Multi-dimensional band structure spectroscopy in the synthetic frequency dimension.

The concept of synthetic dimensions in photonics provides a versatile platform in exploring multi-dimensional physics. Many of these physics are characterized by band structures in more than one dimensions. Existing efforts on band structure measurements in the photonic synthetic frequency dimension however are limited to either one-dimensional Brillouin zones or one-dimensional subsets of multi-dimensional Brillouin zones. Here we theoretically propose and experimentally demonstrate a method to fully measure multi-dimensional band structures in the synthetic frequency dimension. We use a single photonic resonator under dynamical modulation to create a multi-dimensional synthetic frequency lattice. We show that the band structure of such a lattice over the entire multi-dimensional Brillouin zone can be measured by introducing a gauge potential into the lattice Hamiltonian. Using this method, we perform experimental measurements of two-dimensional band structures of a Hermitian and a non-Hermitian Hamiltonian. The measurements reveal some of the general properties of point-gap topology of the non-Hermitian Hamiltonian in more than one dimensions. Our results demonstrate experimental capabilities to fully characterize high-dimensional physical phenomena in the photonic synthetic frequency dimension.

Artificial Non-Abelian Lattice Gauge Fields for Photons in the Synthetic Frequency Dimension.

Non-Abelian gauge fields give rise to nontrivial topological physics. Here we develop a scheme to create an arbitrary SU(2) lattice gauge field for photons in the synthetic frequency dimension using an array of dynamically modulated ring resonators. The photon polarization is taken as the spin basis to implement the matrix-valued gauge fields. Using a non-Abelian generalization of the Harper-Hofstadter Hamiltonian as a specific example, we show that the measurement of the steady-state photon amplitudes inside the resonators can reveal the band structures of the Hamiltonian, which show signatures of the underlying non-Abelian gauge field. These results provide opportunities to explore novel topological phenomena associated with non-Abelian lattice gauge fields in photonic systems.

Hsa_circ_0000119 promoted ovarian cancer development via enhancing the methylation of CDH13 by sponging miR-142-5p.

Ovarian cancer is the leading cause of gynecological cancer-related death in women, and is difficult to treat. The aim of our study is to explore the role and action mechanism of hsa_circ_0000119 in ovarian cancer, thus to analyze whether the circular RNA is a potential target for the treatment of the disease. In this present study, our data shows that hsa_circ_0000119 and DNA methyltransferase 1 (DNMT1) was increased, while miR-142-5p was decreased in ovarian cancer. Overexpression of hsa_circ_0000119 promoted tumor growth, while silencing of hsa_circ_0000119 resulted in an opposite effects. Decreasing of hsa_circ_0000119 also notably inhibited the proliferation, migration, and invasion of the ovarian cancer cells. Moreover, the data proves that hsa_circ_0000119 negatively regulated miR-142-5p and cadherin 13 (CDH13) expression, but positively regulated DNMT1 expression. miR-142-5p could interact with hsa_circ_0000119 and DNMT1 3'-UTR. Silencing of DNMT1 could reverse the inhibition of hsa_circ_0000119 to miR-142-5p and CDH13 expression. Importantly, higher level of CDH13 promoter methylation existed in the ovarian tumors than that in matched normal tissues. DNA methyltransferase inhibitor could increase the expression of CDH13 in ovarian cancer cells. In addition, our results also prove that increasing of CDH13 or miR-142-5p effectively reversed the inhibition of hsa _circ_0000119 to the cell malignant phenotypes. Overall, our data demonstrate that hsa_circ_0000119 facilitated ovarian cancer development through increasing CDH13 expression via promoting DNMT1 expression by sponging miR-142-5p. Our data demonstrate the potential role of hsa_circ_0000119 in the treatment of ovarian cancer.

Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice.

Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm-sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mechanisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Furthermore, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.

CircRNA hsa_circ_0001627 aggravates cervical cancer progression through upregulation of FNDC3B and activating PI3K/mTOR signaling pathway.

