Modulation of immunity by the secreted phospholipase A2 family.

Among the phospholipase A2 (PLA2 ) superfamily, which typically catalyzes the sn-2 hydrolysis of phospholipids to yield fatty acids and lysophospholipids, the secreted PLA2 (sPLA2 ) family contains 11 isoforms in mammals. Individual sPLA2 s have unique enzymatic specificity toward fatty acids and polar heads of phospholipid substrates and display distinct tissue/cellular distributions, suggesting their distinct physiological functions. Recent studies using knockout and/or transgenic mice for a full set of sPLA2 s have revealed their roles in modulation of immunity and related disorders. Application of mass spectrometric lipidomics to these mice has enabled to identify target substrates and products of individual sPLA2 s in given tissue microenvironments. sPLA2 s hydrolyze not only phospholipids in the plasma membrane of activated, damaged or dying mammalian cells, but also extracellular phospholipids such as those in extracellular vesicles, microbe membranes, lipoproteins, surfactants, and dietary phospholipids, thereby exacerbating or ameliorating various diseases. The actions of sPLA2 s are dependent on, or independent of, the generation of fatty acid- or lysophospholipid-derived lipid mediators according to the pathophysiological contexts. In this review, we make an overview of our current understanding of the roles of individual sPLA2 s in various immune responses and associated diseases.

Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis.

Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS-ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.

Photo-Responsive Hydrogen-Bonded Molecular Networks Capable of Retaining Crystalline Periodicity after Isomerization.

The molecular conformation, crystalline morphology, and properties of photochromic organic crystals can be controlled through photoirradiation, making them promising candidates for functional organic materials. However, photochromic porous molecular crystals with a networked framework structure are rare due to the difficulty in maintaining space that allows for photo-induced molecular motion in the crystalline state. This study describes a photo-responsive single crystal based on hydrogen-bonded (H-bonded) network of dihydrodimethylbenzo[e]pyrene derivative 4BDHP. A crystal composed of H-bonded undulate layers, 4BDHP-2, underwent photo-isomerization in the crystalline state due to loose stacking of the layers. Particularly, enantio-pure crystal (S,S)-4BDHP-2 allowed to reveal the structure of the photoisomerized crystal, in which the closed form (4BDHP) and open form (4CPD) were arranged alternately with keeping crystalline periodicity, although side reactions were also implied. The present proof-of-concept system of a photochromic framework that retains crystalline periodicity after photo-isomerization may provide new light-driven porous functional materials.

Development of an Iron(II) Complex Exhibiting Thermal- and Photoinduced Double Proton-Transfer-Coupled Spin Transition in a Short Hydrogen Bond.

Multiple proton transfer (PT) controllable by external stimuli plays a crucial role in fundamental chemistry, biological activity, and material science. However, in crystalline systems, controlling multiple PT, which results in a distinct protonation state, remains challenging. In this study, we developed a novel tridentate ligand and iron(II) complex with a short hydrogen bond (HB) that exhibits a PT-coupled spin transition (PCST). Single-crystal X-ray and neutron diffraction measurements revealed that the positions of the two protons in the complex can be controlled by temperature and photoirradiation based on the thermal- and photoinduced PCST. The obtained results suggest that designing molecules that form short HBs is a promising approach for developing multiple PT systems in crystals.

Metallic State of a Mixed-Sequence Oligomer Salt That Models Doped PEDOT Family.

