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Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects.

Summary: Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry. NZ-804 potently inhibits SARS-CoV-2 Mpro (0.009 μM IC50) as well as SARS-CoV-2 replication in human lung cell lines (0.008 μM EC50) and primary human airway epithelial cell cultures. Antiviral activity is maintained against distantly related sarbecoviruses and endemic human CoV OC43. In SARS-CoV-2 mouse and hamster disease models, NZ-804 therapy given once or twice daily significantly diminished SARS-CoV-2 replication and pathogenesis. NZ-804 synthesis is low cost and uncomplicated, simplifying global production and access. These data support the exploration of NZ-804 as a therapy for COVID-19 and future emerging sarbecovirus infections.

Abstract The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.

Abstract Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.

Inflammation has been shown to trigger a wide range of chronic diseases, particularly inflammatory diseases. As a result, the focus of research has been on anti-inflammatory drugs and foods. In recent years, the field of medicinal and edible homology (MEH) has developed rapidly in both medical and food sciences, with 95% of MEH being associated with plants. Phenolic acids are a crucial group of natural bioactive substances found in medicinal and edible homologous plants (MEHPs). Their anti-inflammatory activity is significant as they play a vital role in treating several inflammatory diseases. These compounds possess enormous potential for developing anti-inflammatory drugs and functional foods. However, their development is far from satisfactory due to their diverse structure and intricate anti-inflammatory mechanisms. In this review, we summarize the various types, structures, and distribution of MEHP phenolic acids that have been identified as of 2023. We also analyze their anti-inflammatory activity and molecular mechanisms in inflammatory diseases through NF-κB, MAPK, NLRP3, Nrf2, TLRs, and IL-17 pathways. Additionally, we investigate their impact on regulating the composition of the gut microbiota and immune responses. This analysis lays the groundwork for further exploration of the anti-inflammatory structure-activity relationship of MEHP phenolic acids, aiming to inspire structural optimization and deepen our understanding of their mechanism, and provides valuable insights for future research and development in this field.

Abstract Depression is a prevalent mental illness that imposes a substantial public health burden. However, the diverse clinical phenotypes observed in patients make it difficult to realize precise diagnosis. Recently, accumulating preclinical and clinical evidence has suggested that inflammation is involved in the pathophysiology of depression. Herein, a molecular imaging–based strategy was proposed as a means to diagnose depression precisely by specifically visualizing the inflammation status associated with depression. Inflammation-targeting MRI nanoprobes were constructed by attaching an intercellular cell adhesion molecule-1 (ICAM-1)-targeting peptide to biocompatible Fe3O4 nanoparticles. Systematic studies demonstrated that the nanoprobes could specifically target inflamed vascular endothelial cells and visualize the spatial distribution of inflammation in the depressed brain in vivo through susceptibility-weighted imaging (SWI), which was further confirmed by histological analysis. Additionally, these inflammatory brain regions identified by nanoprobe-based imaging are consistent with the focal regions closely associated with the symptoms of depression as reported in previous behavioral studies. Overall, this is the first study to directly visualize the distribution of inflammation in the depressed brain in vivo through a molecular imaging strategy, which may not only facilitate insight into the biological mechanism underlying depression but also provide a potential target within the depressed brain for the further development of anti-inflammatory therapies.

Abstract Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

Individual sociability and alcohol drinking are interacted to escalate alcohol use. An impairment in perceiving and discriminating the difference in incentive values between social interaction and drinking behavior indicates a shift from moderate alcohol consumption to misuse. However, few studies have evaluated the incentive value of these two behaviors in the same scenario. Thus, we modified a behavioral test protocol to evaluate rodents’ ability to perceive and discriminate the differences in incentive value between alcohol drinking and interaction with their social partners. The present protocol is simple and practicable. Only 2–3 days are required to complete the whole process. Compared with existing methods, our protocol is simple and practicable. Our findings suggested that subtle changes in the incentive value of distinct behaviors can be accurately and reliably assessed using the present protocol in mice with low or high levels of alcohol preference. • We described a modified behavioral test protocol to simultaneously evaluate the incentive value of alcohol drinking and social interaction. • The subtle changes in the incentive value of mice with different levels of alcohol preference can be accurately and reliably assessed in the present protocol. • Using our modified protocol, the differences of incentive value between distinct behaviors can be accurately and reliably assessed in mice with different risks to develop into AUD.

Accurate estimation of desert vegetation biomass is crucial for monitoring changes in carbon stocks and productivity status. Unmanned aerial vehicle (UAV) remote sensing allows large-scale biomass surveys at the individual or patch scale. However, since desert shrubs are short and sparse, the UAV-based techniques do not always accurately capture biomass-related indicators at any flight height. This study investigated the effects of flight height on above-ground biomass (AGB) estimation using UAV images of typical shrub communities (Reaumuria soongarica) captured at different heights (i.e., 30 m, 50 m, 70 m, 90 m, 110 m, 130 m, and 150 m) in desert-grassland ecosystems. Several structural indicators associated with shrub allometric growth were extracted for AGB modeling, including canopy area (horizontal properties), canopy height (vertical properties), and canopy volume. Results revealed that the values of canopy height and volume decreased with increasing flight height, which made the poor performance of AGB models based on these indicators worse. For example, the variance explained (VE) of the models based on the mean canopy height decreased from about 62% to -137%, while the root mean square error (RMSE) increased from about 39 g to 92 g. In contrast, the canopy area was less affected by flight height, maintaining stable AGB models with VE around 72% and RMSE at 33 g. Adjusting the coefficients of linear models based on canopy height and volume with flight height significantly improved their predictive performance, with VE between 54% and 77% and RMSE between 30 g and 43 g for the optimized models based on mean canopy height. Furthermore, a higher flight height (e.g., 90–110 m) could be chosen to enhance operational efficiency while ensuring the accuracy of biomass observation. Our study offers valuable insights and guidance for vegetation surveys and research in desert-grassland ecosystems.

