Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis.

Activating mutations in NRAS account for 20%-30% of melanoma, but despite decades of research and in contrast to BRAF, no effective anti-NRAS therapies have been forthcoming. Here, we identify a previously uncharacterized serine/threonine kinase STK19 as a novel NRAS activator. STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation. A recurrent D89N substitution in STK19 whose alterations were identified in 25% of human melanomas represents a gain-of-function mutation that interacts better with NRAS to enhance melanocyte transformation. STK19D89N knockin leads to skin hyperpigmentation and promotes NRASQ61R-driven melanomagenesis in vivo. Finally, we developed ZT-12-037-01 (1a) as a specific STK19-targeted inhibitor and showed that it effectively blocks oncogenic NRAS-driven melanocyte malignant transformation and melanoma growth in vitro and in vivo. Together, our findings provide a new and viable therapeutic strategy for melanomas harboring NRAS mutations.

DELLA-mediated gene repression is maintained by chromatin modification in rice.

DELLA proteins are master regulators of gibberellic acid (GA) signaling through their effects on gene expression. Enhanced DELLA accumulation in rice and wheat varieties has greatly contributed to grain yield increases during the green revolution. However, the molecular basis of DELLA-mediated gene repression remains elusive. In this work, we show that the rice DELLA protein SLENDER RICE1 (SLR1) forms a tripartite complex with Polycomb-repressive complex 2 (PRC2) and the histone deacetylase HDA702 to repress downstream genes by establishing a silent chromatin state. The slr1 mutation and GA signaling resulted in dissociation of PRC2 and HDA702 from GA-inducible genes. Loss-of-function or downregulation of the chromatin regulators impaired SLR1-dependent histone modification and gene repression. Time-resolved analysis of GA signaling revealed that GA-induced transcriptional activation was associated with a rapid increase of H3K9ac followed by H3K27me3 removal. Collectively, these results establish a general epigenetic mechanism for DELLA-mediated gene repression and reveal details of the chromatin dynamics during transcriptional activation stimulated by GA signaling.

Cold-induced deposition of bivalent H3K4me3-H3K27me3 modification and nucleosome depletion in Arabidopsis.

Epigenetic regulation of gene expression plays a crucial role in plant development and environmental adaptation. The H3K4me3 and H3K27me3 have not only been discovered in the regulation of gene expression in multiple biological processes but also in responses to abiotic stresses in plants. However, evidence for the presence of both H3K4me3 and H3K27me3 on the same nucleosome is sporadic. Cold-induced deposition of bivalent H3K4me3-H3K27me3 modifications and nucleosome depletion over a considerable number of active genes is documented in potato tubers and provides clues on an additional role of the bivalent modifications. Limited by the available information of genes encoding PcG/TrxG proteins as well as their corresponding mutants in potatoes, the molecular mechanism underlying the cold-induced deposition of the bivalent mark remains elusive. In this study, we found a similar deposition of the bivalent H3K4me3-H3K27me3 mark over 2129 active genes in cold-treated Arabidopsis Col-0 seedlings. The expression levels of the bivalent mark-associated genes tend to be independent of bivalent modification levels. However, these genes were associated with greater chromatin accessibility, presumably to provide a distinct chromatin environment for gene expression. In mutants clf28 and lhp1, failure to deposit H3K27me3 in active genes upon cold treatment implies that the CLF is potentially involved in cold-induced deposition of H3K27me3, with assistance from LHP1. Failure to deposit H3K4me3 during cold treatment in atx1-2 suggests a regulatory role of ATX1 in the deposition of H3K4me3. In addition, we observed a cold-induced global reduction in nucleosome occupancy, which is potentially mediated by LHP1 in an H3K27me3-dependent manner.

A coiled-coil protein associates Polycomb Repressive Complex 2 with KNOX/BELL transcription factors to maintain silencing of cell differentiation-promoting genes in the shoot apex.