Circular RNAs (CircRNAs) are key regulators in the development and progression of human cancers. However, the biological roles and mechanisms of circRNAs in gastric cancer (GC) remain largely unknown. Analyzing circRNA microarray dataset (GSE102686) and clinical specimens, a novel circRNA termed hsa_circ_0001627, was identified and it was highly expressed in CC cancerous tissues and cells, and was associated with poor clinical outcomes. Functionally, hsa_circ_0001627 silencing impaired the malignant progression of CC cells and the growth of CC xenografts in nude mice. Mechanistically, hsa_circ_0001627 acted as a miR-1225-5p sponge, thus indirectly regulating FNDC3B and leading to the activation of PI3K/mTOR signaling pathway. Collectively, the present study indicates that hsa_circ_0001627 regulates miR-1225-5p/FNDC3B/PI3K/mTOR axis and functions as an oncogene in CC progression, suggesting the potential therapeutic use of hsa_circ_0001627 in CC treatment.

Heteroepitaxy of Large-Area, Monocrystalline Lead Halide Perovskite Films on Gallium Arsenide.

Lead halide perovskite materials have been emerging as promising candidates for high-performance optoelectronic devices. Significant efforts have sought to realize monocrystalline perovskite films on a large scale. Here, we epitaxially grow monocrystalline methylammonium lead tribromide (MAPbBr3) films on lattice-matched gallium arsenide (GaAs) substrates on a centimeter scale. In particular, a solution-processed lead(II) sulfide (PbS) layer provides a lattice-matched and chemical protective interface for the solid-gas reaction to form MAPbBr3 films on GaAs. Structure characterizations identify the crystal orientations in the trilayer MAPbBr3/PbS/GaAs epistructure and confirm the monocrystalline nature of MAPbBr3 on PbS/GaAs. The dynamic evolution of surface morphologies during the growth indicates a two-step epitaxial process. These fundamental understandings and practical growth techniques offer a viable guideline to approach high-quality perovskite films for previously inaccessible applications.

Technologically feasible quasi-edge states and topological Bloch oscillation in the synthetic space.

The dimensionality of a physical system is one of the major parameters defining its physical properties. The recently introduced concept of synthetic dimension has made it possible to arbitrarily manipulate the system of interest and harness light propagation in different ways. It also facilitates the transformative architecture of system-on-a-chip devices enabling far reaching applications such as optical isolation. In this report, a novel architecture based on dynamically-modulated waveguide arrays with the Su-Schrieffer-Heeger configuration in the spatial dimension is proposed and investigated with an eye on a practical implementation. The propagation of light through the one-dimensional waveguide arrays mimics time evolution of the field in a synthetic two-dimensional lattice. The addition of the effective gauge potential leads to an exotic topologically protected one-way transmission along adjacent boundary. A cosine-shape isolated band, which supports the topological Bloch oscillation in the frequency dimension under the effective constant force, appears and is localized at the spatial boundary being robust against small perturbations. This work paves the way to improved light transmission capabilities under topological protections in both spatial and spectral regimes and provides a novel platform based on a technologically feasible lithium niobate platform for optical computing and communication.

Multidisciplinary treatment of retroperitoneal ectopic pregnancy: a case report and literature review.

BACKGROUND: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications. CASE PRESENTATION: A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (ß-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum ß-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum ß-hCG returned to normal range on the 23th postoperative day. CONCLUSIONS: Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.

CircWHSC1 expedites cervical cancer progression via miR-532-3p/LTBP2 axis.

Dysregulated circRNAs have potential roles in the progression of various cancer types, including cervical cancer (CaCx). The carcinogenic roles of circRNA Wolf-Hirschhorn syndrome candidate gene-1 (circWHSC1) are described in the development of diverse cancers. The objective of this study was to investigate the expression and the underlying role of circWHSC1 in CaCx. The expression of circWHSC1 was detected by real-time PCR. After the suppression of circWHSC1 expression, the changes in the proliferation, migration, invasion, and apoptosis capacities were detected by CCK-8 assay, colony formation assay, Transwell assays, flow cytometry, and the determination of apoptosis-related proteins. The interplay among circWHSC1, miR-532-3p, and latent transforming growth factor-ß binding protein 2 (LTBP2) was confirmed by luciferase reporter and biotinylated RNA pull-down assays. A nude mice xenograft tumor model was established to evaluate the anti-tumorigenic role of circWHSC1 silencing in vivo. CircWHSC1 was overexpressed in CaCx tissues and cell lines and its high expression was inversely associated with the survival rate of patients with CaCx. CircWHSC1 silencing was capable of suppressing the proliferation, metastasis, and invasion of tumor cells and inducing apoptosis. Investigation to its molecular mechanism revealed that circWHSC1 functioned as a competitive endogenous RNA (ceRNA), mediating LTBP2 expression by targeting miR-532-3p. The in vivo experiments further confirmed the inhibition of tumor growth and metastasis by circWHSC1 knockdown. The circWHSC1-mediated miR-532-3p/LTBP2 signaling axis might be a novel therapeutic target for CaCx.

Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe.

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable. Here we report bidirectional neuronal activity manipulation accomplished by a wireless, dual-color optogenetic probe in synergy with the co-expression of two spectrally distinct opsins (ChrimsonR and stGtACR2) in a rodent model. The flexible probe comprises vertically assembled, thin-film microscale light-emitting diodes with a lateral dimension of 125 × 180 µm2, showing colocalized red and blue emissions and enabling chronic in vivo operations with desirable biocompatibilities. Red or blue irradiations deterministically evoke or silence neurons co-expressing the two opsins. The probe interferes with dopaminergic neurons in the ventral tegmental area of mice, increasing or decreasing dopamine levels. Such bidirectional regulations further generate rewarding and aversive behaviors and interrogate social interactions among multiple mice. These technologies create numerous opportunities and implications for brain research.

Transfer-printed, tandem microscale light-emitting diodes for full-color displays.

Inorganic semiconductor-based microscale light-emitting diodes (micro-LEDs) have been widely considered the key solution to next-generation, ubiquitous lighting and display systems, with their efficiency, brightness, contrast, stability, and dynamic response superior to liquid crystal or organic-based counterparts. However, the reduction of micro-LED sizes leads to the deteriorated device performance and increased difficulties in manufacturing. Here, we report a tandem device scheme based on stacked red, green, and blue (RGB) micro-LEDs, for the realization of full-color lighting and displays. Thin-film micro-LEDs (size ∼100 µm, thickness ∼5 µm) based on III-V compound semiconductors are vertically assembled via epitaxial liftoff and transfer printing. A thin-film dielectric-based optical filter serves as a wavelength-selective interface for performance enhancement. Furthermore, we prototype arrays of tandem RGB micro-LEDs and demonstrate display capabilities. These materials and device strategies provide a viable path to advanced lighting and display systems.

A fully biodegradable and self-electrified device for neuroregenerative medicine.

Peripheral nerve regeneration remains one of the greatest challenges in regenerative medicine. Deprivation of sensory and/or motor functions often occurs with severe injuries even treated by the most advanced microsurgical intervention. Although electrical stimulation represents an essential nonpharmacological therapy that proved to be beneficial for nerve regeneration, the postoperative delivery at surgical sites remains daunting. Here, a fully biodegradable, self-electrified, and miniaturized device composed of dissolvable galvanic cells on a biodegradable scaffold is achieved, which can offer both structural guidance and electrical cues for peripheral nerve regeneration. The electroactive device can provide sustained electrical stimuli beyond intraoperative window, which can promote calcium activity, repopulation of Schwann cells, and neurotrophic factors. Successful motor functional recovery is accomplished with the electroactive device in behaving rodent models. The presented materials options and device schemes provide important insights into self-powered electronic medicine that can be critical for various types of tissue regeneration and functional restoration.

Perovskite hetero-anionic-sublattice interfaces for optoelectronics and nonconventional electronics.

The perovskite structure provides a versatile framework for functional materials and their high-quality heteroepitaxial interfaces. Perovskite halides (PH) have attracted intense interest for their application in optoelectronics. Oxides are another major class of perovskites that are widely used in fuel cells, nonconventional electronics and electrochemistry. Interfacing different perovskite oxides (POs) has led to a multitude of fascinating discoveries. By introducing anionic degree of freedom, we expect that perovskite hetero-anionic-sublattice interfaces can provide a new platform for emergent phenomena that may or may not have homo-oxygen-sublattice interface analogues. In this work, we investigate the interfaces between the all-inorganic PH CsPbBr3, the emerging double perovskite halide (dPH) Cs2TiBr6 and various common POs. Based on the band alignment properties, these POs are considered to be suitable carrier transport materials (CTMs) for CsPbBr3 and Cs2TiBr6 in either light-harvesting or light-emitting devices. In addition, these perovskite hetero-anionic-sublattice interfaces are found to be defect- and dangling bond-free due to compatible crystal lattices, making POs potentially outperform conventional binary transition-metal-oxide and organic CTMs. Besides optoelectronics, the potential of perovskite hetero-anionic-sublattice interfaces for nonconventional electronics is also explored. As examples, two-dimensionally confined electron-hole systems are predicted at the asymmetric interfaces in both Cs2TiBr6:LaAlO3 and CsPbBr3:LaAlO3 superlattice structures. This finding, along with the optically active properties of PHs, may spark novel applications of light-electron interaction in perovskite systems. This work presents new opportunities for perovskite heteroepitaxial interfaces.