Abstract Background Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4+ T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4+ cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4+ Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect. Methods In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain–blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4+ cells were investigated. Results We noticed that restrained rats showed significant depressive-like symptoms, concomitant BBB disruption and neuroinflammation in the dorsal striatum (DS). We further observed a time-dependent increase in thymus- and spleen-derived naïve CD4+ T cells, as well as the aggregation of inflammatory Th17 cells in the DS during the period of chronic restraint stress (CRS) exposure. Moreover, increased Th17-derived cytokines in the brain can further impair the BBB integrity, thus allowing more immune cells and cytokines to gain easy access to the CNS. Our findings suggested that, through a complex cascade of events, peripheral immune responses were propagated to the CNS, and gradually exacerbated depressive-like symptoms. Furthermore, inhibiting the differentiation and function of CD4+ T cells with SR1001 in the early stages of CRS exposure ameliorated CRS-induced depressive-like behaviour and the inflammatory response. Conclusions Our data demonstrated that inflammatory Th17 cells were pivotal in accelerating the onset and exacerbation of depressive symptoms in CRS-exposed rats. This subtype of CD4+ T cells may be a promising therapeutic target for the early treatment of stress-induced depression.

To identify the mechanism of the low-temperature CO + NH3 coupling selective catalytic reduction (SCR) denitration process, a series of Mn–Ce/activated carbon catalysts differing in the Ce content were prepared and characterized via SEM, EDS, XRD, XPS, FTIR and evaluated in the CO + NH3 coupling SCR denitration. The results show that the denitrification rates of Mn-Ce/AC catalysts are in the order of 7Mn-3Ce/AC > 7Mn-5Ce/AC > 7Mn-1Ce/AC at a temperature range of 150 °C–300 °C and an oxygen content of 9%. A moderate Ce content provides a smooth catalyst surface with a homogeneous distribution of metal particles and pores, resulting in the optimization of the physical and chemical performance of the Mn-based catalyst. As a result, more active oxygen species and lattice defects are formed, which promoted the dispersion of active components on the catalyst surface, increased the adsorption sites of CO and NH3, and provided more active sites for denitration reaction. Mn4+ and Ce3+ both increased to varying degrees, and oxygen-containing functional groups carboxyl and lactone groups increased, which promoted the synergistic reaction between MnCe, enhancing the NO adsorption and conversion rate. At 150 °C–250 °C, the CO + NH3 coupling denitration is mainly governed by physical adsorption, whereas chemical adsorption is the predominant mechanism at 250 °C–300 °C. The denitration process includes four stages: reaction gas adsorption, adsorption molecular dissociation, catalytic denitration of metal active components and product desorption.

Abstract Osteoarthritis (OA) is a degenerative disease that often causes cartilage lesions and even osteochondral damage. Osteochondral defects induced by OA are accompanied by an inflammatory arthrosis microenvironment with overproduced reactive oxygen species (ROS), resulting in the exacerbation of defects and difficulty regenerating osteochondral tissues. Therefore, it is urgently needed to develop osteochondral scaffolds that can not only promote the integrated regeneration of cartilage and subchondral bone, but also possess ROS‐scavenging ability to protect tissues from oxidative stress. Herein, zinc‐cobalt bimetallic organic framework (Zn/Co‐MOF) functionalized bioceramic scaffolds are designed for repairing osteochondral defects under OA environment. By functionalizing Zn/Co‐MOF on the 3D‐printed beta‐tricalcium phosphate (β‐TCP) scaffolds, the Zn/Co‐MOF functionalized β‐TCP (MOF‐TCP) scaffolds with broad‐spectrum ROS‐scavenging ability are successfully developed. Benefiting from its catalytic active sites and degradation products, Zn/Co‐MOF endows the scaffolds with excellent antioxidative and anti‐inflammatory properties to protect cells from ROS invasion, as well as dual‐bioactivities of simultaneously inducing osteogenic and chondrogenic differentiation in vitro. Furthermore, in vivo results confirm that MOF‐TCP scaffolds accelerate the integrated regeneration of cartilage and subchondral bone in severe osteochondral defects. This study offers a promising strategy for treating defects induced by OA as well as other inflammatory diseases.

Abstract Probiotics plus dietary fiber has demonstrated efficacy in improving metabolic abnormalities. However, the efficacy of probiotics and dietary fiber as well as their association with microbiota in attenuating antipsychotic-induced weight gain and metabolic disturbance remains poorly understood. Here we analyzed results from the double-blind, randomized, placebo-controlled study to compare and evaluate the effects of probiotics, dietary fiber, and their combination for antipsychotic-induced weight gain in patients with a severe mental disorder. We found that probiotics plus dietary fiber was significantly superior to probiotics alone, dietary fiber only, and the placebo for weight, BMI, and total cholesterol reduction; insulin resistance was worse in the placebo group, with significant increases during the 12-week treatment; probiotics plus dietary fiber significantly reduced weight and prevented further deterioration of metabolic disturbances; and probiotics or dietary fiber alone can prevent further weight gain. We further performed 16 S ribosomal RNA sequencing revealed an increased abundance of microbiota after probiotics plus dietary fiber treatment. Moreover, logistic regression analyses revealed that the higher richness of microbiota was associated with favorable weight loss. These findings suggested that probiotics and dietary fiber co-administration were safe and effective interventions to reduce weight gain in patients treated with antipsychotic medications.

Voltage fluctuation and power mismatch which are caused by the decentralization, randomness, and intermittence of distributed energy resource along with load variability cause severe impacts on the security and quality of power network operation. Aiming at alleviating this issue, the structure of an AC/DC hybrid microgrid based on solid-state transformer is presented in this paper. A proper control coordination is developed to guarantee stable and reliable operation of the system. An energy management strategy is proposed to coordinate the power flow among the solid-state transformer, AC microgrid, DC microgrid and energy storage and to effectively suppress the fluctuation of the DC bus voltage. A novel adaptive droop control for the energy storage is proposed to prolong the supercapacitor life and achieve an optimum economic benefit to consumers. The droop coefficient is obtained by fuzzy logic controller of which the state of charge of the supercapacitor and unit-time electricity charge are assumed to be the input parameters. Simulation attest the feasibility of the proposed control coordination and energy management strategy.

Abstract The controlled introduction of elastic strains is an appealing strategy for modulating the physical properties of semiconductor materials. With the recent discovery of large elastic deformation in nanoscale specimens as diverse as silicon and diamond, employing this strategy to improve device performance necessitates first-principles computations of the fundamental electronic band structure and target figures-of-merit, through the design of an optimal straining pathway. Such simulations, however, call for approaches that combine deep learning algorithms and physics of deformation with band structure calculations to custom-design electronic and optical properties. Motivated by this challenge, we present here details of a machine learning framework involving convolutional neural networks to represent the topology and curvature of band structures in k-space. These calculations enable us to identify ways in which the physical properties can be altered through “deep” elastic strain engineering up to a large fraction of the ideal strain. Algorithms capable of active learning and informed by the underlying physics were presented here for predicting the bandgap and the band structure. By training a surrogate model with ab initio computational data, our method can identify the most efficient strain energy pathway to realize physical property changes. The power of this method is further demonstrated with results from the prediction of strain states that influence the effective electron mass. We illustrate the applications of the method with specific results for diamonds, although the general deep learning technique presented here is potentially useful for optimizing the physical properties of a wide variety of semiconductor materials.

Objective To analyze perioperative complications, resource consumption, and inpatient mortality of patients who receive total joint arthroplasty (TJA) with a concomitant diagnosis of a primary hypercoagulable state (PHS). The following questions were posed in the present paper. First, do patients undergoing TJA with PHS have increased risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and periprosthetic joint infection (PJI)? Second, what other in‐hospital complications are more likely among PHS patients undergoing TJA? Third, do TJA patients with PHS usually consume greater in‐hospital resources? Fourth, do PHS patients suffer higher mortality rates compared to non‐PHS patients? Finally, have PHS patients received proper anticoagulant management in past arthroplasties? Methods The National Inpatient Sample (NIS) database for the years between 2003 and 2014 was searched to identify patients undergoing primary TJA. Patients with PHS were identified with the ICD‐9‐CM code 289.81. The χ2‐test, the Pearson test, and adjusted multivariate regression analysis were performed to evaluate the difference and odds ratios between the positive and negative diagnosis groups. Results From 2003 to 2014, a total of 2,044,356 patients were identified in the NIS as undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) in the United States. A total of 4664 patients (0.2%) were identified as having PHS. Compared with the non‐PHS group, TJA patients with PHS had a higher risk of DVT (THA: odds ratio [OR] = 8.343, 95% CI: 5.362–12.982, P

ObjectiveThis study was conducted in order to gain a better understanding of the molecular mechanisms of stomach adenocarcinoma (STAD), which is necessary to predict the prognosis of STAD and develop novel gene therapy strategies.MethodsIn this study, the gene expression profile of GSE118916 in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Program (TCGA) was used to explore the differential co-expression genes of STAD and normal tissues.ResultsA total of 407 STAD samples were collected, consisting of 375 from stomach adenocarcinoma tissues and 32 from normal tissues, as well as RNA-seq count data for 19,600 genes. Forty-two differentially expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed gene analysis. According to the functional annotation analysis of the clusterProfiler R package, these genes were analyzed for GO function enrichment, digestion (biological process), tube bottom material membrane (cell component), and oxidoreductase activity (molecular function). The KEGG pathway was enriched in gastric acid secretion and chemical carcinogenesis. In addition, Cytoscape’s cytoHubba plug-in was used to identify seven hub genes (EWSR1, ESR1, CLTC, PCMT1, TP53, HUWE1, and HDAC1) in a protein–protein interaction (PPI) network consisting of 7 nodes and 11 edges. Compared with normal tissues, CLTC and TP53 genes were upregulated in stomach adenocarcinoma (P

Hydrogen energy is considered one of the cleanest and most promising alternatives to fossil fuel because the only combustion product is water. The development of water splitting electrocatalysts with Earth abundance, cost-efficiency, and high performance for large current density industrial applications is vital for H2 production. However, most of the reported catalysts are usually tested within relatively small current densities (< 100 mA cm−2), which is far from satisfactory for industrial applications. In this minireview, we summarize the latest progress of effective non-noble electrocatalysts for large current density hydrogen evolution reaction (HER), whose performance is comparable to that of noble metal-based catalysts. Then the design strategy of intrinsic activities and architecture design are discussed, including self-supporting electrodes to avoid the detachment of active materials, the superaerophobicity and superhydrophilicity to release H2 bubble in time, and the mechanical properties to resist destructive stress. Finally, some views on the further development of high current density HER electrocatalysts are proposed, such as scale up of the synthesis process, in situ characterization to reveal the micro mechanism, and the implementation of catalysts into practical electrolyzers for the commercial application of as-developed catalysts. This review aimed to guide HER catalyst design and make large-scale hydrogen production one step further.

Abstract Background Chronic alcohol consumption disrupts psychomotor and cognitive functions, most of which are subserved by the dysfunction of hippocampus. Dysregulated excitatory glutamatergic transmission is implicated in repeated alcohol induced psychomotor and cognitive impairment. Ginsenoside Rg1, one of the main active ingredient of the traditional tonic medicine Panax ginseng C.A. Meyer (Araliaceae), has been used to treat cognitive deficits. Particularly, Rg1 has been demonstrated to improve hippocampus-dependent learning in mice and attenuate glutamate-induced excitotoxicity in vitro. Thus, in the present research, we sought to investigate the therapeutic effects of Ginsenoside Rg1 on repeated alcohol induced psychomotor and cognitive deficits in hippocampal-dependent behavioral tasks and unravel the underpinnings of its neuroprotection. Methods Male ICR (CD-1) mice were consecutively intragastrically treated with 20% (w/v) alcohol for 21 days. Then, behavior tests were conducted to evaluate repeated alcohol induced psychomotor and cognitive deficits. Histopathological changes, and biochemical and molecular alterations were assessed to determine the potential neuroprotective mechanism of Rg1. Results The results suggested that Rg1, at the optimal dose of 6 mg/kg, has the potential to ameliorate repeated alcohol induced cognitive deficits by regulating activities of NR2B containing NMDARs and excitotoxic signaling. Conclusion Our findings further provided a new strategy to treat chronic alcohol exposure induced adverse consequences.

Abstract Since the successful fabrication of two-dimensional (2D) tellurium (Te) in 2017, its fascinating properties including a thickness dependence bandgap, environmental stability, piezoelectric effect, high carrier mobility, and photoresponse among others show great potential for various applications. These include photodetectors, field-effect transistors, piezoelectric devices, modulators, and energy harvesting devices. However, as a new member of the 2D material family, much less known is about 2D Te compared to other 2D materials. Motivated by this lack of knowledge, we review the recent progress of research into 2D Te nanoflakes. Firstly, we introduce the background and motivation of this review. Then, the crystal structures and synthesis methods are presented, followed by an introduction to their physical properties and applications. Finally, the challenges and further development directions are summarized. We believe that milestone investigations of 2D Te nanoflakes will emerge soon, which will bring about great industrial revelations in 2D materials-based nanodevice commercialization.

When an input terminal is connected to a solar panel with a low voltage level and large power range fluctuation, a Boost type CLLC converter controlled by fixed frequency pulse width modulation (PWM) reduces the utilization of PV electric energy, and the synchronous drive of the secondary side and primary side ensures that the converter operates with low efficiency when the duty cycle is shifted by 0.5. To maximize the utilization of photovoltaic (PV) energy in a PV power generation system and improve the conversion efficiency, this paper studies a Boost CLLC converter with high gain and soft switching controlled by PWM-pulse frequency modulation (PFM) hybrid modulation for PV power generation. By controlling the duty cycle and switching frequency of the primary MOSFETs, the converter can stabilize the output voltage while tracking the PV maximum power point. Under such a hybrid control, the resonant gain of the converter is greater than 1, the voltage gain is large, one of the MOSFETs at the primary side is in a zero-voltage-switching-open (ZVS-ON) state, two diodes are used to realize zero-current-switching (ZCS) soft switching on the secondary side, and the efficiency of the converter is high. In addition, this paper studies the phenomenon of backflow power in the resonant circuit and the influence of a change in the switching frequency on the magnitude of the backflow power. Finally, a 500W experimental prototype was constructed to verify the accuracy of the theoretical analysis and the feasibility of the control method.

