Network and Experimental Pharmacology on Mechanism of Yixintai Regulates the TMAO/PKC/NF-κB Signaling Pathway in Treating Heart Failure.

Objective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation. Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson's, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting. Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1ß, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC. Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.

IMU/Magnetometer-Based Azimuth Estimation with Norm Constraint Filtering.

A typical magnetometer-based measurement-while-drilling (MWD) system determines the azimuth of the bottom hole assembly during the drilling process by employing triaxial accelerometers and magnetometers. The geomagnetic azimuth solution is susceptible to magnetic interference, especially strong magnetic interference and so a rotary norm constraint filtering (RNCF) method for azimuth estimation, designed to support a gyroscope-aided magnetometer-based MWD system, is proposed. First, a new magnetic dynamical system, one whose output is observed by the magnetometers triad, is designed based on the Coriolis equation of the desired geomagnetic vector. Second, given that the norm of the non-interfered geomagnetic vector can be approximated as a constant during a short-term drilling process, a norm constraint procedure is introduced to the Kalman filter. This is achieved by the normalization of the geomagnetic part of the state vector of the dynamical system and is undertaken in order to obtain a precise geomagnetic component. Simulation and actual drilling experiments show that the proposed RNCF method can effectively improve the azimuth measurement precision with 98.5% over the typical geomagnetic solution and 37.1% over the KF in a RMSE sense when being strong magnetic interference environment.

A high-throughput response to the SARS-CoV-2 pandemic.

Four years after the beginning of the COVID-19 pandemic, it is important to reflect on the events that have occurred during that time and the knowledge that has been gained. The response to the pandemic was rapid and highly resourced; it was also built upon a foundation of decades of federally funded basic and applied research. Laboratories in government, pharmaceutical, academic, and non-profit institutions all played roles in advancing pre-2020 discoveries to produce clinical treatments. This perspective provides a summary of how the development of high-throughput screening methods in a biosafety level 3 (BSL-3) environment at Southern Research Institute (SR) contributed to pandemic response efforts. The challenges encountered are described, including those of a technical nature as well as those of working under the pressures of an unpredictable virus and pandemic.

Characterization and Function Analysis of miRNA Editing during Fat Deposition in Chinese Indigenous Ningxiang Pigs.

This study aimed to identify active miRNA editing sites during adipose development in Ningxiang pigs and analyze their characteristics and functions. Based on small RNA-seq data from the subcutaneous adipose tissues of Ningxiang pigs at four stages-30 days (piglet), 90 days (nursery), 150 days (early fattening), and 210 days (late fattening)-we constructed a developmental map of miRNA editing in the adipose tissues of Ningxiang pigs. A total of 505 miRNA editing sites were identified using the revised pipeline, with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G, and G-to-U. Importantly, these four types of miRNA editing exhibited base preferences. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. A total of nine miRNA editing sites were identified in the miRNA seed region, with significant differences in editing levels (p < 0.05) located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and KEGG enrichment analyses indicated that the editing of miR-497 might potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Erratum: [Corrigendum] PF­2341066 combined with celecoxib promotes apoptosis and inhibits proliferation in human cholangiocarcinoma QBC939 cells.

[This corrects the article DOI: 10.3892/etm.2018.5967.].

CRISPR-Cas9-mediated chicken prmt5 gene knockout and its critical role in interferon regulation.

Protein arginine methyltransferase 5 (PRMT5), a type II arginine methyltransferase, controls arginine dimethylation of a variety of substrates. While many papers have reported the function of mammalian PRMT5, it remains unclear how PRMT5 functions in chicken cells. In this study, we found that chicken (ch) PRMT5 is widely expressed in a variety of chicken tissues and is distributed in both the cytoplasm and the nucleus. Ectopic expression of chPRMT5 significantly suppresses chIFN-ß activation induced by chMDA5. In addition, a prmt5 gene-deficient DF-1 cell line was constructed using CRISPR/Cas9. In comparison with the wild-type cells, the prmt5-/- DF-1 cells displays normal morphology and maintain proliferative capacity. Luciferase reporter assay and overexpression showed that prmt5-/- DF-1 cells had increased IFN-ß production. With identified chicken PRMT5 and CRISPR/Cas9 knockout performed in DF-1 cells, we uncovered a functional link of chPRMT5 in suppression of IFN-ß production and interferon-stimulated gene expression.

