The aging behavior of degradable plastic polylactic acid under the interaction of environmental factors.

Microplastics leaching from aging biodegradable plastics pose potential environmental threats. This study used response surface methodology (RSM) to investigate the impact of temperature, light, and humidity on the aging characteristics of polylactic acid (PLA). Key evaluation metrics included the C/O ratio, functional groups, crystallinity, surface topography, and mechanical properties. Humidity was discovered to have the greatest effect on the ageing of PLA, followed by light and temperature. The interactions between temperature and light, as well as humidity and sunlight, significantly impact the aging of PLA. XPS analysis revealed PLA underwent aging due to the cleavage of the ester bond (O-C=O), resulting in the addition of C=O and C-O. The aging process of PLA was characterized by alterations in surface morphology and augmentation in crystallinity, resulting in a decline in both tensile strength and elongation. These findings might offer insights into the aging behavior of degradable plastics under diverse environmental conditions.

Microbial community structure and diversity attached to the periphyton in different urban aquatic habitats.

Periphyton is a complex community composed of diverse prokaryotes and eukaryotes; understanding the characteristics of microbial communities within periphyton becomes crucial for biogeochemical cycles and energy dynamics of aquatic ecosystems. To further elucidate the community characteristics of periphyton across varied aquatic habitats, including unpolluted ecologically restored lakes, aquaculture ponds, and areas adjacent to domestic and industrial wastewater treatment plant outfalls, we explored the composition and diversity of prokaryotic and eukaryotic communities in periphyton by employing Illumina MiSeq sequencing. Our findings indicated that the prokaryotic communities were predominantly composed of Proteobacteria (40.92%), Bacteroidota (21.01%), and Cyanobacteria (10.12%), whereas the eukaryotic communities were primarily characterized by the dominance of Bacillariophyta (24.09%), Chlorophyta (20.83%), and Annelida (15.31%). Notably, Flavobacterium emerged as a widely distributed genus among the prokaryotic community. Unclassified_Tobrilidae exhibited higher abundance in unpolluted ecologically restored lakes. Chaetogaster and Nais were enriched in aquaculture ponds and domestic wastewater treatment plant outfall area, respectively, while Surirella and Gomphonema dominated industrial sewage treatment plant outfall area. The alpha diversity of eukaryotes was higher in unpolluted ecologically restored lakes. pH and nitrogen content ( NO 2 - - N , NO 3 - - N , and TN) significantly explained the variations for prokaryotic and eukaryotic community structures, respectively. Eukaryotic communities exhibited a more pronounced response to habitat variations compared to prokaryotic communities. Moreover, the association networks revealed an intensive positive correlation between dominant Bacillariophyta and Bacteroidota. This study provided useful data for identifying keystone species and understanding their ecological functions.

Enhanced surfactant remediation of diesel-contaminated soil using O3 nanobubbles.

Currently, nanobubbles are widely discussed in environmental research due to their unique properties, including significant specific surface area, transfer efficiency, and free radical generation. In this study, O2 and O3 nanobubbles (diameters ranging from 0 to 500 nm) were combined with conventional surfactant technology to investigate their enhanced efficacy in removing diesel contaminants from soil. The impact of various factors such as surfactant concentration, temperature, and soil aging duration on pollutant removal rates was examined across different experimental approaches (stirring/flushing). Soil samples subjected to different treatments were characterized using TG-DTG and FTIR analysis, while GC/MS was employed to assess the degradation products of diesel constituents in the soil. The results indicated that the elution efficiencies of the three surfactants (SDS, SDBS, and TX-100) for diesel in soil correlated positively with concentration (0.3-1.4 CMC) and temperature (18-60 °C), and inversely with aging time (10-300 days), with the elution capacity was SDS > SDBS > TX-100. Mechanical stirring (500 rpm) and temperature variations (18-60 °C) did not affect the stability of the nanobubbles. Upon the introduction of O3 nanobubbles to the surfactant solution, there was a consistent increase in both the removal (degraded and removed) efficiency and rate of diesel under varying experimental conditions, resulting in an enhancement of removal rates by approximately 8-15%. FTIR spectroscopy showed that surfactants containing O3 nanobubbles mitigated the impact on the primary functional groups of soil organic matter. GC/MS analyses indicated that residual pollutants were predominantly alkanes, with degradation difficulty ranking as: alkanes < alkenes < cycloalkanes < aromatic compounds. TG-DTG coupled with GC/MS analysis demonstrated that O3 nanobubbles contributed to a reduction in surfactant residues. This study significantly advances our understanding of how nanobubbles facilitate and optimize surfactant-assisted remediation of contaminated soil, thereby advancing the precise application of nanobubble technology in soil remediation.

The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors.

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

Efficient Single Correspondence Voting for Point Cloud Registration.

3D point cloud registration is a crucial task in a variety of fields, including remote sensing mapping, computer vision, virtual reality, and autonomous driving. However, this task is still challenging due to the challenges of noise, non-uniformity, partial overlap, and repeated local features in large scene point clouds. In this paper, we propose an efficient single correspondence voting method for large scene point cloud registration. Specifically, we first propose an efficient hypothetical transformation prediction method called SCVC, which determines the 5 degrees of freedom of the transformation through one correspondence, and then uses Hough voting to determine the last degree of freedom. This algorithm can significantly improve the accuracy of registration in both indoor and outdoor scenes. On the other hand, we propose a more robust transformation verification function called VDIR, which can obtain the optimal registration result of two raw point clouds. Finally, we conduct a series of experiments that demonstrate that our method achieves state-of-the-art performance on four real-world datasets: 3DMatch, 3DLoMatch, KITTI, and WHU-TLS. Our code is available at https://github.com/xingxuejun1989/SCVC.

Iliopsoas fibrosis after revision of total hip arthroplasty revealed by 68Ga-FAPI PET/CT: a case report.

Background: Total hip arthroplasty (THA) is a well-established surgical procedure that has been extensively validated to alleviate pain, enhance joint function, improve the ability to perform daily activities, and enhance overall quality of life. However, this procedure is associated with certain complications, among which skeletal muscle fibrosis is a frequently overlooked but significant complication that can lead to persistent pain. Currently, there is no effective method for diagnosing skeletal muscle fibrosis following total hip arthroplasty. Case report: We report a 75-year-old male patient who complained of left groin pain after revision total hip arthroplasty. Serological examinations, X-rays, and bone scan results were all normal. However, during the 68Ga-FAPI PET/CT examination, we observed significant radiotracer uptake along the iliopsoas muscle. This abnormal uptake pattern suggested potential biological activity in this specific area. Combined with physical examination, the patient was diagnosed with iliopsoas fibrosis. Conclusions: The presented images indicated that the uptake pattern was an important indicator for diagnosis, and the prospect of fibroblast activation protein in the diagnosis of skeletal muscle fibrosis has shown certain application value.

Structural and functional characterization of AfsR, an SARP family transcriptional activator of antibiotic biosynthesis in Streptomyces.

Streptomyces antibiotic regulatory proteins (SARPs) are widely distributed activators of antibiotic biosynthesis. Streptomyces coelicolor AfsR is an SARP regulator with an additional nucleotide-binding oligomerization domain (NOD) and a tetratricopeptide repeat (TPR) domain. Here, we present cryo-electron microscopy (cryo-EM) structures and in vitro assays to demonstrate how the SARP domain activates transcription and how it is modulated by NOD and TPR domains. The structures of transcription initiation complexes (TICs) show that the SARP domain forms a side-by-side dimer to simultaneously engage the afs box overlapping the -35 element and the σHrdB region 4 (R4), resembling a sigma adaptation mechanism. The SARP extensively interacts with the subunits of the RNA polymerase (RNAP) core enzyme including the ß-flap tip helix (FTH), the ß' zinc-binding domain (ZBD), and the highly flexible C-terminal domain of the α subunit (αCTD). Transcription assays of full-length AfsR and truncated proteins reveal the inhibitory effect of NOD and TPR on SARP transcription activation, which can be eliminated by ATP binding. In vitro phosphorylation hardly affects transcription activation of AfsR, but counteracts the disinhibition of ATP binding. Overall, our results present a detailed molecular view of how AfsR serves to activate transcription.

Off-axis bifocal metalens for displacement measurement.

Metasurface is a new type of micro-optical element developed in recent years. It can intelligently modulate electromagnetic waves by adjusting the geometrical parameters and arrangement of dielectric structures. In this paper, a bifocal metalens based on modulation of propagation phase was designed for the potential application in displacement measurement. The phase of the bifocal lens is designed by the optical holography-like method, which is verified by the scalar diffraction theory. We designed a square aperture lens with a side length of 200µm to realize two focal spots with focal lengths of 900 and 1100µm. The two focal spots aren't on one optical axis. The polarization insensitive TiO2cylinders are chosen as structure units. Four structures with different radius were selected to achieve the four phase steps. We fabricated the designed bifocal metalens using electron beam lithography and atomic layer deposition techniques, and measured the light intensity in the areas near the two foci in the direction of the longitudinal axis. The differential signal was calculated, from which we obtained a linear interval. It demonstrates the ability of bifocal differential measurement to be applied to displacement measurement. Because the metasurfaces production process is semiconductor compatible, the bifocal lens is easy to integrate and can be used for miniaturized displacement measurements, micro-resonators, acceleration measurements, and so on.

Anticoagulant therapy in orthopedic surgery - a review on anticoagulant agents, risk factors, monitoring, and current challenges.

Orthopedic surgeries are associated with high-risk of thromboembolism which occurs in 40% to 60% of orthopedic patients in the absence of thromboprophylaxis. Conventionally heparin anticoagulants were used for thromboprophylaxis and currently direct oral anticoagulants (DOACs) are widely used due to their minimal complexity. Anticoagulant use carries bleeding risk and requires optimal laboratory monitoring through conventional thrombin-based assays, anti-Xa assay, anti-IIa assay and contemporary ecarin chromogenic assay (ECA) and rotational thromboelastometry. Monitoring requires multiple hospital visits and hence, the development of point-of-care assays is gaining momentum. Also, a thorough risk assessment model (RAM) is necessary for successful anticoagulant therapy since it enables personalized approach for better thromboprophylaxis outcomes. Despite welcoming changes, lack of guideline consensus, population-based thromboprophylaxis, deficiencies in risk stratification and non-adherence are still a concern. Stronger clinical and process support system with uniform guidelines approaches and patient-specific RAM can aid in the successful implementation of anticoagulant therapy.

Probing the critical nucleus size in tetrahydrofuran clathrate hydrate formation using surface-anchored nanoparticles.

Controlling the formation of clathrate hydrates is crucial for advancing hydrate-based technologies. However, the microscopic mechanism underlying clathrate hydrate formation through nucleation remains poorly elucidated. Specifically, the critical nucleus, theorized as a pivotal step in nucleation, lacks empirical validation. Here, we report uniform nanoparticles, e.g., graphene oxide (GO) nanosheets and gold or silver nanocubes with controlled sizes, as nanoprobes to experimentally measure the size of the critical nucleus of tetrahydrofuran (THF) clathrate hydrate formation. The capability of the nanoparticles in facilitating THF clathrate hydrate nucleation displays generally an abrupt change at a nanoparticle-size-determined specific supercooling. It is revealed that the free-energy barrier shows an abrupt change when the nanoparticles have an approximately the same size as that of the critical nucleus. Thus, it is inferred that THF clathrate hydrate nucleation involves the creation of a critical nucleus with its size being inversely proportional to the supercooling. By proving the existence and determining the supercooling-dependent size of the critical nucleus of the THF clathrate hydrates, this work brings insights in the microscopic pictures of the clathrate hydrate nucleation.

Ultrasound-Controlled Delivery of Growth Factor-Loaded Cerasomes Combined with Polycaprolactone Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells for Biomimetic Tendon-to-Bone Interface Engineering.

Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFß1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.

Aryl hydrocarbon receptor restricts axon regeneration of DRG neurons in response to injury.

Injured neurons sense environmental cues to balance neural protection and axon regeneration, but the mechanisms are unclear. Here, we unveil aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, as molecular sensor and key regulator of acute stress response at the expense of axon regeneration. We demonstrate responsiveness of DRG sensory neurons to ligand-mediated AhR signaling, which functions to inhibit axon regeneration. Ahr deletion mimics the conditioning lesion in priming DRG to initiate axonogenesis gene programs; upon peripheral axotomy, Ahr ablation suppresses inflammation and stress signaling while augmenting pro-growth pathways. Moreover, comparative transcriptomics revealed signaling interactions between AhR and HIF-1α, two structurally related bHLH-PAS α units that share the dimerization partner Arnt/HIF-1ß. Functional assays showed that the growth advantage of AhR-deficient DRG neurons requires HIF-1α; but in the absence of Arnt, DRG neurons can still mount a regenerative response. We further unveil a link between bHLH-PAS transcription factors and DNA hydroxymethylation in response to peripheral axotomy, while neuronal single cell RNA-seq analysis revealed a link of the AhR regulon to RNA polymerase III regulation and integrated stress response (ISR). Altogether, AhR activation favors stress coping and inflammation at the expense of axon regeneration; targeting AhR can enhance nerve repair.

Docosahexaenoic Acid Explains the Unexplained in Visual Transduction.

In George Wald's Nobel Prize acceptance speech for "discoveries concerning the primary physiological and chemical visual processes in the eye", he noted that events after the activation of rhodopsin are too slow to explain visual reception. Photoreceptor membrane phosphoglycerides contain near-saturation amounts of the omega-3 fatty acid docosahexaenoic acid (DHA). The visual response to a photon is a retinal cis-trans isomerization. The trans-state is lower in energy; hence, a quantum of energy is released equivalent to the sum of the photon and cis-trans difference. We hypothesize that DHA traps this energy, and the resulting hyperpolarization extracts the energized electron, which depolarizes the membrane and carries a function of the photon's energy (wavelength) to the brain. There, it contributes to the creation of the vivid images of our world that we see in our consciousness. This proposed revision to the visual process provides an explanation for these previously unresolved issues around the speed of information transfer and the purity of conservation of a photon's wavelength and supports observations of the unique and indispensable role of DHA in the visual process.

Severe pneumonia with empyema caused by Parvimonas micra and Streptococcus constellatus co-infection: a case report.

Empyema is a common complication of pneumonia, caused by the accumulation of purulent exudate due to pathogenic bacteria invading the pleural cavity. Parvimonas micra and Streptococcus constellatus are pathogens that rarely cause pneumonia with empyema. Herein, a case of severe empyema caused by these two pathogens, confirmed by metagenomic next-generation sequencing (mNGS) of pleural effusion cultures, is reported. A male Chinese patient in his late sixties presented with wheezing, cough, sputum expectoration, and fever. Blood and sputum cultures were negative for pathogens, but the pleural effusion culture was positive for S. constellatus, and was also found to contain P. micra, confirmed by mNGS. The patient's symptoms improved after treatment with cefoperazone/sulbactam and moxifloxacin. Pneumonia caused by P. micra and S. constellatus is rare; however, coinfection with these pathogens may cause severe pneumonia, with or without empyema.

Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.

During development, animals generate distinct cell populations with specific identities, functions, and morphologies. We mapped transcriptionally distinct populations across 489,686 cells from 62 stages during wild-type zebrafish embryogenesis and early larval development (3-120 h post-fertilization). Using these data, we identified the limited catalog of gene expression programs reused across multiple tissues and their cell-type-specific adaptations. We also determined the duration each transcriptional state is present during development and identify unexpected long-term cycling populations. Focused clustering and transcriptional trajectory analyses of non-skeletal muscle and endoderm identified transcriptional profiles and candidate transcriptional regulators of understudied cell types and subpopulations, including the pneumatic duct, individual intestinal smooth muscle layers, spatially distinct pericyte subpopulations, and recently discovered best4+ cells. To enable additional discoveries, we make this comprehensive transcriptional atlas of early zebrafish development available through our website, Daniocell.

Advances in circadian clock regulation of reproduction.