Autoimmune hepatitis (AIH) is characterized by chronic progressive liver inflammatory, but there is still no safe and effective medicine. Therefore, glucocorticoid remains the top choice for AIH treatment. In previous studies, it has been confirmed that ginsenosides (GSS) can produce glucocorticoid-like effects and therapeutic effects on various autoimmune diseases. However, the mechanism of GSS for AIH remains unclear. As an important part of the innate immune system, bone marrow-derived suppressor cells (MDSC) have been identified as an important driver of follow-up acquired immune response in many autoimmune diseases, including AIH. Herein, it was found out that GSS intervention can be effective in regulating the immune microenvironment and liver impairment induced by Con A in AIH mice. In vitro, the MDSCs derived from healthy mice and the T cells deried from AIH mice were co-cultured. Then, different drugs were intervened with to explore the therapeutic mechanism. Besides, the proliferation and differentiation of MDSCs and T cells were analyzed by flow cytometry, while GR, Hippo-YAP signal pathway and the expression of MDSC-related genes and proteins were detected through qRT-PCR and Western Blot. The changes in NO and ROS levels were further analyzed. The trend of related cytokines expression (IFN- γ, TGF- β, IL-10, IL-6, IL-17) was detected by ELISA. Furthermore, an analysis was conducted as to the ALT and liver pathology of mice for evaluating the liver function of mice. It was discovered that MDSCs proliferation was inhibited, and that T cells tended to differentiate into Th17 rather than Treg in AIH mice. Moreover, the intervention of GSS activated GR and Yap, in addition to promoting the proliferation of MDSCs, especially M-MDSCs. This further promoted the differentiation of Treg to enable immune tolerance, thus alleviating liver impairment. Therefore, it was proposed that GSS can alleviate AIH by modulating the innate immunity and adaptive T cell immunity, which may be the underlying mechanism for GSS to mitigate the liver impairment induced by AIH.

Numerical investigations were conducted of the plasmonically induced transparency (PIT) effect observed in a metal–insulator–metal waveguide coupled to asymmetric three-rectangle resonators, wherein, of the two PIT peaks that were generated, one PIT peak fell while the other PIT peak rose. PIT has been widely studied due to its sensing, slow light, and nonlinear effects, and it has a high potential for use in optical communication systems. To gain a better understanding of the PIT effect in multi-rectangle resonators, its corresponding properties, effects, and performance were numerically investigated based on PIT peak fluctuations. By modifying geometric parameters and filling dielectrics, we not only realized the off-to-on PIT optical response within single or double peaks but also obtained the peak fluctuation. Furthermore, our findings were found to be consistent with those of finite element simulations. These proposed structures have wide potential for use in sensing applications.

Background: To investigate the effect and potential molecular mechanisms of Dipsacoside B (DB), an herb monomer extracted from Dipsacusasper or Lonicera macranthoides, on the migration and proliferation of vascular smooth muscle cells (VSMCs) and balloon-induced neointimal formation. Methods: In vivo, rat abdominal aorta balloon injury model was utilized to investigate the effect of DB on the neointimal formation. In vitro, cultured VSMCs were used to investigate the effect of DB on Angiotensin-II (Ang-II)-induced migration and proliferation of VSMCs. Western blot and immunofluorescence were used to measure PTEN expression. Results: As compared to vehicle control balloon-injury group, DB treatment significantly inhibited the neointimal formation together up-regulated the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN). Cell proliferations (MTT and Edu incorporation) assays and wound migration measurement further revealed that treatment with DB significantly blunted Ang-II-induced proliferation and migration potential of VSMCs. Western blot analysis exhibited that DB upregulated the expression of PTEN in vivo and in vitro. Conclusions: DB treatment suppresses the proliferation and migration of VSMCs and reduces neointimal formation by the mechanisms involving regulating the phenotype switch of VSMCs via upregulating PTEN expression.

Two-dimensional (2D) materials have garnered considerable attention due to their advantageous properties, including tunable bandgap, prominent carrier mobility, tunable response and absorption spectral band, and so forth. The above-mentioned properties ensure that 2D materials hold great promise for various high-performance infrared (IR) applications, such as night vision, remote sensing, surveillance, target acquisition, optical communication, etc. Thus, it is of great significance to acquire better insight into IR applications based on 2D materials. In this review, we summarize the recent progress of 2D materials in IR light emission device applications. First, we introduce the background and motivation of the review, then the 2D materials suitable for IR light emission are presented, followed by a comprehensive review of 2D-material-based spontaneous emission and laser applications. Finally, further development directions and challenges are summarized. We believe that milestone investigations of 2D-material-based IR light emission applications will emerge soon, which are beneficial for 2D-material-based nano-device commercialization.

Since atomically thin two-dimensional (2D) graphene was successfully synthesized in 2004, it has garnered considerable interest due to its advanced properties. However, the weak optical absorption and zero bandgap strictly limit its further development in optoelectronic applications. In this regard, other 2D materials, including black phosphorus (BP), transition metal dichalcogenides (TMDCs), 2D Te nanoflakes, and so forth, possess advantage properties, such as tunable bandgap, high carrier mobility, ultra-broadband optical absorption, and response, enable 2D materials to hold great potential for next-generation optoelectronic devices, in particular, mid-infrared (MIR) band, which has attracted much attention due to its intensive applications, such as target acquisition, remote sensing, optical communication, and night vision. Motivated by this, this article will focus on the recent progress of semiconducting 2D materials in MIR optoelectronic devices that present a suitable category of 2D materials for light emission devices, modulators, and photodetectors in the MIR band. The challenges encountered and prospects are summarized at the end. We believe that milestone investigations of 2D materials beyond graphene-based MIR optoelectronic devices will emerge soon, and their positive contribution to the nano device commercialization is highly expected.

Abstract 2D materials, such as graphene, black phosphorous and transition metal dichalcogenides, have gained persistent attention in the past few years thanks to their unique properties for optoelectronics. More importantly, introducing 2D materials into silicon photonic devices will greatly promote the performance of optoelectronic devices, including improvement of response speed, reduction of energy consumption, and simplification of fabrication process. Moreover, 2D materials meet the requirements of complementary metal‐oxide‐semiconductor compatible silicon photonic manufacturing. A comprehensive overview and evaluation of state‐of‐the‐art 2D photonic integrated devices for telecommunication applications is provided, including light sources, optical modulators, and photodetectors. Optimized by unique structures such as photonic crystal waveguide, slot waveguide, and microring resonator, these 2D material‐based photonic devices can be further improved in light‐matter interactions, providing a powerful design for silicon photonic integrated circuits.

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness.Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function.Results: The analysis of biomarkers from the patients’ CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p < 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ − (−5.505 + 55.314 * ratio of p/T-tau − 1.586 * numbers of combined symptoms). The combined indicators (−5.505 + 0.553 * percentage of p/T-tau − 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively.Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

ObjectiveTo investigate the effects of ketogenic metabolism on macrophage polarization, inflammation inhibition, and function recovery after acute spinal cord injury (SCI) in rats.MethodsSixty-four adult male Sprague–Dawley rats were randomly and equally divided into sham, standard diet (SD), ketone diet (KD), and 1, 3-butanediol (BD) groups. All animals underwent C5 unilateral laminectomy, whereas the SD, KD, and BD groups underwent C5 spinal cord hemi-contusion. The impact rod with a diameter of 1.5 mm was aligned 22.5° to the left and 1.4 mm to the midline, and then triggered to deliver a set displacement of 1.5 mm at a speed of 100 mm/s. The gene expression of inflammatory factors as well as the protein expression of inducible nitric oxide synthase, arginase-1, and inflammatory factors were measured at 1 week post-injury. Serum ketone and behavior were evaluated every second week for 12 weeks. Then, histological analyses of the gray and white matter at the epicenter were conducted at 12 weeks post-injury.ResultsThe serum ketone levels of the KD and BD groups were significantly increased when compared with the SD group. The gene and protein expression of TNF-α and IL-1β tended to increase after the SCI, but were inhibited in the KD and BD groups. The protein expression of inducible nitric oxide synthase, marker of M1 macrophage, was inhibited in the KD and BD groups; on the other hand, the expression of arginase-1, marker of M2 macrophage, was boosted in the KD and BD groups. The usage of the ipsilateral forelimb was higher in the KD group than in the SD group. The hemi-contusive injury resulted in an obvious ipsilateral lesion area at the epicenter, and there was no significant difference between groups regarding the lesion size. However, the spared gray matter area was significantly greater in the KD group than in the SD and BD groups.ConclusionThe present study suggests that ketogenic metabolism promotes macrophage polarization to M2, inhibits an inflammatory response, and alleviates the loss of gray matter after SCI. A higher ketone level, such as that induced by the ketogenic diet, seems to benefit function recovery after SCI.

Abstract Background Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia by greatly improving its solubility. Results This system (size 23.50 ± 1.67 nm, zeta potential − 3.35 ± 0.03 mV) was prepared with RH40 (surfactant), 1,2-propanediol (co-surfactant), squalene (oil) and BBR using low-energy emulsification methods. The system loaded BBR successfully according to thermal gravimetric, differential scanning calorimetry, and Fourier transform infrared spectroscopy analyses. The release profile results showed that BBR SNE released BBR more slowly than BBR solution. The relative oral bioavailability of this novel system in rabbits was significantly enhanced by 3.41-fold over that of BBR. Furthermore, Caco-2 cell monolayer transport studies showed that this system could help enhance permeation and prevent efflux of BBR. Importantly, mice with BBR SNE treatment had significantly longer survival time than BBR-treated mice (P

Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the “single cortical microinfarct model” generated via occluding a penetrating arteriole by femtosecond laser ablation and the “multiple diffuse microinfarcts model” induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ω-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ω-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ω-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ω-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ω-3 PUFAs in the treatment or prophylaxis in vascular dementia. Keywords: Fish oil, Cognitive decline, Vascular dementia, Neuropsychiatric disorders

MXenes are a class of two-dimensional nanomaterials with exceptional tailor-made properties, making them promising candidates for a wide variety of critical applications from energy systems, optics, electromagnetic interference shielding to those advanced sensors, and medical devices. Owing to its mechano-ceramic nature, MXenes have superior thermal, mechanical, and electrical properties. Recently, MXene-based materials are being extensively explored for solar cell applications wherein materials with superior sustainability, performance, and efficiency have been developed in demand to reduce the manufacturing cost of the present solar cell materials as well as enhance the productivity, efficiency, and performance of the MXene-based materials for solar energy harvesting. It is aimed in this review to study those MXenes employed in solar technologies, and in terms of the layout of the current paper, those 2D materials candidates used in solar cell applications are briefly reviewed and discussed, and then the fabrication methods are introduced. The key synthesis methods of MXenes, as well as the electrical, optical, and thermoelectric properties, are explained before those research efforts studying MXenes in solar cell materials are comprehensively discussed. It is believed that the use of MXene in solar technologies is in its infancy stage and many research efforts are yet to be performed on the current pitfalls to fill the existing voids.

Background and objective Postoperative prolonged air leaks is one of the most common complications secondary to pulmonary resections. Digital drainage system (DDS) is considered as an accurate and objective device which has been found to be comfortable and well tolerated by patients, economical as well. The aim of this study is to explore the application of DDS in patients with postoperative refractory prolonged air leaks after pulmonary surgery. Methods Prolonged air leak (PAL) is defined as air leaks lasting for more than 5 d after video-assisted surgery or more than 7 d after thoracotomy. Postoperative refractory prolonged air leak is defined as a kind of air leak lasting for twice than PAL with grade 2 or 3 air leak, or air leak with severe complications such as subcutaneous or mediastinal emphysema in our study. A total of 8 patients who had postoperative refractory prolonged air leaks after pulmonary resection were treated with digital drainage system combined with pleurodesis from January to December in 2016 in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. All the relevant clinical data of patients were collected for analysis. Results In our study, 6 patients accepted lobectomy, the other 2 patients underwent segmentectomy. The average air leak and chest tube duration of the patients with postoperative refractory prolonged air leaks after pulmonary resection was (17.3±5.1) d. The average postoperative DDS duration was (5.6±3.7) d. The mean drainage volume of the patients was (2,615.6±1,741.2) mL and (935.0±242.7) mL before and after the application of DDS. The average length of hospital stay was (18.1±5.0) d. Conclusion It is safe and feasible to apply digital drainage system to patients with postoperative refractory prolonged air leaks after pulmonary resection. Compared with the conventional drainage system, digital drainage system is more accurate and objective which can offer a larger suction pressure and promote lung recruitment maneuver for pleurodesis, shortening the drainage time and length of hospital stay.

Thermal conductive materials with reliable and high performances such as thermal interface materials are crucial for rapid heat transferring in thermal management. In this work, carbon fiber fabric and graphene reinforced segmented polyurethane composites (CFF-G/SPU) were proposed and prepared to obtain superior thermal, mechanical and electrical properties using the hot-pressing method. The composites exhibit excellent tensile strength and can withstand a tensile force of at least 350 N without breaking. The results show that, comparing with the SPU material, the thermal conductivity is increased by 28% for the CFF-G/SPU composite, while the in-plane electrical conductivity is increased by 8 orders of magnitude to 175 S·m−1. The application of CFF-G/SPU composite as a winding thermal interface material with electric-driven self-heating effect presents good performances of fluidity and interface wettability. The composite has great advantages in phase transition and filling the interfacial gap in the short time of few seconds under the condition of electrical field, with the interface temperature difference between two layers significantly reduced.

The present study aimed to establish a genus-specific PCR-based assay to detect helicobacters using 16S rRNA gene as the target template. We designed the hemi-nested primers based on sequences of 16S rRNA gene of 34 types of Helicobacter species. The inclusivity, sensitivity, and specificity of the PCR assay using these primers were examined in three different models, comprising feces simulated samples, BLAB/c mice infection model and clinic patients samples. The detection sensitivity of Helicobacter pylori, Helicobacter hepaticus and Helicobacter bilis strains from feces simulated samples was all 102 CFU/ml. We successfully detected H. hepaticus and H. bilis in the liver, cecum and feces of experimentally infected mice. H. pylori was successfully detected in the feces samples from 3 patients infected with H. pylori while not in the feces samples from 3 healthy human. However, the C97/C05–C97/C98 PCR assay detected H. pylori in the 2 positive samples. Due to the PCR assay’s excellent inclusivity, high sensitivity and specificity it may be used to detect the presence of Helicobacters.

Stroke is the leading cause of adult disability in the world. In general, recovery from stroke is incomplete. Accumulating evidences have shown that focal cerebral infarction leads to dynamic trans-neuronal degeneration in non-ischemic remote brain regions, with the disruption of connections to synapsed neurons sustaining ischemic insults. Previously, we had reported that the ipsilateral striatum, thalamus degenerated in succession after permanent distal branch of middle cerebral artery occlusion (dMCAO) in Sprague-Dawley (SD) rats and cathepsin (Cath) B was activated before these relay degeneration. Here, we investigate the role of CathB in the secondary degeneration of ipsilateral substantia nigra (SN) after focal cortical infarction. We further examined whether the inhibition of CathB with L-3-trans-(Propyl-carbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester (CA-074Me) would attenuate secondary degeneration through enhancing the cortico-striatum-nigral connections and contribute to the neuroprotective effects. Our results demonstrated that secondary degeneration in the ipsilateral SN occurred and CathB was upregulated in the ipsilateral SN after focal cortical infarction. The inhibition of CathB with CA-074Me reduced the neuronal loss and gliosis in the ipsilateral SN. Using biotinylated dextran amine (BDA) or pseudorabies virus (PRV) 152 as anterograde or retrograde tracer to trace striatum-nigral and cortico-nigral projections pathway, CA-074Me can effectively enhance the cortico-striatum-nigral connections and exert neuroprotection against secondary degeneration in the ipsilateral SN after cortical ischemia. Our study suggests that the lysosomal protease CathB mediates the secondary damage in the ipsilateral SN after dMCAO, thus it can be a promising neuroprotective target for the rehabilitation of stroke patients.

Two types of 500 MPa anti-seismic rebars were produced by V-Nb microalloyed combined with controlled rolling and cooling technology, the strengthening and toughening mechanism of which were investigated. The complex phase microstructures of specimens consist of ferrite, pearlite and bainite (6 – 10 %). Furthermore, a large number of V(C,N) and Nb(C,N) precipitates with size of 5 – 30 nm formed in the ferrite matrix, grain boundaries and on dislocation lines, promoting the precipitation strengthening and inhibiting grain coarsening to controlled cooling microstructure. The mechanical performance of the steels was improved by solution and grain refinement strengthening, precipitation and microstructure strengthening. And the best strengthening effect was obtained by grain refinement, which increased the yield strength more than 35 % strength increment contribution ratio to yield strength. Moreover, about 16.5 % microstructure strengthening increment was obtained due to bainite formation. The plasticity and low-temperature toughness enhancement were mainly attributed to ferrite grain refinement improvement.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9710

Emerging evidence suggests that gut microbiota contribute to the treatment of post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate abdominal pain and diarrhea in PI-IBS rats. However, little is known about the underlying mechanism and whether the gut microbiota mediate the effect of Wuji Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague-Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility abnormality and visceral hypersensitivity. Analysis of the fecal microbiota showed that Wuji Wan could reverse the reduction in richness of the gut microbiota and significantly increase the relative abundances of Akkermansia, Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell proliferation in the colonic mucosa by increasing the release of mucin, up-regulating the distribution of tight junction proteins Occludin and ZO-1 and down-regulating the expression of MLCK in colonic epithelial cells. These findings suggest that Wuji Wan may remit IBS by modulating the gut microbiota and stabilizing the gut mucosal barrier, indicating that the use of a classical formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect may be a promising strategy for PI-IBS treatment.

BackgroundAnti-tuberculosis (anti-TB) drug-induced liver injury (ADLI) is one of the most common adverse effects associated with TB treatment. Cytochrome P450 (CYP) 1A1 and glutathione S-transferase (GST) P1 are important phase I/II metabolizing enzymes involved in drug metabolism and detoxification. Genetic polymorphism and CpG island methylation have been reported as factors influencing the expression of CYP1A1 and GSTP1.ObjectiveThis study aimed to determine the potential relationships of CYP1A1 and GSTP1 polymorphisms and CpG island methylation with ADLI risk.DesignThis was a population-based one-to-one matched case-control study.SettingThe subjects were patients with TB receiving treatment in China from December 2010 to June 2013.PatientsIn total, 127 patients with TB and ADLI (case group) and 127 patients with TB but without liver injury (control group) were included in this study. Subjects were matched in terms of sex, age, and therapeutic regimen.MethodsThe general condition of each patient was assessed using questionnaires. The CYP1A1 MspI and GSTP1 Ile105Val polymorphisms as well as methylation status were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the methylation-specific PCR method.ResultsWe found no significant difference in GSTP1 and CYP1A1 genotypes between the two groups, probably because the sample size was not large enough; however, patients with ADLI had significantly higher GSTP1 and CYP1A1 promoter methylation rates than control subjects [odds ratio (OR) = 2.467 and 2.000, respectively]. After adjusting for drinking, which significantly differed between the groups as per univariate analysis, we found that hypermethylation of GSTP1 and CYP1A1 promoters was associated with ADLI (OR = 2.645 and 2.090, respectively).ConclusionHypermethylation of CpG islands of GSTP1 and CYP1A1 promoters may thus play important roles in the development of ADLI and provide evidence of being used as novel markers for ADLI risk prediction.

Voltage source converter (VSC)-based high voltage direct current (VSC-HVDC) interconnectors can realize accurate and fast control of power transmission among AC networks, and provide emergency power support for AC networks. VSC-HVDC interconnectors bring exclusive fault characteristics to AC networks, thus influencing the performance of traditional protections. Since fault characteristics are related to the control schemes of interconnectors, a fault ride-through (FRT) strategy which is applicable to the interconnector operating characteristic of working in four quadrants and capable of eliminating negative-sequence currents under unbalanced fault conditions is proposed first. Then, the additional terms of measured impedances of distance relays caused by fault resistances are derived using a symmetrical component method. Theoretical analysis shows the output currents of interconnectors are controllable after faults, which may cause malfunctions in distance protections installed on lines emanating from interconnectors under the effect of fault resistances. Pilot protection is also inapplicable to lines emanating from interconnectors. Furthermore, a novel pilot protection principle based on the ratio between phase currents and the ratio between negative-sequence currents flowing through both sides is proposed for lines emanating from the interconnectors whose control scheme aims at eliminating negative-sequence currents. The validity of theoretical analysis and the protection principle is verified by PSCAD/EMTDC simulations.

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery.