Complete genome and pathogenesis of a novel recombinant Senecavirus A isolate in P.R. China.

Senecavirus A (SVA), formerly called Seneca Valley virus (SVV) was first isolated from the USA in 2002. This study isolated an SVA strain from a pig herd in Shandong Province, PR China and designated it SVA-CH-SDGT-2017. The full-length genome, excluding the poly(A) tails of the SVA isolates, was 7280 nucleotides long, with the genomic organization resembling and sharing high nucleotide identities of 90.7-96.9 % with other previously reported SVA isolates. To investigate the pathogenicity of the SVA isolates, experimental infections of pigs were performed. The SVA strains successfully infected the pigs, as evidenced by the presence of virus shedding and robust serum neutralizing antibody responses. In addition, the contact-exposed experiment showed that the virus shedding of the contact-exposed pigs was approximately a 100-fold reduced compared to that of the inoculated group, indicating that the virus is capable of transmission to pigs. Our findings provide useful data for studying the pathogenesis and transmission of SVA in pigs.

Incidence and mortality of ovarian cancer at the global, regional, and national levels, 1990-2017.

BACKGROUND: Ovarian cancer (OC) is a commonly diagnosed gynecologic cancer. Knowing the incidence and mortality rates of OC is critical to understanding the disease burden and updating prevention strategies. METHODS: We retrieved the age-standardized incidence and mortality rates (ASIR and ASMR, respectively) of OC from the Global Burden of Disease study online database. Estimated average percentage change (EAPC) was used to quantify the trends of OC incidence and mortality from 1990 to 2017. RESULTS: Worldwide, the number of incident cases and deaths from OC increased from 152.1 and 95.5 thousand in 1990 to 286.1 and 176.0 thousand in 2017, respectively. Both the ASIR and ASMR decreased slightly during the study period (EAPC = -0.10, 95% CI, -0.16, -0.03; EAPC = -0.32, 95% CI, -0.38, -0.27). The greatest decreases of ASIR and ASMR were observed in Western Europe (EAPC = -1.22, 95% CI, -1.31, -1.14; EAPC = -1.31, 95% CI, -1.37, -1.25). A total of 137, 10, and 48 countries or territories experienced an increase, remained stable, and experienced a decrease in OC ASIR, respectively, between 1990 and 2017. For ASMR, a total of 129, 9, and 57 countries or territories experienced an increase, remained stable, and experienced a decrease, respectively, during the same period. The greatest increases in the ASIR and the ASMR were found in countries located in the Caribbean and Latin America. CONCLUSIONS: The incidence and mortality of OC significantly decreased in developed countries. However, remarkable increases were observed in more than two-thirds of all countries, suggesting that OC will be more frequently diagnosed in developing countries.

Investigation of the chromatographic regulation properties of benzyl groups attached to bridging nitrogen atoms in a calixtriazine-bonded stationary phase.

Two reversed-phase/anion-exchange mixed-mode stationary phases for high-performance liquid chromatography using calixtriazines as chromatographic ligands were investigated with Tanaka test solutes, monosubstituted benzenes, aromatic positional isomers, and inorganic anions. Calixtriazine as a chromatographic ligand has been reported previously, but the benzylated nitrogen-bridged calixtriazine-bonded silica gel reported in this study is new. The experimental data showed that the calixtriazine platform is a unique chromatographic selector because its multiple active sites are available for different solutes and its chromatographic selectivity could be tuned by introducing substituent on the bridging nitrogen atoms present in the calixtriazine matrix. The synergistic effects of aromatic rings, nitrogen atoms, benzyl groups, and tunable cavity in the host molecule influenced the separation selectivity by multiple retention mechanisms. Such hybrid stationary phases provide more versatility and have great potential in the analysis of complex samples. Moreover, the synthetic protocols presented herein may provide an alternative understanding on macrocyclic host-guest chemistry, leading to new and selective separation media.

High-Frequency Ultrasonic Imaging with Lead-free (Na,K)(Nb,Ta)O3 Single Crystal.