The mammalian circadian clock is an endogenously regulated oscillator that is synchronized with solar time and cycle within a 24-h period. The circadian clock exists not only in the suprachiasmatic nucleus (SCN) of the hypothalamus, a central pacemaker of the circadian clock system, but also in numerous peripheral tissues known as peripheral circadian oscillators. The SCN and peripheral circadian oscillators mutually orchestrate the diurnal rhythms of various physiological and behavioral processes in a hierarchical manner. In the past two decades, peripheral circadian oscillators have been identified and their function has been determined in the mammalian reproductive system and its related endocrine glands, including the hypothalamus, pituitary gland, ovaries, testes, uterus, mammary glands, and prostate gland. Increasing evidence indicates that both the SCN and peripheral circadian oscillators play discrete roles in coordinating reproductive processes and optimizing fertility in mammals. The present study reviews recent evidence on circadian clock regulation of reproductive function in the hypothalamic-pituitary-gonadal axis and reproductive system. Additionally, we elucidate the effects of chronodisruption (as a result of, for example, shift work, jet lag, disrupted eating patterns, and sleep disorders) on mammalian reproductive performance from multiple aspects. Finally, we propose potential behavioral changes or pharmaceutical strategies for the prevention and treatment of reproductive disorders from the perspective of chronomedicine. Conclusively, this review will outline recent evidence on circadian clock regulation of reproduction, providing novel perspectives on the role of the circadian clock in maintaining normal reproductive functions and in diseases that negatively affect fertility.

Meniscal Fibrocartilage Repair Based on Developmental Characteristics: A Proof-of-Concept Study.

BACKGROUND: Unlike the adult meniscus, the fetal meniscus possesses robust healing capacity. The dense and stiff matrix of the adult meniscus provides a biophysical barrier for cell migration, which is not present in the fetal meniscus. Inspired by developmental characteristics, modifying the matrix of the adult meniscus into a fetal-like, loose and soft microenvironment holds opportunity to facilitate repair, especially in the avascular zone. HYPOTHESIS: Modifying the dense and stiff matrix of the adult meniscus into a fetal-like, loose and soft microenvironment could enhance cell migration to the tear interface and subsequent robust healing capacity. STUDY DESIGN: Controlled laboratory study. METHODS: Fresh porcine menisci were treated with hyaluronidase or collagenase. The density and arrangement of collagen fibers were assessed. The degradation of proteoglycans and collagen was evaluated histologically. Cell migration within the meniscus or the infiltration of exogenous cells into the meniscus was examined. Dendritic silica nanoparticles with relatively large pores were used to encapsulate hyaluronidase for rapid release. Mesoporous silica nanoparticles with relatively small pores were used to encapsulate transforming growth factor-beta 3 (TGF-ß3) for slow release. A total of 24 mature male rabbits were included. A longitudinal vertical tear (0.5 cm in length) was prepared in the avascular zone of the medial meniscus. The tear was repaired with suture, repaired with suture in addition to blank silica nanoparticles, or repaired with suture in addition to silica nanoparticles releasing hyaluronidase and TGF-ß3. Animals were sacrificed at 12 months postoperatively. Meniscal repair was evaluated macroscopically and histologically. RESULTS: The gaps between collagen bundles increased after hyaluronidase treatment, while collagenase treatment resulted in collagen disruption. Proteoglycans degraded after hyaluronidase treatment in a dose-dependent manner, but collagen integrity was maintained. Hyaluronidase treatment enhanced the migration and infiltration of cells within meniscal tissue. Last, the application of fibrin gel and the delivery system of silica nanoparticles encapsulating hyaluronidase and TGF-ß3 enhanced meniscal repair responses in an orthotopic longitudinal vertical tear model. CONCLUSION: The gradient release of hyaluronidase and TGF-ß3 removed biophysical barriers for cell migration, creating a fetal-like, loose and soft microenvironment, and enhanced the fibrochondrogenic phenotype of reparative cells, facilitating the synthesis of matrix and tissue integration. CLINICAL RELEVANCE: Modifying the adult matrix into a fetal-like, loose and soft microenvironment via the local gradient release of hyaluronidase and TGF-ß3 enhanced the healing capacity of the meniscus.