Genome-Wide Association Study and Identification of Candidate Genes for Intramuscular Fat Fatty Acid Composition in Ningxiang Pigs.

Ningxiang pigs exhibit a diverse array of fatty acids, making them an intriguing model for exploring the genetic underpinnings of fatty acid metabolism. We conducted a genome-wide association study using a dataset comprising 50,697 single-nucleotide polymorphisms (SNPs) and samples from over 600 Ningxiang pigs. Our investigation yielded novel candidate genes linked to five saturated fatty acids (SFAs), four monounsaturated fatty acids (MUFAs), and five polyunsaturated fatty acids (PUFAs). Significant associations with SFAs, MUFAs, and PUFAs were found for 37, 21, and 16 SNPs, respectively. Notably, some SNPs have significant PVE, such as ALGA0047587, which can explain 89.85% variation in Arachidic acid (C20:0); H3GA0046208 and DRGA0016063 can explain a total of 76.76% variation in Elaidic Acid (C18:1n-9(t)), and the significant SNP ALGA0031262 of Arachidonic acid (C20:4n-6) can explain 31.76% of the variation. Several significant SNPs were positioned proximally to previously reported genes. In total, we identified 11 candidate genes (hnRNPU, CEPT1, ATP1B1, DPT, DKK1, PRKG1, EXT2, MEF2C, IL17RA, ITGA1 and ALOX5), six candidate genes (ALOX5AP, MEDAG, ISL1, RXRB, CRY1, and CDKAL1), and five candidate genes (NDUFA4L2, SLC16A7, OTUB1, EIF4E and ROBO2) associated with SFAs, MUFAs, and PUFAs, respectively. These findings hold great promise for advancing breeding strategies aimed at optimizing meat quality and enhancing lipid metabolism within the intramuscular fat (IMF) of Ningxiang pigs.

Research on Processability and Transmission Performance of Low Temperature Co-Fired Ceramic Ball Grid Array Packaging Based on Electroless Plating Surface Modification for Microwave Transceiver Circuits.

A microwave transmitter/receiver using the low-temperature co-fired ceramic substrate and ball grid array packaging demonstrates superior properties, including high integration, miniaturization, and high electromagnetic shielding. However, it holds limitations of inadequate hermeticity (that is, gas or moist impermeability), high cost, and low reproducibility. In this work, we aim to overcome these difficulties by introducing a new packing technique. The packaging utilizes an electroless plated Ni/Pd/Au surface, resulting in a significant enhancement of the packaging hermeticity by orders of magnitude, approaching the level of <5 × 10-9 Pa·m3/s. Both Sn63Pb37 and Au80Sn20 solder alloys demonstrate exceptional solderability, attributed to Pd atoms diffusing to the Au layer during soldering at 310 °C. A reliability test of the packaging shows that the shear strength of the solder balls drops after thermal shocks but negligibly affects the hermeticity of the packaging. Furthermore, a meticulously designed internal vertical interconnect structure and I/O interconnections were engineered in the ball grid array packaging, showcasing excellent transmission characteristics within the 10-40 GHz frequency range while ensuring effective isolation between ports.

Obese Ningxiang pig-derived microbiota rewires carnitine metabolism to promote muscle fatty acid deposition in lean DLY pigs.

The gut microbiota consistently shows strong correlations with lipid metabolism in humans and animals, and whether the gut microbiota contributes to muscle fatty acid (FA) deposition and meat traits in farm animals has not been fully resolved. In this study, we aimed to unveil the microbial mechanisms underlying muscle FA deposition in pigs. First, we systematically revealed the correlation between the gut microbiome and muscle FA levels in 43 obese Ningxiang pigs and 50 lean Duroc Landrace Yorkshire (DLY) pigs. Mutual fecal microbial transplantation showed that the obese Ningxiang pig-derived microbiota increased the muscle FA content and improved meat quality by reshaping the gut microbial composition in lean DLY pigs. Lactobacillus reuteri has been identified as a potential microbial biomarker in obese Ningxiang pig-derived microbiota-challenged DLY pigs. A gavage experiment using lean DLY pigs confirmed that L. reuteri XL0930 isolated from obese Ningxiang pigs was the causal species that increased the muscle FA content. Mechanistically, SLC22A5, a carnitine transporter, was downregulated in L. reuteri XL0930-fed DLY pigs, resulting in reduced muscle carnitine levels. Muscle and intestinal L-carnitine levels, which correlated with the muscle FA content, impeded fat synthesis and FA accumulation in in vitro and in vivo models. In conclusion, we uncovered an unexpected and important role of the obese Ningxiang pig-derived microbiota in regulating muscle FA metabolism via the SLC22A5-mediated carnitine system.

Identifying Genetic Architecture of Carcass and Meat Quality Traits in a Ningxiang Indigenous Pig Population.

Ningxiang pig is a breed renowned for its exceptional meat quality, but it possesses suboptimal carcass traits. To elucidate the genetic architecture of meat quality and carcass traits in Ningxiang pigs, we assessed heritability and executed a genome-wide association study (GWAS) concerning carcass length, backfat thickness, meat color parameters (L.LD, a.LD, b.LD), and pH at two postmortem intervals (45 min and 24 h) within a Ningxiang pig population. Heritability estimates ranged from moderate to high (0.30~0.80) for carcass traits and from low to high (0.11~0.48) for meat quality traits. We identified 21 significant SNPs, the majority of which were situated within previously documented QTL regions. Furthermore, the GRM4 gene emerged as a pleiotropic gene that correlated with carcass length and backfat thickness. The ADGRF1, FKBP5, and PRIM2 genes were associated with carcass length, while the NIPBL gene was linked to backfat thickness. These genes hold the potential for use in selective breeding programs targeting carcass traits in Ningxiang pigs.

OsTOC1 plays dual roles in the regulation of plant circadian clock by functioning as a direct transcription activator or repressor.

Plant clock function relies on precise timing of gene expression through complex regulatory networks consisting of activators and repressors at the core of oscillators. Although TIMING OF CAB EXPRESSION 1 (TOC1) has been recognized as a repressor involved in shaping oscillations and regulating clock-driven processes, its potential to directly activate gene expression remains unclear. In this study, we find that OsTOC1 primarily acts as a transcriptional repressor for core clock components, including OsLHY and OsGI. Here, we show that OsTOC1 possesses the ability to directly activate the expression of circadian target genes. Through binding to the promoters of OsTGAL3a/b, transient activation of OsTOC1 induces the expression of OsTGAL3a/b, indicating its role as an activator contributing to pathogen resistance. Moreover, TOC1 participates in regulating multiple yield-related traits in rice. These findings suggest that TOC1's function as a transcriptional repressor is not inherent, providing flexibility to circadian regulations, particularly in outputs.

Dual single guide RNAs-mediating deletion of mature myostatin peptide results in concomitant muscle fibre hyperplasia and adipocyte hypotrophy in pigs.

Myostatin (MSTN) is a major gene target for skeletal muscle overgrowth in animals. We hypothesized that deletion of the entire mature peptide encoded by MSTN in pigs would knock out its bioactive form and accordingly stimulate skeletal muscle overgrowth. Thus, we engineered two pairs of single-guide RNAs (sgRNAs) to target exons 1 and 3 of MSTN in primary fetal fibroblasts of Taoyuan black pigs. We found that sgRNAs targeting exon 3, which encodes the mature peptide, had higher biallelic null mutation efficiency than those targeting exon 1. Somatic cell nuclear transfer was conducted using the exon 3 mutation cells as donor cells to generate five cloned MSTN null piglets (MSTN-/-). Growth testing revealed that both the growth rate and average daily weight gain of MST-/- pigs were greater than those of wild-type (MSTN+/+) pigs. Slaughter data demonstrated that the lean ratio of MSTN-/- pigs was 11.3% higher (P < 0.01) while the back-fat thickness was 17.33% lower (P < 0.01) than those of MSTN+/+ pigs. Haematoxylin-eosin staining indicated that the increased leanness of MSTN-/- pigs resulted from muscle fibre hyperplasia rather than hypertrophy.HE staining showed markedly decreased adipocyte size in MSTN-/- pigs. We also critically examined the off-target and random integration by resequencing, which showed that the founder MSTN-/- pigs contained no non-target mutations or exogenous plasmid elements. This study is the first to report the successful knock out of the mature MSTN peptide using dual sgRNA-mediated deletion, leading to the most prominent alteration of meat production traits in pigs published thus far. This new strategy is expected to have a wide impact on genetic improvements in food animals.

Towards Large-Scale Small Object Detection: Survey and Benchmarks.

With the rise of deep convolutional neural networks, object detection has achieved prominent advances in past years. However, such prosperity could not camouflage the unsatisfactory situation of Small Object Detection (SOD), one of the notoriously challenging tasks in computer vision, owing to the poor visual appearance and noisy representation caused by the intrinsic structure of small targets. In addition, large-scale dataset for benchmarking small object detection methods remains a bottleneck. In this paper, we first conduct a thorough review of small object detection. Then, to catalyze the development of SOD, we construct two large-scale Small Object Detection dAtasets (SODA), SODA-D and SODA-A, which focus on the Driving and Aerial scenarios respectively. SODA-D includes 24828 high-quality traffic images and 278433 instances of nine categories. For SODA-A, we harvest 2513 high resolution aerial images and annotate 872069 instances over nine classes. The proposed datasets, as we know, are the first-ever attempt to large-scale benchmarks with a vast collection of exhaustively annotated instances tailored for multi-category SOD. Finally, we evaluate the performance of mainstream methods on SODA. We expect the released benchmarks could facilitate the development of SOD and spawn more breakthroughs in this field.

A Chinese soil conservation dataset preventing soil water erosion from 1992 to 2019.

Soil conservation service (SC) is defined as the ability of terrestrial ecosystems to control soil erosion and protect soil function. A long-term and high-resolution estimation of SC is urgent for ecological assessment and land management on a large scale. Here, a 300-m resolution Chinese soil conservation dataset (CSCD) from 1992 to 2019, for the first time, is established based on the Revised Universal Soil Loss Equation (RUSLE) model. The RUSLE modelling was conducted based on five key parameters, including the rainfall erosivity (interpolation of daily rainfall), land cover management (provincial data), conservation practices (weighted by terrain and crop types), topography (30 m), and soil properties (250 m). The dataset agrees with previous measurements in all basins (R2 > 0.5) and other regional simulations. Compared with current studies, the dataset has long-term, large-scale, and relatively high-resolution characteristics. This dataset will serve as a base to open out the mechanism of SC variations in China and could help assess the ecological effects of land management policies.

Efficient Semi-Transparent Wide-Bandgap Perovskite Solar Cells Enabled by Pure-Chloride 2D-Perovskite Passivation.