Polycomb repressive complex 2 (PRC2), which mediates the deposition of H3K27me3 histone marks, is important for developmental decisions in animals and plants. In the shoot apical meristem (SAM), Three Amino acid Loop Extension family KNOTTED-LIKE HOMEOBOX /BEL-like (KNOX/BELL) transcription factors are key regulators of meristem cell pluripotency and differentiation. Here, we identified a PRC2-associated coiled-coil protein (PACP) that interacts with KNOX/BELL transcription factors in rice (Oryza sativa) shoot apex cells. A loss-of-function mutation of PACP resulted in differential gene expression similar to that observed in PRC2 gene knockdown plants, reduced H3K27me3 levels, and reduced genome-wide binding of the PRC2 core component EMF2b. The genomic binding of PACP displayed a similar distribution pattern to EMF2b, and genomic regions with high PACP- and EMF2b-binding signals were marked by high levels of H3K27me3. We show that PACP is required for the repression of cell differentiation-promoting genes targeted by a rice KNOX1 protein in the SAM. PACP is involved in the recruitment or stabilization of PRC2 to genes targeted by KNOX/BELL transcription factors to maintain H3K27me3 and gene repression in dividing cells of the shoot apex. Our results provide insight into PRC2-mediated maintenance of H3K27me3 and the mechanism by which KNOX/BELL proteins regulate SAM development.

MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.

Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue damage. Hence, it is critical to program activated T cells to achieve ROS equilibrium. Here, we determined that miR-23a is indispensable for effector CD4(+) T cell expansion, particularly by providing early protection from excessive necrosis. Mechanistically, miR-23a targeted PPIF, gatekeeper of the mitochondria permeability transition pore, thereby restricting ROS flux and maintaining mitochondrial integrity. Upon acute Listeria monocytogenes infection, deleting miR-23a in T cells resulted in excessive inflammation, massive liver damage, and a marked mortality increase, which highlights the essential role of miR-23a in maintaining immune homeostasis.

Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression.

BACKGROUND: Excess cholesterol accumulation in lesional macrophages elicits complex responses in atherosclerosis. Epsins, a family of endocytic adaptors, fuel the progression of atherosclerosis; however, the underlying mechanism and therapeutic potential of targeting Epsins remains unknown. In this study, we determined the role of Epsins in macrophage-mediated metabolic regulation. We then developed an innovative method to therapeutically target macrophage Epsins with specially designed S2P-conjugated lipid nanoparticles, which encapsulate small-interfering RNAs to suppress Epsins. METHODS: We used single-cell RNA sequencing with our newly developed algorithm MEBOCOST (Metabolite-mediated Cell Communication Modeling by Single Cell Transcriptome) to study cell-cell communications mediated by metabolites from sender cells and sensor proteins on receiver cells. Biomedical, cellular, and molecular approaches were utilized to investigate the role of macrophage Epsins in regulating lipid metabolism and transport. We performed this study using myeloid-specific Epsin double knockout (LysM-DKO) mice and mice with a genetic reduction of ABCG1 (ATP-binding cassette subfamily G member 1; LysM-DKO-ABCG1fl/+). The nanoparticles targeting lesional macrophages were developed to encapsulate interfering RNAs to treat atherosclerosis. RESULTS: We revealed that Epsins regulate lipid metabolism and transport in atherosclerotic macrophages. Inhibiting Epsins by nanotherapy halts inflammation and accelerates atheroma resolution. Harnessing lesional macrophage-specific nanoparticle delivery of Epsin small-interfering RNAs, we showed that silencing of macrophage Epsins diminished atherosclerotic plaque size and promoted plaque regression. Mechanistically, we demonstrated that Epsins bound to CD36 to facilitate lipid uptake by enhancing CD36 endocytosis and recycling. Conversely, Epsins promoted ABCG1 degradation via lysosomes and hampered ABCG1-mediated cholesterol efflux and reverse cholesterol transport. In a LysM-DKO-ABCG1fl/+ mouse model, enhanced cholesterol efflux and reverse transport due to Epsin deficiency was suppressed by the reduction of ABCG1. CONCLUSIONS: Our findings suggest that targeting Epsins in lesional macrophages may offer therapeutic benefits for advanced atherosclerosis by reducing CD36-mediated lipid uptake and increasing ABCG1-mediated cholesterol efflux.

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism.

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.

Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Targeting Epsins to Inhibit Fibroblast Growth Factor Signaling While Potentiating Transforming Growth Factor-ß Signaling Constrains Endothelial-to-Mesenchymal Transition in Atherosclerosis.

