α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice.

BACKGROUND: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. METHODS: In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. RESULTS: AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. CONCLUSION: Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage.

Advanced glycation end product-modified low-density lipoprotein promotes pro-osteogenic reprogramming via RAGE/NF-κB pathway and exaggerates aortic valve calcification in hamsters.

BACKGROUND: Advanced glycation end product-modified low-density lipoprotein (AGE-LDL) is related to inflammation and the development of atherosclerosis. Additionally, it has been demonstrated that receptor for advanced glycation end products (RAGE) has a role in the condition known as calcific aortic valve disease (CAVD). Here, we hypothesized that the AGE-LDL/RAGE axis could also be involved in the pathophysiological mechanism of CAVD. METHODS: Human aortic valve interstitial cells (HAVICs) were stimulated with AGE-LDL following pre-treatment with or without interleukin 37 (IL-37). Low-density lipoprotein receptor deletion (Ldlr-/-) hamsters were randomly allocated to chow diet (CD) group and high carbohydrate and high fat diet (HCHFD) group. RESULTS: AGE-LDL levels were significantly elevated in patients with CAVD and in a hamster model of aortic valve calcification. Our in vitro data further demonstrated that AGE-LDL augmented the expression of intercellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and alkaline phosphatase (ALP) in a dose-dependent manner through NF-κB activation, which was attenuated by nuclear factor kappa-B (NF-κB) inhibitor Bay11-7082. The expression of RAGE was augmented in calcified aortic valves, and knockdown of RAGE in HAVICs attenuated the AGE-LDL-induced inflammatory and osteogenic responses as well as NF-κB activation. IL-37 suppressed inflammatory and osteogenic responses and NF-κB activation in HAVICs. The vivo experiment also demonstrate that supplementation with IL-37 inhibited valvular inflammatory response and thereby suppressed valvular osteogenic activities. CONCLUSIONS: AGE-LDL promoted inflammatory responses and osteogenic differentiation through RAGE/NF-κB pathway in vitro and aortic valve lesions in vivo. IL-37 suppressed the AGE-LDL-induced inflammatory and osteogenic responses in vitro and attenuated aortic valve lesions in a hamster model of CAVD.

Contributing to the Revolution of Electrolyte Systems via In Situ Polymerization at Different Scales: A Review.

Solid-state batteries have become the most anticipated option for compatibility with high-energy density and safety. In situ polymerization, a novel strategy for the construction of solid-state systems, has extended its application from solid polymer electrolyte systems to other solid-state systems. This review summarizes the application of in situ polymerization strategies in solid-state batteries, which covers the construction of polymer, the formation of the electrolyte system, and the design of the full cell. For the polymer skeleton, multiple components and structures are being chosen. In the construction of solid polymer electrolyte systems, the choice of initiator for in situ polymerization is the focus of this review. New initiators, represented by lithium salts and additives, are the preferred choice because of their ability to play more diverse roles, while the coordination with other components can also improve the electrical properties of the system and introduce functionalities. In the construction of entire solid-state battery systems, the application of in situ polymerization to structure construction, interface construction, and the use of separators with multiplex functions has brought more possibilities for the development of various solid-state systems and even the perpetuation of liquid electrolytes.

Highly efficient single-layer graphene electro-absorption modulator.

We propose a single-layer graphene electro-absorption modulator (EAM) with an angled waveguide sidewall. By utilizing the hybridization of the TM0 mode and the TE1 mode in the waveguide, the light-graphene interaction is enhanced. A modulation depth of 0.124 dB/µm and a figure of merit up to 25 are obtained at 1550 nm. Moreover, we show that the longitudinal electric field plays a significant role in making the optical absorption efficient, which indicates that modulation depth can be increased by enhancing the longitudinal electric field in modulators. This provides a promising solution for the future design of graphene optical modulators.

Azobenzene-Based Conjugated Polymers: Synthesis, Properties, and Biological Applications.

Conjugated polymers (CPs) have been developed quickly as an emerging functional material with applications in optical and electronic devices, owing to their highly electron-delocalized backbones and versatile side groups for facile processibility, high mechanical strength, and environmental stability. CPs exhibit multistimuli responsive behavior and fluorescence quenching properties by incorporating azobenzene functionality into their molecular structures. Over the past few decades, significant progress has been made in developing functional azobenzene-based conjugated polymers (azo-CPs), utilizing diverse molecular design strategies and synthetic pathways. This article comprehensively reviews the rapidly evolving research field of azo-CPs, focusing on the structural characteristics and synthesis methods of general azo-CPs, as well as the applications of charged azo-CPs, specifically azobenzene-based conjugated polyelectrolytes (azo-CPEs). Based on their molecular structures, azo-CPs can be broadly categorized into three primary types: linear CPs with azobenzene incorporated into the side chain, linear CPs with azobenzene integrated into the main chain, and branched CPs containing azobenzene moieties. These systems are promising for biomedical applications in biosensing, bioimaging, targeted protein degradation, and cellular apoptosis.

