Depletion Strategies for Crystallized Layers of Two-Dimensional Nanosheets to Enhance Lithium-Ion Conductivity in Polymer Nanocomposites.

The assembly of long-range aligned structures of two-dimensional nanosheets (2DNSs) in polymer nanocomposites (PNCs) is in urgent need for the design of nanoelectronics and lightweight energy-storage materials of high conductivity for electricity or heat. These 2DNS are thin and exhibit thermal fluctuations, leading to an intricate interplay with polymers in which entropic effects can be exploited to facilitate a range of different assemblies. In molecular dynamics simulations of experimentally studied 2DNSs, we show that the layer-forming crystallization of 2DNSs is programmable by regulating the strengths and ranges of polymer-induced entropic depletion attractions between pairs of 2DNSs, as well as between single 2DNSs and a substrate surface, by exclusively tuning the temperature and size of the 2DNS. Enhancing the temperature supports the 2DNS-substrate depletion rather than crystallization of 2DNSs in the bulk, leading to crystallized layers of 2DNSs on the substrate surfaces. On the other hand, the interaction range of the 2DNS-2DNS depletion attraction extends further than the 2DNS-substrate attraction whenever the 2DNS size is well above the correlation length of the polymers, which results in a nonmonotonic dependence of the crystallization layer on the 2DNS size. It is demonstrated that the depletion-tuned crystallization layers of 2DNSs contribute to a conductive channel in which individual lithium ions (Li ions) migrate efficiently through the PNCs. This work provides statistical and dynamical insights into the balance between the 2DNS-2DNS and 2DNS-substrate depletion interactions in polymer-2DNS composites and highlights the possibilities to exploit depletion strategies in order to engineer crystallization processes of 2DNSs and thus to control electrical conductivity.

Precisely Activating cGAS-STING Pathway with a Novel Peptide-Based Nanoagonist to Potentiate Immune Checkpoint Blockade Cancer Immunotherapy.

As an essential intracellular immune activation pathway, the cGAS-STING pathway has attracted broad attention in cancer treatment. However, low bioavailability, nonspecificity, and adverse effects of small molecule STING agonists severely limit their therapeutic efficacy and in vivo application. In this study, a peptide-based STING agonist is first proposed, and KLA is screened out to activate the cGAS-STING pathway by promoting mitochondrial DNA (mtDNA) leakage. To precisely activate the cGAS-STING pathway and block the PD-1/PD-L1 pathway, a multi-stimuli activatable peptide nanodrug (MAPN) is developed for the effective delivery of KLA and PD-L1 antagonist peptide (CVR). With rational design, MAPN achieved the site-specific release of KLA and CVR in response to multiple endogenous stimuli, simultaneously activating the cGAS-STING pathway and blocking PD-1/PD-L1 pathway, ultimately initiating robust and durable T cell anti-tumor immunity with a tumor growth inhibition rate of 78% and extending the median survival time of B16F10 tumor-bearing mice to 40 days. Overall, antimicrobial peptides, which can promote mtDNA leakage through damaging mitochondrial membranes, may be potential alternatives for small molecule STING agonists and giving a new insight for the design of novel STING agonists. Furthermore, MAPN presents a universal delivery platform for the effective synergy of multiple peptides.

Pharmacokinetics and Bioequivalence of Fluconazole Capsules Manufactured in France and China in Healthy Chinese Participants: Open-Label, Randomized, Single-Dose, 2-Way, Crossover Bioequivalence Study Under Fasted and Fed Conditions.

This was an open-label, randomized study in healthy Chinese participants to assess the bioequivalence of 2 fluconazole 150-mg capsules under fasted and fed conditions. The study consisted of 2 treatment periods, separated by a 14-day washout period. Thirty-six participants were enrolled, with 18 participants each in the fasted and fed groups. In each treatment period, participants received a single oral dose of the test or reference fluconazole 150-mg capsule. After washout, participants received the alternate treatment. Blood samples for pharmacokinetic analysis were collected from 1 hour before dosing to 72 hours after dosing. The median plasma concentration-time profiles were similar for both treatments under fasted and fed conditions. Bioequivalence of fluconazole between the 2 capsules was demonstrated as 90% confidence intervals of the geometric mean ratios for the maximum plasma concentration and area under the plasma concentration-time curve from time 0 to 72 hours after dosing under fasted and fed conditions were within the acceptable range of 80%-125%. Overall, 7 participants reported at least 1 treatment-emergent adverse event; all were mild in severity. No serious adverse events or deaths were reported. The test fluconazole capsule was bioequivalent to the reference capsule, and a single dose was well tolerated. Clinicaltrials.gov ID: NCT03621072.

