The gut microbiota composition and metabolites are different in women with hypertensive disorders of pregnancy and normotension: A pilot study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are one of the main causes of perinatal morbidity. Gut microbiota influences host inflammatory pathways, glucose, and lipid metabolism. However, there is a lack of studies available on gut microbiota in HDP. OBJECTIVES: We investigate the mechanistic and pathogenic role of microbiota in the development of HDP, and want to treat HDP with gut microbiota. METHODS: We performed a case-control study to compare fecal samples of HDP and normotensive pregnant women by 16S ribosomal RNA sequencing. Fecal samples, collected from pregnant women, were divided into groups P and C (pregnant women with HDP and normotension, respectively). There were six pregnant women in group P and nine pregnant women in group C. Age of pregnant women is from 18 to 40 years and gestational age is from 27 to 40 weeks. DNA was extracted from fecal samples; a gene library was constructed and analyzed using bioinformatics. Finally, we determined the changes in the microbiome by alpha diversity, beta diversity, classification abundance, and taxonomic composition analyses. RESULTS: Escherichia (10.48% in group P and 0.61% in group C) was the dominant bacterium in HDP patients by classification abundance analysis, which can lead to the development of preeclampsia through inflammatory response. We found that pregnant women with HDP had higher abundance of Rothia (p = 0.04984), Actinomyces (p = 0.02040), and Enterococcus (p = 0.04974) and lower abundance of Coprococcus (p = 0.04955) than pregnant women with normotension for the first time by taxonomic composition analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database analysis, physiological and biochemical functions of HDP patients were significantly weakened, especially in energy metabolism. CONCLUSIONS: We found the effect of changes in gut microbiota on the development of HDP. In comparison with group C, group P contained more harmful bacteria and less beneficial bacteria, which are associated with HDP. Our research further provides a basis for a clinical application for HDP treatment using antibiotics and probiotic supplementation.

Dual-branch fusion model for lensless imaging.

A lensless camera is an imaging system that replaces the lens with a mask to reduce thickness, weight, and cost compared to a lensed camera. The improvement of image reconstruction is an important topic in lensless imaging. Model-based approach and pure data-driven deep neural network (DNN) are regarded as two mainstream reconstruction schemes. In this paper, the advantages and disadvantages of these two methods are investigated to propose a parallel dual-branch fusion model. The model-based method and the data-driven method serve as two independent input branches, and the fusion model is used to extract features from the two branches and merge them for better reconstruction. Two types of fusion model named Merger-Fusion-Model and Separate-Fusion-Model are designed for different scenarios, where Separate-Fusion-Model is able to adaptively allocate the weights of the two branches by the attention module. Additionally, we introduce a novel network architecture named UNet-FC into the data-driven branch, which enhances reconstruction by making full use of the multiplexing property of lensless optics. The superiority of the dual-branch fusion model is verified by drawing comparison with other state-of-the-art methods on public dataset (+2.95dB peak signal-to-noise (PSNR), +0.036 structural similarity index (SSIM), -0.0172 Learned Perceptual Image Patch Similarity (LPIPS)). Finally, a lensless camera prototype is constructed to further validate the effectiveness of our method in a real lensless imaging system.

Hand gestures recognition in videos taken with a lensless camera.

A lensless camera is an imaging system that uses a mask in place of a lens, making it thinner, lighter, and less expensive than a lensed camera. However, additional complex computation and time are required for image reconstruction. This work proposes a deep learning model named Raw3dNet that recognizes hand gestures directly on raw videos captured by a lensless camera without the need for image restoration. In addition to conserving computational resources, the reconstruction-free method provides privacy protection. Raw3dNet is a novel end-to-end deep neural network model for the recognition of hand gestures in lensless imaging systems. It is created specifically for raw video captured by a lensless camera and has the ability to properly extract and combine temporal and spatial features. The network is composed of two stages: 1. spatial feature extractor (SFE), which enhances the spatial features of each frame prior to temporal convolution; 2. 3D-ResNet, which implements spatial and temporal convolution of video streams. The proposed model achieves 98.59% accuracy on the Cambridge Hand Gesture dataset in the lensless optical experiment, which is comparable to the lensed-camera result. Additionally, the feasibility of physical object recognition is assessed. Further, we show that the recognition can be achieved with respectable accuracy using only a tiny portion of the original raw data, indicating the potential for reducing data traffic in cloud computing scenarios.

