Emergence and genomic chion of Proteus mirabilis harboring blaNDM-1 in Korean companion dogs.

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-ß-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a "one health approach".

Visible-Light-Promoted Selenylation/Cyclization of o-Alkynyl Benzylazides/o-Propargyl Arylazides: Synthesis of Seleno-Substituted Isoquinolines and Quinolines.

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

Effect of Spleen Aminopeptide Oral Lyophilized Powder and Fluticasone/salmeterol Powder Inhaler on Pulmonary Function and Incidence of Adverse Reactions in Children with Cough Variant Asthma.

Background: Cough variant asthma is a prevalent condition among children with chronic cough, significantly impacting their health and well-being. Objective: This study aimed to assess the impact of spleen aminopeptide oral lyophilized powder and fluticasone/salmeterol powder inhaler on pulmonary function and the incidence of adverse reactions in children with cough variant asthma. Methods: A total of 60 children with cough variant asthma admitted to the Pediatric Department of Cangzhou Central Hospital between July 2019 and June 2020 were enrolled in the study. Using the random number table method, they were assigned to either the observation group or the control group, with 30 cases in each group. The control group received treatment with fluticasone/salmeterol powder inhalers, while the observation group received a combination of fluticasone/salmeterol powder inhalers and spleen aminopeptide oral lyophilized powder. After 8 weeks of treatment, various clinical parameters, including forced vital capacity, forced expiratory volume per second/forced vital capacity, peak expiratory flow, fractional exhaled nitric oxide (FeNO), interleukin-4 (IL-4), IL-10, eosinophils in induced sputum, and serum CD4+ and CD8+ levels, were compared between the two groups. Results: The observation group exhibited a higher total effective rate of clinical efficacy compared to the control group [90.00% vs. 63.33%; OR (95% CI) 3.00 (1.01-8.92), P = .048)]. After 8 weeks, the observation group demonstrated higher levels of forced vital capacity, forced expiratory volume per second/forced vital capacity, peak expiratory flow [OR (95% CI) 0.48 (0.26-0.88), P = .017; OR (95% CI) 0.29 (0.14-0.57) 2.57 (1.46-4.52) 0.33 (0.16-0.70), P = .000, .001, .003], IL-10 [OR (95% CI) 0.29 (0.14-0.57), P = .000], and lower levels of FeNO [OR (95% CI) 0.48 (0.26-0.88), P = .017], IL-4, and eosinophils [OR (95% CI) 2.57 (1.46-4.52) 0.33 (0.16-0.70), P = .001, .003] compared to the control group (P < .05). Furthermore, the observation group exhibited higher levels of CD4+ and CD4+/CD8+ compared to the control group [OR (95% CI) 0.41 (0.25-0.67) 0.33 (0.20-0.56) 1.73 (1.18-2.55), P = .000, .000, .001]. Computed tomography measurements revealed significantly lower airway wall thickness, basement membrane thickness, and total airway wall area in the observation group compared to the control group [OR (95% CI) 0.18 (0.10-0.33) 0.23 (0.13-0.41) 0.28 (0.15-0.51), P = .000, .000, .000]. The incidence of adverse reactions did not significantly differ between the groups (6.67% vs. 3.33%; P > .05). Conclusion: The combination treatment of spleen aminopeptide oral lyophilized powder and fluticasone/salmeterol powder inhaler effectively improves lung function, FeNO levels, and airway inflammation, while enhancing cellular and humoral immune function in children with cough variant asthma. These findings have significant clinical implications and warrant further promotion and application of this treatment approach.

An Improved OMP Algorithm for Enhancing the Anti-Interference Performance of Array Antennas.

The demand for precise positioning in noisy environments has propelled the development of research on array antenna radar systems. Although the orthogonal matching pursuit (OMP) algorithm demonstrates superior performance in signal reconstruction, its application efficacy in noisy settings faces challenges. Consequently, this paper introduces an innovative OMP algorithm, DTM_OMP_ICA (a dual-threshold mask OMP algorithm based on independent component analysis), which optimizes the OMP signal reconstruction framework by utilizing two different observation bases in conjunction with independent component analysis (ICA). By implementing a mean mask strategy, it effectively denoises signals received by array antennas in noisy environments. Simulation results reveal that compared to traditional OMP algorithms, the DTM_OMP_ICA algorithm shows significant advantages in noise suppression capability and algorithm stability. Under optimal conditions, this algorithm achieves a noise suppression rate of up to 96.8%, with its stability also reaching as high as 99%. Furthermore, DTM_OMP_ICA surpasses traditional denoising algorithms in practical denoising applications, proving its effectiveness in reconstructing array antenna signals in noisy settings. This presents an efficient method for accurately reconstructing array antenna signals against a noisy backdrop.