Lead-free (Na,K)(Nb,Ta)O3 (KNNT) piezoelectric single crystal has been successfully grown using the top-seeded solution growth technique. The electromechanical coupling factors are very high ( k33 = 0.827, kt = 0.646), and the dielectric loss tangent is as low as 0.004. Acoustic impedance was calculated to be 26.5 MRayl. From the single crystal, a single element transducer was fabricated. The transducer achieved a 57.6% -6 dB bandwidth and 32.3 µm axial resolution at the center frequency of 45.4 MHz, which can identify the cornea of porcine eyeball with high resolution. Comparison between KNNT single crystal and lead-based single crystal was discussed. The results suggest that this single crystal transducer is an excellent candidate to replace lead-containing transducer for high-frequency ultrasonic imaging applications.

(K, Na, Li)(Nb, Ta)O3:Mn lead-free single crystal with high piezoelectric properties.

Lead-free single crystal, (K, Na, Li)(Nb, Ta)O3:Mn, was successfully grown using top-seeded solution growth method. Complete matrix of dielectric, piezoelectric and elastic constants for [001]C poled single crystal was determined. The piezoelectric coefficient d33 measured by the resonance method was 545 pC/N, which is almost three times that of its ceramic counterpart. The values measured by the Berlincourt meter ( [Formula: see text]) and strain-field curve ( [Formula: see text]) were even higher. The differences were assumed to relate with the different extrinsic contributions of domain wall vibration and domain wall translation during the measurements by different approaches, where the intrinsic contribution (on the order of 539 pm/V) was supposed to be the same. The crystal has ultrahigh electromechanical coupling factor (k33 ~ 95%) and high ultrasound velocity, which make it promising for high frequency medical transducer applications.

Extended and contorted conformations of alkanediammonium ions in symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril cavity.

Binding interactions between symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril (TMeQ[6]) and a series of alkyldiammonium ions in aqueous solution and in the solid state were investigated by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, X-ray crystallography, and isothermal titration calorimetry (ITC). Their (1)H NMR spectra reveal that the actual binding behaviors vary depending upon the alkyl chain length. Their single-crystal X-ray diffraction analyses indicate the guest 1,2-ethanediammonium is located outside of the TMeQ[6] portal, while the other four alkyldiammonium guests can be accommodated in the TMeQ[6] cavity, forming 1:1 inclusion complexes. Most importantly, the long-chain alkyldiammoniums (1,8-octanediammonium and 1,10-decanediammonium) take a contorted conformation when bound within the TMeQ[6] cavity. Additionally, ITC experiments show that the complexation of the alkyldiammonium guests with TMeQ[6] is mainly enthalpy driven, which benefits from ion-dipole interactions.

Giant Electroresistance in Ferroelectric Tunnel Junctions via High-Throughput Designs: Toward High-Performance Neuromorphic Computing.

Ferroelectric tunnel junctions (FTJs) have been regarded as one of the most promising candidates for next-generation devices for data storage and neuromorphic computing owing to their advantages such as fast operation speed, low energy consumption, convenient 3D stack ability, etc. Here, dramatically different from the conventional engineering approaches, we have developed a tunnel barrier decoration strategy to improve the ON/OFF ratio, where the ultrathin SrTiO3 (STO) dielectric layers are periodically mounted onto the BaTiO3 (BTO) ferroelectric tunnel layer using the high-throughput technique. The inserted STO enhances the local tetragonality of the BTO, resulting in a strengthened ferroelectricity in the tunnel layer, which greatly improves the OFF state and reduces the ON state. Combined with the optimized oxygen migration, which can further manipulate the tunneling barrier, a record-high ON/OFF ratio of ∼108 has been achieved. Furthermore, utilizing these FTJ-based artificial synapses, an artificial neural network has been simulated via back-propagation algorithms, and a classification accuracy as high as 92% has been achieved. This study screens out the prominent FTJ by the high-throughput technique, advancing the tunnel layer decoration at the atomic level in the FTJ design and offering a fundamental understanding of the multimechanisms in the tunnel barrier.