A wireless, implantable optoelectrochemical probe for optogenetic stimulation and dopamine detection.

Physical and chemical technologies have been continuously progressing advances in neuroscience research. The development of research tools for closed-loop control and monitoring neural activities in behaving animals is highly desirable. In this paper, we introduce a wirelessly operated, miniaturized microprobe system for optical interrogation and neurochemical sensing in the deep brain. Via epitaxial liftoff and transfer printing, microscale light-emitting diodes (micro-LEDs) as light sources and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-coated diamond films as electrochemical sensors are vertically assembled to form implantable optoelectrochemical probes for real-time optogenetic stimulation and dopamine detection capabilities. A customized, lightweight circuit module is employed for untethered, remote signal control, and data acquisition. After the probe is injected into the ventral tegmental area (VTA) of freely behaving mice, in vivo experiments clearly demonstrate the utilities of the multifunctional optoelectrochemical microprobe system for optogenetic interference of place preferences and detection of dopamine release. The presented options for material and device integrations provide a practical route to simultaneous optical control and electrochemical sensing of complex nervous systems.

Influence of calcium chloride impregnation on the thermal and high-temperature carbonization properties of bamboo fiber.

In this study, bamboo fiber was pretreated with calcium chloride (CaCl2) solution by using an ultrasonic method, and then heat-treated at 250°C and carbonized at 1000°C. The effect of impregnation with CaCl2 on the thermal and chemical properties and morphology of bamboo fiber was determined using thermogravimetric and differential thermogravimetric analyses, in situ Fourier transform infrared spectroscopy, and scanning electron microscopy. The pore structure of the carbonized bamboo fiber was investigated. The results revealed that bamboo fiber pretreated with 5% CaCl2 (BFCa5) showed a downward shift in the temperature of the maximum rate of weight loss253°C and increase in char residue to 31.89%. BFCa5 was expected to undergo dehydration under the combined effect of oxygen-rich atmosphere and CaCl2 catalysis from 210°C, and cellulose decomposition would be remarkable at 250°C. Pretreatment with 5% CaCl2 promoted the formation of porous structure of the carbonized fiber, which exhibited a typical Type-IV isotherm, with the Brunauer-Emmett-Teller specific surface area of 331.32 m2/g and Barrett-Joyner-Halenda adsorption average pore diameter of 13.6440 nm. Thus, CaCl2 was found to be an effective catalyst for the pyrolysis of bamboo fiber, facilitating the formation of porous carbonized fiber.

Microscale optoelectronic infrared-to-visible upconversion devices and their use as injectable light sources.

Optical upconversion that converts infrared light into visible light is of significant interest for broad applications in biomedicine, imaging, and displays. Conventional upconversion materials rely on nonlinear light-matter interactions, exhibit incidence-dependent efficiencies, and require high-power excitation. We report an infrared-to-visible upconversion strategy based on fully integrated microscale optoelectronic devices. These thin-film, ultraminiaturized devices realize near-infrared (∼810 nm) to visible [630 nm (red) or 590 nm (yellow)] upconversion that is linearly dependent on incoherent, low-power excitation, with a quantum yield of ∼1.5%. Additional features of this upconversion design include broadband absorption, wide-emission spectral tunability, and fast dynamics. Encapsulated, freestanding devices are transferred onto heterogeneous substrates and show desirable biocompatibilities within biological fluids and tissues. These microscale devices are implanted in behaving animals, with in vitro and in vivo experiments demonstrating their utility for optogenetic neuromodulation. This approach provides a versatile route to achieve upconversion throughout the entire visible spectral range at lower power and higher efficiency than has previously been possible.

Correction: PD-1 Blockade and OX40 Triggering Synergistically Protects against Tumor Growth in a Murine Model of Ovarian Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0089350.].

Effect of ß-sitosterol on the expression of HPV E6 and p53 in cervical carcinoma cells.

