to change the straight incision into a curved zigzag incision (final scar in the shape of a "thunderbolt"), making the scar irregular and less conspicuous. RESULTS: Postoperatively, all patients were followed up for ≥ 12 months. Among the patients, epicanthus tarsalis (60.12%) and palpebralis (36.19%) were the commonest epicanthus types, followed by epicanthus supraciliaris (3.07%) and inversus (0.61%). The average preoperative intercanthal distance was 42.25 ± 1.66 mm. This distance decreased significantly to 37.14 ± 1.78 mm (average, 5.11 ± 0.21 mm; p = 0.036) at the 12-month postoperative follow-up. Mild cicatricial redness was observed in the medial canthal area in six patients (1.2%) during the early postoperative period. The redness diminished within 6 months postoperatively. All patients obtained natural and aesthetically pleasing results without prominent hypertrophic scarring or other complications in the medial canthal area. CONCLUSION: The thunderbolt Z-epicanthoplasty is safe and effective for treating medial epicanthal folds. It is potentially helpful in minimizing postoperative medial canthal scarring and can be applied to various types of epicanthal folds with long-lasting results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Non-Surgical Aesthetic IV.

Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, ADMET, and Molecular Dynamics (MD) Simulation of Potential Inhibitors of PD-L1 from the Library of Marine Natural Products.

BACKGROUND: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. METHOD: 52,765 marine natural products were screened against PD-L1(PDBID: 6R3K). To identify natural compounds, a structure-based pharmacophore model was generated, following by virtual screening and molecular docking. Then, the absorption, distribution, metabolism, and excretion (ADME) test was carried out to select the most suitable compounds. Finally, molecular dynamics simulation was also performed to validate the binding property of the top compound. RESULTS: Initially, 12 small marine molecules were screened based on the pharmacophore model. Then, two compounds were selected for further evaluation based on the molecular docking scores. After ADME and toxicity studies, molecule 51320 was selected for further verification. By molecular dynamics analysis, molecule 51320 maintains a stable conformation with the target protein, so it has the chance to become an inhibitor of PD-L1. CONCLUSIONS: Through structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET approaches, and molecular dynamics (MD) simulation, the marine natural compound 51320 can be used as a small molecule inhibitor of PD-L1.

Novel Diketopyrrolopyrrole-Based π-Conjugated Molecules Synthesized Via One-Pot Direct Arylation Reaction.

Diketopyrrolopyrrole (DPP) is an important type of π-conjugated building block for high-performance organic electronic materials. DPP-based conjugated materials are usually synthesized via Suzuki, Stille, or Negishi cross-coupling reactions, which require organometallic precursors. In this paper, a series of novel phenyl-cored DPP molecules, including five meta-phenyl-cored molecules and four para-phenyl-cored molecules, have been synthesized in moderate to good yields, in a facile manner, through the Pd-catalyzed direct arylation of C-H bonds, and their optoelectrical properties have been investigated in detail. All new molecules have been fully characterized by NMR, MALDI-TOF MS, elemental analysis, UV-visible spectroscopy, and cyclic voltammetry. This synthetic strategy has evident advantages of atom- and step-economy and low cost, compared with traditional cross-coupling reactions.

Correlation between the level of microRNA expression in peripheral blood mononuclear cells and symptomatology in patients with generalized anxiety disorder.

This study investigated the correlation between the level of microRNA expression in peripheral blood mononuclear cells (PBMCs) and symptomatology in patients with generalized anxiety disorder (GAD). MicroRNA array was performed in peripheral blood mononuclear cells (PBMCs) obtained from GAD patients with gender, age, ethnicity-matched healthy controls. Then real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the top 7 miRNAs with the highest fold-change values in 76 GAD patients and 39 healthy controls. It demonstrated that 5 miRNAs showed significantly differences in expression levels (P<0.01). These 5 GAD-associated miRNAs were finally selected into our study to analyze the association between the plasma level of miRNAs expression and symptomatology scores in Hamilton Anxiety Scale (HAMA). Results showed that the level of miR-4505 and miR-663 was negatively correlated with the total HAMA scores in GAD patients (r=0.2228, r=0.264 P<0.05). MiR-663 was selected into the regression equation of HAMA total scores and psychic anxiety symptomatology scores, and it could explain 5.3% of the HAMA total scores and 15.3% of the anxiety symptomatology scores. This study analyzed preliminarily possible circulating miRNAs expression changes in GAD patients, and the expression level of miR-663 highly correlated with psychic anxiety symptoms, further molecular mechanism of which needs to be explored.

miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia.

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients.

The advancement of polysaccharides in disease modulation: Multifaceted regulation of programmed cell death.

Programmed cell death (PCD), also known as regulatory cell death (RCD), is a process that occurs in all organisms and is closely linked to both normal physiological processes and disease states. Various signaling pathways, such as TP53, KRAS, NOTCH, hypoxia, and metabolic reprogramming, have been found to regulate RCD. Polysaccharides, which are essential natural products, have been the subject of extensive research in the fields of food, nutrition, and medicine due to their wide range of pharmacological effects. Studies have shown that polysaccharides have biological activities and the potential to target signal transduction pathways for the treatment of diseases. This paper provides a review of the mechanisms through which polysaccharides exert their therapeutic effects at different levels and explores the relationship between different types of RCD and human diseases. The aim of this review is to provide a theoretical basis for the further clinical use and application of polysaccharide bioactivities.

Identifying the Pattern Characteristics of Anoikis-related Genes in Keloid.

OBJECTIVE: Anoikis, a kind of programmed cell death that is triggered when cells lose contact with each other or with the matrix. However, the potential value of anoikis-related genes (ARGs) in keloid (KD) has not been investigated. APPROACH: We downloaded three keloid fibroblast (KF) RNA-seq datasets from the GEO and obtained 338 ARGs from a search of the GeneCards database and PubMed articles. WGCNA was used to construct the coexpression network, and obtain the KF-related ARGs. The LASSO-Cox method was used to screen the hub ARGs and construct the best prediction model. Then, GEO single cell sequencing datasets were used to verify the expression of hub genes. We used whole RNA sequencing for gene-level validation, and the correlation between KD immune infiltration and anoikis. RESULTS: Our study comprehensively analyzed the role of ARGs in KD for the first time. LASSO regression analysis identified six hub ARGs (HIF1A, SEMA7A, SESN1, CASP3, LAMA3 and SIK2). A large number of miRNAs participate in the regulation of hub ARGs. In addition, correlation analysis revealed that ARGs were significantly correlated with the infiltration levels of multiple immune cells in KD patients. Innovation We explored the expression characteristics of ARGs in KD, which is extremely important for determining the molecular pathways and mechanisms underlying KD. CONCLUSIONS: This study provides a useful reference for revealing the characteristics of ARGs in the pathogenesis of KD. The identified hub genes may provide potential therapeutic targets for patients. This study provides new ideas for individualized therapy and immunotherapy.

Targeted therapeutic strategies for melanoma.

ABSTRACT: Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.

Could hyperbaric oxygen be an effective therapy option for pathological scars? A systematic review and meta-analysis.

BACKGROUND: Hyperbaric oxygen (HBO) therapy involves breathing pure oxygen or a high oxygen concentration above atmospheric (ATM) pressure in an enclosed chamber. Studies on pathological scars have demonstrated that HBO can inhibit the formation of pathological scars. OBJECTIVE: To evaluate the efficacy of HBO in the treatment of pathological scars via meta-analysis. METHODS: Searches were run on various databases, including the Cochrane, Embase, PubMed, Web of Science, and CNKI databases. A comparative study was conducted on patients with pathological scars treated with or without HBO. We used RevMan 5.4 software to determine the recurrence rate, treatment satisfaction, and Vancouver Scar Scale(VSS) score in the pathological scar. RESULTS: A total of 543 publications were identified; after screening, four were selected for review, including one randomized controlled trial (RCT), one controlled clinical trial (CCT), and two retrospective cohort studies. Meta-analysis results showed that HBO treatment reduced the pathological scar recurrence rate after surgery and radiotherapy (OR = 0.26, 95% CI: 0.13-0.52, p = 0.0001). Patients had higher satisfaction after HBO therapy (OR = 4.45, 95% CI: 1.49-13.30, p = 0.007). The Vancouver scar scale (VSS) score of patients with pathological scars was significantly improved in the HBO group (SMD: -3.82, 95% CI: -6.07to -0.49, p = 0.02). CONCLUSIONS: HBO treatment decreased the recurrence rate of pathological scars after surgery and radiotherapy, increased patient satisfaction, and reduced the VSS score, thus providing a new way to treat pathological scar hyperplasia. However, evaluation of the longer-term effects of HBO treatment requires further comprehensive studies, including more RCTs.

Polysome Profiling in Adult Mouse Testes.

Polysome profiling is widely used to isolate and analyze polysome fractions, which consist of actively translating mRNAs and ribosomes. Compared to ribosome profiling and translating ribosome affinity purification, polysome profiling is simpler and less time consuming in sample preparation and library constructions. Spermiogenesis, i.e., the post-meiotic phase of male germ cell development, is a highly coordinated developmental process in which transcription and translation are decoupled because of nuclear condensation, resulting in translation regulation as the major mode for the regulation of gene expression in post-meiotic spermatids. To understand the translation regulation during spermiogenesis, an overview of translational state of spermiogenic mRNAs is required. Here, we describe a protocol to identify translating mRNAs using polysome profiling. Briefly, mouse testes are gently homogenized to release polysomes containing translating mRNAs, following polysome-bound mRNAs isolated by sucrose density gradient purification and characterized by RNA-seq. This protocol allows to quickly isolate translating mRNAs from testes and analyze the discrepancy of translational efficiency in mouse testes from different mouse lines. Key features Quickly obtain polysome RNAs from testes. Omit RNase digestion and RNA recovery from gel. High efficiency and robustness compared to ribo-seq. Graphical overview Schematic illustrating the experimental design for polysome profiling in mouse testes. Mouse testes are homogenized and lysed in Sample preparation, and polysome RNAs are enriched by sucrose gradient centrifugation and used to calculate translation efficiency in Sample analysis.

Virtual Screening Based on Machine Learning Explores Mangrove Natural Products as KRASG12C Inhibitors.

Mangrove secondary metabolites have many unique biological activities. We identified lead compounds among them that might target KRASG12C. KRAS is considered to be closely related to various cancers. A variety of novel small molecules that directly target KRAS are being developed, including covalent allosteric inhibitors for KRASG12C mutant, protein-protein interaction inhibitors that bind in the switch I/II pocket or the A59 site, and GTP-competitive inhibitors targeting the nucleotide-binding site. To identify a candidate pool of mangrove secondary metabolic natural products, we tested various machine learning algorithms and selected random forest as a model for predicting the targeting activity of compounds. Lead compounds were then subjected to virtual screening and covalent docking, integrated absorption, distribution, metabolism and excretion (ADME) testing, and structure-based pharmacophore model validation to select the most suitable compounds. Finally, we performed molecular dynamics simulations to verify the binding mode of the lead compound to KRASG12C. The lazypredict function package was initially used, and the Accuracy score and F1 score of the random forest algorithm exceeded 60%, which can be considered to carry a strong ability to distinguish the data. Four marine natural products were obtained through machine learning identification and covalent docking screening. Compound 44 and compound 14 were selected for further validation after ADME and toxicity studies, and pharmacophore analysis indicated that they had a favorable pharmacodynamic profile. Comparison with the positive control showed that they stabilized switch I and switch II, and like MRTX849, retained a novel binding mechanism at the molecular level. Molecular dynamics analysis showed that they maintained a stable conformation with the target protein, so compound 44 and compound 14 may be effective inhibitors of the G12C mutant. These findings reveal that the mangrove-derived secondary metabolite compound 44 and compound 14 might be potential therapeutic agents for KRASG12C.