Wide-bandgap (WBG) perovskite solar cells suffer from severe non-radiative recombination and exhibit relatively large open-circuit voltage (VOC) deficits, limiting their photovoltaic performance. Here, we address these issues by in-situ forming a well-defined 2D perovskite (PMA)2PbCl4 (phenmethylammonium is referred to as PMA) passivation layer on top of the WBG active layer. The 2D layer with highly pure dimensionality and halide components is realized by intentionally tailoring the side-chain substituent at the aryl ring of the post-treatment reagent. First-principle calculation and single-crystal X-ray diffraction results reveal that weak intermolecular interactions between bulky PMA cations and relatively low cation-halide hydrogen bonding strength are crucial in forming the well-defined 2D phase. The (PMA)2PbCl4 forms improved type-I energy level alignment with the WBG perovskite, reducing the electron recombination at the perovskite/hole-transport-layer interface. Applying this strategy in fabricating semi-transparent WBG perovskite solar cells (indium tin oxide as the back electrode), the VOC deficits can be reduced to 0.49 V, comparable with the reported state-of-the-art WBG perovskite solar cells using metal electrodes. Consequently, we obtain hysteresis-free 18.60%-efficient WBG perovskite solar cells with a high VOC of 1.23 V.

A LTCC-Based Ku-Band 8-Channel T/R Module Integrated with Drive Amplification and 7-Bit True-Time-Delay.

Ku-band drive amplification and a 7-bit true-time-delay (TTD) function were realized as a part of a LTCC-based T/R module to increase integration. The 8-channel T/R module was fabricated and its key characteristics were measured, including a 3-bit (1/2/4 λ) TTD, 4-bit (0.25/0.5/1/2 λ) TTD, receive gain, noise figure and output power. The 8-channel T/R module can be further adopted to increase bandwidth and scanning angle of phased arrays without beam squint.

Effect of steam explosion on nutritional components, physicochemical and rheological properties of brown rice powder.

Brown rice powder is underutilized mainly due to its lower starch digestibility and poor processing performance. The present study investigated the potential of steam explosion on the improvement of nutritional and physicochemical characteristic in brown rice powder and rheological property of paste. Compared with native brown rice powder, steam explosion at 0.5 MPa for 7 min increased the water-extractable arabinoxylans (5.77%), reducing sugar content (21.04%), and iodine blue value (30.38%), which indicated steam explosion that destroyed the intact cells of brown rice. Later the crystalline structure of brown rice powder was destroyed into an amorphous structure by steam explosion. Steam explosion enhanced the degree of gelatinization (4.76~351.85%) and solvent retention capacity (SRC) of brown rice powder, compared with native sample. The effect on the intact cells and starch structure of brown rice caused the starch digestibility enhancement remarkable. Viscoelastic profiles confirmed that steam explosion weakened the paste strength and elasticity corresponded with hardness and cohesiveness by increasing the loss factor (tanδ). This work provided important information for brown rice powder modified by steam explosion (0.5 MPa, 7 min) with good nutritional property (nutrients and digestibility) and processability (SRC, textural, and rheological property). Steam exploded brown rice powder (0.5 MPa, 7 min) could serve as a potential ingredient widely used in food products.

Improving bioaccessibility and physicochemical property of blue-grained wholemeal flour by steam explosion.

Whole grain contains many health-promoting ingredients, but due to its poor bioaccessibility and processibility, it is not widely accepted by consumers. The steam explosion was exploited to modify the nutritional bioaccessibility and the physicochemical properties of wholemeal flour in this study. In vitro starch digestibility, in vitro protein digestibility of wholemeal flour, total flavonoids content, and total phenolics content of digestive juice were used to evaluate the bioaccessibility, and a significant variation (p < 0.05) was noted. Results showed that steam explosion enhanced the gastric protein digestibility ranged from 5.67 to 6.92% and the intestinal protein digestibility ranged from 16.77 to 49.12%. Steam-exploded wholemeal flour (0.5 MPa, 5 min) had the highest protein digestibility and rapidly digestible starch content. Compared with native flour, steam explosion (0.5 MPa, 5 min) contributed to a 0.72-fold and 0.33-fold increment of total flavonoids content and total phenolics content in digestible juice. Chemical changes of wholemeal flour, induced by steam explosion, caused the changes in the solvent retention capacity, rheological property of wholemeal flour, and altered the falling number (and liquefaction number). An increasing tendency to solid-like behavior and the gel strength of wholemeal flour was significantly enhanced by the steam explosion at 0.5 MPa for 5 min, while the gluten was not weakened. This study indicated that steam-exploded wholemeal flour (0.5 MPa, 5 min) could serve as a potential ingredient with the noticeable bioaccessibility and physicochemical properties in cereal products.

Detection of Porcine Circovirus 1/2/3 and Genetic Analysis of Porcine Circovirus 2 in Wild Boar from Jiangxi Province of China.

A number of disorders that harm pig production are linked to porcine circoviruses, including PCV2. PCV2 infection is a substantial contributor to porcine-circovirus-associated illnesses (PCAS) and the post-weaning multi-systemic wasting syndrome (PMWS), which have a significant negative economic impact on pig production. Additionally, PCV infection has been labeled as a global concern to cattle and wildlife. This study's objectives were to examine the prevalence of PCV1/2/3 in Jiangxi Province, China, and to clarify the epidemiological significance of wild boar in PCV epidemiology. The 2020 hunting seasons resulted in the collection of 138 wild boar samples for PCV1/2/3 detection, which was followed by the genetic clarification of PCV2 strains. According to our data, 21.7% (30/138) of the population had PCV1 positivity, 22.5% (31/138) had PCV2 positivity, and 5.8% (8/138) had PCV3 positivity. Additionally, 10 out of 138 wild boar samples had PCV1 and PCV2 co-infections, while 5 out of 138 wild boar samples had PCV2 and PC3 co-infections. Nineteen full-length PCV2 genomes measuring 1767 nt were recovered from various animal tissues using conventional PCR. Eighteen out of nineteen PCV2 strains were identified as PCV2b by phylogenetic tree analysis, which was completed by the reference strain HLJ2015 obtained from domestic pigs in 2015. Additionally, one genotype of PCV2d JX11-2020 (MW889021) shared a sub-branch with the referenced strain TJ (AY181946), which was isolated in domestic pigs in 2002. This finding raises the possibility that domestic pigs could contract PCV2 strains from wild boar, posing a serious threat to the Jiangxi province of China's pig production industry.

Research on Temperature Compensation of Multi-Channel Pressure Scanner Based on an Improved Cuckoo Search Optimizing a BP Neural Network.

A multi-channel pressure scanner is an essential tool for measuring and acquiring various pressure parameters in aerospace applications. It is important to note, however, that the pressure sensor of each of these channels will drift significantly with the increase in the temperature range of the pressure measurement, and the output voltage of each of these channels will show nonlinear characteristics, which will constrain the improvements in the accuracy of the measurement. In the regression fitting process, it is difficult to fit nonlinear data with the traditional least-squares method, which leaves pressure measurement accuracy unsatisfactory. A temperature compensation method based on an improved cuckoo search optimizing a BP neural network for a multi-channel pressure scanner is proposed in this paper to improve pressure measurement accuracy in a wide temperature range. Using the chaotic simplex algorithm, we first improved the cuckoo search algorithm, then optimized the connection weights and thresholds of the BP neural network, and finally constructed an experimental calibration system to investigate the temperature compensation of the multi-channel pressure scanning valves in the -40 °C to 60 °C temperature range. The compensation test results show that the algorithm has a better compensation effect and is more suitable for the temperature compensation of multi-channel pressure scanners than the traditional least-squares method and the standard RBF and BP neural networks. The maximum full-scale error of all 32 channels is 0.02% FS (full-scale error) and below, which realizes its high-accuracy multi-point pressure measurement in a wide temperature range.