AIM OF THE STUDY: In the absence of effective therapeutic strategies, cervical carcinoma continues to be second on the list of mortality rates of malignant tumours found in women. We investigated the effects of ß -sitosterol, a natural product isolated from traditional Chinese herbs, on Caski and HeLa cervical carcinoma cells. MATERIAL AND METHODS: Morphological changes were examined by light microscopy. Ultrastructures of Caski and HeLa cells treated with 20 µmol/l ß-sitosterol were documented by scanning electron microscopy and transmission electron microscopy. Changes in mRNA and protein expression were quantified respectively using Real-Time qPCR and western blot methods. RESULTS: Treatment of Caski and HeLa cells with ß-sitosterol resulted in reduced expression of PCNA, indicative of an inhibitory effect on cell proliferation. This was associated with increased p53 mRNA levels and decreased amounts of HPV E6 transcripts. Expression of p53 and HPV E6 proteins followed a similar trend as that observed for the corresponding transcripts. Caski and HeLa cells treated with ß-sitosterol exhibited loss of cell surface microvilli, increased electron density of cell membrane, and decreased organelles. CONCLUSIONS: In conclusion, treatment of Caski and HeLa cells with ß-sitosterol significantly suppressed the expression of genes involved in cell proliferation and oncogenic transformation, while augmenting the expression of genes involved in apoptosis and tumour suppression. Ultrastuctural characterisation of Caski and HeLa cells treated with ß-sitosterol further confirmed the anti-proliferative and anti-cancer activity of this natural product isolated from traditional Chinese herbs.

Short-term outcomes of adjustable single-incision sling (Ajust™) procedure for stress urinary incontinence: a prospective single-center study.

OBJECTIVES: Slings have become the most widely performed surgical procedure for stress urinary incontinence (SUI) in last two decades. As the third generation sling, the efficacy of the early single-incision mini-sling was controversial. The aim of this study was to determine whether the new adjustable single-incision sling (Ajust™) is safe and effective in management of female SUI at 6-18 months follow-up. STUDY DESIGN: 69 patients with SUI according the inclusion and exclusion criteria were considered adjustable single-incision sling (Ajust™) from September 2012 to September 2013. 67 patients finished 6-18 months follow-up. The data about clinical parameter, operation, complication, Urogenital Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) in Chinese were collected in preoperative, 6-month and 12-month follow-up. RESULTS: All patients underwent successful adjustable single-incision sling (Ajust(TM)) placement. The subjective cure rate and objective cure rate was 82.0%, 92.5% in 6-month follow-up and 82.3%, 91.2% in 12-month follow-up respectively. There were no significant perioperative complications such as bladder perforation, major bleeding requiring blood transfusion in the present study. Sling exposure was observed in two patients (3.2%). CONCLUSIONS: Adjustable single-incision sling (Ajust(TM)) was a safe and effective option for treating female SUI and was associated with comparable subjective and objective success rates when compared to standard midurethral slings (TVT-O) at a 6-18 months follow-up.

PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.

The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. In the present study, we evaluated the antitumor effects and mechanisms of combinatorial PD-1 blockade and OX40 triggering in a murine ID8 ovarian cancer model. Although individual anti-PD-1 or OX40 mAb treatment was ineffective in tumor protection against 10-day established ID8 tumor, combined anti-PD-1/OX40 mAb treatment markedly inhibited tumor outgrowth with 60% of mice tumor free 90 days after tumor inoculation. Tumor protection was associated with a systemic immune response with memory and antigen specificity and required CD4(+) cells and CD8(+) T cells. The anti-PD-1/OX40 mAb treatment increased CD4(+) and CD8(+) cells and decreased immunosuppressive CD4(+)FoxP3(+) regulatory T (Treg) cells and CD11b(+)Gr-1(+) myeloid suppressor cells (MDSC), giving rise to significantly higher ratios of both effector CD4(+) and CD8(+) cells to Treg and MDSC in peritoneal cavity; Quantitative RT-PCR data further demonstrated the induction of a local immunostimulatory milieu by anti-PD-1/OX40 mAb treatment. The splenic CD8(+) T cells from combined mAb treated mice produced high levels of IFN-γ upon tumor antigen stimulation and exhibited antigen-specific cytolytic activity. To our knowledge, this is the first study testing the antitumor effects of combined anti-PD-1/OX40 mAb in a murine ovarian cancer model, and our results provide a rationale for clinical trials evaluating ovarian cancer immunotherapy using this combination of mAb.