Modern organic conductors are typically low-molecular-weight or polymer-based materials. Low-molecular-weight materials can be characterized using crystallographic information, allowing structure-conductivity relationships to be established and conduction mechanisms to be understood. However, controlling their conductive properties through molecular structural modulation is often challenging because of their relatively narrow conjugate areas. In contrast, polymer-based materials have highly π-conjugated structures with wide molecular-weight distributions, and their structural inhomogeneity makes characterizing their structures difficult. Thus, we focused on the less-explored intermediate, i.e., single-molecular-weight oligomers that model doped poly(3,4-ethylenedioxythiophene) (PEDOT). The dimer and trimer models provided clear structures; however, the short oligomers led to much lower conductivities (<10-3 S cm-1) than that of doped PEDOT. Herein, we elongated the oligomer to a tetramer through geometrical tuning based on a mixed sequence. The "P-S-S-P" sequence (S: 3,4-ethylenedithiothiophene; P: 3,4-(2',2'-dimethypropylenedioxy)thiophene) with twisted S-S enhanced the solubility and chemical stability. The subsequent oxidation process planarized the oligomer and expanded the conjugate area. Interestingly, the sequence involving sterically bulky outer P units allowed the doped oligomer to form a pitched π-stack in the single-crystal form. This enabled the inclusion of excess counter anions, which modulated the band filling. The combined effects of conjugate area expansion and band-filling modulation significantly increased the room-temperature conductivity to 36 S cm-1. This is the highest value reported for a single-crystalline oligomer conductor. Furthermore, a metallic state was observed above room temperature in a single-crystalline oligoEDOT for the first time. This unique mixed-sequence strategy for oligomer-based conductors enabled the precise control of conductive properties.

Observation of proton-transfer-coupled spin transition by single-crystal neutron-diffraction measurement.

The application of single-crystal neutron diffraction (SCND) to observe proton-transfer phenomena in crystalline compounds exhibiting unusual protonation states or proton dynamics has garnered significant research interest in recent years. However, proton tautomerism, which results in different protonation states before and after proton transfer, has never been observed using the SCND technique. Thus, to observe the proton tautomerism phenomenon by SCND measurements, we developed an iron(II) complex that forms a large crystal and exhibits a proton-transfer-coupled spin transition (PCST). The presence of the two types of proton tautomers was determined by conventional analysis of the proton position by X-ray crystallography, infrared spectroscopy, and density functional theory calculations. Finally, our results confirmed that proton tautomerism was successfully observed for the first time using variable-temperature SCND measurements.

π-Extended Pyrrole-Fused Heteropine: Synthesis, Properties, and Application in Organic Field-Effect Transistors.

Sulfur-embedded polycyclic aromatic compounds have been used as building blocks for numerous organic semiconductors over the past few decades. While the success is based on thiophene-containing compounds, aromatic compounds that contain thiepine, a sulfur-containing seven-membered-ring arene, has been less well investigated. Here we report the synthesis and properties of π-extended pyrrole-fused heteropine compounds such as thiepine and oxepine. A π-extended pyrrole-fused thiepine exhibited a "pitched π-stacking" structure in the crystal, and exhibited a high charge carrier mobility of up to 1.0 cm2 V-1 s-1 in single-crystal field-effect transistors.

Amplified Chirality Transfer to Aromatic Molecules through Non-specific Inclusion by Amorphous, Hyperbranched Poly(fluorenevinylene) Derivatives.

Optically active, hyperbranched, poly(fluorene-2,4,7-triylethene-1,2-diyl) [poly(fluorenevinylene)] derivatives bearing a neomenthyl group and a pentyl group at the 9-position of the fluorene backbone at various ratios acted as a chirality donor (host polymers) efficiently included naphthalene, anthracene, pyrene, 9-phenylanthracene, and 9,10-diphenyanthracene as a chirality acceptor (guest molecules) in their interior space in film as well as in solution, with the guest molecules exhibiting intense circular dichroism through chirality transfer with chirality amplification. The efficiency of the chirality transfer was much higher with higher-molar-mass polymers than lower-molar-mass ones as well as with hyperbranched polymers compared to the analogous linear ones. The hyperbranched polymers include the small molecules in their complex structure without any specific interactions at various stoichiometries. The included molecules may have ordered intermolecular arrangement that may be somewhat similar to those of liquid crystals. Naphthalene, anthracene, and pyrene included in the polymer exhibited efficient circularly polarized luminescence, where the chirality was remarkably amplified in excited states, and anthracene exhibited especially high anisotropies in the emission on the order of 10-2 .

Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion In Vitro and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease.

Cell-to-cell transmission of α-synuclein (α-syn) pathology is considered to underlie the spread of neurodegeneration in Parkinson's disease (PD). Previous studies have demonstrated that α-syn is secreted under physiological conditions in neuronal cell lines and primary neurons. However, the molecular mechanisms that regulate extracellular α-syn secretion remain unclear. In this study, we found that inhibition of monoamine oxidase-B (MAO-B) enzymatic activity facilitated α-syn secretion in human neuroblastoma SH-SY5Y cells. Both inhibition of MAO-B by selegiline or rasagiline and siRNA-mediated knock-down of MAO-B facilitated α-syn secretion. However, TVP-1022, the S-isomer of rasagiline that is 1000 times less active, failed to facilitate α-syn secretion. Additionally, the MAO-B inhibition-induced increase in α-syn secretion was unaffected by brefeldin A, which inhibits endoplasmic reticulum (ER)/Golgi transport, but was blocked by probenecid and glyburide, which inhibit ATP-binding cassette (ABC) transporter function. MAO-B inhibition preferentially facilitated the secretion of detergent-insoluble α-syn protein and decreased its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Moreover, in a rat model (male Sprague Dawley rats) generated by injecting recombinant adeno-associated virus (rAAV)-A53T α-syn, subcutaneous administration of selegiline delayed the striatal formation of Ser129-phosphorylated α-syn aggregates, and mitigated loss of nigrostriatal dopaminergic neurons. Selegiline also delayed α-syn aggregation and dopaminergic neuronal loss in a cell-to-cell transmission rat model (male Sprague Dawley rats) generated by injecting rAAV-wild-type α-syn and externally inoculating α-syn fibrils into the striatum. These findings suggest that MAO-B inhibition modulates the intracellular clearance of detergent-insoluble α-syn via the ABC transporter-mediated non-classical secretion pathway, and temporarily suppresses the formation and transmission of α-syn aggregates.SIGNIFICANCE STATEMENT The identification of a neuroprotective agent that slows or stops the progression of motor impairments is required to treat Parkinson's disease (PD). The process of α-synuclein (α-syn) aggregation is thought to underlie neurodegeneration in PD. Here, we demonstrated that pharmacological inhibition or knock-down of monoamine oxidase-B (MAO-B) in SH-SY5Y cells facilitated α-syn secretion via a non-classical pathway involving an ATP-binding cassette (ABC) transporter. MAO-B inhibition preferentially facilitated secretion of detergent-insoluble α-syn protein and reduced its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Additionally, MAO-B inhibition by selegiline protected A53T α-syn-induced nigrostriatal dopaminergic neuronal loss and suppressed the formation and cell-to-cell transmission of α-syn aggregates in rat models. We therefore propose a new function of MAO-B inhibition that modulates α-syn secretion and aggregation.

Synthesis of π-Extended Thiele's and Chichibabin's Hydrocarbons and Effect of the π-Congestion on Conformations and Electronic States.

The biradicaloid of Chichibabin's hydrocarbon exits in a unique thermal equilibrium between closed-shell singlet and open-shell triplet forms. Conceptually, the incorporation of nonplanar aromatic groups, such as anthraquinodimethane (AQD), in these species could bring about stabilization of the individual singlet and triplet spin biradicaloids by creating a high energy barrier for conformational interconversion between folded (singlet) and twisted (triplet) forms. Moreover, this alteration could introduce the possibility of controlling spin states through conformational changes induced by chemical and physical processes. Herein, we report the preparation of AQD-containing, π-extended Thiele's (A-TH) and Chichibabin's (A-CH) hydrocarbons, which have highly π-congested structures resulting from the presence of bulky 9-anthryl units. The π-congestion in these substances leads to steric frustration about carbon-carbon double bonds and creates flexible dynamic motion with a moderate activation barrier between folded singlet and twisted triplet states. These constraints make it possible to isolate the twisted triplet state of A-CH. In addition, simple mechanical grinding of the folded singlet of A-CH produces the twisted triplet.