Tunability of electronic properties in the 2D MoS2/α-tellurene/WS2 heterotrilayer via biaxial strain and electric field.

Alpha-tellurene (α-Te), a two-dimensional (2D) material that has been theoretically predicted and experimentally verified, has garnered significant attention due to its unique properties. In this study, we investigated the 2D trilayer MoS2/α-Te/WS2 van der Waals heterostructure with different stacking orders using first-principles calculations. Our results indicate that this heterotrilayer exhibits an intrinsic type-I band alignment and an indirect band gap similar to that of monolayer α-Te. Notably, the band edges of the heterostructure can be modulated by biaxial strain and an external electric field, enabling these edges to arise from different monolayers. This controlled manipulation facilitates the effective separation of photogenerated electron-hole pairs and prolongs the carrier lifetime. Moreover, the heterostructure can undergo a transition from an indirect to a direct band gap under biaxial compressive strain or a moderate negative electric field, and semiconductor-to-metal transition can also be achieved by intensifying the biaxial strain and external electric field. Overall, our research provides valuable theoretical insights into the potential applications of α-Te-based heterostructures, rendering them promising candidates for the next generation of nanodevices.

The pathway of Edwardsiella piscicida infecting Lateolabrax maculatus via the immersion bath.

Edwardsiella piscicida, an infectious bacterium, causes great economic losses to the aquaculture industry. Immersion bath which is the closest way to how the fish infect bacterial pathogens in the natural environment is an effective route of artificial infection. In this study, the dynamic process of E. piscicida infection, in the spotted sea bass (Lateolabrax maculatus) was evaluated via the immersion bath. The results showed that soaking the spotted sea bass with 3 × 106 CFU mL-1 E. piscicida for 30 min could artificially induce edwardsiellosis. The higher culture temperature (28.5 ± 0.5°C) or the longer bath time (30 min) would lead to higher mortality of fish. E.piscicida first invaded the gill, then entered the blood circulation to infect the spleen and kidney, where it is colonized, and gradually multiplied in the liver and brain. Meanwhile, the fluorescence in situ hybridization showed that the localization of E. piscicida in the gill and foregut after the immersion challenge proceeded from the exterior to the interior. The invasion of pathogens triggers the immune response of fish and causes tissue damage to the host. The quantitative real-time PCR results displayed an increase in the relative expression level of immune genes (NK-lysin, LZM, IgM and IgD). Otherwise, the most notable histopathological changes of the infected spotted sea bass were multifocal necrosis. Findings in this study broaden our understanding of the infection conditions of E. piscicida and its pathogenicity to the spotted sea bass.

A meta-analysis of the risk factors for neurosurgical surgical site infection following craniotomy.

The purpose of the meta-analysis was to evaluate and compare the risk factors for neurosurgical surgical site infection (SSI) after craniotomy. Using dichotomous or contentious random or fixed effect models, the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were computed based on the examination of the meta-analysis results. Eighteen analyses, covering 11 068 craniotomies between 2001 and 2023, were included in the current meta-analysis. Subjects with SSIs had a significantly younger age (MD, -2.49; 95% CI, -2.95 to -2.04, p < 0.001), longer operation duration (MD, 10.21; 95% CI, 6.49-13.94, p < 0.001) and longer length of postoperative hospital stay (MD, 1.52; 95% CI, 0.45-2.60, p = 0.006) compared to subjects with no SSI with craniotomy. However, no significant difference was found between craniotomy subjects with SSIs and with no SSI in gender (OR, 0.90; 95% CI, 0.76-1.07, p = 0.23), and combination with other infection (OR, 3.93; 95% CI, 0.28-56.01, p = 0.31). The data that were looked at showed that younger age, longer operation duration and longer length of postoperative hospital stay can be considered as risk factors of SSI in subjects with craniotomy; however, gender and combination with other infections are not. Nonetheless, consideration should be given to their values because several studies only involved a small number of patients, and there are not many studies available for some comparisons.

Development of iron-based single atom materials for general and efficient synthesis of amines.

Heterogeneous catalysts with highly active and at the same time stable isolated metal sites constitute a key factor for the advancement of sustainable and cost-effective chemical synthesis. In particular, the development of more practical, and durable iron-based materials is of central interest for organic synthesis, especially for the preparation of chemical products related to life science applications. Here, we report the preparation of Fe-single atom catalysts (Fe-SACs) entrapped in N-doped mesoporous carbon support with unprecedented potential in the preparation of different kinds of amines. The synthetic protocol of Fe-SACs is based on primary pyrolysis of Fe-nitrogen complexes on SiO2 and subsequent removal of silica resulting in the formation of unique mesoporous N-doped carbon support with the pore size controlled by the size of the original silica nanoparticles. The resulting stable and reusable Fe-SACs allow for the reductive amination of a broad range of aldehydes and ketones with ammonia and amines to produce diverse primary, secondary, and tertiary amines including N-methylated products as well as drugs, agrochemicals, and other biomolecules (amino acid esters and amides) utilizing green hydrogen.

Local Chain Feature Mandated Self-Assembly of Block Copolymers.

This work demonstrates an effective and robust approach to regulate phase behaviors of a block copolymer by programming local features into otherwise homogeneous linear chains. A library of sequence-defined, isomeric block copolymers with globally the same composition but locally different side chain patterns were elaborately designed and prepared through an iterative convergent growth method. The precise chemical structure and uniform chain length rule out all inherent molecular defects associated with statistical distribution. The local features are found to exert surprisingly pronounced impacts on the self-assembly process, which have yet to be well recognized. While other molecular parameters remain essentially the same, simply rearranging a few methylene units among the alkyl side chains leads to strikingly different phase behaviors, bringing about (i) a rich diversity of nanostructures across hexagonally packed cylinders, Frank-Kasper A15 phase, Frank-Kasper σ phase, dodecagonal quasicrystals, and disordered state; (ii) a significant change of lattice dimension; and (iii) a substantial shift of order-to-disorder transition temperature (up to 40 °C). Different from the commonly observed enthalpy-dominated cases, the frustration due to the divergence between the native molecular geometry originating from side chain distribution and the local packing environment mandated by lattice symmetry is believed to play a pivotal role. Engineering the local chain feature introduces another level of structural complexity, opening up a new and effective pathway for modulating phase transition without changing the chemistry or composition.

Transition from semiconductor to conductor of a Mg2N electride induced by strain.

Electrides are a class of materials in which electrons are not bound to atoms but are similar to anions in crystals. To date, there are more than 300 electrides that have been discovered by first-principles. Alkaline-earth metal nitrides (AE2N, AE = Be, Mg, Ca, Sr, and Ba) are an important component of electride materials. Ca2N, Sr2N, and Ba2N structures have been identified and synthesized in previous research studies. Furthermore, the structures of Be2N (R3̄m symmetry) and Mg2N (R3m symmetry) were recently identified. For Mg2N, it has zero-dimension (0D) interstitial localized electrons and band structure with semiconductor properties, which is significantly different from the other AE2N structures (two-dimension electrides and metal properties). Consequently, Mg2N was systematically studied in this work. We found that the pristine Mg2N was an indirect band gap semiconductor with a band gap of 0.243 eV. It transitioned to a metal when 2% stretch stress was applied to the c-axis. Moreover, at 5% stretch stress, the structure exhibited 2D interstitial localized electrons with the superconducting transition temperature (Tc) of 0.3 K. These studies thus provide a deeper understanding of the physicochemical properties of Mg2N as an electride.

Prediction of subsolid pulmonary nodule growth rate using radiomics.

BACKGROUND: Pulmonary nodule growth rate assessment is critical in the management of subsolid pulmonary nodules (SSNs) during clinical follow-up. The present study aimed to develop a model to predict the growth rate of SSNs. METHODS: A total of 273 growing SSNs with clinical information and 857 computed tomography (CT) scans were retrospectively analyzed. The images were randomly divided into training and validation sets. All images were categorized into fast-growth (volume doubling time (VDT) ≤ 400 days) and slow-growth (VDT > 400 days) groups. Models for predicting the growth rate of SSNs were developed using radiomics and clinical features. The models' performance was evaluated using the area under the curve (AUC) values for the receiver operating characteristic curve. RESULTS: The fast- and slow-growth groups included 108 and 749 scans, respectively, and 10 radiomics features and three radiographic features (nodule density, presence of spiculation, and presence of vascular changes) were selected to predict the growth rate of SSNs. The nomogram integrating radiomics and radiographic features (AUC = 0.928 and AUC = 0.905, respectively) performed better than the radiographic (AUC = 0.668 and AUC = 0.689, respectively) and radiomics (AUC = 0.888 and AUC = 0.816, respectively) models alone in both the training and validation sets. CONCLUSION: The nomogram model developed by combining radiomics with radiographic features can predict the growth rate of SSNs more accurately than traditional radiographic models. It can also optimize clinical treatment decisions for patients with SSNs and improve their long-term management.

Diagnostic efficacy and safety of radial probe endobronchial ultrasound-guided transbronchial needle aspiration for adjacent lesions in segmental or subsegmental bronchi: a single-center retrospective study.

BACKGROUND: Peripheral lung lesions can be sampled using various techniques, including computer tomography-guided transthoracic needle aspiration, electromagnetic navigation bronchoscopy, virtual navigation bronchoscopy, and radial probe endobronchial ultrasound transbronchial lung biopsy. Mediastinal lesions can be sampled using techniques like convex probe endobronchial ultrasound-guided transbronchial needle aspiration (CEBUS-TBNA) and endoscopic ultrasound-fine-needle aspiration. However, effective, safe techniques for lesions adjacent to the segmental or subsegmental bronchi are lacking. Herein, we retrospectively evaluated the diagnostic yield and safety of radial probe endobronchial ultrasound-assisted transbronchial needle aspiration (REBUS-TBNA) for lesions adjacent to the segmental bronchi, and explored the factors related to diagnostic yield. METHODS: We retrospectively analyzed the diagnostic yield and safety of REBUS-TBNA cases performed in our department from January 2019 to December 2022. Observation group patients had undergone REBUS-TBNA for lesions adjacent to the segmental bronchi; control group patients had undergone CEBUS-TBNA for mediastinal or hilar lesions. Patient characteristics and lesion sizes, diagnostic yield, adverse events, and relations between diagnostic yield and clinical characteristics were analyzed. RESULTS: There were not statistically significant between-group differences in sex, age, diagnostic yield, or rate of adverse events. The observation group (n = 25; 17 male, 8 female) had a mean age of 64.76 ± 10.75 years. The average lesion size was 4.66 ± 1.07 cm, and lesions were predominantly in the upper lobes (80%). REBUS-TBNA diagnostic yield was 84%, with no adverse events reported. Diagnostic yield was not associated with lesion size or extent of bronchial stenosis; however, it was positively correlated with number of punctures. Patients with > 3 punctures had a significantly higher diagnostic yield than those with ≤ 3 punctures. CONCLUSIONS: REBUS-TBNA is a safe, effective diagnostic technique, particularly for lesions adjacent to the segmental or subsegmental bronchi of the upper lobe. Performing more than three punctures during the procedure improves the diagnostic yield. Larger-scale studies are warranted to confirm these results, and to further explore the clinical value of REBUS-TBNA.

Acrolein increases the concentration of intracellular Zn2⁺ by producing mitochondrial reactive oxygen species in A549 cells.

Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H2O2 was found to increase intracellular Zn2⁺ concentration ([Zn2⁺]ᵢ). However, the specific impact of acrolein on changes in intracellular Zn2⁺ levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn2⁺]ᵢ in A549 cells. We used Mito Tracker Red CM-H2Xros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn2⁺. The results revealed that acrolein increased [Zn2⁺]ᵢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn2⁺ chelator TPEN could inhibit the acrolein-induced elevation of [Zn2⁺]ᵢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn2⁺]ᵢ were significantly decreased by the inhibitors of ROS formation (NaHSO3, NAC). Furthermore, external oxygen free radicals increased both [Zn2⁺]ᵢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn2⁺]ᵢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn2⁺]ᵢ elevation leads to mROS production.

Development of a General and Selective Nanostructured Cobalt Catalyst for the Hydrogenation of Benzofurans, Indoles and Benzothiophenes.

The selective hydrogenation of benzofurans in the presence of a heterogeneous non-noble metal catalyst is reported. The developed optimal catalytic material consists of cobalt-cobalt oxide core-shell nanoparticles supported on silica, which has been prepared by the immobilization and pyrolysis of cobalt-DABCO-citric acid complex on silica under argon at 800 °C. This novel catalyst allows for the selective hydrogenation of simple and functionalized benzofurans to 2,3-dihydrobenzofurans as well as related heterocycles. The versatility of the reported protocol is showcased by the reduction of selected drugs and deuteration of heterocycles. Further, the stability, recycling, and reusability of the Co-nanocatalyst are demonstrated.

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats.

CONTEXT: Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax ginseng C.A. Meyer (Araliaceae)]. OBJECTIVE: This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-ß, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed. RESULTS: There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-ß (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-ß (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury. DISCUSSION AND CONCLUSIONS: These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.

Precisely Encoding Geometric Features into Discrete Linear Polymer Chains for Robust Structural Engineering.

Molecular shape is an essential parameter that regulates the self-organization and recognition process, which has not yet been well appreciated and exploited in block polymers due to the lack of precise and efficient modulation methods. This work (i) develops a robust approach to break the intrinsic symmetry of linear polymers by introducing geometric features into otherwise homogeneous chains and (ii) quantitatively highlights the critical contribution of molecular geometry/architecture to the self-assembly behaviors. Iteratively connecting homologous monomers of different side chains according to pre-designed sequences generates discrete polymers with exact chemical structure, uniform chain length, and programmable side-chain gradient along the backbone, which transcribes into diverse shapes. The precise chemistry eliminates all the defects and heterogeneities, providing a delicate platform for fundamental inquiries into the role of molecular geometry. A rich collection of unconventional complex phases, including Frank-Kasper A15 and σ phases, as well as a dodecagonal quasicrystal phase, were captured in these rigorous single-component systems. The self-assembly behaviors are strikingly sensitive to subtle variations of geometry, such that simply migrating a few methylene units among the side chains would generate substantial differences in lattice size or phase stability, or even trigger a phase transition toward distinct structures. The phenomena can be rationalized with a geometric argument that nonuniform side chain distribution leads to conformational mismatch between two immiscible blocks, resulting in varied interfacial curvatures and distinct lattice symmetries. The profound contribution demonstrates that molecular geometry is an effective and robust parameter for structural engineering.

Demonstration of a 50G-PON with a 45-dB power budget using an IQ-interleaved coherent detection scheme.

The application of traditional coherent detection technology to optical access networks has been undermined due to its high complexity and high cost. In this paper, we propose a novel IQ-interleaved detection method which uses the preset frequency offset of the lasers at the transmitter and receiver to obtain the in-phase and quadrature components of the received signal. It keeps the simple structure of heterodyne detection and avoids the down-conversion process. Without Nyquist pulse shaping, the received signal bandwidth of the proposed scheme is theoretically 0.5B smaller than that of heterodyne detection for signal with a symbol rate of B. The 50-Gb/s NRZ transmission experiment proves that by using the proposed scheme, the receiving sensitivity and the frequency drift tolerance can be improved by ∼1 dB and 1 GHz compared with heterodyne detection under strong bandwidth limitation. Without pulse shaping, the receiving sensitivity, frequency drift tolerance (1-dB sensitivity penalty) and link power budget for 20-km fiber transmission are -31.8 dBm, 11 GHz and 43.5 dB, respectively. A higher power budget of 45 dB can be achieved when Nyquist pulse shaping is applied. The proposed scheme provides a low-complexity potential solution for a next-generation coherent PON.

Two-dimensional topological insulators exfoliated from Na3Bi-like Dirac semimetals.

Topological insulation is widely predicted in two-dimensional (2D) materials realized by epitaxial growth or van der Waals (vdW) exfoliation. Such 2D topological insulators (TI's) host many interesting physical properties such as the quantum spin Hall effect and superconductivity. Here, we extend the search of 2D TI's into the exfoliatable non-vdW 2D crystals. We find that three-dimensional Dirac semimetals A3Bi (A = Na, K, Rb) (P3[combining macron]c1) can be exfoliated into 2D materials with exfoliation energies of 0.479-0.990 J m-2. Our careful examination of the topological invariants of exfoliated A3Bi monolayers/multilayers by using two well-established approaches reveals that bilayer and tetralayer Na3Bi are 2D TI's. It is found that the band gap of 2D TI's can be significantly increased by external strain. We further find that the predicted 2D TI's possess interesting hidden Rashba-like spin textures. Our results suggest a new arena to search for two-dimensional topological insulators and spintronic materials.

Efficacy and safety of tratinterol hydrochloride tablets in bronchial asthma: a randomized double-blind and multicenter clinical trial.

PURPOSE: The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment. METHODS: Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting. FINDINGS: We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEV1), significantly increased in both group after treatment (P < 0.05). Least-squares (LS) means were -0.03/in the full-analysis set (FAS) and -0.02 in the per-protocol set (PPS) set, and 95% confidence intervals (CIs) for these sets were -0.09 to 0.03 and -0.08 to 0.04, respectively. Forced expiratory volume (FVC), morning peak expiratory flow (PEF) and asthma scores were significantly different with pretreatment (P < 0.05). There was no difference in asymptomatic days or frequency of relief medicine use (P > 0.05). No serious adverse events occurred. IMPLICATIONS: Tratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.