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Purpose: Cisplatin-containing combination chemotherapy has been the standard of care since the late 1980s, but the response rate is <50%. Studies have shown that the efficiency of chemotherapy differs among molecular subtypes of bladder cancer. In this study, we aimed to correlate FOXA1, a marker for differentiation of the basal and luminal subtypes, with tumor immune cell infiltration and the effect of chemotherapy in bladder cancer. Materials and Methods: Eighty-three patients with bladder cancer treated with chemotherapy were reviewed. Clinicopathological variables for each case were recorded. FOXA1, M2 tumor-associated macrophage (TAM), dendritic cell (DC), and cytotoxic T lymphocyte (CTL) were examined by immunohistochemistry. The relationship between FOXA1, immune cell infiltration, and clinical response to chemotherapy was assessed. Results: The overall objective response rate was 34%. The objective response rate for tumors with lower FOXA1 expression was 58% and for tumors with higher FOXA1 expression was 12%. Tumors with infiltrated M2 TAM proportion <3% had a higher objective response rate compared with infiltrated M2 TAM proportion >3% tumors (46% vs. 21%, p = 0.02). Tumors with infiltrated CTL proportion >5% had a higher objective response rate compared with infiltrated CTL proportion <5% tumors (50% vs. 17%, p = 0.002). DCs showed no significant differences. We found that the objective response rate for tumors with lower FOXA1 expression, proportion <3% M2 TAM infiltration, and proportion >5% CTL infiltration is 82%. Lower FOXA1 expression was associated with low M2 TAM infiltration and high CTL infiltration. Conclusions: Thus, we showed that in patients with bladder cancer who received chemotherapy, the higher clinical response rate is associated with low FOXA1 expression, low M2 TAM infiltration, and high CTL infiltration. [ABSTRACT FROM AUTHOR]

Developing a ceramic scintillator operating in a phoswich detector is a feasible way for pulse shape discrimination. A YAG:Ce transparent ceramic scintillator has been synthesized by using the vacuum sintering method. In this work, we present a new phoswich detector mainly developed for the determination of low radioactivity levels. The system was constructed by combining a transparent ceramic scintillator, for the detection of α particles, and a CsI:Tl crystal, for the detection of γ-rays. With the device proposed here, the particle identification in a mixed α–γ field has been achieved with the rise time discrimination method. Furthermore, the figure of merit can also be improved using the phoswich detector. The higher reliability, simplicity, and low cost of the design that combines ceramics and crystals make the YAG ceramic have extremely good application prospects. [ABSTRACT FROM AUTHOR]

Background: Cholesterol is an essential component of lipid rafts in cell plasma membrane, which exerts a hepatoprotective role against mycotoxin exposure in pigs, and cholesterol metabolism is vulnerable to epigenetic histone acetylation. Therefore, our present study aimed to investigate whether a histone deacetylase inhibitor (sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol (DON) exposure by modulating cholesterol metabolism. Herein, we randomly divided 28 pigs into four groups, which were fed an uncontaminated basal diet, contaminated diet (4 mg DON/kg), uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet (4 mg DON/kg) supplemented with 0.2% NaBu for 28 d. Results: We found that the serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were all increased in pigs exposed to DON, indicative of significant liver injury. Furthermore, the cholesterol content in the serum of DON-exposed pigs was significantly reduced, compared to the healthy Vehicle group. Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure. In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated. Importantly, NaBu effectively restored parameters associated with liver injury, along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway. Mechanistically, we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment. We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu, as determined by ChIP-qPCR analysis. Notably, nuclear receptor RORγ, a novel regulator of cholesterol biosynthesis, was found in the hyperacetylated regions. Again, a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu. Consistent with RORγ expression, NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR, SQLE, and DHCR24. Furthermore, we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes. Conclusions: Collectively, our results demonstrate the utility of the natural product NaBu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification. [ABSTRACT FROM AUTHOR]

Blockchain-based traceability systems are a promising approach because they are decentralized, transparent, and tamper proof; however, if all traceability data are uploaded to a blockchain platform, it may affect the efficiency or even lead to data explosion. Additionally, it is difficult to guarantee the reliability of the original data source of massive Internet of Things (IoT) devices. Furthermore, when different enterprise nodes adopt different data storage structures, the costs that are associated with data sharing will increase. In this paper, we have proposed a trustworthy product traceability system that is based on hyperledger fabric and Electronic Product Code Information Service (EPCIS), which is not only capable of making products traceable, but it can also authenticate and authorize the IoT devices that are used for data collection. First, we adopted the on-chain and off-chain collaborative management mechanism in order to alleviate data explosion on the chain. Second, we proposed a scheme to authenticate and authorize devices based on blockchain. Third, we complied with EPCIS and Core Business Vocabulary (CBV) standards and provided the EPCIS location discovery service in order to improve the interactivity. Finally, we implemented and tested the proposed traceability system and compared it with the existing research. The proposed solution provides product information traceability, data tamper proofing, data confidentiality, and data source reliability. [ABSTRACT FROM AUTHOR]

In this article, split-tooth stator slot permanent magnet (PM) machines, which have high fault-tolerant capability, are proposed. Compared with the existing 12-slot 10-pole (12S10P) stator slot PM machine, the torque can be improved by 66% by properly choosing the split tooth number and other geometric parameters. It is found that two split teeth stator slot PM machine (ST2) shows the best torque characteristics among the stator slot PM machines with different split tooth number. To further illustrate the merits and demerits of ST2, a conventional 6S4P surface mounted PM machine (SPMM) and a 6S4P variable flux reluctance machine serve as the benchmarks to compare with the 6S11P ST2, at both open circuit condition and load condition. The 6S11P ST2 shows 68% higher torque over the 6S4P VFRM. Although the torque of the 6S11P ST2 is around half of the 6S4P SPMM, the former has 70% higher torque per PM volume than the latter. Furthermore, demagnetization analyses under three-phase short-circuit and pure d-axis currents show that the 6S11P ST2 has much better demagnetization withstand capability over the 6S4P SPMM. A Prototype is manufactured and tested to validate the theoretical analyses. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a formidable cancer to treat due to the lack of effective drugs that can also efficiently cross the blood–brain barrier (BBB). Herein, a novel strategy involving the synthesis of p28 peptide‐conjugated, lexiscan (LEX)‐loaded, bardoxolone methyl (BM) self‐assembled nanoparticles, designated as p28‐LBM NPs, is introduced. These NPs are designed to overcome the dual challenges of effectively killing GBM cells and efficiently penetrating the brain. The p28 peptide is chosen for targeted delivery to brain tumors, and LEX is employed to enhance drug penetration across the BBB. The successful penetration of brain tumors by the p28‐LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28‐LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future. [ABSTRACT FROM AUTHOR]

Spoke array permanent magnet (PM) flux reversal machines (SAFRPMMs), which are suitable for low speed and high torque applications, are able to enhance torque density due to the flux focusing effect. In this paper, what influence both the number of PM per slot and the PM shape have on their electromagnetic performance are investigated. The results show that both the PM number and the PM shape have significant effects on the performance of SAFRPMMs, and proper selections are critical in designing high performance machines. When the PM number per slot is 2, the SAFRPMM exhibits the best electromagnetic performances, i.e., the highest torque, power, efficiency, and power factor. Meanwhile, by properly designing the PM shape, the torque can be further improved by around 11%. A prototype is made and tested to validate the analyses. [ABSTRACT FROM AUTHOR]

In this article, a new type of consequent pole flux reversal permanent magnet (CFRPM) machine, which features more iron poles than PM poles under one stator tooth, is proposed to improve the torque density. The proposed CFRPM machine with 6 slots and 16 poles (6S16P) is compared with a 12S16P FRPM machine and its consequent pole type, as well as a conventional 6S4P surface-mounted PM (SPM) machine. The proposed 6S16P CFRPM shows the highest torque among the four machines, together with the highest torque per PM volume. For a fair comparison with the 12S16P FRPM machine and its consequent pole type, the torque ripple of the proposed 6S16P CFRPM is suppressed by using two-step skewed rotor. After employing 4° two-step skewed rotor, while exhibits comparable torque ripple, the proposed 6S16P CFRPM still has 43% and 22% higher torque compared with the 12S16P FRPM machine and its consequent pole type. [ABSTRACT FROM AUTHOR]

In this article, spoke array permanent magnet (PM) flux reversal machines (SAPM FRM), which feature spoke array PMs distributed along the stator inner surface, are proposed to improve the torque density. Compared with the conventional surface mounted PM flux reversal machine (SPM FRM), the proposed SAPM FRM can produce about 100% larger torque with negligible torque ripple, as well as higher efficiency and higher power factor. Two prototypes have been built and tested to validate the theoretical analyses. [ABSTRACT FROM AUTHOR]

This study investigated the use for bamboo vinegar powder as an antibiotic alternative in the diet of growing–finishing pigs by examining their digestive bacterial communities. Forty-five Duroc × Landrace × Yorkshire growing–finishing pigs were randomly allocated to five diet groups: 0%, 0.5%, 1.0%, or 1.5% bamboo vinegar levels and antibiotics. After 37 days, the digesta in duodenum of four pigs from each treatment were analyzed for their bacterial community compositions using 16S rRNA gene sequencing. The addition of 1.5% bamboo vinegar powder had an effect on the intestinal microflora most similar to that of antibiotics, indicating its potential to promote the growth and development of finishing pigs. We also found the 1.5% bamboo vinegar powder group to have an increased abundance of Firmicutes/Bacteroidetes compared with the other bamboo vinegar powder groups, which may enhance the ability of the host to absorb food energy and store more body fat. Additionally, the effects of bamboo vinegar powder on promoting the abundances of Lactobacillus and Thalassospira and on inhibiting Streptococcus and Prevotella growth revealed it may play an important role in animal production. Moreover, functional predictions of microbes via PICRUSt indicated that feed supplemented with 1.5% bamboo vinegar powder could promote many vital metabolic pathways. [ABSTRACT FROM AUTHOR]

To determine the effect of heat stress (HS) on adipose tissue metabolome, a combination of liquid chromatography-mass spectrometry-based metabolomics profiling approaches was applied to characterize changes of metabolite classes in adipocytes differentiated in culture (in vitro) and mesenteric adipose tissue of pigs exposed to HS (in vivo). Effect of HS on the composition of individual fatty acids in cultured adipocytes, mesenteric adipose tissue, and serum of animals was also investigated using gas chromatography analysis. In vitro, preadipocytes were differentiated either under control (37 °C) or HS (41.5 °C) temperature for 9 d. For the animal experiment, pigs were kept either in control (Con) environment (20 °C) with ad libitum feed intake, HS (35 °C) temperature with ad libitum feed intake (HS), or at 20 °C with pair feeding to the HS pigs. In cultured cells, HS increased triglyceride and decreased monoacylglycerol (P < 0.05) species accumulation compared with control. Phosphatidylinositol and phosphatidylserine were increased by HS, whereas phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol were decreased relative to control (P < 0.05). Heat-stressed adipocytes in culture also had higher concentrations of saturated (SFA) and monounsaturated fatty acids (P < 0.05) relative to control. Pathways of proline and biotin metabolism were elevated (P < 0.05) by HS in adipocytes. The metabolomics signatures in adipocytes cultured under HS indicates that pathways centered around diacylglycerol metabolism are impacted by HS. In adipose tissue from animals in the HS treatment, there was increased (P < 0.05) abundance of 4,8 dimethylnonanoyl carnitine (P < 0.05). Heat-stressed animals also had higher (P < 005) serum linoleic, total polyunsaturated fatty acids, and decreased total SFA than PF (P < 0.05). These results indicate that HS elevates lipogenic pathways while suppressing fatty acid oxidation and demonstrate the usefulness of metabolomics analysis as a tool for determining the impact of HS in pig tissues. [ABSTRACT FROM AUTHOR]

As the city's soft power, culture is the basic core of urban competitiveness. The spatial concentration of cultural facilities can show the development status of the city's cultural functions in the spatial layout. In this paper, POI data of Baidu Maps were used to conduct kernel density analysis and comprehensive evaluation of the spatial distribution of cultural facilities in Shenzhen; mean center point method was used to measure the degree of deviation between Shenzhen population centers and cultural facilities centers; the nearest distance method was used to measure the spatial distribution of cultural facilities space and the accessibility to geometric centers of streets. The results showed that: among the four types of cultural facilities in Shenzhen, libraries were the most concentrated, accounting for 63% of the total number of cultural facilities, followed by culture and arts centers, museums, and galleries; there was a great disparity in the number of cultural facilities in various districts and subdistricts in Shenzhen, with a clear agglomeration effect in space; from the district level, cultural facilities spatially distributed from the southwest to the northeast by three gradients; from the street level, cultural facilities showed the distribution pattern of "decreasing from west to east" and a high degree of recognition for convenient transportation; the cultural facilities inside the Shenzhen Special Economic Zone (except Yantian District) were more reasonable in spatial distribution, and the number of people served was more than that of cultural facilities outside the Shenzhen Special Economic Zone, while residents outside the Shenzhen Special Economic Zone enjoyed significantly more cultural facilities than that inside the Shenzhen Special Economic Zone; the goal of the "10-min cultural circle" in Shenzhen had been initially completed, that is, residents could reach 72.41% of the streets with cultural facilities within a 10-min walk, but there were still 50% districts and 5.1% streets that were equipped with unreasonably distributed cultural facilities or few cultural facilities. [ABSTRACT FROM AUTHOR]

Heat stress (HS) leads to increased lipid storage and expression of cytosolic phosphoenolpyruvate carboxykinase (PCK1) in pig adipocytes. However, the importance of PCK1 activation and lipid storage in the adaptive response to HS is unknown. Therefore, in vitro experiments were conducted to investigate the effect of PCK1 inhibition with 3-mercaptopicolinic acid (3MPA) on lipid storage and adipocyte response during HS. In vitro culture of adipocytes under HS (41.0 °C) increased (P < 0.05) triacylglycerol accumulation compared with control (37.0 °C). HS increased (P < 0.05) reactive oxygen species level and 3MPA further upregulated (P < 0.05) its level. Heat shock protein 70 (HSP70) gene expression was induced (P < 0.05) by HS compared to control, and PCK1 inhibition with 3MPA attenuated (P < 0.05) its induction by HS. The endoplasmic reticulum (ER) stress markers, C/EBP homologous protein (CHOP) was also upregulated by HS and 3MPA further upregulated (P < 0.05) CHOP mRNA level. These results suggest that with inhibition of PCK1 during HS, in vitro cultured adipocytes were less able to induce adaptive responses such as upregulation of HSP70 and triglycerides, and this exacerbated ER stress during HS. Thus, PCK1 may function to alleviate ER stress that occurs during HS. [ABSTRACT FROM AUTHOR]

To realize the discrimination of β particles and γ photons in complex environments, a phoswich detector based on the pulse shape discrimination method was designed. The scintillators EJ-260 and CsI(Tl) are selected for deposition of β particles and γ photons, respectively. The size of the detector was determined by simulating the detector by the Monte Carlo program G eant 4. The detector was assembled for testing, and the pulses were collected using a high-frequency digital capture card. After smoothing the pulse and correcting the rise time, the respective energy spectra of β particles and γ photons in the mixed environment were obtained. The figure of merit value of phoswich detector was 6.35, which can effectively discriminate β particles and γ photons. Results indicate the phoswich detector can be used for the β − γ discrimination in the mixed fields and obtain the respective energy spectrum. • A phoswich detector based on the pulse shape discrimination method was designed. • The size of the detector was determined by simulating the detector by the Monte Carlo program GEANT4. • The respective energy spectra of β particles and γ photons in the mixed environment were obtained. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective agent against apoptosis in many cell types. The mechanism by which HGF protects primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in mature endothelial cells. In this study, we aimed to explore whether FOXO1 and FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1 and FOXO3a are equally important in this process by regulating the expression of Bim, PUMA, FasL, and TRAIL. [ABSTRACT FROM AUTHOR]

Objective: To analyze current evidence comparing the safety and outcomes of regional and global ischemia for partial nephrectomy (PN). Materials and Methods: A systematic search of the PubMed and Web of Science databases was conducted in May 2014 to identify studies comparing the safety and outcomes of regional and global ischemia for PN. A systematic review and meta-analysis was also performed. Results: Six retrospective observational studies were selected for the analysis, including 363 patients who underwent PN (162 regional ischemia and 201 global ischemia cases). Operation times were not statistically different [weighted mean difference (WMD) = 20.35 min, 95% CI: -0.28-40.97, p = 0.05], but estimated blood loss was significantly higher in the regional ischemia group (WMD = 52.04 ml, 95% CI: 14.30-89.78, p = 0.007) than in the global ischemia group. Complication rates [odds ratio (OR) = 1.16; 95% CI: 0.63-2.15, p = 0.63] and blood transfusion rates (OR = 1.85; 95% CI: 0.86-4.01, p = 0.12) of the two groups were not significantly different. The regional ischemia group showed better postoperative renal function (WMD = 4.23 ml/min, 95% CI: 2.61-5.85, p < 0.00001) than the global ischemia group, and all cases in the regional ischemia group showed negative margins. Conclusions: Regional ischemia is as safe to perform as global ischemia, and the former leads to better postoperative renal functions than the latter. These findings support the application of regional ischemia for PN. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Particle discrimination technology is widely used in multiple fields. Phoswich detectors are detectors based on pulse shape discrimination technology that combine two or more scintillators with different time characteristics to achieve particle discrimination. This study focuses on a phoswich detector composed of BGO/EJ-260 and uses machine learning algorithms to classify pulses to achieve β / γ classification. Experiments were conducted using the 137Cs radioactive source and three different models were trained: Gaussian mixture model, support vector machine, and convolutional neural network. The classification capabilities of the three models were tested and the results were discussed. The calculation results show that all three models achieved pulse data classification and accurately marked most pulses to the correct category. The classification ability of low-amplitude pulses by the Gaussian mixture model and support vector machine is limited by data processing, while the convolutional neural network model avoids this problem. For higher amplitude pulses, all three models showed that high classification accuracy, with the convolutional neural network model achieving a classification accuracy of 96.1% in the training set, achieves the expected goal. [ABSTRACT FROM AUTHOR]

