Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.

Beating the break-even point with a discrete-variable-encoded logical qubit.

Quantum error correction (QEC) aims to protect logical qubits from noises by using the redundancy of a large Hilbert space, which allows errors to be detected and corrected in real time1. In most QEC codes2-8, a logical qubit is encoded in some discrete variables, for example photon numbers, so that the encoded quantum information can be unambiguously extracted after processing. Over the past decade, repetitive QEC has been demonstrated with various discrete-variable-encoded scenarios9-17. However, extending the lifetimes of thus-encoded logical qubits beyond the best available physical qubit still remains elusive, which represents a break-even point for judging the practical usefulness of QEC. Here we demonstrate a QEC procedure in a circuit quantum electrodynamics architecture18, where the logical qubit is binomially encoded in photon-number states of a microwave cavity8, dispersively coupled to an auxiliary superconducting qubit. By applying a pulse featuring a tailored frequency comb to the auxiliary qubit, we can repetitively extract the error syndrome with high fidelity and perform error correction with feedback control accordingly, thereby exceeding the break-even point by about 16% lifetime enhancement. Our work illustrates the potential of hardware-efficient discrete-variable encodings for fault-tolerant quantum computation19.

Electrically tunable quantum confinement of neutral excitons.

Confining particles to distances below their de Broglie wavelength discretizes their motional state. This fundamental effect is observed in many physical systems, ranging from electrons confined in atoms or quantum dots1,2 to ultracold atoms trapped in optical tweezers3,4. In solid-state photonics, a long-standing goal has been to achieve fully tunable quantum confinement of optically active electron-hole pairs, known as excitons. To confine excitons, existing approaches mainly rely on material modulation5, which suffers from poor control over the energy and position of trapping potentials. This has severely impeded the engineering of large-scale quantum photonic systems. Here we demonstrate electrically controlled quantum confinement of neutral excitons in 2D semiconductors. By combining gate-defined in-plane electric fields with inherent interactions between excitons and free charges in a lateral p-i-n junction, we achieve exciton confinement below 10 nm. Quantization of excitonic motion manifests in the measured optical response as a ladder of discrete voltage-dependent states below the continuum. Furthermore, we observe that our confining potentials lead to a strong modification of the relative wave function of excitons. Our technique provides an experimental route towards creating scalable arrays of identical single-photon sources and has wide-ranging implications for realizing strongly correlated photonic phases6,7 and on-chip optical quantum information processors8,9.

Viscoelastic control of spatiotemporal order in bacterial active matter.

Active matter consists of units that generate mechanical work by consuming energy1. Examples include living systems (such as assemblies of bacteria2-5 and biological tissues6,7), biopolymers driven by molecular motors8-11 and suspensions of synthetic self-propelled particles12-14. A central goal is to understand and control the self-organization of active assemblies in space and time. Most active systems exhibit either spatial order mediated by interactions that coordinate the spatial structure and the motion of active agents12,14,15 or the temporal synchronization of individual oscillatory dynamics2. The simultaneous control of spatial and temporal organization is more challenging and generally requires complex interactions, such as reaction-diffusion hierarchies16 or genetically engineered cellular circuits2. Here we report a simple technique to simultaneously control the spatial and temporal self-organization of bacterial active matter. We confine dense active suspensions of Escherichia coli cells and manipulate a single macroscopic parameter-namely, the viscoelasticity of the suspending fluid- through the addition of purified genomic DNA. This reveals self-driven spatial and temporal organization in the form of a millimetre-scale rotating vortex with periodically oscillating global chirality of tunable frequency, reminiscent of a torsional pendulum. By combining experiments with an active-matter model, we explain this behaviour in terms of the interplay between active forcing and viscoelastic stress relaxation. Our findings provide insight into the influence of bacterial motile behaviour in complex fluids, which may be of interest in health- and ecology-related research, and demonstrate experimentally that rheological properties can be harnessed to control active-matter flows17,18. We envisage that our millimetre-scale, tunable, self-oscillating bacterial vortex may be coupled to actuation systems to act a 'clock generator' capable of providing timing signals for rhythmic locomotion of soft robots and for programmed microfluidic pumping19, for example, by triggering the action of a shift register in soft-robotic logic devices20.

Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2.

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.

GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.

Detailed understanding of the signaling intermediates that confer the sensing of intracellular viral nucleic acids for induction of type I interferons is critical for strategies to curtail viral mechanisms that impede innate immune defenses. Here we show that the activation of the microtubule-associated guanine nucleotide exchange factor GEF-H1, encoded by Arhgef2, is essential for sensing of foreign RNA by RIG-I-like receptors. Activation of GEF-H1 controls RIG-I-dependent and Mda5-dependent phosphorylation of IRF3 and induction of IFN-ß expression in macrophages. Generation of Arhgef2(-/-) mice revealed a pronounced signaling defect that prevented antiviral host responses to encephalomyocarditis virus and influenza A virus. Microtubule networks sequester GEF-H1 that upon activation is released to enable antiviral signaling by intracellular nucleic acid detection pathways.

Correlated insulating states at fractional fillings of moiré superlattices.

Quantum particles on a lattice with competing long-range interactions are ubiquitous in physics; transition metal oxides1,2, layered molecular crystals3 and trapped-ion arrays4 are a few examples. In the strongly interacting regime, these systems often show a rich variety of quantum many-body ground states that challenge theory2. The emergence of transition metal dichalcogenide moiré superlattices provides a highly controllable platform in which to study long-range electronic correlations5-12. Here we report an observation of nearly two dozen correlated insulating states at fractional fillings of tungsten diselenide/tungsten disulfide moiré superlattices. This finding is enabled by a new optical sensing technique that is based on the sensitivity to the dielectric environment of the exciton excited states in a single-layer semiconductor of tungsten diselenide. The cascade of insulating states shows an energy ordering that is nearly symmetric about a filling factor of half a particle per superlattice site. We propose a series of charge-ordered states at commensurate filling fractions that range from generalized Wigner crystals7 to charge density waves. Our study lays the groundwork for using moiré superlattices to simulate a wealth of quantum many-body problems that are described by the two-dimensional extended Hubbard model3,13,14 or spin models with long-range charge-charge and exchange interactions15,16.

Simulation of Hubbard model physics in WSe2/WS2 moiré superlattices.

The Hubbard model, formulated by physicist John Hubbard in the 1960s1, is a simple theoretical model of interacting quantum particles in a lattice. The model is thought to capture the essential physics of high-temperature superconductors, magnetic insulators and other complex quantum many-body ground states2,3. Although the Hubbard model provides a greatly simplified representation of most real materials, it is nevertheless difficult to solve accurately except in the one-dimensional case2,3. Therefore, the physical realization of the Hubbard model in two or three dimensions, which can act as an analogue quantum simulator (that is, it can mimic the model and simulate its phase diagram and dynamics4,5), has a vital role in solving the strong-correlation puzzle, namely, revealing the physics of a large number of strongly interacting quantum particles. Here we obtain the phase diagram of the two-dimensional triangular-lattice Hubbard model by studying angle-aligned WSe2/WS2 bilayers, which form moiré superlattices6 because of the difference between the lattice constants of the two materials. We probe the charge and magnetic properties of the system by measuring the dependence of its optical response on an out-of-plane magnetic field and on the gate-tuned carrier density. At half-filling of the first hole moiré superlattice band, we observe a Mott insulating state with antiferromagnetic Curie-Weiss behaviour, as expected for a Hubbard model in the strong-interaction regime2,3,7-9. Above half-filling, our experiment suggests a possible quantum phase transition from an antiferromagnetic to a weak ferromagnetic state at filling factors near 0.6. Our results establish a new solid-state platform based on moiré superlattices that can be used to simulate problems in strong-correlation physics that are described by triangular-lattice Hubbard models.

Oil-on-water droplets faceted and stabilized by vortex halos in the subphase.

For almost 200 y, the dominant approach to understand oil-on-water droplet shape and stability has been the thermodynamic expectation of minimized energy, yet parallel literature shows the prominence of Marangoni flow, an adaptive gradient of interfacial tension that produces convection rolls in the water. Our experiments, scaling arguments, and linear stability analysis show that the resulting Marangoni-driven high-Reynolds-number flow in shallow water overcomes radial symmetry of droplet shape otherwise enforced by the Laplace pressure. As a consequence, oil-on-water droplets are sheared to become polygons with distinct edges and corners. Moreover, subphase flows beneath individual droplets can inhibit the coalescence of adjacent droplets, leading to rich many-body dynamics that makes them look alive. The phenomenon of a "vortex halo" in the liquid subphase emerges as a hidden variable.