Ultralow Strain-Induced Emergent Polarization Structures in a Flexible Freestanding BaTiO3 Membrane.

The engineering of ferroic orders, which involves the evolution of atomic structure and local ferroic configuration in the development of next-generation electronic devices. Until now, diverse polarization structures and topological domains are obtained in ferroelectric thin films or heterostructures, and the polarization switching and subsequent domain nucleation are found to be more conducive to building energy-efficient and multifunctional polarization structures. In this work, a continuous and periodic strain in a flexible freestanding BaTiO3 membrane to achieve a zigzag morphology is introduced. The polar head/tail boundaries and vortex/anti-vortex domains are constructed by a compressive strain as low as ≈0.5%, which is extremely lower than that used in epitaxial rigid ferroelectrics. Overall, this study c efficient polarization structures, which is of both theoretical value and practical significance for the development of next-generation flexible multifunctional devices.

Introducing AgNPs-VB2 composites as the dual signal quenching of CeO2-AuNPs-g-CNQDs hybrids for ultrasensitive "on-off" electrochemiluminescence immunosensing of prostate specific antigen.

An ultrasensitive resonance energy transfer based "on-off" switch electrochemiluminescence (ECL) immunosensing strategy was proposed and applied for prostate specific antigen (PSA) detection. In detail, self-enhancing nanohybrids of nano-CeO2 and AuNPs decorated graphitic carbon nitride quantum dots (CeO2-AuNPs-g-CNQDs) were synthesized, which produced high ECL emission with coreactant K2S2O8 for "switch-on" state. Noticeably, due to the reversible Ce3+↔ Ce4+ reaction, nano-CeO2 could serve as highly-efficient coreaction accelerator and induce the decomposition of S2O82- into SO4• -, which endowed the g-CNQDs/K2S2O8 system with enhanced ECL emission. Moreover, AuNPs acted crucial role in promoting the electronic transmission rate and providing sites to immobilize the biomolecules. On the other hand, the AgNPs-VB2 nanocomposites were used as dual labels to quench the ECL signal of g-CNQDs-K2S2O8 system via ECL-RET, leading to the decreased ECL for "switch-off" state. On the basis of sandwich-typed immunosensing strategy, the developed ECL immunosensing platform exhibited sensitive response to PSA in a linear range of 1.0 × 10-5 _ 50 ng mL-1 with a low detection limit of 0.0045 pg mL-1 (S/N = 3). This work provided a promising tool in early clinical diagnostics of prostate cancer.

Investigating the influence of primary uterine tumor site on pelvic and para-aortic lymph node metastatic pattern and evaluating the risk factors for lymph node metastases in endometrial carcinoma: A retrospective study.

To assess the metastatic pattern in pelvic and para-aortic lymph nodes in relation with the primary uterine tumor site and to evaluate risk factors for lymph node metastases. 212 patients with endometrial cancer who underwent surgical treatment from December 2014 to December 2019 were selected. The clinical and pathological data were retrospectively analyzed. The factors and uterine primary tumor site related to lymph node metastasis were analyzed by univariate and multivariate analysis. Among the 212 patients with endometrial cancer, 17 cases had lymph node metastasis, and thus the metastasis rate was 8.02%. Univariate analysis revealed that lymph node metastasis was significantly correlated with Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, tumor size, pathological grade, and lymphovascular space invasion (P < .05) and was not correlated with age, pathological type, and cervical involvement (P > .05). Primary uterine tumor site (fundus, horns, body or lower uterine segment) with or without cervical involvement was associated with different lymph nodes' metastatic sites. The lymph node metastatic pathways of endometrial cancer mainly include obturator lymph nodes and para-aortic lymph nodes, and skip metastasis may occur; endometrial carcinoma may jump and metastasize to para-aortic lymph nodes, specially when the lesion is located in the uterine fundus and uterine horns (cornua of uterus); there is a significant correlation between the location of lymph node metastasis and the location of primary uterine malignant tumor.