Signal Processing and Machine Learning for Smart Sensing Applications.

The Special Issue "Signal Processing and Machine Learning for Smart Sensing Applications" focused on the publication of advanced signal processing methods by means of state-of-the-art machine learning technologies for smart sensing applications [...].

The Time-of-Arrival Offset Estimation in Neural Network Atomic Denoising in Wireless Location.

With the increasing demand for wireless location services, it is of great interest to reduce the deployment cost of positioning systems. For this reason, indoor positioning based on WiFi has attracted great attention. Compared with the received signal strength indicator (RSSI), channel state information (CSI) captures the radio propagation environment more accurately. However, it is necessary to take signal bandwidth, interferences, noises, and other factors into account for accurate CSI-based positioning. In this paper, we propose a novel dictionary filtering method that uses the direct weight determination method of a neural network to denoise the dictionary and uses compressive sensing (CS) to extract the channel impulse response (CIR). A high-precision time-of-arrival (TOA) is then estimated by peak search. A median value filtering algorithm is used to locate target devices based on the time-difference-of-arrival (TDOA) technique. We demonstrate the superior performance of the proposed scheme experimentally, using data collected with a WiFi positioning testbed. Compared with the fingerprint location method, the proposed location method does not require a site survey in advance and therefore enables a fast system deployment.

A 215-bp indel at intron I of BoFLC2 affects flowering time in Brassica oleracea var. capitata during vernalization.

KEY MESSAGE: In response to cold, a 215-bp deletion at intron I of BoFLC2 slows its silencing activity by feedback to the core genes of the PHD-PRC2 complex, resulting in late flowering in cabbage. Cabbage is a plant-vernalization-responsive flowering type. In response to cold, BoFLC2 is an important transcription factor, which allows cabbage plants to remain in the vegetative phase. However, there have been few reports on the detailed and functional effects of genetic variation in BoFLC2 on flowering time in cabbage. Herein, BoFLC2E and BoFLC2L, cloned from extremely early and extremely late flowering cabbages, respectively, exhibited a 215-bp indel at intron I, three non-synonymous SNPs and a 3-bp indel at exon II. BoFLC2L was found to be related to late flowering, as verified in 40 extremely early/late flowering accessions, a diverse set of cabbage inbred lines and two F2 generations by using indel-FLC2 marker. Among the genetic variation of BoFLC2, the 215-bp deletion at intron I was the main reason for the delayed flowering time, as verified in the transgenic progenies of seed-vernalization-responsive Arabidopsis thaliana (Col) and rapid cycler B. oleracea (TO1000, boflc2). This is the first report to show that the intron I indel of BoFLC2 affects the flowering time of cabbage. Although the intron I 215-bp indel between BoFLC2E and BoFLC2L did not cause alternative splicing, it slowed BoFLC2L silencing during vernalization and feedback to the core genes of the PHD-PRC2 complex, resulting in their lower transcription levels. Our study not only provides an effective molecular marker-assisted selective strategy for identifying bolting-resistant resources and breeding improved varieties in cabbage, but also provides an entry point for exploring the mechanisms of flowering time in plant-vernalization-responsive plants.

A Reference-Scaled Average Bioequivalence Study of Azithromycin Tablets Manufactured in China and the United States: An Open-Label, Randomized, Single-Dose, 3-Way Crossover Study in Healthy Chinese Subjects Under Fasted and Fed Conditions.

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects. This study aimed to support a generic consistency evaluation program, initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the within-subject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population.

An Indoor Navigation Algorithm Using Multi-Dimensional Euclidean Distance and an Adaptive Particle Filter.

The inertial navigation system has high short-term positioning accuracy but features cumulative error. Although no cumulative error occurs in WiFi fingerprint localization, mismatching is common. A popular technique thus involves integrating an inertial navigation system with WiFi fingerprint matching. The particle filter uses dead reckoning as the state transfer equation and the difference between inertial navigation and WiFi fingerprint matching as the observation equation. Floor map information is introduced to detect whether particles cross the wall; if so, the weight is set to zero. For particles that do not cross the wall, considering the distance between current and historical particles, an adaptive particle filter is proposed. The adaptive factor increases the weight of highly trusted particles and reduces the weight of less trusted particles. This paper also proposes a multidimensional Euclidean distance algorithm to reduce WiFi fingerprint mismatching. Experimental results indicate that the proposed algorithm achieves high positioning accuracy.

Development of Ogura CMS restorers in Brassica oleracea subspecies via direct RfoB gene transformation.