Partially Oxidized Purely Organic Zwitterionic Neutral Radical Conductor: Multi-step Phase Transitions and Crossover Caused by Intra- and Intermolecular Electronic Interactions.

Formation of a partially charge-transfer or partially oxidized/reduced state has been one of the most important requirements for the development of highly conducting molecular materials, such as organic metals and superconductors. This requirement has been fulfilled by combining appropriate electron-donor and acceptor molecules to construct multi-component molecular complexes/salts, such as (TTF+0.59)(TCNQ-0.59) and (BEDT-TTF+0.5)2X-, where TTF = tetrathiafulvalene, TCNQ = tetracyanoquinodimethane, BEDT-TTF = bis(ethylenedithio)tetrathiafulvalene, and X = monovalent inorganic anion. Here, we propose a methodology to fulfill this requirement by a single neutral molecule; namely, we have connected two TTF+0.5-type partially oxidized π-skeletons through a boron anion to design a purely organic zwitterionic neutral radical {[(PDT-TTF-Cat)2]+B-}•. This molecule was successfully obtained as air-stable crystals containing solvent tetrahydrofuran (THF) molecules. Measurements of electrical resistivity, magnetic susceptibility, and X-ray diffraction reveal that the partially oxidized state is certainly formed, which enables realization of a 3/4-filled electron band. Furthermore, this system has intramolecular charge degrees of freedom, attributable to the two TTF+0.5 π-skeletons introduced into the molecule. The resulting interplay of intra- and intermolecular charge degrees of freedom (or simply, intra- and intermolecular electronic interactions) has led to multi-step phase transitions and crossover, providing unique strongly correlated electron properties, such as the formation of a three-dimensional charge-ordered dimer-Mott insulating state and its melting triggered by disorder-order transformation of the co-crystallized solvent THF molecules at low temperatures.

Sterically Frustrated Aromatic Enes with Various Colors Originating from Multiple Folded and Twisted Conformations in Crystal Polymorphs.

Overcrowded ethylenes composed of 10-methyleneanthrone and two bulky aromatic rings contain a twisted carbon-carbon double (C=C) bond as well as a folded anthrone unit. As such, they are unique frustrated aromatic enes (FAEs). Various colored crystals of these FAEs, obtained in different solvents, correspond to multiple metastable conformations of the FAEs with various twist and fold angles of the C=C bond, as well as various dihedral angles of attached aryl units with respect to the C=C bond. The relationships between color and these parameters associated with conformational features around the C=C bond were elucidated in experimental and computational studies. Owing to the fact that they are separated by small energy barriers, the variously colored conformations in the FAE crystal change in response to various external stimuli, such as mechanical grinding, hydrostatic pressure and thermal heating.

Synthesis of π-Extended Carbazole Dimers Via Oxidative Cyclization Using DDQ and Sulfonic Acid and Elucidation of the Reaction Mechanism.

This paper describes the synthesis of various π-extended carbazole dimers via intramolecular oxidative cyclization using a chain precursor consisting of two carbazole units bridged by a nitrogen atom. A careful selection of the reaction conditions using 2,3-dichloro-5,6-dicyano-p-benzoquinone/sulfonic acid enabled the selective synthesis of a π-extended analogue with an angular (L-shape) structure in moderate yield. The preferential positions for the bonding of the two carbazole units in this π-extended derivative were determined by performing density functional theory calculations.

Capturing the Trajectory of Metal-Ion-Cluster Formation: Stepwise Accumulation of Zn(II) Ions in a Robust Coordination Space Formed by a Rigid Tridentate Carboxylate Ligand.