Automatic and label-free detection of meningioma in dura mater using the combination of multiphoton microscopy and image analysis.

Significance: To prevent meningioma recurrence, it is necessary to detect and remove all corresponding tumors intraoperatively, including those in the adjacent dura mater. Aim: Currently, the removal of meningiomas from the dura mater depends solely on cautious visual identification of lesions by a neurosurgeon. Inspired by the requirements for resection, we propose multiphoton microscopy (MPM) based on two-photon-excited fluorescence and second-harmonic generation as a histopathological diagnostic paradigm to assist neurosurgeons in achieving precise and complete resection. Approach: Seven fresh normal human dura mater samples and 10 meningioma-infiltrated dura mater samples, collected from 10 patients with meningioma, were acquired for this study. First, multi-channel mode and lambda mode detection were utilized in the MPM to characterize the architectural and spectral features of normal and meningioma-infiltrated dura mater, respectively. Three imaging algorithms were then employed to quantify the architectural differences between the normal and meningioma-infiltrated dura mater through calculations of the collagen content, orientation, and alignment. Finally, MPM was combined with another custom-developed imaging algorithm to locate the meningioma within the dura mater and further delineate the tumor boundary. Results: MPM not only detected meningioma cells in the dura mater but also revealed the morphological and spectral differences between normal and meningioma-infiltrated dura mater, providing quantitative information. Furthermore, combined with a self-developed image-processing algorithm, the precise borders of meningiomas in the dura mater could be accurately delineated. Conclusions: MPM can automatically detect meningiomas in the dura mater label-free. With the development of advanced multiphoton endoscopy, MPM combined with image analysis can provide decision-making support for histopathological diagnosis, as well as offer neurosurgeons more precise intraoperative resection guidance for meningiomas.

METTL14 and FTO mediated m6A modification regulate PCV2 replication by affecting miR-30a-5p maturity.

The epigenetic modification of the N6-methyladenosine (m6A) methylation plays an important role in virus infection and replication. However, its role in Porcine circovirus type 2 (PCV2) replication has not been well studied. Here, we demonstrated that m6A modifications are increased in PK-15 cells after PCV2 infection. In particular, PCV2 infection could increase the expression of methyltransferase METTL14 and demethylase FTO. Moreover, interfering with METTL14 accumulation reduced the m6A methylation level and virus reproduction, whereas depleting the FTO demethylase enhanced the m6A methylation level and stimulated virus reproduction. Besides, we showed that METTL14 and FTO regulate PCV2 replication by affecting the process of miRNA maturity, especially the miRNA-30a-5p. Taken together, our results demonstrated that the m6A modification positively affects PCV2 replication and the role of m6A modification in the replication mechanism of the PCV2 virus provides a new idea for the prevention and control of the PCV2.

High-Energy Storage Properties over a Broad Temperature Range in La-Modified BNT-Based Lead-Free Ceramics.

The development of high-performance energy storage materials is decisive for meeting the miniaturization and integration requirements in advanced pulse power capacitors. In this study, we designed high-performance [(Bi0.5Na0.5)0.94Ba0.06](1-1.5x)LaxTiO3 (BNT-BT-xLa) lead-free energy storage ceramics based on their phase diagram. A strategy combining phase adjustment and domain control via doping was proposed to enhance the energy storage performance. The obtained results showed that La3+ ions doped into BNT-BT improved the crystal structure symmetry and induced a strong dielectric relaxation behavior, which destroyed the long-term ferroelectric order and effectively promoted the formation of polar nanoregions. At x = 0.12, a high recoverable energy density (Wrec) of ∼5.93 J/cm3 and a relatively large energy storage efficiency (η) of 77.6% were obtained under a high breakdown electric field of 440 kV/cm. By using a two-step sintering approach for the microstructural optimization, the energy storage performance was further improved, yielding much higher Wrec (6.69 J/cm3) and η (87.0%). Additionally, both conventionally sintered and two-step-sintered samples showed excellent frequency stability (0.5-500 Hz), thermal endurance (25-180 °C), and fatigue resistance (105 cycles). Regarding the pulse charge-discharge performance, the samples exhibited ultrashort discharge time (t0.9 ∼ 89 ns for the conventionally sintered sample and ∼75 ns for the two-step-sintered sample) under an electric field of 240 kV/cm. Furthermore, the breakdown process of the material was simulated based on the finite element analysis, and it was shown that high breakdown strength of the material could be ascribed to fine grains, which significantly hindered the crack propagation during the application of the electric field. These results show that the presented materials have great potential as high-energy storage capacitors.