KEY MESSAGE: The Ogura CMS RfoB restorer developing via RfoB gene transformation was utilized to produce specific morphological Ogura CMS restorers and clubroot resistance lines in Brassica oleracea subspecies. Brassica oleracea vegetables including cabbage, cauliflower, kohlrabi, Brussels sprouts and Chinese kale are morphologically very different despite being members of the same species. The Ogura cytoplasmic male sterility (CMS) system is the most stable strategy for the hybrid breeding of these species. However, this limits the utilization of some excellent genes due to the lack of fertile restorer genes in the system. Herein, to efficaciously use Ogura CMS, the Ogura CMS RfoB restorer was produced by transforming the modified RfoB restorer gene into the Ogura CMS line 'CMS2016' of B. oleracea var. capitata. This gene was shown to recover fertility of natural Ogura CMS lines in B. oleracea subspecies and create transient Ogura CMS RfoB restorers such as the clubroot resistance Ogura CMS RfoB restorer. Interestingly, clubroot resistant individuals without transgenic elements were screened in the progenies of hybrids between B. oleracea inbred lines and the clubroot resistance Ogura CMS RfoB restorer. In addition, 18 different morphological Ogura CMS restorers were developed to specifically recover fertile of Ogura CMS cultivars in B. oleracea subspecies.

Progress in the synthesis of imide-based N-type polymer semiconductor materials.

Based on the development situation and challenge of organic photovoltaics (OPVs) and organic field-effect transistors (OFETs), it is necessary to develop N-type polymer building blocks with specific structures and performance. After decades of development, some excellent polymer receptor building blocks have been developed to construct N-type organic semiconductors, which have been applied in OFETs and OPVs. In this paper, four kinds of imide (bisthiophene imide BTI, bisthiazolimide BTz, naphthalimide NDI, and perylene imide PDI)-based N-type polymer semiconductor materials are introduced, and their applications in OFETs and OPVs are analyzed, too. The molecular structure design and the performance of corresponding materials are summarized to provide further guidance and reference for the design and development of high performance N-type polymer semiconductors.

Pedestrian Dead Reckoning-Assisted Visual Inertial Odometry Integrity Monitoring.

Visual inertial odometers (VIOs) have received increasing attention in the area of indoor positioning due to the universality and convenience of the camera. However, the visual observation of VIO is more susceptible to the environment, and the error of observation affects the final positioning accuracy. To address this issue, we analyzed the causes of visual observation error that occur under different scenarios and their impact on positioning accuracy. We propose a new method of using the short-time reliability of pedestrian dead reckoning (PDR) to aid in visual integrity monitoring and to reduce positioning error. The proposed method selects optimized positioning by automatically switching between outputs from VIO and PDR. Experiments were carried out to test and evaluate the proposed PDR-assisted visual integrity monitoring. The sensor suite of experiments consisted of a stereo camera and an inertial measurement unit (IMU). Results were analyzed in detailed and indicated that the proposed system performs better for indoor positioning within an environment that contains low illumination, little background texture information, or few moving objects.

A Gyroscope Bias Estimation Algorithm Based on Map Specific Information.

In an inertial navigation system, especially in a pedestrian dead-reckoning system, gyroscope bias can demonstrably reduce positioning accuracy. A novel gyroscope bias estimation algorithm is proposed, which estimates the bias of a gyroscope under any set of angle observations. Moreover, a method for obtaining Euler angles using map corridor information is proposed. The heading information obtained from a map is used to estimate the bias, and the estimated bias is used to correct the trajectories. Experimental results show that it is feasible for the algorithm to estimate the bias of the gyroscope.

An INS/WiFi Indoor Localization System Based on the Weighted Least Squares.

For smartphone indoor localization, an INS/WiFi hybrid localization system is proposed in this paper. Acceleration and angular velocity are used to estimate step lengths and headings. The problem with INS is that positioning errors grow with time. Using radio signal strength as a fingerprint is a widely used technology. The main problem with fingerprint matching is mismatching due to noise. Taking into account the different shortcomings and advantages, inertial sensors and WiFi from smartphones are integrated into indoor positioning. For a hybrid localization system, pre-processing techniques are used to enhance the WiFi signal quality. An inertial navigation system limits the range of WiFi matching. A Multi-dimensional Dynamic Time Warping (MDTW) is proposed to calculate the distance between the measured signals and the fingerprint in the database. A MDTW-based weighted least squares (WLS) is proposed for fusing multiple fingerprint localization results to improve positioning accuracy and robustness. Using four modes (calling, dangling, handheld and pocket), we carried out walking experiments in a corridor, a study room and a library stack room. Experimental results show that average localization accuracy for the hybrid system is about 2.03 m.

A Novel Energy-Efficient Approach for Human Activity Recognition.

In this paper, we propose a novel energy-efficient approach for mobile activity recognition system (ARS) to detect human activities. The proposed energy-efficient ARS, using low sampling rates, can achieve high recognition accuracy and low energy consumption. A novel classifier that integrates hierarchical support vector machine and context-based classification (HSVMCC) is presented to achieve a high accuracy of activity recognition when the sampling rate is less than the activity frequency, i.e., the Nyquist sampling theorem is not satisfied. We tested the proposed energy-efficient approach with the data collected from 20 volunteers (14 males and six females) and the average recognition accuracy of around 96.0% was achieved. Results show that using a low sampling rate of 1Hz can save 17.3% and 59.6% of energy compared with the sampling rates of 5 Hz and 50 Hz. The proposed low sampling rate approach can greatly reduce the power consumption while maintaining high activity recognition accuracy. The composition of power consumption in online ARS is also investigated in this paper.

Effects of ETS on Apoptosis of Human Colorectal Cancer HT-29 Cells / 中国中医药信息杂志

Objective To study the apoptosis of human colorectal cancer HT-29 cells induced by Aralia elata Seem leaf total saponin (ETS) and its effects on the expression of relevant proteins. Methods MTT assay was used to detect the proliferation of human colorectal cancer HT-29 cells cultivated with different concentrations (6.25, 12.5, 25, 50, 100, 200 mg/kg) of ETS. Hoechst33258 staining and laser confocal imaging were used to detect the apoptotic cells. Morphological changes were observed. The expressions of Bcl-2 and Bax were detected by immuno-histochemistry. Results ETS could induce apoptosis of HT-29 cells and apoptosis was in a dose-dependent manner in a certain range. ETS could decrease the expression of Bcl-2 and increase the expression of Bax in HT-29 cells (P<0.05, P<0.01), showing a significant dose-effect relationship. Conclusion ETS can induce the apoptosis of HT-29 cells, and the mechanism may be related to reducing the expression of Bcl-2 and increasing the expression of Bax.

Determination of LBPT in human plasma by high performance liquid chromatography-tandem mass spectrometry.

A rapid and selective HPLC-MS/MS method was developed for the determination of LBPT in human plasma. The analyte was extracted from plasma samples by solid-phase extraction and then chromatographed on a C18 analytical column. The mobile phase consisted of acetonitrile-10mM ammonium formate in 0.1% formic acid (30:70, v/v) and the flow rate was 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reactions monitoring (MRM) mode using positive electrospray ionization (ESI). The method was validated over the concentration range of 0.2-100 ng/mL. Inter- and intra-day precision (RSD %) were less than 9.2% and the accuracy (RE %) ranged from 0 to 11.0%. The lower limit of quantitation (LLOQ) was 0.2 ng/mL. The extraction recovery was on average 75% and the detection was not affected by the matrix. The method was successfully applied to the pharmacokinetic study of LBPT in healthy Chinese subjects.

Quantitative determination of buagafuran in human plasma by liquid chromatography-tandem mass spectrometry.

A sensitive and selective high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of buagafuran in human plasma. The analyte was extracted from plasma samples with hexane after addition of isotopic internal standard and chromatographed on a RP-C(8) column. The mobile phase consisted of methanol-water (90:10, v/v) and the flow rate was 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reactions monitoring (MRM) mode using positive electrospray ionization (ESI). The method was validated over the concentration range of 0.5-200 ng/mL. Inter- and intra-day precision (RSD%) were all within 15% and the accuracy (RE%) was equal or lower than 9.5%. The lower limit of quantitation (LLOQ) was 0.5 ng/mL. The extraction recovery was on average 38.1% and the detection was not affected by the matrix. The method was successfully applied to the pharmacokinetic study of buagafuran in healthy Chinese volunteers.

Simultaneous determination of a novel antifibrotic agent and three metabolites in human urine by LC-MS/MS.

A robust and validated high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous determination of F351 (5-methyl-1-(4-hydroxylphenyl)-2-(1H)-pyridone) and three major metabolites in human urine sample. This assay method has also been validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery. Chromatography was carried out on an XTerra RP 18 column and mass spectrometric analysis was performed using an API 4000 mass spectrometer coupled with electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 202-->109, 232-->93, 282-->202 and 378-->202 were used to quantify F351 and three metabolites, respectively. Retention times for F351 and three metabolites were 2.54, 1.38, 1.53 and 1.34 min, respectively. The assay was validated from 20 to 4000 ng/mL for F351 and M1, from 80 to16,000 ng/mL for M2 and M3. Intra- and inter-day precision for all analytes was <6.3%, method accuracy was between -11.2 and 0.3%. This assay was used to support a clinical study where multiple oral doses were administered to healthy subjects to investigate the pharmacokinetics, safety, and tolerability of F351.