Transcriptomic congruence analysis for evaluating model organisms.

Model organisms are instrumental substitutes for human studies to expedite basic, translational, and clinical research. Despite their indispensable role in mechanistic investigation and drug development, molecular congruence of animal models to humans has long been questioned and debated. Little effort has been made for an objective quantification and mechanistic exploration of a model organism's resemblance to humans in terms of molecular response under disease or drug treatment. We hereby propose a framework, namely Congruence Analysis for Model Organisms (CAMO), for transcriptomic response analysis by developing threshold-free differential expression analysis, quantitative concordance/discordance scores incorporating data variabilities, pathway-centric downstream investigation, knowledge retrieval by text mining, and topological gene module detection for hypothesis generation. Instead of a genome-wide vague and dichotomous answer of "poorly" or "greatly" mimicking humans, CAMO assists researchers to numerically quantify congruence, to dissect true cross-species differences from unwanted biological or cohort variabilities, and to visually identify molecular mechanisms and pathway subnetworks that are best or least mimicked by model organisms, which altogether provides foundations for hypothesis generation and subsequent translational decisions.

Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome.

As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.e. a 'free trisomy' independent of gene dosage effects. Presently, there are no reports of attempts to functionally separate these two types of effects in mammals. To fill this gap, here we describe a strategy that employed two new mouse models of DS, Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey. Both models carry triplications of the same 103 human chromosome 21 gene orthologs; however, only Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy. Comparison of these models revealed the gene dosage-independent impacts of an extra chromosome at the phenotypic and molecular levels for the first time. They are reflected by impairments of Ts65Dn;Df(17)2Yey/+ males in T-maze tests when compared with Dp(16)1Yey/Df(16)8Yey males. Results from the transcriptomic analysis suggest the extra chromosome plays a major role in trisomy-associated expression alterations of disomic genes beyond gene dosage effects. This model system can now be used to deepen our mechanistic understanding of this common human aneuploidy and obtain new insights into the effects of free trisomies in other human diseases such as cancers.

A small peptide inhibits siRNA amplification in plants by mediating autophagic degradation of SGS3/RDR6 bodies.

Selective autophagy mediates specific degradation of unwanted cytoplasmic components to maintain cellular homeostasis. The suppressor of gene silencing 3 (SGS3) and RNA-dependent RNA polymerase 6 (RDR6)-formed bodies (SGS3/RDR6 bodies) are essential for siRNA amplification in planta. However, whether autophagy receptors regulate selective turnover of SGS3/RDR6 bodies is unknown. By analyzing the transcriptomic response to virus infection in Arabidopsis, we identified a virus-induced small peptide 1 (VISP1) composed of 71 amino acids, which harbor a ubiquitin-interacting motif that mediates interaction with autophagy-related protein 8. Overexpression of VISP1 induced selective autophagy and compromised antiviral immunity by inhibiting SGS3/RDR6-dependent viral siRNA amplification, whereas visp1 mutants exhibited opposite effects. Biochemistry assays demonstrate that VISP1 interacted with SGS3 and mediated autophagic degradation of SGS3/RDR6 bodies. Further analyses revealed that overexpression of VISP1, mimicking the sgs3 mutant, impaired biogenesis of endogenous trans-acting siRNAs and up-regulated their targets. Collectively, we propose that VISP1 is a small peptide receptor functioning in the crosstalk between selective autophagy and RNA silencing.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A diRNA-protein scaffold module mediates SMC5/6 recruitment in plant DNA repair.

In eukaryotes, the STRUCTURAL MAINTENANCE OF CHROMOSOME 5/6 (SMC5/6) complex is critical to maintaining chromosomal structures around double-strand breaks (DSBs) in DNA damage repair. However, the recruitment mechanism of this conserved complex at DSBs remains unclear. In this study, using Arabidopsis thaliana as a model, we found that SMC5/6 localization at DSBs is dependent on the protein scaffold containing INVOLVED IN DE NOVO 2 (IDN2), CELL DIVISION CYCLE 5 (CDC5), and ALTERATION/DEFICIENCY IN ACTIVATION 2B (ADA2b), whose recruitment is further mediated by DNA-damage-induced RNAs (diRNAs) generated from DNA regions around DSBs. The physical interactions of protein components including SMC5-ADA2b, ADA2b-CDC5, and CDC5-IDN2 result in formation of the protein scaffold. Further analysis indicated that the DSB localization of IDN2 requires its RNA-binding activity and ARGONAUTE 2 (AGO2), indicating a role for the AGO2-diRNA complex in this process. Given that most of the components in the scaffold are conserved, the mechanism presented here, which connects SMC5/6 recruitment and small RNAs, will improve our understanding of DNA repair mechanisms in eukaryotes.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

Reduced surface accumulation of swimming bacteria in viscoelastic polymer fluids.

Surface-associated bacterial communities flourish in nature and in the body of animal hosts with abundant macromolecular polymers. It is unclear how the endowed viscoelasticity of polymeric fluids influences bacterial motile behavior in such environments. Here, we combined experiment and theory to study near-surface swimming of flagellated bacteria in viscoelastic polymer fluids. In contrast to the swimming behavior in Newtonian fluids, we discovered that cells swim in less curved trajectories and display reduced near-surface accumulation. Using a theoretical analysis of the non-Newtonian hydrodynamic forces, we demonstrated the existence of a generic lift force acting on a rotating filament near a rigid surface, which arises from the elastic tension generated along curved flow streamlines. This viscoelastic lift force weakens the hydrodynamic interaction between flagellated swimmers and solid surfaces and contributes to a decrease in surface accumulation. Our findings reveal previously unrecognized facets of bacterial transport and surface exploration in polymer-rich environments that are pertinent to diverse microbial processes and may inform the design of artificial microswimmers capable of navigating through complex geometries.

Regulating Second Coordination Shell of Ce Atom Site and Reshaping of Carrier Enable Single-Atom Nanozyme to Efficiently Express Oxidase-like Activity.

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.

Hybrid Moiré Excitons and Trions in Twisted MoTe2-MoSe2 Heterobilayers.

We report experimental and theoretical studies of MoTe2-MoSe2 heterobilayers with rigid moiré superlattices controlled by the twist angle. Using an effective continuum model that combines resonant interlayer electron tunneling with stacking-dependent moiré potentials, we identify the nature of moiré excitons and the dependence of their energies, oscillator strengths, and Landé g-factors on the twist angle. Within the same framework, we interpret distinct signatures of bound complexes among electrons and moiré excitons in nearly collinear heterostacks. Our work provides a fundamental understanding of hybrid moiré excitons and trions in MoTe2-MoSe2 heterobilayers and establishes the material system as a prime candidate for optical studies of correlated phenomena in moiré lattices.

ReUseData: an R/Bioconductor tool for reusable and reproducible genomic data management.

BACKGROUND: The increasing volume and complexity of genomic data pose significant challenges for effective data management and reuse. Public genomic data often undergo similar preprocessing across projects, leading to redundant or inconsistent datasets and inefficient use of computing resources. This is especially pertinent for bioinformaticians engaged in multiple projects. Tools have been created to address challenges in managing and accessing curated genomic datasets, however, the practical utility of such tools becomes especially beneficial for users who seek to work with specific types of data or are technically inclined toward a particular programming language. Currently, there exists a gap in the availability of an R-specific solution for efficient data management and versatile data reuse. RESULTS: Here we present ReUseData, an R software tool that overcomes some of the limitations of existing solutions and provides a versatile and reproducible approach to effective data management within R. ReUseData facilitates the transformation of ad hoc scripts for data preprocessing into Common Workflow Language (CWL)-based data recipes, allowing for the reproducible generation of curated data files in their generic formats. The data recipes are standardized and self-contained, enabling them to be easily portable and reproducible across various computing platforms. ReUseData also streamlines the reuse of curated data files and their integration into downstream analysis tools and workflows with different frameworks. CONCLUSIONS: ReUseData provides a reliable and reproducible approach for genomic data management within the R environment to enhance the accessibility and reusability of genomic data. The package is available at Bioconductor ( https://bioconductor.org/packages/ReUseData/ ) with additional information on the project website ( https://rcwl.org/dataRecipes/ ).

GOLM1 Promotes Pulmonary Fibrosis through Upregulation of NEAT1.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)-induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1-knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1-KLF4-NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis.