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Gardenia (Gardenia jasminoides) is a popular and economically vital plant known for its ornamental and medicinal properties. Despite its widespread cultivation, there has been no documentation of plant viruses on gardenia yet. In the present study, gardenia leaves exhibiting symptoms of plant viral diseases were sampled and sequenced by both metatranscriptome and small RNA sequencing. As a consequence, bean common mosaic virus (BCMV) was identified in gardenia for the first time and named BCMV-gardenia. The full genome sequence of BCMV-gardenia is 10,054 nucleotides (nt) in length (excluding the poly (A) at the 3′ termini), encoding a large polyprotein of 3,222 amino acids. Sequence analysis showed that the N-termini of the polyprotein encoded by BCMV-gardenia is less conserved when compared to other BCMV isolates, whereas the C-termini is the most conserved. Maximum likelihood phylogenetic analysis showed that BCMV-gardenia was clustered closely with other BCMV isolates identified outside the leguminous plants. Our results indicated that the majority of BCMV-gardenia virus-derived small interfering RNAs (vsiRNAs) were 21 nt and 22 nt, with 21 nt being more abundant. The first nucleotide at the 5′ termini of vsiRNAs derived from BCMV-gardenia preferred U and A. The ratio of vsiRNAs derived from sense (51.1%) and antisense (48.9%) strands is approaching, and the distribution of vsiRNAs along the viral genome is generally even, with some hot spots forming in local regions. Our findings could provide new insights into the diversity, evolution, and host expansion of BCMV and contribute to the prevention and treatment of this virus.

Continuous and autonomous system identification is an alternative to regular inspection during operations, which is essential for structural integrity management (SIM) as well as structural health monitoring (SHM). In this regard, online (or real-time) system identification techniques that have recently received considerable attention can be used to assess the current condition and performance during operations and, in the meantime, can be utilized to detect any damage or deterioration. For example, stochastic subspace identification (SSI), based on recursive formulation, has proven its capability in tracking modal parameters as well as time-variant dynamic behaviors. This study proposes the implementation of recursive SSI (RSSI) using the matrix inversion lemma to track slow time-varying parameter changes under ambient excitations. Subsequently, some investigations for practical implementation are examined and discussed. For verifying the reliability of SHM applications based on the proposed methods, two datasets measured from different experiments are exploited to identify the modal parameters reclusively. The results from both numerical simulations and experimental investigations demonstrated the effectiveness of tracking the modal parameters exhibiting time-varying dynamic characteristics under white noise excitations (or ambient excitations).

Piezoelectric-actuated precision positioning stages are widely used in high-precision instruments and high-end equipment due to their advantages of high resolution, fast response, and compact size. However, due to the strong nonlinearity of hysteresis, the presence of hysteresis in piezoelectric actuators seriously affects the positioning accuracy of the system. In addition, it is challenging to identify the model parameters for hysteresis. In this paper, an adaptive backstepping time delay control method is proposed for piezoelectric devices system with unknown hysteresis. Firstly, the Bouc–Wen model is used to describe the hysteresis characteristics, and the model is interpreted as a linear term and a bounded uncertain hysteresis term. Then, the time delay estimation technique is used to estimate the hysteresis term of the Bouc–Wen model online, and the unknown parameters of the system and hysteresis model are obtained through adaptive updating laws. Furthermore, the stability of the control scheme is proved based on Lyapunov stability theory. Finally, the effectiveness and superiority of the proposed control scheme are demonstrated by comparing it with two typical hysteresis compensation control algorithms through three different sets of input signals.

Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF via inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.

Background: Congenital sucrase isomaltase deficiency (CSID), an inherited carbohydrate malabsorption disorder, is difficult to diagnose because of overlapping symptoms with other gastrointestinal (GI) diseases. An at-home study was conducted in CSID and healthy adults to evaluate the diagnostic utility of self-reported GI symptoms following administration of a sucrose challenge. Methods: This study investigated the optimum symptom scoring with a sucrose challenge symptoms test (SCST) for diagnosing CSID in 45 confirmed patients and 118 healthy controls. Subjects self-reported the severity of GI symptoms using a 10-point Likert scale after ingesting 50 grams of sucrose on an empty stomach. The receiver operator characteristics curve (ROC) was used to identify the diagnostic variable with the highest Youden Index, a measure of diagnostic performance. Results: All six symptoms were significantly worse in the CSID group within 2 hours after the sucrose challenge. The diagnostic variable with the highest Youden Index was worsening in global symptoms scores at 1- and 2-hours (11.7 [CSID] vs 3.2 [Controls]; P<0.001.) Optimized by gender, the sensitivity and specificity for this diagnostic variable were 87% and 81%, respectively. Conclusions: The SCST is a simple, non-invasive at-home test that can aid in a CSID diagnosis. [ABSTRACT FROM AUTHOR]

From the past years, the most commonly reported state‐of‐the‐art binary bulk heterojunction organic solar cells (OSCs) are mostly based on mixtures of polymer donors and fullerene‐free acceptors (polymer:NFA). However, along with it are a number of contradictory propositions, including (but not limited to) strategies to reduce energy loss and improve photocurrent generation through energy level alignments. Due to the resulting high similarity of molecular fragments from polymer:NFA heterojunctions, the effects of vertical molecular stratification are not yet well studied. Herein, the time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) molecular depth profiling reveals a vertical stratification in PM6:IT‐4Cl and illustrates how it can significantly influence the photovoltaic properties. The said inhomogeneity is also bound to introduce microstructure variations within device active layers. Consequently, it is systematically demonstrated how thin‐film microstructures can influence optoelectronic properties, wherein important metrics (e.g., energy losses and molecular energy offsets) are highly dependent. Thus, the understanding from this work provides foundations for more precise development of strategies to further advance OSC technology in future studies.

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) serves as a footprint of the nucleosome occupancy status of transcription start sites (TSSs), and has been subject to wide development for use in noninvasive health monitoring and disease detection. However, the requirement for high sequencing depth limits its clinical use. Here, we introduce a deep-learning pipeline designed for TSS coverage profiles generated from shallow cfDNA sequencing called the Autoencoder of cfDNA TSS (AECT) coverage profile. AECT outperformed existing single-cell sequencing imputation algorithms in terms of improvements to TSS coverage accuracy and the capture of latent biological features that distinguish sex or tumor status. We built classifiers for the detection of breast and rectal cancer using AECT-imputed shallow sequencing data, and their performance was close to that achieved by high-depth sequencing, suggesting that AECT could provide a broadly applicable noninvasive screening approach with high accuracy and at a moderate cost.

Arsenic content in copper concentrates is continuously increasing worldwide. It is desirable to remove arsenic from copper in the earlier stages of copper making due to the deposition of arsenic to cathode copper during the electrorefining process. Effects of temperature, flux, and oxygen on the distribution of arsenic during copper converting and fire refining processes were studied using FactSage 8.2. The results showed that arsenic can be effectively removed by proper selection of converting and refining slags. The decrease in Fe/SiO2 or Fe/CaO ratio in the converting slag is favorable for arsenic distributed to slag. CaO is more effective than SiO2 in decreasing the liquidus temperature of the slag and arsenic content in the blister copper during the converting process. Na2O or CaO as a flux is effective to remove arsenic in the fire refining process.

As one of the most catastrophic natural disasters worldwide, earthquakes and their effect on structures are very important to structural health monitoring (SHM), particularly for the ones living around the Pacific ring of fire. In this regard, SHM techniques with real-time or online processing can be used to identify states of structures, track modal parameters, provide a warning message about damage, and help post-earthquake reconnaissance and rehabilitation. For instance, a recursive formulation based on subspace identification (SI) has been demonstrated that it is capable to track system changes. In this study, a recursive subspace identification (RSI) algorithm with a fixed window is proposed to investigate the time-varying dynamic characteristics under seismic excitations. Subsequently, some suggestion is described and discussed for practical implementation. For verifying the proposed algorithm, different datasets from full-scale experiments are applied to examine its applicability. In other words, the practicability of implementing RSI in real-time or online has been developed and examined in this paper.

PurposeCiliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia.MethodsA five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year.ResultsPupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors.ConclusionsCiliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.).

This study introduces a novel method integrating CO2 flooding with radial borehole fracturing for enhanced oil recovery and CO2 underground storage, a solution to the limited vertical stimulation reservoir volume in horizontal well fracturing. A numerical model is established to investigate the production rate, reservoir pressure field, and CO2 saturation distribution corresponding to changing time of CO2 flooding with radial borehole fracturing. A sensitivity analysis on the influence of CO2 injection location, layer spacing, pressure difference, borehole number, and hydraulic fractures on oil production and CO2 storage is conducted. The CO2 flooding process is divided into four stages. Reductions in layer spacing will significantly improve oil production rate and gas storage capacity. However, serious gas channeling can occur when the spacing is lower than 20 m. Increasing the pressure difference between the producer and injector, the borehole number, the hydraulic fracture height, and the fracture width can also increase the oil production rate and gas storage rate. Sensitivity analysis shows that layer spacing and fracture height greatly influence gas storage and oil production. Research outcomes are expected to provide a theoretical basis for the efficient development of shale oil reservoirs in the vertical direction. [ABSTRACT FROM AUTHOR]

Diethyl malonate-based fluorescent probe NE-N2H4 was constructed for monitoring hydrazine (N2H4). The novel probe NE-N2H4 exhibits good properties, such as large Stokes shift (about 125 nm), good selectivity, and low cytotoxicity. This sensing probe NE-N2H4 can be operated to detect hydrazine in living HeLa cells. Especially after soaking in probe solution, the thin-layer chromatography (TLC) plate could detect the vapor of hydrazine. Therefore, the probe NE-N2H4 might be used to monitor hydrazine in biosamples and environmental problem.

Interferon-gamma (IFN-γ) is a major effector molecule of immunity and a common feature of tumors responding to immunotherapy. Active IFN-γ signaling can directly trigger apoptosis and cell cycle arrest in human cancer cells. However, the mechanisms underlying these actions remain unclear. Here, we report that IFN-γ rapidly increases protein synthesis and causes the unfolded protein response (UPR), as evidenced by the increased expression of glucose-regulated protein 78, activating transcription factor-4, and c/EBP homologous protein (CHOP) in cells treated with IFN-γ. The JAK1/2-STAT1 and AKT-mTOR signaling pathways are required for IFN-γ-induced UPR. Endoplasmic reticulum (ER) stress promotes autophagy and restores homeostasis. Surprisingly, in IFN-γ-treated cells, autophagy was impaired at the step of autophagosome-lysosomal fusion and caused by a significant decline in the expression of lysosomal membrane protein-1 and −2 (LAMP-1/LAMP-2). The ER stress inhibitor 4-PBA restored LAMP expression in IFN-γ-treated cells. IFN-γ stimulation activated the protein kinase-like ER kinase (PERK)-eukaryotic initiation factor 2a subunit (eIF2α) axis and caused a reduction in global protein synthesis. The PERK inhibitor, GSK2606414, partially restored global protein synthesis and LAMP expression in cells treated with IFN-γ. We further investigated the functional consequences of IFN-γ-induced ER stress. We show that inhibition of ER stress significantly prevents IFN-γ-triggered apoptosis. CHOP knockdown abrogated IFN-γ-mediated apoptosis. Inhibition of ER stress also restored cyclin D1 expression in IFN-γ-treated cells. Thus, ER stress and the UPR caused by IFN-γ represent novel mechanisms underlying IFN-γ-mediated anticancer effects. This study expands our understanding of IFN-γ-mediated signaling and its cellular actions in tumor cells.

PurposeTo evaluate the safety and effect on visual function of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP).DesignCiliary neurotrophic factor for late-stage retinitis pigmentosa study 3 (CNTF3; n = 65) and ciliary neurotrophic factor for early-stage retinitis pigmentosa study 4 (CNTF4; n = 68) were multicenter, sham-controlled dose-ranging studies.MethodsPatients were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoints were change in best-corrected visual acuity (BCVA) at 12 months for CNTF3 and change in visual field sensitivity at 12 months for CNTF4. Patients had the choice of retaining or removing the implant at 12 months for CNTF3 and 24 months for CNTF4.ResultsThere were no serious adverse events related to either the encapsulated cell implant or the surgical procedure. In CNTF3, there was no change in acuity in either ciliary neurotrophic factor- or sham-treated eyes at 1 year. In CNTF4, eyes treated with the high-dose implant showed a significant decrease in sensitivity while no change was seen in sham- and low dose-treated eyes at 12 months. The decrease in sensitivity was reversible upon implant removal. In both studies, ciliary neurotrophic factor treatment resulted in a dose-dependent increase in retinal thickness.ConclusionsLong-term intraocular delivery of ciliary neurotrophic factor is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit in the primary outcome variable.

BackgroundCone photoreceptors are responsible for color and central vision. In the late stage of retinitis pigmentosa and in geographic atrophy associated with age-related macular degeneration, cone degeneration eventually causes loss of central vision. In the present work, we investigated cone degeneration secondary to rod loss in the S334ter-3 transgenic rats carrying the rhodopsin mutation S334ter.Methodology/principal findingsRecombinant human ciliary neurotrophic factor (CNTF) was delivered by intravitreal injection to the left eye of an animal, and vehicle to the right eye. Eyes were harvested 10 days after injection. Cone outer segments (COS), and cell bodies were identified by staining with peanut agglutinin and cone arrestin antibodies in whole-mount retinas. For long-term treatment with CNTF, CNTF secreting microdevices were implanted into the left eyes at postnatal day (PD) 20 and control devices into the right eyes. Cone ERG was recorded at PD 160 from implanted animals. Our results demonstrate that an early sign of cone degeneration is the loss of COS, which concentrated in many small areas throughout the retina and is progressive with age. Treatment with CNTF induces regeneration of COS and thus reverses the degeneration process in early stages of cone degeneration. Sustained delivery of CNTF prevents cones from degeneration and helps them to maintain COS and light-sensing function.Conclusions/significanceLoss of COS is an early sign of secondary cone degeneration whereas cell death occurs much later. At early stages, degenerating cones are capable of regenerating outer segments, indicating the reversal of the degenerative process. Sustained delivery of CNTF preserves cone cells and their function. Long-term treatment with CNTF starting at early stages of degeneration could be a viable strategy for preservation of central vision for patients with retinal degenerations.

This study discussed the problem of target detection for digital radio mondiale (DRM)-based passive bistatic radar (PBR). In the surveillance signal, the power of zero Doppler contribution (ZDC) is stronger than the echoes of weak targets. These targets can hardly be shown in the range-Doppler map of classical cross-ambiguity function (CAF). The clutter should be removed before using CAF-matched correlator. The authors utilised Doppler channel detector (CHAD) to solve the above problem for DRM-based PBR in this study. It can unify the ZDC rejection and the target detection in one process. Compared to CAF detector, the CHAD had a lower random pedestal for low Doppler frequency shifts. The results of experiment data proved the effectiveness of the CHAD for DRM-based PBR.

Background: There is debate as to whether c-Myc predicts prognosis in colorectal cancer (CRC). In this study, we aimed to review the association between c-Myc and CRC prognosis.Methods: Pertinent studies were identified by searching electronic databases and carefully reviewing the reference lists of pertinent studies until March 2016. The summary hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated to study the association between c-Myc and CRC prognosis.Results: Eight cohort studies (including seven studies about overall survival [OS] and one study about disease free survival [DFS]) were included. The pooled HR of OS was 1.13 (95% CI: 0.66–1.95). In subgroup analysis, no significant association between c-Myc and CRC prognosis was found in the studies either from Western countries (HR: 0.87, 95% CI: 0.68–1.10) or Asian countries (HR: 1.89, 95% CI: 0.62–5.77). HRs were 0.86 (95% CI: 0.38–1.94) and 1.57 (95% CI: 0.73–3.39) for the studies using univariate analysis and multivariate analysis, respectively. HR from the studies that examined DNA level was significantly different (HR: 2.05, 95% CI: 1.22–3.46); while that about RNA level or protein level was not significantly different.Conclusion: c-Myc was not associated with CRC prognosis in this meta-analysis. However, the conclusion is preliminary and should be examined in future studies.

Hydrogels containing nanoparticles have enhanced mechanical properties that can be limited if the size of the crosslinking nanoparticles is too large. Here, Zhang and others have produced non-aggregated spherulite nanoparticles with diameters of less than 5 nm and investigated their effect on hydrogels.

Acoustic and vibration control for an underwater structure under mechanical excitation has been investigated by using negative feedback control algorithm. The underwater structure is modeled with cylindrical shells, conical shells, and circular bulkheads, of which the motion equations are built with the variational approach, respectively. Acoustic property is analyzed by the Helmholtz integration formulation with boundary element method. Based on negative feedback control algorithm, a control loop with a coupling use of piezoelectric sensor and actuator is built, and accordingly some numerical examples are carried out on active control of structural vibration and acoustic response. Effects of geometrical and material parameters on acoustic and vibration properties are investigated and discussed.