Organic ligand-directed synthesis of metal-ion clusters with a well-defined number and arrangement of metal ions is an important subject toward the development of functional inorganic-organic nanohybrids. Here we report the synthesis of multinuclear Zn-oxo clusters using a triptycene-based rigid ligand (H3L) featuring three metal-coordination sites arranged in a triangular shape. Upon complexation of H3L with zinc acetate dihydrate, a decanuclear Zn-oxo cluster and multinuclear Zn-oxo clusters with a smaller number of Zn(II) ions were formed as the final product and its intermediates, respectively. A comparison of the X-ray structure of the final product with those of the intermediates revealed the cluster-formation process, where four triptycene ligands preorganize to form a robust coordination space to which Zn(II) ions accumulate in a stepwise manner. This stepwise metal-ion accumulation, along with the formation of a large tetrahedral decanuclear Zn-oxo cluster, highlights the potential of ligand design using 1,8,13-substituted triptycenes for the development of various metal-ion clusters.

Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy. CASE PRESENTATION: The proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20). CONCLUSIONS: Our cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.

Mechanical Force Induced Formation of Extrinsic Micropores in Coordination Polymers.

Mechanical force can be employed not only to efficiently synthesize new materials under environmentally friendly conditions but also to change the macroscopic and microscopic properties of materials. Although coordination polymers (CPs) are attractive functional materials because they possess high structural designability and diversity, mechanical force-induced structural and functional changes of CPs are challenging issues. In this study, two one-dimensional CPs, one a densely packed nonporous CP [Cu2(bza)4(pyr)] (1) and the other a porous CP [Cu2(1-nap)4(pyr)] (2) (bza = benzoate, 1-nap = 1-naphthoate and pyr = pyrimidine), were subjected to ball-milling to assess the effect of mechanical force on their porosities. Ball mill treatments were found to induce an amorphization and cause a 30 fold enhancement of the CO2 adsorption amount at 195 K and P/P0 ∼ 1 for 1 and a slightly decreased CO2 adsorption amount for 2. The results of thorough characterization studies suggest that the formation of extrinsic micropores in addition to extrinsic mesopores/macropores between particles takes place by ball milling.

Prevalence and development of idiopathic normal pressure hydrocephalus: A 16-year longitudinal study in Japan.

OBJECTIVE: We previously investigated the preclinical state of idiopathic normal pressure hydrocephalus (iNPH): asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM) found in community inhabitants. The aim of the study was to determine how iNPH develops longitudinally. MATERIALS AND METHODS: A previous longitudinal prospective community-based cohort study was initiated in 2000. The 271 70 year-old participants were followed up in 2016 at the age of 86 years. At this time, 104 participants could be reached for clinical examinations and brain magnetic resonance imaging (MRI). iNPH in this study was diagnosed if the participant had more than one symptom in the clinical triad and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on MRI, fulfilling at least an Evans index >0.3 (ventricular enlargement, VE) and a narrowing of the subarachnoid space at the high convexity (tight high convexity, THC). Asymptomatic VE (AVE) plus THC were considered AVIM. RESULTS: Longitudinally throughout 16 years, 11 patients with iNPH were found. The hospital consultation rate was only 9%. Five of the eight patients with AVIM (62.5%) and six of 30 with AVE (20.0%) developed iNPH. Cross-sectionally, eight patients had iNPH (8/104, 7.7% prevalence at the age of 86) in 2016. Disease development was classified into THC-preceding and VE-preceding iNPH. One VE-preceding iNPH case was considered a comorbidity of Alzheimer's dementia. CONCLUSION: Idiopathic normal pressure hydrocephalus had a high prevalence among octogenarians in the evaluated community. iNPH developed not only via AVIM but also via AVE, the latter was also frequent in the elderly.

Magnet Creation by Guest Insertion into a Paramagnetic Charge-Flexible Layered Metal-Organic Framework.