Decoration of nickel hexacyanoferrate nanocubes onto reduced graphene oxide sheets as high-performance cathode material for rechargeable aqueous zinc-ion batteries.

Prussian blue analogues (PBA) have attracted much attention in energy research due to their unique three-dimensional open framework structure, adjustable metal ions, and facile synthesis. However, the application of PBA as a cathode material for aqueous zinc-ion batteries (ZIBs) is restricted by its poor cycling performance and lower capacity. In this paper, we develop a new PBA-based hybrid cathode material for aqueous ZIBs by loading uniform nickel hexacyanoferrate (NiHCF) nanocubes onto reduced graphene oxide (RGO) sheets. In the NiHCF/RGO hybrid, NiHCF nanoparticles are well anchored on the RGO layers, forming a conductive network. The strong synergy between NiHCF and highly conductive RGO effectively increases the specific surface area, accelerates the electron and ion transport, and inhibits the structural collapse of the NiHCF/RGO electrode during the Zn2+ insertion/extraction process. Benefiting from the above advantages, the NiHCF/RGO hybrid exhibits a remarkable reversible capacity of 94.5 mAh g-1 at a current density of 5 mA g-1, excellent rate performance of 50.1 mAh g-1 at 200 mA g-1, and enhanced cycling stability with a capacity retention of 80.3% after 1000 cycles at 200 mA g-1. This work provides a simple and effective way to improve the electrochemical performance of PBA-based cathodes for aqueous ZIBs application.

Fabrication of alkali lignin-based emulsion electrospun nanofibers for the nanoencapsulation of beta-carotene and the enhanced antioxidant property.

For the greater utilization of ß-carotene in antioxidant material, ß-carotene-loaded emulsion stabilized by alkali lignin (AL) was successfully electrospinning with poly (vinyl alcohol) (PVA) (PVA/AL/ß-carotene nanofiber). Transmission electron microscopy demonstrated the core-shell structure of nanofiber with the average diameter being 356.31 nm, and 85.7 % of ß-carotene was effectively encapsulated into the core section. Fourier transform infrared spectra and differential scanning calorimetry revealed the good compatibility and decreased crystallinity of ß-carotene, favoring its stability and solubility, respectively. As expected, the PVA/AL/ß-carotene nanofiber exhibited higher antioxidant activity than free ß-carotene due to the protection of AL matrix and the special structure of nanofiber, as the DPPH free radical scavenging rate being 90.7 % at 7th day. The sustained release behavior of ß-carotene and AL from fiber followed Fickian diffusion model, contributing to the greater protection for fish oil than that of emulsion. Thus, this study provides an approach to develop hydrophobic compounds-loaded emulsion electrospun antioxidant material with controlled release property and enhanced activity.

Copper-catalyzed asymmetric 1,6-conjugate addition of in situ generated para-quinone methides with ß-ketoesters.

A Cu-catalyzed asymmetric 1,6-conjugate addition of in situ generated para-quinone methides (p-QMs) with ß-ketoester has been developed to construct a ketoester skeleton bearing an adjacent tertiary-quaternary carbon stereocenter in good yields and high enantioselectivities. This is the first example of metal-catalyzed asymmetric transformations of the in situ generated p-QMs, avoiding using pre-synthesized p-QMs requiring bulky 2,6-substitutions and highlighting a new dual catalytic activation with the chiral bis(oxazoline)-metal complex acting as a normal Lewis acid to activate the ß-ketoesters and a source of Brønsted acid responsible for generating the p-QMs in situ.

LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs.

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X-related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.