Pseudorabies virus kinase UL13 phosphorylates H2AX to foster viral replication.

The DNA damage response (DDR) pathway is critical for maintaining genomic integrity and sustaining organismal development. Viruses can either utilize or circumvent the DDR to facilitate their replication. Pseudorabies virus (PRV) infection was shown to induce apoptosis via stimulating DDR. However, the underlying mechanisms have not been fully explored to date. This study showed that PRV infection robustly activates the ATM and DNA-PK signaling pathways shortly after infection. However, inhibition of ATM, but not DNA-PK, could dampen PRV replication in cells. Importantly, we found that PRV-encoded serine/threonine kinase UL13 interacts with and subsequently phosphorylates H2AX. Furthermore, we found that UL13 deletion largely attenuates PRV neuroinvasiveness and virulence in vivo. In addtion, we showed that UL13 contributes to H2AX phosphorylation upon PRV infection both in vitro and in vivo, but does not affect ATM phosphorylation. Finally, we showed that knockdown of H2AX reduces PRV replication, while this reduction can be further enhanced by deletion of UL13. Taken together, we conclude that PRV-encoded kinase UL13 regulates DNA damage marker γH2AX and UL13-mediated H2AX phosphorylation plays a pivotal role in efficient PRV replication and progeny production.

An Ultrasonic RF Acquisition System for Plant Stems Based on Labview Double Layer Multiple Triggering.

Ultrasound is widely used in medical and engineering inspections due to its non-destructive and easy-to-use characteristics. However, the complex internal structure of plant stems presents challenges for ultrasound testing. The density and thickness differences in various types of stems can cause different attenuation of ultrasonic signal propagation and the formation of different echo locations. To detect structural changes in plant stems, it is crucial to acquire complete ultrasonic echo RF signals. However, there is currently no dedicated ultrasonic RF detection equipment for plant stems, and some ultrasonic acquisition equipment has limited memory capacity that cannot store a complete echo signal. To address this problem, this paper proposes a double-layer multiple-timing trigger method, which can store multiple trigger sampling memories to meet the sampling needs of different plant stems with different ultrasonic echo locations. The method was tested in experiments and found to be effective in acquiring complete ultrasonic RF echo signals for plant stems. This approach has practical significance for the ultrasonic detection of plant stems.

Hexachlorophene, a selective SHP2 inhibitor, suppresses proliferation and metastasis of KRAS-mutant NSCLC cells by inhibiting RAS/MEK/ERK and PI3K/AKT signaling pathways.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for 35% of the genetic alterations in non-small cell lung cancer (NSCLC). The Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is closely involved in RAS downstream pathways and development of many tumors by affecting cell proliferation, differentiation, and immunity. Targeting SHP2 with small molecules may be a promising avenue for the treatment of KRAS-mutant (mut) NSCLC. Herein, hexachlorophene (HCP) was identified as a SHP2 inhibitor with an IC50 value of 5.63 ± 0.75 µM through screening of the FDA-approved drug library. HCP specifically inhibited SHP2 rather than other phosphatases. Molecular docking showed that HCP displayed an orientation favorable for nucleophilic attack in the catalytic domain of SHP2. HCP suppressed viability of multiple KRAS-mut and KRAS-wild type cells and induced senescence and apoptosis in KRAS-mut cells. Moreover, HCP reversed epithelial-mesenchymal transition to suppress metastasis in KRAS-mut cells, and inhibited the RAS/MEK/ERK and PI3K/AKT signaling pathways by suppression of SHP2 phosphorylation and formation SHP2/Grb2/Gab1/SOS1 complex. In summary, HCP can act as a specific SHP2 inhibitor to inhibit KRAS-mut NSCLC cell proliferation and metastasis and induce senescence through suppression of the RAF/MEK/ERK and PI3K/AKT pathways. HCP warrants further investigation as a new compound skeleton for the development of selective SHP2 inhibitors for the treatment of NSCLC.

Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISD) has been recommended as a first-line treatment. Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered. We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival and failure-free survival were 87.1±2.5% and 89.3±3.7% (P=0.173) and 86.5±2.6% versus 88.1±3.8% (P=0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft-versus-host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year time points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA-identical related or unrelated donor.

Iterative Synthesis of Inulin-Type Fructooligosaccharides Enabled by Stereoselective ß-d-Fructofuranosylation.

Inulin-type fructooligosaccharides (FOSs) constitute an abundant subgroup of fructans with important biological activities. However, the availability of individual fructooligosaccharides with an accurate structure in high purity and quality remains challenging. We herein report the first iterative synthesis of five inulin-type FOSs with degrees of polymerization ranging from 3 to 7 via highly stereoselective ß-(2 → 1)-d-fructofuranosylation on a gram scale. Central to the synthesis is the decisive use of the 1-O-TIPS-6-O-picoloyl-protected fructofuranosyl thioglycoside donor, which assured the excellent ß-selective glycosylation by the hydrogen-bond-mediated aglycone delivery (HAD).

Relationship between left ventricular mechanical synchrony and left ventricular systolic function: a CZT-SPECT analysis.

BACKGROUND: CZT-SPECT has good agreement in the evaluation of mechanical synchronization compared with conventional SPECT. The aim of this study was to evaluate the correlation between left ventricular mechanical contraction synchrony and left ventricular systolic function by gated myocardial perfusion imaging (GMPI) using cadmium-zine-telluride (CZT) single photon emission computed tomography (SPECT). METHODS: This retrospective study involved 371 patients (239 males and 132 females, mean age 61.06 ± 11.78 years old) who underwent GMPI at the Nuclear Medicine Department of Shanxi Cardiovascular Hospital from January 2020 to August 2020. Systolic synchrony parameters and left ventricular systolic function parameters were calculated via Emory Cardiac Toolbox, including PP, PSD, PHB, HS, HK, EDV, ESV, and LVEF. Based on LVEF value, patients were divided into the severe reduction group (group 1, 127 cases, EF < 35%), moderate reduction group (group 2, 47 cases, 35% ≤ EF < 45%), mild reduction group (group 3, 50 cases, 45% ≤ EF < 50%) and normal group (group 4, 147 cases, EF ≥ 50%). Differences in PP, PSD, PHB, HS and HK among the four groups were compared using one-way ANOVA. Differences between two groups were compared using LSD-t test. The correlation among functional and mechanical contraction synchrony factors were analyzed using Pearson test. RESULTS: PP, PSD, PHB, HS and HK were significantly different among the four groups (F = 5.20, 188.72, 202.88, 171.05, 101.36, P < 0.001). Pairwise comparison tests showed significant differences in PSD and PHB in each two groups, and HS and HK in each two groups except for group 2 and 3 (t = 0.28 and 0.39, both P > 0.001). PP was significantly higher in group 1, relative to group 3 (t = 2.43, P < 0.001) and group 4 (t = 3.67, P < 0.001). Pearson correlation analysis revealed that LVEF negatively correlates with PP, PSD, PHB (r = 0.194, - 0.790, - 0.799, all P < 0.001). HS and HK showed positive correlation for LVEF (r = 0.778 and 0.795, P < 0.001), PSD, PHB and ESV were had good positive correlation (r = 0.778, 0.795, P < 0.001), PSD, PHB and EDV had good positive correlation (r = 0.722, 0.732, P < 0.001). However, PP had poor correlation with EDV (r = 0.095, P > 0.001). HS and HK were negatively correlated with EDV and ESV (r = - 0.700 to - 0.594, P < 0.001). CONCLUSION: CZT SPECT GMPI provided left ventricular mechanical contraction synchrony parameters that correlated well with left ventricular systolic function. Worse left ventricular mechanical contraction synchrony lead to decreased LVEF, making the systolic synchrony parameters valuable in the prediction of left ventricular systolic function.

Detection of Water Changes in Plant Stems In Situ by the Primary Echo of Ultrasound RF with an Improved AIC Algorithm.

The detection of water changes in plant stems by non-destructive online methods has become a hot spot in studying the physiological activity of plant water. In this paper, the ultrasonic radio-frequency echo (RFID) technique was used to detect water changes in stems. An algorithm (improved hybrid differential Akaike's Information Criterion (AIC)) was proposed to automatically compute the position of the primary ultrasonic echo of stems, which is the key parameter of water changes in stems. This method overcame the inaccurate location of the primary echo, which was caused by the anisotropic ultrasound propagation and heterogeneous stems. First of all, the improved algorithm was analyzed and its accuracy was verified by a set of simulated signals. Then, a set of cutting samples from stems were taken for ultrasonic detection in the process of water absorption. The correlation between the moisture content of stems and ultrasonic velocities was computed with the algorithm. It was found that the average correlation coefficient of the two parameters reached about 0.98. Finally, living sunflowers with different soil moistures were subjected to ultrasonic detection from 9:00 to 18:00 in situ. The results showed that the soil moisture and the primary ultrasonic echo position had a positive correlation, especially from 12:00 to 18:00; the average coefficient was 0.92. Meanwhile, our results showed that the ultrasonic detection of sunflower stems with different soil moistures was significantly distinct. Therefore, the improved AIC algorithm provided a method to effectively compute the primary echo position of limbs to help detect water changes in stems in situ.

Network pharmacology and experimental evidence reveal the protective mechanism of Yi-Qi Cong-Ming decoction on age-related hearing loss.

CONTEXT: Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly. OBJECTIVE: To explore the mechanism of YQCM decoction in the treatment of ARHL. MATERIALS AND METHODS: The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 µM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot. RESULTS: The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 µg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels. CONCLUSIONS: Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.

Structural characterization and antibacterial properties of konjac glucomannan/soluble green tea powder blend films for food packaging.

Antimicrobial activity is a promising property for food packaging which could prolong the shelf life of food products. In this paper, the physicochemical and antimicrobial properties of konjac glucomannan (KGM)/soluble green tea powder (SGTP) edible films were firstly prepared and analyzed through light barrier properties, Fourier transform infrared spectroscopy (FT-IR), tensile strength (TS), X-ray diffraction (XRD), thermogravimetric analysis and scanning electron microscope (SEM). The results showed that appropriate addition of SGTP could improve the TS of composite films. With the increase of SGTP content, the transmittance of the films in the ultraviolet region decreased obviously, and the thermal stability was improved in a SGTP dependent manner. KGM/SGTP films present a fairly smooth and flat surface without any fracture when 0.5% SGTP was provided. The bacteriostatic test showed that the bacteriostatic performance of the composite films against Staphylococcus aureus and Escherichia coli was also significantly enhanced. When 1% SGTP was provided, the zones of inhibition for Escherichia coli and Staphyloccocus aureus reached to 13.45 ± 0.94 mm and 13.76 ± 0.92 mm, respectively. Overall, the KGM/SGTP films showed great potential as bioactive packaging materials to extend food shelf life.

Gag Protein Oriented Supramolecular Nets as Potential HIV Traps.

For HIV/AIDS treatment, the cocktail therapy which uses a combination of anti-retroviral drugs remains the most widely accepted practice. However, the potential drug toxicity, patient tolerability, and emerging drug resistance have limited its long-term efficiency. Here, we design a HIV Gag protein-targeting redox supramolecular assembly (ROSA) system for potential HIV inhibition. An assembling precursor was constructed through conjugation of an oxidation-activatable fluorogenic compound BQA with a selected tetrapeptide GGFF. Since BQA shares a similar structure with the known Gag inhibitor, the precursor could bind to HIV Gag protein with moderate affinity. Moreover, after oxidation, the corresponding nanofibers could bind to Gag protein and trap HIV to realize virus control, thus providing a potential anti-HIV strategy.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).

Improved Swarm Intelligent Blind Source Separation Based on Signal Cross-Correlation.

In recent years, separating effective target signals from mixed signals has become a hot and challenging topic in signal research. The SI-BSS (Blind source separation (BSS) based on swarm intelligence (SI) algorithm) has become an effective method for the linear mixture BSS. However, the SI-BSS has the problem of incomplete separation, as not all the signal sources can be separated. An improved algorithm for BSS with SI based on signal cross-correlation (SI-XBSS) is proposed in this paper. Our method created a candidate separation pool that contains more separated signals than the traditional SI-BSS does; it identified the final separated signals by the value of the minimum cross-correlation in the pool. Compared with the traditional SI-BSS, the SI-XBSS was applied in six SI algorithms (Particle Swarm Optimization (PSO), Genetic Algorithm (GA), Differential Evolution (DE), Sine Cosine Algorithm (SCA), Butterfly Optimization Algorithm (BOA), and Crow Search Algorithm (CSA)). The results showed that the SI-XBSS could effectively achieve a higher separation success rate, which was over 35% higher than traditional SI-BSS on average. Moreover, SI-SDR increased by 14.72 on average.

PRV UL13 inhibits cGAS-STING-mediated IFN-ß production by phosphorylating IRF3.

Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky's disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-ß production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-ß secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS-STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS-STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-ß gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS-STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-ß gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS-STING-mediated IFN-ß production by phosphorylating IRF3.

Phenolic Compounds, Antioxidant Activities, and Inhibitory Effects on Digestive Enzymes of Different Cultivars of Okra (Abelmoschus esculentus).

In this study, the phenolic profiles and bioactivities of five representative cultivars of okra collected in China were investigated. Noticeable variations of phenolic compounds and their bioactivities were observed among these different cultivars of okra. The contents of total flavonoids (TFC) in "Shuiguo", "Kalong 8", "Kalong 3", "Wufu", and "Royal red" ranged from 1.75 to 3.39 mg RE/g DW, of which "Shuiguo" showed the highest TFC. Moreover, five individual phenolic compounds were found in okra by high performance liquid chromatography analysis, including isoquercitrin, protocatechuic acid, quercetin-3-O-gentiobioside, quercetin, and rutin, while isoquercitrin and quercetin-3-O-gentiobioside were detected as the main phenolic compounds in okra. Moreover, all tested okra exhibited significant antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, 2,2'-azino-bis (3-ethylenzthiazoline-6-sulphonic acid) radical scavenging capacity, and ferric reducing antioxidant power) and inhibitory effects on digestive enzymes (lipase, α-glucosidase, and α-amylase). Indeed, "Shuiguo" exhibited much better antioxidant activities and inhibitory activities on digestive enzymes, which might be attributed to its high TFC. Results suggested that okra, especially "Shuiguo", could be developed as natural antioxidants and inhibitors against hyperlipidemia and hyperglycemia in the fields of functional foods and pharmaceuticals, which could meet the increasing demand for high-quality okra with health-promoting properties in China.

Ultrasonic-Assisted Extraction, Structural Characterization, Chain Conformation, and Biological Activities of a Pectic-Polysaccharide from Okra (Abelmoschus esculentus).

The purpose of this study was to better understand the chemical characteristics and chain conformation of okra polysaccharides extracted by ultrasonic-assisted extraction. A pectic-polysaccharide, named OPP-D, was obtained, which was mainly composed of rhamnose, galacturonic acid, and galactose with a molar ratio of 1.01:1.00:2.31. Combined with NMR analysis, -4)-α-d-GalAp-(1,2,4)-α-l-Rhap-(1- were identified as the backbone with galactan side chains substituted partly at O-4 of Rhap. Molecular weight and radius of gyration of OPP-D were determined as 2.19 × 105 Da and 27.0 nm, respectively. OPP-D was determined as an air-core sphere with branching chains in 0.9% NaCl solution by high-performance size-exclusion chromatography coupled with multi-angle laser light scattering and dynamic light scattering for the first time. Moreover, OPP-D exhibited typical shear-thinning behavior. In addition, OPP-D exhibited remarkable in vitro antioxidant activities and prebiotic activities, while the relatively high molecular weight, high degree of esterification, high content of uronic acids, and highly branched globular conformation of OPP-D might contribute to its in vitro anti-diabetic activities and binding capacities. Results can contribute to a better understanding of the structure-bioactivity relationship of OPPs, and OPP-D has great potential applications in the functional food and pharmaceutical industries.

Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent joint disease, and there are still no effective therapeutic agents or clinical methods for the cure of this disease to date. The degradation of cartilage extracellular matrix (ECM) is a major cause of OA. METHOD: IL-1ß was used to induce chondrogenic degradation. Q-PCR and Western blotting were used to detect mRNA and protein level, respectively. ELISA was used to detect the secreted TNF-α and IL-6 level. Immunofluorescence was used to detect the protein level of Aggrecan, Collagen II and ki67. TUNEL and flow cytometry were used to examine cell apoptosis of chondrocytes. ChIP and luciferase assay were used to study molecular gene regulation. Osteoarthritic animal model and Safranin-O staining were used to determine the in vivo OA phenotype. RESULTS: The expression of ADAM8 was up-regulated in osteoarthritic chondrocytes. Knockdown of ADAM8 suppressed the OA phenotype in the in vitro OA cell model. ADAM8 regulated OA progression through the activation of EGFR/ERK/NF-κB signaling pathway. Inhibition of Notch signaling suppressed OA phenotype in the in vitro OA cell model. Notch signaling regulated the gene expression of ADAM8 directly via Hes1. Notch1-ADAM8 positive feedback loop promoted the progression of OA in vivo. CONCLUSION: Notch1-ADAM8 feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression.