The RNA ligase RNA terminal phosphate cyclase B regulates mRNA alternative splicing and is required for mouse oocyte development and maintenance.

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear. RNA terminal phosphate cyclase B (RTCB) is a RNA ligase; we found that RTCB conditional knockout mice have premature ovarian failure and that RTCB plays a crucial role in follicular development. RTCB regulated the splicing of transcripts related to DNA methylation and DNA damage repair. In addition, it regulated the resumption of oocyte meiosis by affecting CDK1 activation. Moreover, the loss of RTCB suppressed zygotic genome activation (ZGA) and decreased translation at the global level. In addition, Rtcb deletion resulted in the accumulation of maternal mRNAs containing unspliced introns and in a decline in the overall level of transcripts. As a result, the Rtcb-/- females were sterile. Our study highlights the important role of RTCB-regulated noncanonical alternative splicing in female reproduction.

CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.

High-Order Topological Pumping on a Superconducting Quantum Processor.

High-order topological phases of matter refer to the systems of n-dimensional bulk with the topology of m-th order, exhibiting (n-m)-dimensional boundary modes and can be characterized by topological pumping. Here, we experimentally demonstrate two types of second-order topological pumps, forming four 0-dimensional corner localized states on a 4×4 square lattice array of 16 superconducting qubits. The initial ground state of the system at half-filling, as a product of four identical entangled 4-qubit states, is prepared using an adiabatic scheme. During the pumping procedure, we adiabatically modulate the superlattice Bose-Hubbard Hamiltonian by precisely controlling both the hopping strengths and on-site potentials. At the half pumping period, the system evolves to a corner-localized state in a quadrupole configuration. The robustness of the second-order topological pump is also investigated by introducing different on-site disorder. Our Letter studies the topological properties of high-order topological phases from the dynamical transport picture using superconducting qubits, which would inspire further research on high-order topological phases.

Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74-/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PLPNs-dSTRFSIs) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PLPNs-BLAPNs) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity.

Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study.

BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16. RESULTS: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.

Lichen planus (LP) is a skin disease that causes itchy, reddish-purple bumps on the skin. LP can affect different parts of the body, including the skin, mouth, genitals and nails. People with LP often experience intense itch, pain and discomfort, which can affect their daily lives. Secukinumab is a drug specifically designed to target and block a protein called 'interleukin-17A', which is found in high amounts in the lesions of LP. We carried out a clinical study to look at the effect of secukinumab separately in three different types of LP: cutaneous LP (CLP), mucosal LP (MLP) and lichen planopilaris (LPP). The study was conducted in the USA, France and Germany. A total of 111 adults who had not responded to topical treatment (treatment applied directly on the skin) took part in the study. Patients were divided into two groups. In one group, patients were treated with secukinumab 300 mg every 4 weeks for 16 weeks and continued with the treatment for another 16 weeks. In the other group, patients received placebo for 16 weeks and then received secukinumab 300 mg every 2 weeks for the next 16 weeks. All the patients were followed up for 8 weeks after stopping treatment. We measured whether secukinumab could reduce symptoms associated with LP using both doctor- and patient-assessed severity and quality-of-life measures. We also measured the side-effects related to the drug. We found that secukinumab was safe for people with LP, but it did not substantially reduce symptoms in people with CLP and only showed a tendency for improvement in people with MLP and LPP.

Gaussian clustering and quantification of the sperm chromatin dispersion test using convolutional neural networks.

Sperm DNA fragmentation is a sign of sperm nuclear damage. The sperm chromatin dispersion (SCD) test is a reliable and economical method for the evaluation of DNA fragmentation. However, the cut-off value for differentiation of DNA fragmented sperms is fixed at 1/3 with limited statistical justification, making the SCD test a semi-quantitative method that gives user-dependent results. We construct a collection of deep neural networks to automate the evaluation of bright-field images for SCD tests. The model can detect valid sperm nuclei and their locations from the input images captured with a 20× objective and predict the geometric parameters of the halo ring. We construct an annotated dataset consisting of N = 3120 images. The ResNet 18 based network reaches an average precision (AP50) of 91.3%, a true positive rate of 96.67%, and a true negative rate of 96.72%. The distribution of relative halo radii is fit to the multi-peak Gaussian function (p > 0.99). DNA fragmentation is regarded as those with a relative halo radius 1.6 standard deviations smaller than the mean of a normal cluster. In conclusion, we have established a deep neural network based model for the automation and quantification of the SCD test that is ready for clinical application. The DNA fragmentation index is determined using Gaussian clustering, reflecting the natural distribution of halo geometry and is more tolerable to disturbances and sample conditions, which we believe will greatly improve the clinical significance of the SCD test.

Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner.

Sister chromatid separation is triggered by the separase-catalyzed cleavage of cohesin. This process is temporally controlled by cell-cycle-dependent factors, but its biochemical mechanism and spatial regulation remain poorly understood. We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner. Separase binds to DNA in vitro, but its proteolytic activity, measured by its autocleavage, is not stimulated by DNA. Instead, biochemical characterizations suggest that DNA mediates cohesin cleavage by bridging the interaction between separase and cohesin. In human cells, a fraction of separase localizes to the mitotic chromosome. The importance of the chromosomal DNA in cohesin cleavage is further demonstrated by the observation that the cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment. Our observations explain why chromosome-associated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in anaphase.

Protective Effect of Salidroside on Acute Kidney Injury in Sepsis by Inhibiting Oxidative Stress, Mitochondrial Damage, and Cell Apoptosis.

Acute kidney injury (AKI) is one of the common complications in patients with sepsis. We aimed to investigate the protective mechanism of salidroside (SLDS) on AKI induced by cecal ligation and perforation (CLP). We established a sepsis model using the CLP, and pretreated the mice with SLDS. We used biochemical methods to measure renal function, inflammatory factors and oxidase levels. We used transmission electron microscopy to observe mitochondrial damage, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) to detect apoptosis in renal tubular epithelial cells (TECs), and RT-quantitative PCR (qPCR) to detect the expression of apoptotic genes. CLP induced renal pathological damage and decreased renal function, activated inflammatory factors and oxidases, leading to mitochondrial damage and increased apoptosis of TECs. SLDS pretreatment improved renal pathological damage, reduced tumor necrosis factor (TNF)-α, interleukin (IL)-6 and malondialdehyde levels, and increased the levels of glutathione peroxidase, superoxide dismutase and catalase. Moreover, SLDS stabilized mitochondrial damage induced by CLP, inhibited TECs apoptosis, increased Bcl-2 mRNA level, and decreased Bax and Caspase-3 mRNA levels. SLDS protects CLP induced AKI by inhibiting oxidative stress, mitochondrial damage, and cell apoptosis in TECs.

Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis.

Mitochondria undergo frequent morphological changes through fission and fusion. Mutations in core members of the mitochondrial fission/fusion machinery are responsible for severe neurodegenerative diseases. However, the mitochondrial fission/fusion mechanisms are poorly understood. We found that the loss of a mitochondrial protein encoding gene, mitoguardin (miga), leads to mitochondrial defects and neurodegeneration in fly eyes. Mammals express two orthologs of miga: Miga1 and Miga2. Both MIGA1 and MIGA2 form homotypic and heterotypic complexes on the outer membrane of the mitochondria. Loss of MIGA results in fragmented mitochondria, whereas overexpression of MIGA leads to clustering and fusion of mitochondria in both fly and mammalian cells. MIGA proteins function downstream of mitofusin and interact with MitoPLD to stabilize MitoPLD and facilitate MitoPLD dimer formation. Therefore, we propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD.

Nuclear poly(A) binding protein 1 (PABPN1) mediates zygotic genome activation-dependent maternal mRNA clearance during mouse early embryonic development.

An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the maternally encoded mRNA decay pathway (M-decay) and the zygotic genome activation (ZGA)-dependent pathway (Z-decay). However, zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identified the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with a previously undescribed cytoplasmic function. Cytoplasmic PABPN1 docks on 3'-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3'-5' exoribonuclease DIS3L2 to its targets, facilitating maternal mRNA decay. Pabpn1-knockout in mice resulted in preimplantation stage mortality due to early developmental arrest at the morula stage. Maternal mRNAs to be eliminated via the Z-decay pathway failed to be removed from Pabpn1-depleted embryos. Furthermore, PABPN1-mediated Z-decay is essential for major ZGA and regulates the expression of cell fate-determining factors in mouse preimplantation embryos. This study revealed an unforeseen cytoplasmic function of PABPN1 coupled with early embryonic development, characterized the presence of a zygotic destabilizer of maternal mRNA, and elucidated the Z-decay process mechanisms, which potentially contribute to human fertility.

USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.

NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells.

Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.

Loading Dyes into Chiral Cd/Zn-Metal-Organic Frameworks for Efficient Full-Color Circularly Polarized Luminescence.

Host-guest chemistry of chiral metal-organic frameworks (MOFs) has endowed them with circularly polarized luminescence (CPL), it is still limited for MOFs to systematically tune full-color CPL emissions and sizes. This work directionally assembles the chiral ligands, metal sites and organic dyes to prepare a series of crystalline enantiomeric D/L-Cd/Zn-n MOFs (n = 1 ~ 5, representing the adding amount of dyes), where D/L-Cd/Zn with the formula of Cd2(D/L-Cam)2(TPyPE) and Zn2(D/L-Cam)2(TPyPE) (D/L-Cam = D/L-camphoric acid, TPyPE = 4,4',4'',4'''-(1,2-henediidenetetra-4,1-phenylene)tetrakis[pyridine]) were used as the chiral platforms.  The framework-dye-enabled emission and through-space chirality transfer facilitate D/L-Cd/Zn-n bright full-color CPL activity. The ideal yellow CPL of D-Cd-5 and D-Zn-4, with |glum| as 4.9 × 10-3 and 1.3 × 10-3 and relatively high photoluminescence quantum yield of 40.79% and 45.40%, are further assembled into a white CPL light-emitting diode. The crystal sizes of D/L-Cd/Zn-n were found to be strongly correlated to the types and additional amounts of organic dyes, that the positive organic dyes allow for the preparation of > 7 mm bulks and negative dyes account for sub-20 µm particles. This work opens a new avenue to fabricate full-color emissive CPL composites and provides a potentially universal method for controlling the size of optical platforms.

CXXC finger protein 1-mediated histone H3 lysine-4 trimethylation is essential for proper meiotic crossover formation in mice.

The most significant feature of meiosis is the recombination process during prophase I. CXXC finger protein 1 (CXXC1) binds to CpG islands and mediates the deposition of H3K4me3 by the SETD1 complex. CXXC1 is also predicted to recruit H3K4me3-marked regions to the chromosome axis for the generation of double-strand breaks (DSBs) in the prophase of meiosis. Therefore, we deleted Cxxc1 before the onset of meiosis with Stra8-Cre The conditional knockout mice were completely sterile with spermatogenesis arrested at MII. Knockout of Cxxc1 led to a decrease in the H3K4me3 level from the pachytene to the MII stage and caused transcriptional disorder. Many spermatogenesis pathway genes were expressed early leading to abnormal acrosome formation in arrested MII cells. In meiotic prophase, deletion of Cxxc1 caused delayed DSB repair and improper crossover formation in cells at the pachytene stage, and more than half of the diplotene cells exhibited precocious homologous chromosome segregation in both male and female meiosis. Cxxc1 deletion also led to a significant decrease of H3K4me3 enrichment at DMC1-binding sites, which might compromise DSB generation. Taken together, our results show that CXXC1 is essential for proper meiotic crossover formation in mice and suggest that CXXC1-mediated H3K4me3 plays an essential role in meiotic prophase of spermatogenesis and oogenesis.

Erk and MAPK signaling is essential for intestinal development through Wnt pathway modulation.

Homeostasis of intestinal stem cells (ISCs) is maintained by the orchestration of niche factors and intrinsic signaling networks. Here, we have found that deletion of Erk1 and Erk2 (Erk1/2) in intestinal epithelial cells at embryonic stages resulted in an unexpected increase in cell proliferation and migration, expansion of ISCs, and formation of polyp-like structures, leading to postnatal death. Deficiency of epithelial Erk1/2 results in defects in secretory cell differentiation as well as impaired mesenchymal cell proliferation and maturation. Deletion of Erk1/2 strongly activated Wnt signaling through both cell-autonomous and non-autonomous mechanisms. In epithelial cells, Erk1/2 depletion resulted in loss of feedback regulation, leading to Ras/Raf cascade activation that transactivated Akt activity to stimulate the mTor and Wnt/ß-catenin pathways. Moreover, Erk1/2 deficiency reduced the levels of Indian hedgehog and the expression of downstream pathway components, including mesenchymal Bmp4 - a Wnt suppressor in intestines. Inhibition of mTor signaling by rapamycin partially rescued Erk1/2 depletion-induced intestinal defects and significantly prolonged the lifespan of mutant mice. These data demonstrate that Erk/Mapk signaling functions as a key modulator of Wnt signaling through coordination of epithelial-mesenchymal interactions during intestinal development.

A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by coordinating somatic and germ cell transcriptomes.

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes.

Lycium barbarum glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. AIMS: In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. METHODS: SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. RESULTS: In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. CONCLUSIONS: In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

All-optical control of thermal conduction in waveguide quantum electrodynamics.

We investigate the heat conduction between two one-dimensional waveguides intermediated by a laser-driving atom. The laser provides the optical control of the heat conduction. The tunable asymmetric conduction of the heat against the temperature gradient is realized. Assisted by the modulated laser, the heat conduction from either waveguide to the other waveguide can be suppressed. The heat currents can be significantly amplified by the energy flow of the laser.

Exceptional Entanglement Phenomena: Non-Hermiticity Meeting Nonclassicality.

Non-Hermitian (NH) extension of quantum-mechanical Hamiltonians represents one of the most significant advancements in physics. During the past two decades, numerous captivating NH phenomena have been revealed and demonstrated, but all of which can appear in both quantum and classical systems. This leads to the fundamental question: what NH signature presents a radical departure from classical physics? The solution of this problem is indispensable for exploring genuine NH quantum mechanics, but remains experimentally untouched so far. Here, we resolve this basic issue by unveiling distinct exceptional entanglement phenomena, exemplified by an entanglement transition, occurring at the exceptional point of NH interacting quantum systems. We illustrate and demonstrate such purely quantum-mechanical NH effects with a naturally dissipative light-matter system, engineered in a circuit quantum electrodynamics architecture. Our results lay the foundation for studies of genuinely quantum-mechanical NH physics, signified by exceptional-point-enabled entanglement behaviors.

Observation of a Superradiant Phase Transition with Emergent Cat States.

Superradiant phase transitions (SPTs) are important for understanding light-matter interactions at the quantum level, and play a central role in criticality-enhanced quantum sensing. So far, SPTs have been observed in driven-dissipative systems, but the emergent light fields did not show any nonclassical characteristic due to the presence of strong dissipation. Here we report an experimental demonstration of the SPT featuring the emergence of a highly nonclassical photonic field, realized with a resonator coupled to a superconducting qubit, implementing the quantum Rabi model. We fully characterize the light-matter state by Wigner matrix tomography. The measured matrix elements exhibit quantum interference intrinsic of a photonic mesoscopic superposition, and reveal light-matter entanglement.