Changing nonmagnetic materials to spontaneous magnets is an alchemy-inspiring concept in materials science; however, it is not impossible. Here, we demonstrate chemical modification from a nonmagnet to a bulk magnet of either a ferrimagnet or antiferromagnet, depending on the adsorbed guest molecule, in an electronic-state-flexible layered metal-organic framework, [{Ru2(2,4-F2PhCO2)4}2TCNQ(EtO)2] (1; 2,4-F2PhCO2- = 2,4-difluorobenzoate; TCNQ(EtO)2 = 2,5-diethoxy-7,7,8,8-tetracyanoquinodimethane). The guest-free paramagnet 1 undergoes a thermally driven intralattice electron transfer involving a structural transition at 380 K. This charge modification can also be implemented by guest accommodations at room temperature; 1 adsorbs several organic molecules, such as benzene (PhH), p-xylene (PX), 1,2-dichloroethane (DCE), dichloromethane (DCM), and carbon disulfide (CS2), forming 1-solv with intact crystallinity. This induces an intralattice electron transfer to produce a ferrimagnetically ordered magnetic layer. According to the interlayer environment tuned by the corresponding guest molecule, the magnetic phase is consequently altered to a ferrimagnet for the guests PhH, PX, DCE, and DCM or an antiferromagnet for CS2. This is the first demonstration of the postsynthesis of bulk magnets using guest-molecule accommodations.

Photothermally Driven High-Speed Crystal Actuation and Its Simulation.

Mechanically responsive crystals have been increasingly explored, mainly based on photoisomerization. However, photoisomerization has some disadvantages for crystal actuation, such as a slow actuation speed, no actuation of thick crystals, and a narrow wavelength range. Here we report photothermally driven fast-bending actuation and simulation of a salicylideneaniline derivative crystal with an o-amino substituent in enol form. Under ultraviolet (UV) light irradiation, these thin (<20 µm) crystals bent but the thick (>40 µm) crystals did not due to photoisomerization; in contrast, thick crystals bent very quickly (in several milliseconds) due to the photothermal effect, even by visible light. Finally, 500 Hz high-frequency bending was achieved by pulsed UV laser irradiation. The generated photothermal energy was estimated based on the photodynamics using femtosecond transient absorption. Photothermal bending is caused by a nonsteady temperature gradient in the thickness direction due to the heat conduction of photothermal energy generated near the crystal surface. The temperature gradient was calculated based on the one-dimensional nonsteady heat conduction equation to simulate photothermally driven crystal bending successfully. Most crystals that absorb light have their own photothermal effects. It is expected that the creation and design of actuation of almost all crystals will be possible via the photothermal effect, which cannot be realized by photoisomerization, and the potential and versatility of crystals as actuation materials will expand in the near future.

Perforated extensible 3-D hyperbolic secant lens antenna for directive antenna applications using additive manufacturing.

In this paper, a novel three-dimensional (3-D) generalized hyperbolic secant (H-S) lens is first introduced using perforated dielectric material. The attractiveness of this new lens is its unique intrinsic flat shape characteristic and extensibility for different configuration scenarios, which provide a potential alternative design for a planar Luneburg and half Maxwell fish-eye lens based on a complex conformal mapping method. A high gain and wideband printed antipodal fermi antenna as a feeding source is employed in the proposed lens antenna prototype. The high radiation performance with low side lobe level of the fabricated lens prototype is validated from 8.2GHz to 12.5GHz, demonstrating 23.8 dBi realized gain at 10 GHz with 3-dB beamwidth of 9° and 2-dB fractional gain bandwidth of 41.6%. Besides, the total radiation efficiency is above ∼40% across all tested frequencies, which suggests the proposed H-S lens itself has a broadband response. The simplicity and low-cost fabrication using additive manufacturing of its lens design indicates great potential in broadband high directive antenna applications.