Data correction and verification of thermal simulation experiments under the influence of bulging belly.

During the thermal simulation compression test, the formation of an obvious bulge in the specimen leads to a certain deviation between the calculated and actual values of the true stress. The finite element method was used to simulate the single-pass compression of specimens of 34CrNi3MoV steel and obtain the actual nonuniform deformation of the bulging belly during the compression process, and the results were applied to correct experimental flow curves. The results showed that the deformation conditions had a significant influence on the nonuniformity of the specimen deformation during the compression process, and all the modified flow curves were lower than the original ones. The size of the bulge and the metal flow line in the finite element simulation were consistent with the test results. The load value obtained by using the modified flow curve was similar to the load value measured in the test, which indicated that the modified flow curve was very close to the real flow force curve of the material. The method used to modify the flow force curve is simple and practical.

Hypoxia activation attenuates progesterone synthesis in goat trophoblast cells via NR1D1 inhibition of StAR expression†.

Trophoblast plays a crucial role in gestation maintenance and embryo implantation, partly due to the synthesis of progesterone. It has been demonstrated that hypoxia regulates invasion, proliferation, and differentiation of trophoblast cells. Additionally, human trophoblasts display rhythmic expression of circadian clock genes. However, it remains unclear if the circadian clock system is present in goat trophoblast cells (GTCs), and its involvement in hypoxia regulation of steroid hormone synthesis remains elusive. In this study, immunofluorescence staining revealed that both BMAL1 and NR1D1 (two circadian clock components) were highly expressed in GTCs. Quantitative real-time PCR analysis showed that several circadian clock genes were rhythmically expressed in forskolin-synchronized GTCs. To mimic hypoxia, GTCs were treated with hypoxia-inducing reagents (CoCl2 or DMOG). Quantitative real-time PCR results demonstrated that hypoxia perturbed the mRNA expression of circadian clock genes and StAR. Notably, the increased expression of NR1D1 and the reduction of StAR expression in hypoxic GTCs were also detected by western blotting. In addition, progesterone secretion exhibited a notable decline in hypoxic GTCs. SR9009, an NR1D1 agonist, significantly decreased StAR expression at both the mRNA and protein levels and markedly inhibited progesterone secretion in GTCs. Moreover, SR8278, an NR1D1 antagonist, partially reversed the inhibitory effect of CoCl2 on mRNA and protein expression levels of StAR and progesterone synthesis in GTCs. Our results demonstrate that hypoxia reduces StAR expression via the activation of NR1D1 signaling in GTCs, thus inhibiting progesterone synthesis. These findings provide new insights into the NR1D1 regulation of progesterone synthesis in GTCs under hypoxic conditions.

Circadian clock regulator Bmal1 gates axon regeneration via Tet3 epigenetics in mouse sensory neurons.

Axon regeneration of dorsal root ganglia (DRG) neurons after peripheral axotomy involves reconfiguration of gene regulatory circuits to establish regenerative gene programs. However, the underlying mechanisms remain unclear. Here, through an unbiased survey, we show that the binding motif of Bmal1, a central transcription factor of the circadian clock, is enriched in differentially hydroxymethylated regions (DhMRs) of mouse DRG after peripheral lesion. By applying conditional deletion of Bmal1 in neurons, in vitro and in vivo neurite outgrowth assays, as well as transcriptomic profiling, we demonstrate that Bmal1 inhibits axon regeneration, in part through a functional link with the epigenetic factor Tet3. Mechanistically, we reveal that Bmal1 acts as a gatekeeper of neuroepigenetic responses to axonal injury by limiting Tet3 expression and restricting 5hmC modifications. Bmal1-regulated genes not only concern axon growth, but also stress responses and energy homeostasis. Furthermore, we uncover an epigenetic rhythm of diurnal oscillation of Tet3 and 5hmC levels in DRG neurons, corresponding to time-of-day effect on axon growth potential. Collectively, our studies demonstrate that targeting Bmal1 enhances axon regeneration.