BACKGROUND: Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, the underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) in atherosclerosis and assessed the efficacy of a therapeutic peptide in a preclinical model of this disease. METHODS: Using single-cell RNA sequencing combined with molecular, cellular, and biochemical analyses, we investigated the role of epsins in stimulating EndoMT using knockout in Apoe-/- and lineage tracing/proprotein convertase subtilisin/kexin type 9 serine protease mutant viral-induced atherosclerotic mouse models. The therapeutic efficacy of a synthetic peptide targeting atherosclerotic plaques was then assessed in Apoe-/- mice. RESULTS: Single-cell RNA sequencing and lineage tracing revealed that epsins 1 and 2 promote EndoMT and that the loss of endothelial epsins inhibits EndoMT marker expression and transforming growth factor-ß signaling in vitro and in atherosclerotic mice, which is associated with smaller lesions in the Apoe-/- mouse model. Mechanistically, the loss of endothelial cell epsins results in increased fibroblast growth factor receptor-1 expression, which inhibits transforming growth factor-ß signaling and EndoMT. Epsins directly bind ubiquitinated fibroblast growth factor receptor-1 through their ubiquitin-interacting motif, which results in endocytosis and degradation of this receptor complex. Consequently, administration of a synthetic ubiquitin-interacting motif-containing peptide atheroma ubiquitin-interacting motif peptide inhibitor significantly attenuates EndoMT and progression of atherosclerosis. CONCLUSIONS: We conclude that epsins potentiate EndoMT during atherogenesis by increasing transforming growth factor-ß signaling through fibroblast growth factor receptor-1 internalization and degradation. Inhibition of EndoMT by reducing epsin-fibroblast growth factor receptor-1 interaction with a therapeutic peptide may represent a novel treatment strategy for atherosclerosis.

Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis.

OBJECTIVE: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS: We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

Comparative transcriptome analysis reveals transcriptional regulation of anthocyanin biosynthesis in purple radish (Raphanus sativus L.).

Radish exhibits significant variation in color, particularly in sprouts, leaves, petals, fleshy roots, and other tissues, displaying a range of hues such as green, white, red, purple, and black. Although extensive research has been conducted on the color variation of radish, the underlying mechanism behind the variation in radish flower color remains unclear. To date, there is a lack of comprehensive research investigating the variation mechanism of radish sprouts, leaves, fleshy roots, and flower organs. This study aims to address this gap by utilizing transcriptome sequencing to acquire transcriptome data for white and purple radish flowers. Additionally, the published transcriptome data of sprouts, leaves, and fleshy roots were incorporated to conduct a systematic analysis of the regulatory mechanisms underlying anthocyanin biosynthesis in these four radish tissues. The comparative transcriptome analysis revealed differential expression of the anthocyanin biosynthetic pathway genes DFR, UGT78D2, TT12 and CPC in the four radish tissues. Additionally, the WGCNA results identified RsDFR.9c and RsUGT78D2.2c as hub genes responsible for regulating anthocyanin biosynthesis. By integrating the findings from the comparative transcriptome analysis, WGCNA, and anthocyanin biosynthetic pathway-related gene expression patterns, it is hypothesized that genes RsDFR.9c and RsUGT78D2.2c may serve as pivotal regulators of anthocyanins in the four radish tissues. Furthermore, the tissue-specific expression of the four copies of RsPAP1 is deemed crucial in governing anthocyanin synthesis and accumulation. Our results provide new insights into the molecular mechanism of anthocyanin biosynthesis and accumulation in different tissues of radish.

Pd(0)-Catalyzed Asymmetric Cyclization/Coupling Cascade of Alkyne-Tethered Unsaturated Carbonyls: Development and Mechanism Elucidation.

While the Pd(0)-catalyzed cyclization of alkyne-tethered unsaturated carbonyl substrates has been reported, the mechanism has not been well elucidated, and the potential asymmetric version remains to be developed. Here, we disclose that a chiral Pd(0) complex can efficiently promote the desymmetrizative cyclization of alkyne-tethered cyclohexadienones in CH3OH, and the resultant Pd(II) intermediates further undergo an array of tandem coupling reactions, including Suzuki, Sonogashira, and even chemoselective reduction by CH3OH in the absence of additional coupling partners. As a result, a broad spectrum of hydrobenzofuran derivatives, having a tetra- or trisubstituted exo-alkene motif, is constructed with moderate to outstanding enantioselectivity in an exclusive cis-difunctionalization pattern. In addition, this enantioselective protocol can be well expanded to linear alkyne-tethered unsaturated carbonyls, and a new desymmetrizative and asymmetric cyclization/coupling cascade of bis-alkyne-tethered enones is further realized efficiently, furnishing diversely structured frameworks with high stereoselectivity. Moreover, kinetic transformation for various racemic alkyne-tethered enones can be accomplished under similar catalytic conditions, and unusual kinetic reactions by chemoselectively undertaking Suzuki or Sonogashira coupling, or reduction by CH3OH, occur sequentially, finally yielding two types of chiral products, both with high enantioselectivity via either ligand- or substrate-based control. The experimental results demonstrate that the current Pd(0)-based strategy is superior to the classical Pd(II)-catalyzed carbopalladation/cyclization process of the identical substrates with regard to enantioselectivity and synthetic versatility. Moreover, density functional theory calculations are conducted to rationalize the Pd(0)-catalyzed oxidative cyclometalation pathway in the key cyclization step, which leads to the observed cis-difunctionalized products exclusively.

NLRP12-associated autoinflammatory disease: A novel causal mutation and bioinformatics analyses.

Nucleotide-binding leucine-rich repeat-containing receptor 12-associated autoinflammatory disease (NLRP12-AID) is a rare autosomal dominant disorder. In this study, we reported a case of this rare disease with a novel NLRP12 mutation (A218V, rs749659859). The patient displayed typical symptoms, including recurrent fever, arthralgia, and skin allergies. Elevated serum IgE, decreased apolipoprotein A1, high-density lipoprotein cholesterol, and fluctuating levels of various leukocyte subtypes, procalcitonin, IL6, creatine kinase, and 25-hydroxyvitamin D were also detected. Inflammatory lesions were observed in multiple organs using 18F-FDG PET/CT. By mining single-cell transcriptome data, we identified relatively high expression of NLRP12 in monocytes compared to other human peripheral blood mononuclear cells. NLRP12-positive monocytes exhibited reduced expression of IL18, CCL3, and TNFA compared to NLRP12-negative monocytes. Structural analyses suggested that the A218V mutation, along with A218T and F402L, may reduce the ATP-binding affinity of the NLRP12 protein. These findings may provide new insights into the mechanisms of NLRP12-AID, and suggest the potential ATP-based therapy for further investigation.

Molecular evolution analysis of MYB5 in Brassicaceae with specific focus on seed coat color of Brassica napus.

BACKGROUND: MYB transcription factors are splay a vital role in plant biology, with previous research highlighting the significant impact of the R2R3-MYB-like transcription factor MYB5 on seed mucilage biosynthesis, trichome branching, and seed coat development. However, there is a dearth of studies investigating its role in the regulation of proanthocyanidin (PA) biosynthesis. RESULTS: In this study, a total of 51 MYB5 homologous genes were identified across 31 species belonging to the Brassicaceae family, with particular emphasis on Brassica napus for subsequent investigation. Through phylogenetic analysis, these genes were categorized into four distinct subclasses. Protein sequence similarity and identity analysis demonstrated a high degree of conservation of MYB5 among species within the Brassicaceae family. Additionally, the examination of selection pressure revealed that MYB5 predominantly underwent purifying selection during its evolutionary history, as indicated by the Ka/Ks values of all MYB5 homologous gene pairs being less than one. Notably, we observed a higher rate of non-synonymous mutations in orthologous genes compared to paralogous genes, and the Ka/Ks value displayed a stronger correlation with Ka. In B. napus, an examination of expression patterns in five tissues revealed that MYB5 exhibited particularly high expression in the black seed coat. The findings from the WGCNA demonstrated a robust correlation between MYB5 and BAN(ANR) associated with PA biosynthesis in the black seed coat, providing further evidence of their close association and co-expression. Furthermore, the results obtained from of the analysis of protein interaction networks offer supplementary support for the proposition that MYB5 possesses the capability to interact with transcriptional regulatory proteins, specifically TT8 and TT2, alongside catalytic enzymes implicated in the synthesis of PAs, thereby making a contribution to the biosynthesis of PAs. These findings imply a plausible and significant correlation between the nuique expression pattern of MYB5 and the pigmentation of rapeseed coats. Nevertheless, additional research endeavors are imperative to authenticate and substantiate these findings. CONCLUSIONS: This study offers valuable insights into the genetic evolution of Brassicaceae plants, thereby serving as a significant reference for the genetic enhancement of Brassicaceae seed coat color.

From Sheep Track to Motorway: Supramolecular-Mediated 2D Nanofluidic Channels for Ultrafast Water Transport.

Atomic thick 2D materials hold great potential as building blocks to construct highly permeable membranes, yet the permeability of laminar 2D material membranes is still limited by their irregularity sheep track-like interlayer channels. Herein, a supramolecular-mediated strategy to induce the regular assembly of high-throughput 2D nanofluidic channels based on host-guest interactions is proposed. Inspired by the characteristics of motorways, supramolecular-mediated ultrathin 2D membranes with broad and continuous regular water transport channels are successfully constructed using graphene oxide (GO) as an example. The prepared membrane achieves an ultrahigh water permeability (369.94 LMH bar-1) more than six times higher than that of the original membranes while maintaining dye rejection above 98.5%, which outperforms the reported 2D membranes. Characterization and simulation results show that the introduction of hyaluronate-grafted ß-cyclodextrin not only expands the interlayer channels of GO membranes but also enables the membranes to operate stably under harsh conditions with the help of host-guest interactions. This universal supramolecular assembly strategy provides new opportunities for the preparation of 2D membranes with high separation performance and reliable and stable nanofluidic channels.

Micropillar with Radial Gradient Modulus Enables Robust Adhesion and Friction.

The gradient modulus in beetle setae plays a critical role in allowing it to stand and walk on natural surfaces. Mimicking beetle setae to create a modulus gradient in microscale, especially in the direction of setae radius, can achieve reliable contact and thus strong adhesion. However, it remains highly challenging to achieve modulus gradient along radial directions in setae-like structures. Here, polydimethylsiloxane (PDMS) micropillar with radial gradient modulus, (termed GM), is successfully constructed by making use of the polymerization inhibitor in the photosensitive resin template. GM gains adhesion up to 84 kPa, which is 2.3 and 4.7 times of soft homogeneous micropillars (SH) and hard homogeneous micropillars (HH), respectively. The radial gradient modulus facilitates contact formation on various surfaces and shifts stress concentration from contact perimeter to the center, resulting in adhesion enhancement. Meanwhile, GM achieves strong friction of 8.1 mN, which is 1.2 and 2.6 times of SH and HH, respectively. Moreover, GM possesses high robustness, maintaining strong adhesion and friction after 400 cycles of tests. The work here not only provides a robust structure for strong adhesion and friction, but also establishes a strategy to create modulus gradient at micron-scale.

Asymptotic approach for stable computations of the spherically layered media theory with large orders and small arguments.

The computation of electromagnetic wave scatterings of a layered sphere is a canonical problem. Lorentz-Mie theory is suitable for plane wave incidence whereas spherically layered media theory can deal with arbitrary incident waves. Both theories suffer from the notorious numerical instabilities due to the involved Bessel functions with large order, small argument or high loss. Logarithmic derivative method has been proposed to solve the numerical issues with these theories. In this paper, by employing the equivalence between the asymptotic formulas of Bessel functions for small argument and for large order, the numerical issues with the spherically layered theory under both large order case and small argument case can be solved in a unified manner by canceling out the diverging terms in the asymptotic formulas. The derived stable formulas are simpler and faster than those based on logarithmic derivative method. It is shown that the derived formulas are good approximations to the canonical ones but are more numerically stable. The large lossy issue can be solved similarly.

Magnetic-free polarization rotation in an atomic vapor cell.

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

Genomic editing of intronic enhancers unveils their role in fine-tuning tissue-specific gene expression in Arabidopsis thaliana.

Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.