Text detection and recognition based on a lensless imaging system.

Lensless cameras are characterized by several advantages (e.g., miniaturization, ease of manufacture, and low cost) as compared with conventional cameras. However, they have not been extensively employed due to their poor image clarity and low image resolution, especially for tasks that have high requirements on image quality and details such as text detection and text recognition. To address the problem, a framework of deep-learning-based pipeline structure was built to recognize text with three steps from raw data captured by employing lensless cameras. This pipeline structure consisted of the lensless imaging model U-Net, the text detection model connectionist text proposal network (CTPN), and the text recognition model convolutional recurrent neural network (CRNN). Compared with the method focusing only on image reconstruction, U-Net in the pipeline was able to supplement the imaging details by enhancing factors related to character categories in the reconstruction process, so the textual information can be more effectively detected and recognized by CTPN and CRNN with fewer artifacts and high-clarity reconstructed lensless images. By performing experiments on datasets of different complexities, the applicability to text detection and recognition on lensless cameras was verified. This study reasonably demonstrates text detection and recognition tasks in the lensless camera system, and develops a basic method for novel applications.

3D imaging scanner.

This paper proposes a multi-view three-dimensional display method based on a scanning imaging system with the light-intensity characteristic recorded by an improved flatbed scanner. Within the effective scanning depth of the imaging sensor, two transmission images are each simultaneously acquired by two linear CCD modules with different focal planes. Then the phase gradient information of the target can be obtained by an appropriate retrieval algorithm. Further, the multi-view three-dimensional effect is presented through dynamic angles of view. Theoretical analysis of this method is discussed, and experiments are carried out by building a scanner. The experiment results are presented with an algae specimen and transparent beads. We hope this method can be applied to present the three-dimensional effect of objects of flat translucent multilayer structure with a wide field of view.

Evolution of matrinic ethanol derivatives as anti-HCV agents from matrine skeleton.

Twenty-two novel 12N-substituted matrinic ethanol derivatives were synthesized and evaluated for their antiviral activities against HCV taking compound 1 as the lead. The SAR study indicated that the shortening of the 11-butyl chain to ethyl chain did not affect the activity significantly. Out of the target compounds, matrinic ethanol 6a demonstrated a potential anti-HCV effect with an EC50 value of 3.2µM and a SI value of 96.6. The free hydroxyl arm in 6a made it possible as a parent structure to prepare pro-drug for the potential application in HCV treatment. This study provided powerful information on further strategic optimization and development of this kind of compounds into a novel family of anti-HCV agents.

[The influence of intracellular keratin 8 on hepatitis C virus replication].

The level of intracellular keratin 8(KRT-8) is associated with liver diseases, whose expression is increased in hepatitis C virus(HCV)-infected patients with hepatocarcinoma and in cultural cells infected with HCV. However, it is not clear whether KRT-8 will impact HCV replication. In this paper, the HCV replication was analyzed in response to high expression and silence of KRT-8. The inhibitory activities against wild-type and mutant HCV were also analyzed by silence of KRT-8 or combined with known anti-HCV drug telaprevir. Results showed that the protein level of KRT-8 was increased in proportion with the HCV replication. The high expression was found to facilitate HCV replication, while the silence of KRT-8 was able to inhibit HCV replication and enhanced the anti-HCV activity of telaprevir. It also inhibited A156 T and D168 V mutant HCV, which are resistant to protease inhibitors. These results suggest that KRT-8 is a co-factor for HCV replication. Down-regulation of KRT-8 can inhibit wild type and mutant HCV replication to enhance the anti-HCV activity of known anti-HCV drugs. Therefore, KRT-8 may be a new target in the development of anti-HCV agents.

Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305.

High-producing cell line could improve the affordability and availability of biotherapeutic products. A post-approval production cell line change, low-titer CHO-K1S to high-titer CHO-K1SV GS-KO, was performed for a China marketed bevacizumab biosimilar IBI305. Currently, there is no regulatory guideline specifically addressing the requirements for comparability study of post-approval cell line change, which is generally regarded as the most complex process change for biological products. Following the quality by design principle and risk assessment, an extensive analytical characterization and three-way comparison was performed by using a panel of advanced analytical methods. Orthogonal and state-of-the-art techniques including nuclear magnetic resonance and high-resolution mass spectrometry were applied to mitigate the potential uncertainties of higher-order structures and to exclude any new sequence variants, scrambled disulfide bonds, glycan moiety and undesired process-related impurities such as host cell proteins. Nonclinical and clinical pharmacokinetics (PK) studies were conducted subsequently to further confirm the comparability. The results demonstrated that the post-change IBI305 was analytically comparable to the pre-change one and similar to the reference product in physicochemical and biological properties, as well as the degradation behaviors in accelerated stability and forced degradation studies. The comparability was further confirmed by comparable PK, pharmacodynamics, toxicological and immunogenicity profiles of nonclinical and clinical studies. The comparability strategy presented here might extend to cell line changes of other post-approval biological products, and particularly set a precedent in China for post-approval cell line change of commercialized biosimilars.

Wireless power transfer based on 2D routing.

In this paper, a dual-frequency wireless power transfer method is proposed, capable of achieving controllable routing and providing power through magnetic coupling resonance to various positions on a two-dimensional plane. The plane is composed of multiple power supply units with a uniform structure. Every unit has two different resonant states to switch, an activated state to power the receiver and a low-power inactive state adopted to maintain power required for state-switching. By switching and combining units in different states through wireless control circuits, directional wireless transfer of power on the plane can be realized. The circuit of power transfer through coupling is modelled and analysed. Electromagnetic simulations are conducted, followed by implementation and test of an experimental system. Both single-receiver and multiple-receiver situations are applicable in this method. The highest transmission efficiency can reach 93.3% under single receiver situation after coupling 5 units, which reveals satisfactory ability in flexibility and efficiency. Embedded in multiple application scenes, we envision further possibilities of this method such as indoor-device wireless charging and free-moving robot charging systems in factories.

LncRNA FLVCR1-AS1 mediates miR-23a-5p/SLC7A11 axis to promote malignant behavior of cervical cancer cells.

Cervical cancer (CC) is the most common gynecological malignant tumor in the world. Long non-coding RNA (lncRNAs) plays an important role in cell activities of various cancers including CC. This study aims to reveal the biological function of FLVCR1-AS1 in CC and clarify its possible mechanism of action. The findings suggest that the expression of FLVCR1-AS1 was elevated in CC tissues and cell lines, and that high expression of FLVCR1-AS1 was associated with poor prognosis of CC patients. In addition, knockdown of FLVCR1-AS1 could inhibit the proliferation and migration, invasion and epithelial-mesenchymal transformation (EMT) of CC cells, as well as accelerating apoptosis, to inhibit the development of CC. In addition, via the dual-luciferase reporting assay and RIP assay were confirmed that FLVCR1-AS1 acted as a competitive endogenous RNA to inhibit the expression of microRNA (miR)-23a-5p, and miR-23a-5p targeted the 3'-untranslated region site of Solute carrier family 7 member 11 (SLC7A11) and negatively regulated the expression of SLC7A11. Functional rescue experiments showed that miR-23a-5p inhibitors reversed the inhibitory effect of FLVCR1-AS1-silencing on proliferation, EMT, migration and invasion, and the promoting impact of apoptosis of CC cells. In addition, SLC7A11 rescued the effect of miR-23a-5p overexpression on progression of CC cells. In conclusion, FLVCR1-AS1 is involved in the malignant phenotype of CC cells through miR-23a-5p/SLC7A11 axis, which may provide a beneficial direction for the treatment of CC.

Optically switched multiband antenna based on Vivaldi structure.

In this study, an optically frequency-reconfigurable antenna with multiband characteristics is proposed utilizing photodiodes. It is developed on the basis of a Vivaldi antenna structure, while the composite radiation structure is realized by introducing three parallel branches in the antenna slot. Three photodiodes on the branches function as photoconductive switches to make the antenna reconfigurable at multiple low frequencies and stable at high frequencies. When the illumination irradiates different photodiodes, the proposed antenna is capable to switch between three narrowband modes, including 300 MHz, 677 MHz, and 1.02 GHz. The radiation gain is measured to reach 0.91 dB, 1.69 dB, 2.96 dB, respectively, while the variation in illumination states is 6.82 dB, 9.93 dB, 17.13 dB, respectively. Meanwhile, this antenna can continue to work stably at 3.2-3.8 GHz and 5.1-6.5 GHz regardless of illumination, with the maximum gain of 7.51 dB. Both simulation and experimental results substantiate the feasibility of the proposed design. This antenna design can transmit and shield the signal of specific frequency with optical control, and has good working characteristics at both high and low frequencies. In the future, it has promising application potential of communication and radar integration.

Crowding in or crowding out? How local government debt influences corporate innovation for China.

The pressure upon local governments to redeem their debt could affect government fiscal ability. It could consequently affect their fiscal policies on corporations, which might distort corporate innovation. Based on the data of Chinese Shanghai and Shenzhen A-share listed companies and the local government implicit short-term debt financed by local government financing vehicles (LGFVs) in 31 provinces, this paper shows that local government debt (LGD) negatively affects corporate R&D investment in China, thereby suggesting a strong crowding-out effect. The crowding-out effect is more pronounced when the firm is a non-state-owned enterprise (NSOE), the firm's size is small, the firm's age is young, or the firm is in the lower market competition. This paper provide evidence by interacting the terms that local government actions, such as consumption of fiscal resources, strengthening tax collection efforts, or consumption of credit resources, might partially account for the crowding-out effect. This study illustrates the innovation costs of local government debt.

Demonstration of topological wireless power transfer.

Recent advances in non-radiative wireless power transfer (WPT) technique essentially relying on magnetic resonance and near-field coupling have successfully enabled a wide range of applications. However, WPT systems based on double resonators are severely limited to short- or mid-range distance, due to the deteriorating efficiency and power with long transfer distance. WPT systems based on multi-relay resonators can overcome this problem, which, however, suffer from sensitivity to perturbations and fabrication imperfections. Here, we experimentally demonstrate a concept of topological wireless power transfer (TWPT), where energy is transferred efficiently via the near-field coupling between two topological edge states localized at the ends of a one-dimensional radiowave topological insulator. Such a TWPT system can be modelled as a parity-time-symmetric Su-Schrieffer-Heeger (SSH) chain with complex boundary potentials. Besides, the coil configurations are judiciously designed, which significantly suppress the unwanted cross-couplings between nonadjacent coils that could break the chiral symmetry of the SSH chain. By tuning the inter- and intra-cell coupling strengths, we theoretically and experimentally demonstrate high energy transfer efficiency near the exceptional point of the topological edge states, even in the presence of disorder. The combination of topological metamaterials, non-Hermitian physics, and WPT techniques could promise a variety of robust, efficient WPT applications over long distances in electronics, transportation, and industry.

Erratum: Author correction to 'Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication' [Acta Pharmaceutica Sinica B 9 (2019) 769-781].

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

LncRNA SNHG3 promotes cell growth by sponging miR-196a-5p and indicates the poor survival in osteosarcoma.

Abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with the pathogenesis of multiple malignancies, and lncRNA small nucleolar RNA host genes (SNHGs) play critical roles in tumor progression. However, the mechanism by which SNHG3 contributes to osteosarcoma (OS) remains elusive. The association between SNHG3 expression and the clinicopathological characteristics in OS patients was analyzed using the TCGA (The Cancer Genome Atlas) dataset. Cell viability and colony number were estimated by MTT and colony formation assays. MiR-196a-5p-specific binding with SNHG3 or HOXC8 was confirmed by the luciferase report assay. As a result, the expression of SNHG3 was dramatically increased in OS tissue as compared with the adjacent normal tissues. High expression of SNHG3 was associated with tumor size and acted as an independent prognostic factor of poor survival in OS patients. Knockdown of SNHG3 inhibited cell viability and colony formation, but its overexpression reversed these effects. SNHG3 was further identified to act as a sponge of miR-196a-5p, which counteracted the tumor-promoting effects caused by SNHG3 in OS cells. The expression of miR-196a-5p had a negative correlation with SNHG3 and the poor survival in OS patients. In conclusion, lncRNA SNHG3 promoted cell growth by sponging miR-196a-5p and indicated a poor prognosis in OS patients.

Farnesoid X receptor agonist GW4064 indirectly inhibits HCV entry into cells via down-regulating scavenger receptor class B type I.

Farnesoid X receptor (FXR) agonists play important regulatory roles in bile acid, lipid and glucose metabolism in vitro and in vivo. Thus, FXR agonists exhibit potential therapeutic effects on metabolism-related diseases that are associated with extrahepatic manifestations induced by hepatitis C virus (HCV) infection. This study investigated the effect and mechanism of FXR agonist GW4064 against HCV in vitro to explore the potential application of FXR agonists. Results showed that GW4064 and other FXR agonists have potent antiviral activity against HCV in Huh7.5 cells. GW4064 down-regulated the expression of scavenger receptor class B type I protein via FXR and thereby indirectly inhibited HCV entry into cells, leading to interruption of HCV life cycle. GW4064 also exhibited synergistic anti-HCV effect with known direct-acting antiviral agents (DAAs) used in the clinic and remained sensitive to DAA-resistant HCV mutations. Therefore, FXR agonists are also a kind of antiviral agent, and might be helpful in treatment of HCV-induced hepatic and extrahepatic manifestations.

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication.

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

Internal driving factors leading to extrahepatic manifestation of the hepatitis C virus infection.

The hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, which are correlated with poor outcomes, and thus increase the morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding the internal linkages between systemic manifestations and HCV infection is helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the systemic diseases remains to be elucidated. In the present study, using gene set enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a comprehensive analysis of microarray data of mRNAs was conducted in HCV-infected and -uninfected Huh7.5 cells, and signaling pathways (which are significantly activated or inhibited) and certain molecules (which are commonly important in those signaling pathways) were selected. Forty signaling pathways were selected using GSEA, and eight signaling pathways were selected with SPIA. These pathways are associated with cancer, metabolism, environmental information processing and organismal systems, which provide important information for further clarifying the intrinsic associations between syndromes of HCV infection, of which seven pathways were not previously reported, including basal transcription factors, pathogenic Escherichia coli infection, shigellosis, gastric acid secretion, dorso-ventral axis formation, amoebiasis and cholinergic synapse. Ten genes, SOS1, RAF1, IFNA2, IFNG, MTHFR, IGF1, CALM3, UBE2B, TP53 and BMP7 whose expression may be the key internal driving molecules, were selected using the online tool Anni 2.1. Furthermore, the present study demonstrated the internal linkages between systemic manifestations and HCV infection, and presented the potential molecules that are key to those linkages.

A Simple but Accurate Method for Evaluating Drug-Resistance in Infectious HCVcc System.

Use of direct-acting antivirals sometimes causes viral drug resistance, resulting in inefficiency in treated patients in real-world practice. Therefore, how to rapidly and accurately evaluate drug resistance is an urgent problem to be solved for rational use and development of antivirals in the future. Here, we aim to develop a new method by which we can evaluate easily but effectively whether a drug will still be efficient in the future treatment in infectious hepatitis C virus cell culture system. HCV-infected Huh7.5 cells were treated with drugs and the culture supernatants were replaced with fresh culture media containing the same drugs at 24 hours. The supernatants were harvested at 48 hours and incubated with naïve Huh7.5 cells. Intracellular HCV RNAs or proteins in the newly infected cells were extracted and analyzed at 48 hours or longer. Results showed that after being treated with telaprevir mutant viruses were easily detected which were resistant to telaprevir, while after being treated with sofosbuvir drug-resistant viruses did not emerge. In conclusion, the new method is simple and quick but accurate to evaluate whether a drug will be still efficient in the forthcoming therapeutic regimen and whether drug resistance will occur after long-term treatment with drugs.

CD36 is a co-receptor for hepatitis C virus E1 protein attachment.

The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication. The HCV co-receptor effect of CD36 was independent of that of SR-BI. CD36 monoclonal antibodies neutralized the effect of CD36 and reduced HCV replication. CD36 inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound CD36 but not SR-BI, significantly interrupted HCV entry, and therefore inhibited HCV replication. SSO's antiviral effect was seen only in HCV but not in other viruses. SSO in combination with known anti-HCV drugs showed additional inhibition against HCV. SSO was considerably safe in mice. Conclusively, CD36 interacts with HCV E1 and might be a co-receptor specific for HCV entry; thus, CD36 could be a potential drug target against HCV.