Inverse Design of Ferroelectric-Order in Perovskite Crystal for Self-Powered Ultraviolet Photodetection.

It has always been a hot topic to design an orderly mesoscopic structure in functional materials to tailor the macroscopic properties or realize new functions. The existence of domains in ferroelectric materials has been proven to affect the macroscopic properties, being actively studied in nonlinear optical conversion and piezoelectric effects. However, the high-efficiency photoelectric conversion capability of ferroelectric crystals has not yet been explored. Here, the authors study the orderly arrangement of ferroelectric order in KTa1- x Nbx O3 (KTN) perovskite crystals, and design the "head-to-head" domains by tuning the Curie temperature Tc , thereby generating abundant charged domain walls and robust conductive channels for electrons and holes. An ultrahigh ultraviolet photoresponsivity is achieved in the KTN crystal under zero bias voltage, being about four orders magnitude higher than that of the well-known ferroelectric materials. The substantial improvement can be attributed to the judiciously designed ferroelectric order, as demonstrated by the conductive atomic force microscopy. In addition, KTN detector exhibits high stability and reliability after high-temperature and fatigue treatment. KTN crystal features giant photoresponsivity, high electric-optical coefficient, and large χ(2) nonlinearity concurrently, indicating its great potential for application of all-optical devices on photonic chips.

B-Site Nanoscale-Ordered Structure Enables Ultra-High Tunable Performance.

Tunable devices constructed by ferroelectric thin films are often desired to possess a low dielectric loss while maintainging a high dielectric tunability over a broad operating temperature range in applications, for example, resonators, filters, or phase shifters. However, it is difficult to simultaneously achieve these characteristics by traditional strategies, such as doping and strain modifying. Here, we demonstrate that the dielectric tunability of the sol-gel-prepared Pb(Sc1/2Nb1/2)0.9(Mg1/3Nb2/3)0.1O3 (PSNMN) thin film can be almost doubled from ~47% to ~80.0% (at 10 kHz) at a low electric field (~530 kV/cm), and the dielectric loss can be sharply reduced by more than an order of magnitude, from ~0.50 to ~0.037 (at 1 kHz) when the thin film was annealed in air at 650°C for 15 h under the help of an atmosphere-compensating-block (ACB) made from the proto-PSNMN gel. Moreover, the PSNMN thin film annealed with ACB also exhibited an extremely high thermally-stable dielectric tunability in an ultrabroad temperature range (>130 K), which could be attributed to the Maxwell-Wagner (MW) effect generated by the interface between the PSNMN disordered matrix and the B-site nanoscale-ordered structure formed during the long-term annealing process. The reduced dielectric loss is mainly benefited from the reduced concentration of oxygen vacancy and the possible MW effects, and the enhanced dielectric tunability could be ascribed to the weaker domain-pinning effect by oxygen vacancy. The breakthrough provides a new universal strategy to achieve utrahigh tunable performance in A(B'1/2B"1/2)O3 ferroelectric thin films with a B-site nanoscale-ordered structure, meanwhile it paves the way for ultraintergrated tunable thin-film-devices with great phase shifter performance in practical applications.

Domain Switching in BaTiO3 Films Induced by an Ultralow Mechanical Force.

Low-energy switching of ferroelectrics has been intensively studied for energy-efficient nanoelectronics. Mechanical force is considered as a low-energy consumption technique for switching the polarization of ferroelectric films due to the flexoelectric effect. Reduced threshold force is always desirable for the considerations of energy saving, easy domain manipulation, and sample surface protection. In this work, the mechanical switching behaviors of BaTiO3/SrRuO3 epitaxial heterostructure grown on Nb:SrTiO3 (001) substrate are reported. Domain switching is found to be induced by an extremely low tip force of 320 nN (estimated pressure ∼0.09 GPa), which is the lowest value ever reported. This low mechanical threshold is attributed to the small compressive strain, the low oxygen vacancy concentration in BaTiO3 film, and the high conductivity of the SrRuO3 electrode. The flexoelectricity under both perpendicular mechanical load (point measurement) and sliding load (scanning measurement) are investigated. The sliding mode shows a much stronger flexoelectric field for its strong trailing field. The mechanical written domains show several advantages in comparison with the electrically written ones: low charge injection, low energy consumption, high density, and improved stability. The ultralow-pressure switching in this work presents opportunities for next-generation low-energy and high-density memory electronics.

Whole-Genome/Exome Sequencing Uncovers Mutations and Copy Number Variations in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.

Background/objective: Identification of key genetic alterations is of importance in the targeted therapies of primary central nervous system lymphoma (PCNSL). However, only a small number of studies have been carried out in PCNSL. In this study, we further described the genetic mutations and copy number variations (CNVs) in PCNSL patients using whole-genome/exome sequencing (WGS/WES), as well as revealed their associations with patients' clinicopathological features and prognosis. Methods: Tumor specimens from 38 patients with primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) were enrolled to WGS (n = 24) or WES (n = 14). The CNVs and mutations of 24 samples (WGS) and 38 samples (WGS/WES) were characterized, respectively. The associations between CNVs and mutations with the overall survival rates of PCNSL patients were also evaluated. Results: The most common mutations were identified in IGLL5 (68%), PIM1 (63%), MYD88 (55%), CD79B (42%), BTG2 (39%), PCLO (39%), KMT2D (34%), and BTG1 (29%) genes. Among the mutated genes, EP300, ETV6, and HIST1H1E mutations were exclusively detected in the elderly, while DUSP2 mutations were associated with the immune microenvironment indicators. In addition, KMT2D mutation was associated with a poor prognosis. In addition, 488 CNVs including 91 gains and 397 deletions were observed across 24 samples from WGS results. Notably, 1q31.3 amplification was closely associated with the poor prognosis of PCNSL patients. Conclusion: This study further characterizes the genomic landscape of primary CNS DLBCL using WGS/WES, which provides insight into understanding the pathogenesis of PCNSL and fosters new ideas for the targeted treatment of PCNSL.

A Clinicopathological and Molecular Analysis of Sellar/Suprasellar Neurocytoma Mimicking Pituitary Adenoma.

Objective: To investigate the clinicopathological characteristics, molecular genetic characteristics and prognosis of extraventricular neurocytoma located in the sellar/suprasellar region. Methods: Seven archived tumor samples derived from 4 patients with neurocytoma in the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian Medical University and the Affiliated Hospital of Qingdao University and retrospectively analyzed for clinical manifestations, imaging features, and histopathological features. Neuronal and pituitary biomarkers and molecular features were detected in these tumor tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature was reviewed. Results: Three patients were female, while 1 was male, with an average age of 35.5 years (range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision in both eyes. The first MRI examination showed marginally enhancing masses in the intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based on imaging features. The levels of pituitary hormones were normal. Histologically, the tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely packed close to one another and were separated only by a delicate neuropil background. There was no evident mitosis, necrosis or microvascular proliferation. The three cases of recurrent tumors were highly cellular and showed increased mitotic activity. Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100 proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative. Pituitary transcription factors and anterior pituitary hormones were negative. Molecular genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q, MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range 23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery. Conclusion: The morphological features and immunophenotypes of neurocytoma in the sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis is relatively good. Gross-subtotal resection and atypical subtype may be related to tumor recurrence.

Simultaneously achieving giant piezoelectricity and record coercive field enhancement in relaxor-based ferroelectric crystals.

A large coercive field (EC) and ultrahigh piezoelectricity are essential for ferroelectrics used in high-drive electromechanical applications. The discovery of relaxor-PbTiO3 crystals is a recent breakthrough; they currently afford the highest piezoelectricity, but usually with a low EC. Such performance deterioration occurs because high piezoelectricity is interlinked with an easy polarization rotation, subsequently favoring a dipole switch under small fields. Therefore, the search for ferroelectrics with both a large EC and ultrahigh piezoelectricity has become an imminent challenge. Herein, ternary Pb(Sc1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 crystals are reported, wherein the dispersed local heterogeneity comprises abundant tetragonal phases, affording a EC of 8.2 kV/cm (greater than that of Pb(Mg1/3Nb2/3)O3-PbTiO3 by a factor of three) and ultrahigh piezoelectricity (d33 = 2630 pC/N; d15 = 490 pC/N). The observed EC enhancement is the largest reported for ultrahigh-piezoelectric materials, providing a simple, practical, and universal route for improving functionalities in ferroelectrics with an atomic-level understanding.

Observation of Clinicopathologic Features of Pituitary Adenoma With Neuronal Differentiation.

Objective: To investigate the clinicopathologic features of pituitary adenoma with neuronal differentiation. Methods: Four patients with mixed gangliocytoma-pituitary adenomas between January 2011 and January 2021 and 111 new-onset patients with adenomas between January 2019 and June 2021 who attended the First Affiliated Hospital of Fujian Medical University were included in the study. The histological and immunohistochemical findings were analyzed. Neuronal differentiation marker staining was performed on new-onset adenomas, and the related literature was reviewed. Results: Altogether, more than 100 mixed gangliocytoma-pituitary adenoma cases have been reported in the literature until now, of which pituitary-specific POU-class homeodomain transcription 1 (PIT1) positive adenomas are more frequently observed. In the present study, all 4 patients we described were female, aged 29 to 53 years (mean 39 years). Clinically, 3/4 patients presented with acromegaly, and 1/2 patients presented with headache. Histologically, the tumor was composed of two distinct mixed components. The one was a population of neoplastic ganglionic cells with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm embedded in a fibrillary background. Stains of chromograninA (CgA), synaptophysin (Syn), Calretinin (CR) were positive. Axotomy-like expression was observed in neurofilament (NF) staining. PIT1 was expressed in partial ganglionic cells in all cases. The other component was a population of small uniform cells with round nuclei and acidophilic cytoplasm. Prolactin (PRL) and growth hormone (GH) were positive in all 4 cases. PIT1 was positive in the nuclei of adenomas. Although adenomas and ganglionic regions varied in histology, there was a population of cells with neuronal differentiation expressing PIT1. Additionally, axotomy-like expression of NF staining could be seen in a distant area of adenoma regions. A total of 111 cases of adenomas without ganglionic cells were included in this study, including 7 cases with neuronal differentiation. Among them, 4 cases were prolactinomas, 2 cases were somatotroph adenomas, and 1 case was corticotroph adenoma. 6/7 cases were PIT1-positive adenomas. And the remaining one case is T-PIT-positive adenoma. Conclusions: Mixed gangliocytoma-pituitary adenomas are rare tumors with neuronal differentiation. The majority of MGAs are associated with endocrinopathies, mainly acromegaly. Our results suggest that PIT1-positive pituitary adenomas may have neural differentiation potential, which may not be unusual. This indication supports the possibility that the neuronal transdifferentiation of adenomatous cells is a possible mechanism, and the underlying mechanism requires further elucidation.