Abstract: In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, twenty-six new piperine-based hydrazone derivatives were synthesized from piperine, an alkaloid isolated from Piper nigrum Linn. The single-crystal structures of 6c, 6q and 6w were unambiguously confirmed by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo. Especially compounds 6b, 6i and 6r, the final mortality rates of which, at the concentration of 1mg/mL, were 62.1%, 65.5% and 65.5%, respectively, exhibited more pronounced insecticidal activity compared to toosendanin at 1mg/mL, a commercial botanical insecticide isolated from Melia azedarach. It suggested that introduction of the substituents at the C-2 position on the phenyl ring of the hydrazone derivatives was important for their insecticidal activity. [Copyright &y& Elsevier]

• Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. • STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection. • The absence of STAT1 results in increased internalization of PDCoV. • PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1. Porcine deltacoronavirus (PDCoV) is an enteropathogen found in many pig producing countries. It can cause acute diarrhea, vomiting, dehydration, and death in newborn piglets, seriously affecting the development of pig breeding industries. To date, our knowledge of the pathogenesis of PDCoV and its interactions with host cell factors remains incomplete. Using Co-IP coupled with LC/MS-MS, we identified 67 proteins that potentially interact with PDCoV in LLC-PK1 cells; five of the identified proteins were chosen for further evaluation (IMMT, STAT1, XPO5, PIK3AP1, and TMPRSS11E). Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. In these knockdown cells lines, only STAT1KD resulted in a significantly greater virus yield. Knockdown of the remaining four genes resulted, to varying degrees, in a lower virus yield that wild-type LLC-PK1 cells. The absence of STAT1 did not significantly affect the attachment of PDCoV to cells, but did result in increased viral internalization. Additionally, PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1 (IFIT1, IFIT2, RADS2, ISG15, MX1, and OAS1) while knockdown of STAT1 resulted in a greater than 80 % decrease in the expression of all six ISGs. Our findings show that STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection. [ABSTRACT FROM AUTHOR]

Researchers have developed a new nanotechnology-based approach for treating glioblastoma, a type of brain tumor. The approach involves the synthesis of self-assembled nanoparticles made of bardoxolone methyl, which have shown the ability to penetrate brain tumors and effectively inhibit glioblastoma growth. This promising method could potentially improve outcomes for patients with glioblastoma. The study was conducted by a team of researchers including Qianxue Chen, Xuan Xiao, Shenqi Zhang, and others. [Extracted from the article]

In this article, a new dual-permanent magnet spoke-type flux-reversal machine (dual-PM SFRM) for direct-drive applications is proposed. Tangentially magnetized permanent magnets (PMs) sandwiched with iron poles are set in stator slots. To increase the torque density within the geometric restrictions, PMs are introduced in the rotor as well and magnetized radially to form a consequent-pole rotor. Global optimizations are conducted and comparisons are made on torque, torque ripple, and torque/PM volume with the existing single-PM SFRM. It is found that the proposed dual-PM SFRM can produce 22.6% larger torque with an optimal PM volume and a 17.5% larger torque with the same PM volume compared with the single-PM counterpart. Moreover, major magnetic field space harmonics are derived analytically and verified by finite-element analysis (FEA) and the torque components produced by the working harmonics are calculated and compared in terms of different stator/rotor pole number combinations. Comparisons are made on back electromotive force, cogging torque, torque performance, and efficiency between dual-PM SFRM and conventional flux-reversal machine. The influence of different stator configurations, i.e., the slot opening, the iron bridge, and the unequal tooth, on torque performance in the proposed dual-PM SFRM has been studied and highlighted. A prototype has been built and tested to validate the FEA calculations. [ABSTRACT FROM AUTHOR]

Porcine deltacoronavirus (PDCoV) is a newly emerging enteric pathogen in swine that causes diarrhea in neonatal piglets and creates an additional economic burden on porcine industries in Asia and North America. In this study, a PDCoV isolate, CHN-SC2015, was isolated from Sichuan Province in southwest China. The isolate was characterized by a cytopathic effect, immunofluorescence, and electron microscopy. CHN-SC2015 titers in LLC-PK cells ranged from 104.31 to 108.22 TCID50/mL during the first 30 passages. During serial passage, 11 nucleotide mutations occurred in the S gene, resulting in nine amino acid changes. A whole genome sequencing analysis demonstrated that CHN-SC2015 shares 97.5%–99.1% identity with 59 reference strains in GenBank. Furthermore, CHN-SC2015 contained 6-nt deletion and 9-nt insertion in the ORF1ab gene, 3-nt deletion in the S gene and 11-nt deletion in its 3′UTR compared with other reference strains available in GenBank. A phylogenetic analysis showed that CHN-SC2015 is more closely related to other PDCoV strains in China than to the strains from Southeast Asia, USA, Japan, and South Korea, indicating the diversity of genetic relationships and regional and epidemic characteristics among these strains. A recombination analysis indicated that CHN-SC2015 experienced recombination events between SHJS/SL/2016 and TT-1115. In vivo infection demonstrated that CHN-SC2015 is highly pathogenic to sucking piglets, causing diarrhea, vomiting, dehydration, and death. Virus was shed daily in the feces of infected piglets and upon necropsy, was found distributed in the gastrointestinal tract and in multiple organs. CHN-SC2015 is the first systematically characterized strain from southwest China hitherto reported. Our results enrich the body of information on the epidemiology, pathogenicity and molecular evolution associated with PDCoV. [ABSTRACT FROM AUTHOR]

Alternaria alternata, as a main decay fungus of goji berry, can produce mycotoxins such as alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA). Carvacrol (CVR) has exhibited a broad-spectrum antifungal activity in vitro. We assumed that CVR can also be applied to control Alternaria rot on goji berries and mycotoxins produced by the pathogens. To investigate whether CVR impacts the accumulation of mycotoxins and cell membrane damage of A. alternata, the antifungal activity of CVR on the fungal growth and mycotoxin production was evaluated in this study. The results showed that the minimum inhibitory concentration (MIC) of CVR against A. alternata was 0.12 µL/mL. Meanwhile, the destruction of plasma membrane integrity, cytoplasmic leakage, intracellular oxidative damage, and inhibitory effect in vivo were also observed in A. alternata treated with CVR. Moreover, CVR significantly reduced the accumulation of AOH, AME, and TeA. Transcriptomic profiling was performed by means of comparative RNA-Seq analysis to research the gene expression level of A. alternata, which attested to significant changes in nitrogen metabolism, carbon utilization, fatty acid oxidation, and antioxidant enzymes in CVR-treated A. alternata. This study suggests a new understanding of the molecular mechanism of response to CVR treatment in A. alternata, indicating that CVR is a novel antifungal agent with the potential to be applied to various fungi. [ABSTRACT FROM AUTHOR]

3D imaging techniques are facilitating autonomous vehicles to build intelligent systems. Optical phased arrays (OPAs) featured by all solid‐state configurations are becoming a promising solution for 3D imaging. However, the majority of state‐of‐art OPAs commonly suffer from severe power degradation at the edge of the field of view (FoV), resulting in limited effective FoV and deteriorating 3D imaging quality. Here, the chained grating antenna and the vernier concept is synergized to design a novel OPA for realizing a record wide 160°‐FoV 3D imaging. By virtue of the chained antenna, the OPA exhibits less than 3‐dB beam power variation within the 160°FoV. In addition, two OPAs with different pitches are integrated monolithically to form a quasi‐coaxial Vernier OPA transceiver. With the aid of a flat beam power profile provided by the chained antennas, the OPA exhibits uniform beam quality at an arbitrary steering angle. The superior beam steering performance enables the OPA to accomplish 160° wide‐FoV 3D imaging based on the frequency‐modulated continuous‐wave (FMCW) LiDAR scheme. The ranging accuracy is 5.5‐mm. Moreover, the OPA is also applied to velocity measurement for 4D sensing. To the best of knowledge, it is the first experimental implementation of a Vernier OPA LiDAR on 3D imaging to achieve a remarkable FoV. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that provides multiple health benefits. CUR can reduce the toxicities induced by mycotoxins, but the underlying molecular mechanisms remain largely unknown. To explore the effects of CUR on OTA toxicity and identify the key regulators and metabolites involved in the biological processes, we performed metabolomic and transcriptomic analyses of livers from OTA-exposed mice. We found that CUR can alleviate the toxic effects of OTA on body growth and liver functions. In addition, CUR supplementation significantly affects the expressions of 1584 genes and 97 metabolites. Integrated analyses of transcriptomic and metabolomic data showed that the pathways including Arachidonic acid metabolism, Purine metabolism, and Cholesterol metabolism were significantly enriched. Pantothenic acid (PA) was identified as a key metabolite, the exogenous supplementation of which was observed to significantly alleviate the OTA-induced accumulation of reactive oxygen species and cell apoptosis. Further mechanistical analyses revealed that PA can downregulate the expression level of proapoptotic protein BAX, enhance the expression level of apoptosis inhibitory protein BCL2, and decrease the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). This study demonstrated that CUR can alleviate the adverse effects of OTA by influencing the transcriptomic and metabolomic profiles of livers, which may contribute to the application of CUR in food and feed products for the prevention of OTA toxicity. [ABSTRACT FROM AUTHOR]

Introduction: Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. Methods: This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. Results: The VPU group recorded significantly lower MSPP incidence (1–12 months), PONV, and postoperative dizziness (1–10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. Conclusions: The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model. [ABSTRACT FROM AUTHOR]

By structural modification of piperine, some piperine-based phenylsulfonylhydrazone derivatives exhibited an unprecedented and potent narcotic activity against the oriental armyworm, Mythimna separata (Walker). The ND50 values of compounds 6c and 6e against the third-instar larvae of M. separata, which were more potent than those of wilfortrine and wilforgine, were 0.0074 μmol (after 3.5 h), and 0.0075 μmol (after 7 h) per larvae, respectively. By transmission electron microscope, it demonstrated that mitochondria were vacuolated and swollen in the ganglion cell of M. separata after treatment with 6c. More importantly, 6c selectively displayed the inhibition activity on acetylcholine esterase (AchE) of M. separata. This work paved the way for further studying the insecticidal mechanism of 6c as a new and promising botanical narcotic agent. [ABSTRACT FROM AUTHOR]

The insecticidal activity of new piperine-based hydrazine derivatives (III), (V)/(VI) is evaluated against pre-third-instar larvae of Mythimna separata Walker in vivo. [ABSTRACT FROM AUTHOR]

Zirconium alloy is used as nuclear fuel cladding in nuclear reactors because it offers the merits of low neutron absorption cross-section, high corrosion resistance, excellent mechanical properties, and satisfactory creep resistance under operating conditions. However, the cladding experiences uniaxial and multiaxial stresses, which can lead to material failure due to the ratcheting effect. In this context, in this study, a series of uniaxial and multiaxial ratcheting tests were conducted on zirconium alloy tubes at 350 °C. The experimental results show that the temperature significantly affects the properties of zirconium alloy, and its ductility at 350 °C is poorer than that at room temperature. The axial ratcheting strain rate greatly increases with increase in the mean stress, stress amplitude, and peak stress holding time. In addition, the loading history also greatly affects the uniaxial and multiaxial ratcheting of zirconium tubes. A lower stress level after a loading history with higher stress level leads to shakedown of the ratcheting, while a higher mean stress after a loading history with lower mean stress brings down the ratcheting strain rate. The existence of a constant internal pressure significantly retards the failure of the zirconium tubes. [ABSTRACT FROM AUTHOR]

The anti-Compton phoswich (ACP) detector, which is composed of multiple scintillators with one photomultiplier tube, takes into account the Compton suppression function and portability, and therefore, a discussion on how to design its shape to improve the performance of the detector has become necessary. Based on an ACP detector using a well-typed LaBr3:Ce/NaI:Tl composite scintillator that has been developed in the laboratory in early work, this study uses GEANT4 to simulate and study the influence of the change in the shape and size of the secondary scintillator on the performance of the detector, such as the Compton suppression ratio, the energy resolution, and the full-energy peak (FEP) loss. In the course of the study, we mainly investigate the variation of the performance of the detector in two ways. First, the inclination angle of the truncated cone is gradually changed to compare its FEP address and Compton suppression ratio. Second, the case of the well-shaped and annular-shaped secondary scintillators is compared, respectively, to find out their impact on energy resolution and FEP address. The final results show that, compared with the ACP detector using a φ75 × 90 mm2 LaBr3:Ce/NaI:Tl cylindrical composite scintillator, a truncated cone-shaped composite scintillator of 0.8 inclination may have an equivalent 137% light yield (137% signal-to-noise ratio), a Compton suppression ratio of 89.62% (at 662 keV), 89.98% FWHM energy resolution, and a volume reduction of 36.74%, which means that the weight of the detector is reduced by 2.107 kg. [ABSTRACT FROM AUTHOR]

This paper examined the impact of the isotope effect on the lattice structure of monocrystalline silicon, as well as the defects caused by proton irradiation. First, by using the molecular dynamics simulation, the number of point defects of monocrystalline silicon exposed to protons was calculated, and the number of stable defects in 30Si was 11%–14% lower than that in 28Si. Second, the structures of various isotopes at 300 K were simulated through ab initio molecular dynamics simulations based on the density functional theory. In addition, the thermal stability of the two structures was determined. The results indicated that pure 30Si had superior radiation resistance to pure 28Si, which suggested a new idea for the radiation resistance enhancement of silicon materials. [ABSTRACT FROM AUTHOR]

The excessive intake of caffeine might adversely affect health, so decaffeinated food becomes a hot topic for investigation. Penicillium simplicissimum 4–17 was inoculated into sun-dried green tea for the pile fermentation (QZTWP) at a pilot scale to develop decaffeinated Qingzhuan tea (QZT). Through comparisons in chemical compositions, fungal community structure and sensory qualities, the results showed that after 21-d pile fermentation, most quality components in QZTWP were same or similar to those in naturally fermented QZT, except caffeine. Caffeine decreased nearly 50%, and some quality components were better in QZTWP than those in naturally fermented QZT. The addition of P. simplicissimum 4–17 couldn't change the dominant strains in the pile fermentation of QZT, but was conducive to increasing the amount of Saccharomyces , Candida , and Penicillium and to inhibiting the unfavorable strains. The results confirmed that P. simplicissimum 4–17 not only contributed high caffeine degradation ability of pilot fermentation of QZT, but also helped to improve the comprehensive quality of QZT. It means that there is a great potential of P. simplicissimum 4–17 for industrial production of decaffeinated QZT. • P. simplicissimum effectively decreased caffeine in pile fermentation of Qingzhuan tea at pilot scale. • The inoculation of P. simplicissimum inhibited the harmful fungi in the pile fermentation. • The inoculation of P. simplicissimum was conducive to increasing the amount of Saccharomyces , Candida, and Penicillium. • P. Simplicissimum has an great potential for industrial production of decaffeinated Qingzhuan tea. [ABSTRACT FROM AUTHOR]

Background & Aims: Disruption of lipid metabolism is largely linked to metabolic disorders, such as hypercholesterolemia (HCL) and liver steatosis. While cholesterol metabolic re‐programmers can serve as targets for relevant interventions. Here we explored the dietary conjugated linoleic acids (CLA)‐induced HCL in mice and the molecular regulation behind it. Methods: A high dose of CLA supplementation in the diet was used to induce HCL in mice and was found to cause a hyper‐activated cholesterol biosynthesis programme in the liver, leading to cholesterol metabolism dysregulation. The effects of a small‐molecule drug targeting PPARα, i.e., GW6471 were studied in vivo in mice fed diets with CLA supplementation for 28 days, and in primary hepatocytes derived from HCL‐mice in vitro. Results: We demonstrate that CLA induced HCL and liver steatosis through multiple pathways. Among which was the PPARα‐mediated cholesterogenesis. It was found to cooperate with SREBP2 via binding to Hmgcr and Dhcr7 (genes encoding key enzymes of the cholesterol biosynthetic pathway) and recruits the histone marks H3K27ac and H3K4me1 and cofactors. PPARα inhibition disrupts its physical association with SREBP2 by blocking cobinding of PPARα and SREBP2 to the genomic DNA response element. We showed that NR RORγ functions as an essential mediator that facilitates the interaction of PPARα and SREBP2 to modulate the cholesterol biosynthesis genes expression. Conclusions: Our study unravels that the small‐molecule compound GW6471 exerts an attractive therapeutic effect for CLA‐induced HCL, involving multiple pathways with the "PPARα‐RORγ‐SREBP2" being a potential complex player in this hepatic cholesterol biosynthesis programming. [ABSTRACT FROM AUTHOR]

Pathological cardiac remodelling, including cardiac hypertrophy and fibrosis, is a key pathological process in the development of heart failure. However, effective therapeutic approaches are limited. The β-adrenergic receptors are pivotal signalling molecules in regulating cardiac function. G-alpha interacting protein (GAIP)-interacting protein, C-terminus 1 (GIPC1) is a multifunctional scaffold protein that directly binds to the C-terminus of β1-adrenergic receptor (β1-adrenergic receptor). However, little is known about its roles in heart function. Therefore, we investigated the role of GIPC1 in cardiac remodelling and its underlying molecular mechanisms. Pathological cardiac remodelling in mice was established via intraperitoneal injection of isoprenaline for 14 d or transverse aortic constriction surgery for 8 weeks. Myh6-driving cardiomyocyte-specific GIPC1 conditional knockout (GIPC1 cKO) mice and adeno-associated virus 9 (AAV9)-mediated GIPC1 overexpression mice were used. The effect of GIPC1 on cardiac remodelling was assessed using echocardiographic, histological, and biochemical analyses. GIPC1 expression was consistently reduced in the cardiac remodelling model. GIPC1 cKO mice exhibited spontaneous abnormalities, including cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, AAV9-mediated GIPC1 overexpression in the heart attenuated isoproterenol-induced pathological cardiac remodelling in mice. Mechanistically, GIPC1 interacted with the β1-adrenergic receptor and stabilised its expression by preventing its ubiquitination and degradation, maintaining the balance of β1-adrenergic receptor/β2-adrenergic receptor, and inhibiting hyperactivation of the mitogen-activated protein kinase signalling pathway. These results suggested that GIPC1 plays a cardioprotective role and is a promising therapeutic target for the treatment of cardiac remodelling and heart failure. [Display omitted] [ABSTRACT FROM AUTHOR]

Scintillation phoswich detectors can be used for particle discrimination and Compton suppression, and their function is based on pulse shape discrimination (PSD) methods. The conventional PSD methods mainly including Rise Time Discrimination (RTD), Rise and Decay time discrimination (R&D), Constant Time Discrimination (CTD), etc., but linear PSD methods have their limitations in processing pulse signals. Neural network tools can achieve nonlinear output by adjusting the weights between neurons during the training, which are suitable for identifying nonlinear signals generated by detectors. The self-organizing feature mapping (SOM) is the most commonly used clustering neural network, which can cluster signals based on their similarity through competitive training of neural networks without prior data. In this study, 3 SOM networks with different size are trained, and after comparison with the single LaBr 3 :Ce detector, the total accuracy of the phoswich detector using the SOM neural network for discrimination reaches over 99.5%, which is a 7.59% increase in accuracy compared to the RTD method, and the peak-to-total ratio (P/T) is improved by 1.07%. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the phytochemical structure of Cedrus deodara, an evergreen tree growing on the slopes of the Himalayas. The study isolates and elucidates the structure of phenylpropanoid and nine compounds, such as Shikimic Acid, Dibutylphthalate and Protocatechuic Acid, obtained from the pine needles of Cedrus deodara. Result shows that the compound 1-[3-(4-hydroxyphenyl)-2-propenoate]-α-D-glucopyranoside was identified.

An entrance window surrounded phoswich design of GAGG:Ce/CsI:Tl has been implemented for a low-background and Compton-suppressed detector. Not as the common phoswich detector does, the GAGG:Ce scintillator with the well-type CsI:Tl scintillator entrance window surrounded makes the efficient large-angle Compton suppression. This design also makes results measured by the phoswich detector have no degradation compared with the single GAGG:Ce detector. The Compton continuum and other backgrounds are reduced by identifying the gamma-ray energy depositions in different scintillators using the real-time rise time discrimination (RTD) method. The background rate is suppressed approximately 74%. The peak-to-total (P/T) ratio at 137Cs and 60Co point sources are 0.769 and 0.561, respectively. The Compton suppression is highly efficient at all the energy range of Compton continuums. The reduction of the Compton continuum and other backgrounds and the improvement of the P/T ratio will greatly expand the application range of the GAGG:Ce detector in low-intensity measurements. [ABSTRACT FROM AUTHOR]

Simple Summary: Porcine epidemic diarrhea virus seriously threatens the health of suckling pigs. In this study, global mapping of H3K4me3 and transcriptomic analyses in the jejunum of porcine epidemic diarrhea virus (PEDV)-infected and healthy piglets were performed by using chromatin immunoprecipitation sequencing and RNA-seq techniques. A subset of genes and H3K4 trimethylation (H3K4me3) histone modifications that are associated with PEDV infections were identified. The results revealed previously unknown and intriguing elements involved in the regulation of genes responsive to PEDV infections, which may aid in identifying key regulators and genetic resistant markers for PEDV infections. Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses. [ABSTRACT FROM AUTHOR]

As one of the detectors with superior performances, the Compton continuum in the spectra of the Cerium-doped Lanthanum 3-Bromide (LaBr 3 :Ce) detector should be suppressed for better performances. A compacted LaBr 3 :Ce/NaI:Tl phoswich detector has been designed to reduce the Compton continuum and improve the peak-to-total (P/T) ratio of the photopeaks. The LaBr 3 :Ce scintillator is surrounded by a well-type NaI:Tl scintillator and is coupled to a single photomultiplier tube (PMT). The Compton continuum is reduced by identifying the gamma-ray energy depositions in different scintillators using the real-time rise time discrimination (RTD) method. A Geant4 code with actual geometry was performed to simulate the suppressed and unsuppressed spectra. The peak efficiency of total energy at 1332 keV and 662 keV is 1.58% and 2.75%, the peak to total ratio at 137Cs point source and 60Co point source are 0.545 and 0.367, respectively. The reduction of the Compton continuum and the improvement of the P/T ratio will greatly expand the application range of the LaBr 3 : Ce detector in low-intensity measurements. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a myocardial injury caused by coronary thrombosis or persistent ischemia and hypoxia. Due to its high morbidity and mortality, a safer and more effective treatment strategy is urgently needed. Daming capsule (DMC), a hypolipidemic drug, reportedly exerts cardioprotective effects in clinical and basic research, although its protective mechanism remains unknown. To investigate the mechanism underlying DMC-mediated improvement of cardiac function post-MI, C57/BL6 mice subjected to coronary artery ligation were administered DMC for 4 weeks. Our data demonstrated that DMC significantly improved cardiac structure and function compared to the saline group. Moreover, DMC inhibited inflammatory response and oxidative stress and improved mitochondrial structure and function in MI mice and hypoxia-stressed cardiomyocytes. Next, our research proved that DMC increased the expression of mitophagy receptor NLRX1. Interestingly, with the administration of DMC and siNLRX1, NLRX1 expression, mitochondria and lysosome colocalization, and mitochondrial membrane potential decreased, while mitochondrial ROS accumulation increased, suggesting that DMC promoted mitophagy to improve mitochondrial function via NLRX1 regulation. Further analysis showed that DMC activated the SIRT1/AMPK signaling pathway in vivo and in vitro. Our data showed that SIRT1 knockdown downregulated NLRX1 expression, leading to structural damage and functional impairment in mitochondria, as well as increased oxidative stress, inflammatory response, and decreased cardiac function in MI mice. Collectively, our findings reveal that DMC improves cardiac function post-MI by increasing mitophagy and inhibiting oxidative stress and inflammotory response in cardiomyocytes through the SIRT1/AMPK signaling pathway. [Display omitted] • For the first time, we demonstrate that DMC promotes mitophagy, and reduces oxidative stress and inflammation induced by MI. • The cardioprotective effect of DMC may regulate mitophagy through the SIRT1/AMPK signaling pathway. • DMC is a promising drug for treating cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract: To find new natural products-based insecticidal agents, and substantially extend our previous work, we have designed and stereoselectively synthesized 4α-acyloxy-2α/β-bromopodophyllotoxin derivatives from podophyllotoxin. Interestingly, 4α-acyloxy-2α-bromopicropodophyllotoxins were easily converted to a more rigid compound 14 by an intramolecular Friedel–Crafts alkylation reaction in the presence of BF3·Et2O when the reaction time was prolonged to 4–18 h. Compounds 5g, 6h, 6i, and 14 displayed the more promising and pronounced insecticidal activity than toosendanin, a commercial insecticide derived from Melia azedarach, against the pre-third-instar larvae of Mythimna separata. [Copyright &y& Elsevier]

Two new myricetin glycosides, myricetin-3- O-(6″- O- E- p-coumaroyl)- α- D-glucocopyranoside ( 1) and 3′,5′-di- O-methylmyricetin-3- O-(6″- O-acetyl)- α-D-glucopyranoside ( 2), and three known flavonoids, myricetin ( 3), cedrin ( 4), and 2 R,3 R-dihydromyricetin ( 5), were isolated from the pine needles of Cedrus deodara. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidence. [ABSTRACT FROM AUTHOR]

The article presents research which examined the anticancer constituents of ethyl acetate extract from euphorbia helioscopia. Topics covered include the distribution of the plant in the different parts of China. Also mentioned is the importance of the plant extract to prevent colorectal cancer cell lines.

This paper presents three novel configurations of single-phase (SP) short-stroke (SS) tubular permanent magnet oscillating machines (TPMOMs) with partitioned stator (PS), termed PS-SPSS-TPMOMs. The machine structures are described and the influence of permanent magnet pole alignment with either stator slot or stator tooth is investigated. It is found that the PM poles should be aligned with the stator slots in order to ease the oscillation. The electromagnetic performance of these proposed machines is analyzed and compared. The results show that such machines have the advantages of low mover mass and low magnet eddy current loss, compared with a conventional surface-mounted SPSS-TPMOM. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a common diabetes complication that can cause arrhythmia, heart failure, and even sudden death. Ranolazine is an antianginal agent used to treat chronic stable angina and has been demonstrated as an effective treatment for many cardiovascular diseases. However, the mechanism by which ranolazine alleviates DCM is unclear, motivating this study investigating the effects of ranolazine in DCM. DCM rats were treated with one of three doses of ranolazine (10, 30, and 90 mg/kg/day) for 12 weeks. B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), Notch homolog 1 (NOTCH1), and Neuregulin 1 (NRG1) expression was assayed using western blot and qRT-PCR. Cardiac changes were assayed using echocardiography, CT, HE staining, and Masson's trichrome staining. TUNEL staining and flow cytometry were used to detect cell apoptosis. NOTCH1 inhibitor (DAPT) was used to explore the mechanism of ranolazine. Compared with the DCM group, the ranolazine groups had no obvious weight loss and significantly decreased blood glucose levels. Ranolazine prevented diabetes-caused cardiac injury. Ranolazine also decreased the number of apoptotic cells and altered the expression of apoptosis-related mRNAs and proteins. Ranolazine-induced NOTCH1 activated NRG1 and inhibited the downstream apoptosis-related pathway, while DAPT partially inhibited ranolazine-induced NOTCH1 and NRG1 expression. To our knowledge, this study is the first to demonstrate that ranolazine protects against DCM-induced apoptosis by activating the NOTCH1/NRG1 signaling pathway. Moreover, our study identified new mechanisms involved in DCM. [ABSTRACT FROM AUTHOR]

• The immunodominant region of the porcine deltacoronavirus S protein, is the C-terminal domain of its S1 subunit. • Three truncations of the PDCoV S protein were generated, the C and N-terminal domains of the S1 subunit, and S2 subunit. • Three S protein truncations are capable of inducing PDCoV-neutralizing antibody responses in vivo. • The C-terminal domains of the S1 subunit-specific antisera showed the most potent PDCoV-neutralizing effect. Porcine deltacoronavirus (PDCoV), is an emerging enteropathogenic coronavirus in pigs, that poses a novel threat to swine husbandry worldwide. Crucial to halting PDCoV transmission and infection is the development of effective therapies and vaccines. The spike (S) protein of coronavirus is the major target of host neutralizing antibodies, however the immunodominant neutralizing region in the S protein of PDCoV has not been defined. Here, three truncations of the PDCoV S protein were generated, the N-terminal domain of the S1 subunit (NTD, amino acids (aa) 50–286), the C-terminal domain of the S1 subunit (CTD, aa 278–616), and S2 subunit (aa 601–1087). The proteins were expressed using an E. coli expression system. Polyclonal antisera against the three recombinant proteins were produced in rabbits and mice. All three antisera were able to inhibit PDCoV infection in vitro , as determined by virus neutralization assay, fluorescent focus neutralization assay, and plaque-reduction neutralization. The CTD-specific antisera had the most potent PDCoV-neutralizing effect, indicating that the CTD region may contain the major neutralizing epitope(s) in the PDCoV S protein. Based on these findings, CTD may be a promising target for development of an effective vaccine against PDCoV infection in pigs. [ABSTRACT FROM AUTHOR]