Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model.

BACKGROUND: Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days. RESULTS: The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. CONCLUSIONS: The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

Baicalin ameliorates high fat diet-induced nonalcoholic fatty liver disease in mice via adenosine monophosphate-activated protein kinase-mediated regulation of SREBP1/Nrf2/NF-κB signaling pathways.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease around the world, imposing severe threats on human health. Unfortunately, no clinically approved drugs are available for use as yet. Baicalin (BA) is reported to have hepatoprotective effects, and it is not clear whether BA can treat NAFLD and how. Here, a high-fat diet (HFD)-induced NAFLD mouse model was established to explore the protective roles and mechanisms of BA against HFD-induced NAFLD. Physiochemical results showed that BA exhibited significantly protective effects against HFD-induced NAFLD in mice. Liver transcriptomic analysis revealed that BA attenuated HFD-induced NAFLD via activating AMPK pathway, which was confirmed by the AMPK inhibitor Compound C. Additionally, the expression changes of AMPK downstream genes demonstrated that BA exerted ameliorative effects against NAFLD through AMPK-mediated inhibition of SREBP1 and NF-κB pathways, and activation of Nrf2 pathway. Taken together, our study reveals the protective roles of BA against HFD-caused NAFLD through AMPK-mediated modulation of SREBP1/Nrf2/NF-κB pathways, suggesting that BA has potential drug development implications. Most importantly, our study creates a paradigm through the combination of molecular biology and bioinformatics for further studies of action mechanisms of biomolecules combating diseases.

Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.

Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1ß mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1ß mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1ß mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1ß mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.

Target Discovery of Matrine against PRRSV in Marc-145 Cells via Activity-Based Protein Profiling.

Porcine reproductive and respiratory syndrome (PRRS) seriously endangers the sustainable development of the pig industry. Our previous studies have shown that matrine can resist porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study aimed to explore the anti-PRRSV targets of matrine in Marc-145 cells. Biotin-labeled matrine 1 and 2 were used as probes. MTT assay was used to determine the maximum non-cytotoxic concentration (MNTC) of each probe in Marc-145 cells. The anti-PRRSV activity of each probe was evaluated via MTT, qPCR and Western blot, and its anti-inflammatory activity was evaluated via qPCR and Western blot. The targets of matrine in Marc-145 cells were searched using activity-based protein profiling (ABPP), and compared with the targets predicted via network pharmacology for screening the potential targets of matrine against PRRSV. The protein-protein interaction networks (PPI) of potential targets were constructed using a network database and GO/KEGG enrichment analysis was performed. ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1 were identified as potential targets of matrine, and their functions were related to antiviral capacity and immunity. Matrine may play an anti-PRRSV role by directly acting on ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1.

Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans.

OBJECTIVE: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. SUMMARY BACKGROUND DATA: Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). METHODS: We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). RESULTS: Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. CONCLUSIONS: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.

Interfacial Assembly of Nanowire Arrays toward Carbonaceous Mesoporous Nanorods and Superstructures.

Synthesis of anisotropic carbonaceous nano- and micro-materials with well-ordered mesoporous structures has attracted increasing attention for a broad scope of applications. Although hard-templating method has been widely employed, overcoming the viscous forces to prepare anisotropic mesoporous materials is particularly challenging via the universal soft-templating method, especially from sustainable biomass as a carbon resource. Herein, the synthesis of biomass-derived nanowire-arrays based mesoporous nanorods and teeth-like superstructures is reported, through a simple and straightforward polyelectrolyte assisted soft-templating hydrothermal carbonization (HTC) approach. A surface energy induced interfacial assembly mechanism with the synergetic interactions between micelles, nanowire, nanorods, and polyelectrolyte is proposed. The polyelectrolyte acts not only as a stabilizer to decrease the surface energy of cylindrical micelles, nanowires and nanorods, but also as a structure-directing agent to regulate the oriented attachment and anisotropic assembly of micelles, nanowires, and nanorods. After a calcination treatment, the carbon nanorod and teeth-like superstructure are successfully coupled with Ru to directly produce supported catalysts for the hydrogen evolution reaction, exhibiting much better performance than the isotropic nanospheres based catalyst. This HTC approach will open up new avenues for the synthesis of anisotropic materials with various morphologies and dimensions, expanding the palette of materials selection for many applications.

Deoxynivalenol damages the intestinal barrier and biota of the broiler chickens.

BACKGROUND: In the livestock feed industry, feed and feed raw materials are extremely susceptible to mycotoxin contamination. Deoxynivalenol (DON) is one of the main risk factors for mycotoxin contamination in broiler feed and feedstuff, however, there is still little knowledge about this. Hence, the purpose of this study was to explore the toxicity effect of DON on the intestinal barrier and the microecological balance of the biota in broiler chickens. RESULTS: In our present study, we compared the pathological scores of the small intestines of broilers on the 5th, 7th, and 10th day, and chose the 7th day to analyze the small intestine histomorphology, tight junctions, and cecal biota of the broilers. The results showed the damage to the small intestine worsened over time, the small intestinal villi of broilers were breakage, the tight junctions of the small intestine were destroyed, the cecal biota was unbalanced, and the growth performance of broilers was reduced on the 7th day. CONCLUSIONS: DON could damage the functional and structural completeness of the intestinal tract, disorder the Intestinal biota, and finally lead to declined broiler performance. Our study provided a basis for the prevention and treatment of DON in broiler production.

Curcumol inhibits EMCV replication by activating CH25H and inhibiting the formation of ROs.

BACKGROUND: Zedoary turmeric oil extracted from the roots of curcuma (Curcuma aeruginosa Roxb.) is used for the treatment of myocarditis in China. EMCV infection causes abortion in pregnant sows and myocarditis in piglets. Our previous studies demonstrated that curcumol significantly increased the expression of IFN-ß in EMCV infected HEK-293T cells. The present results showed that curcumol inhibits EMCV replication by interfering the host cell cholesterol homeostasis and reducing ROs production through activation of the JAK/STAT signaling pathway. METHOD: This study was designed to explore whether curcumol can inhibit the replication of encephalomyocarditis viruses (EMCV) in cell culture. The expression level of JAK1, IRF9, STAT2, P-STAT2, CH25H, PI4KA and OSBP in EMCV-infected HEK-293T cells treated with curcumol, ribavirin or hydroxypropyl-ß-CD (HPCD) were determined by Western blotting (WB). The cholesterol level in EMCV infected HEK-293T cells treated with curcumol and HPCD were detected using Amplex™ Red Cholesterol Assay Kit. The antiviral effects of curcumol and HPCD on EMCV were also quantitatively detected by real-time fluorescence quantitative PCR (q-PCR). The amount and morphology of ROs were observed by transmission electron microscopy (TEM). RESULTS: The results demonstrated that curcumol significantly (P < 0.05) increased the expression of JAK1, IRF9, P-STAT2 and CH25H proteins, while that of STAT2, PI4KA and OSBP were remained unchanged. Compared with virus group (0.134 µg.µg-1 proteins), the total cholesterol level was significantly (P < 0.05) reduced by curcumol (0.108 µg.µg-1 proteins) and HPCD (0.089 µg.µg-1 proteins). Compared with virus group (88237 copies), curcumol (41802 copies) and HPCD (53 copies) significantly (P < 0.05) reduced EMCV load. Curcumol significantly reduced the production of ROs in EMCV-infected HEK-293T cells and activated CH25H through the JAK/STAT signaling pathway. CONCLUSION: Curcumol inhibited EMCV replication by affecting the cholesterol homeostasis and the production of ROs in HEK-293T cell.

Sequential Superassembly of Nanofiber Arrays to Carbonaceous Ordered Mesoporous Nanowires and Their Heterostructure Membranes for Osmotic Energy Conversion.

The capture of sustainable energy from a salinity gradient, in particular, using renewable biomass-derived functional materials, has attracted significant attention. In order to convert osmotic energy to electricity, many membrane materials with nanofluidic channels have been developed. However, the high cost, complex preparation process, and low output power density still restrict the practical application of traditional membranes. Herein, we report the synthesis of highly flexible and mechanically robust nanofiber-arrays-based carbonaceous ordered mesoporous nanowires (CMWs) through a simple and straightforward soft-templating hydrothermal carbonization approach. This sequential superassembly strategy shows a high yield and great versatility in controlling the dimensions of CMWs with the aspect ratio changes from about 3 to 39. Furthermore, these CMWs can be used as novel building blocks to construct functional hybrid membranes on macroporous alumina. This nanofluidic membrane with asymmetric geometry and charge polarity exhibits low resistance and high-performance energy conversion. This work opens a solution-based route for the one-pot preparation of CMWs and functional heterostructure membranes for various applications.

Damage to intestinal barrier integrity in piglets caused by porcine reproductive and respiratory syndrome virus infection.

Porcine reproductive and respiratory syndrome (PRRS) induces respiratory disease and reproductive failure accompanied by gastroenteritis-like symptoms. The mechanism of intestinal barrier injury caused by PRRSV infection in piglets has yet to be investigated. An in vivo PRRSV-induced model was established in 30-day-old piglets by the intramuscular injection of 2 mL of 104 TCID50/mL PRRSV for 15 days. Observations of PRRSV replication and histology were conducted in the lungs and intestine, and goblet cell counts, relative MUC2 mRNA expression, and tight junction protein, proinflammatory cytokine, TLR4, MyD88, IκB and p-IκB expression were measured. PRRSV replicated in the lungs and small intestine, as demonstrated by absolute RT-qPCR quantification, and the PRRSV N protein was detected in the lung interstitium and jejunal mucosa. PRRSV infection induced both lung and gut injury, markedly decreased villus height and the villus to crypt ratio in the small intestine, and obviously increased the number of goblet cells and the relative expression of MUC2 mRNA in the jejunum. PRRSV infection aggravated the morphological depletion of tight junction proteins and increased IL-1ß, IL-6, IL-8 and TNF-α expression by activating the NF-κB signalling pathway in the jejunum. PRRSV infection impaired intestinal integrity by damaging physical and immune barriers in the intestine by inducing inflammation, which may be related to the regulation of the gut-lung axis. This study also provides a new hypothesis regarding the pathogenesis of PRRSV-induced diarrhoea.

MRI features of and factors related to ankle injuries in asymptomatic amateur marathon runners.

OBJECTIVE: To analyze the MRI manifestations of and factors related to ankle injuries in asymptomatic amateur marathon runners. MATERIALS AND METHODS: A total of 113 amateur marathon runners without any ankle joint symptoms were recruited. Each participant was asked to complete a questionnaire at the beginning of the study and underwent MRI of the ankle. The MRI manifestations of ankle injuries were summarized, and binary logistic regression analysis was applied to analyze the factors related to ankle injuries. RESULTS: The main MRI features were bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. Others included Achilles tendinopathy, cyst-like lesions, osteochondral lesions, and subcutaneous soft tissue edema. The risk factor for bone marrow edema-like signal intensity in amateur marathon runners was a rearfoot strike pattern (p = 0.028, OR = 1.172); the risk factors for peritendinous effusion were a higher weekly running distance (p = 0.013, OR = 1.685) and increased running years (p = 0.039, OR = 1.113), whereas a rearfoot strike pattern (p = 0.005, OR = 0.831) was a protective factor for peritendinous effusion; the risk factor for Achilles tendinopathy was increased age (p = 0.008, OR = 1.412); the risk factors for anterior talofibular ligament injury were a rearfoot strike pattern (p = 0.017, OR = 1.346) and higher weekly running distance (p = 0.022, OR = 1.171); and the factors for calcaneofibular ligament injury were a higher weekly running distance (p = 0.029, OR = 1.570) and rearfoot strike pattern (p = 0.035, OR = 1.463). CONCLUSION: The main MRI features of asymptomatic amateur marathon runners are bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. In addition, increased age, increased running years, higher weekly running distance, and different foot strike patterns are risk factors for ankle injuries.

Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2.

BACKGROUND: Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism. RESULTS: Osthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control. CONCLUSIONS: The combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.

Cepharanthine and Curcumin inhibited mitochondrial apoptosis induced by PCV2.

BACKGROUND: Porcine circovirus type 2 (PCV2) is an immunosuppressive pathogen with high prevalence rate in pig farms. It has caused serious economic losses to the global pig industry. Due to the rapid mutation of PCV2 strain and co-infection of different genotypes, vaccination could not eradicate the infection of PCV2. It is necessary to screen and develop effective new compounds and explore their anti-apoptotic mechanism. The 13 natural compounds were purchased, with a clear plant origin, chemical structure and content and specific biological activities. RESULTS: The maximum no-cytotoxic concentration (MNTC) and 50% cytotoxic concentration (CC50) of 13 tested compounds were obtained by the cytopathologic effect (CPE) assay and (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in PK-15 cells. The results of qPCR and Western blot showed that, compared with the PCV2 infected group, the expression of Cap in Paeonol (0.4 mg/mL and 0.2 mg/mL), Cepharanthine (0.003 mg/mL, 0.0015 mg/mL and 0.00075 mg/mL) and Curcumin (0.02 mg/mL, 0.001 mg/mL and 0.005 mg/mL) treated groups were significantly lowered in a dose-dependent manner. The results of Annexin V-FITC/PI, JC-1, Western blot and ROS analysis showed that the expression of cleaved caspase-3 and Bax were up-regulated Bcl-2 was down-regulated in Cepharanthine or Curcumin treated groups, while ROS and MMP value were decreased at different degrees and the apoptosis rate was reduced. In this study, Ribavirin was used as a positive control. CONCLUSIONS: Paeonol, Cepharanthine and Curcumin have significant antiviral effect. And the PCV2-induced Mitochondrial apoptosis was mainly remitted by Cepharanthine and Curcumin.

Dynamic Restructuring of Cu7S4/Cu for Efficient CO2 Electro-reduction to Formate.

Optimized catalytic properties and reactant adsorption energy played a crucial role in promoting CO2 electrocatalysis. Herein, Cu7S4/Cu underwent in situ dynamic restructuring to generate S-Cu2O/Cu hybrid catalyst for effective electrochemical CO2 reduction to formate that outperformed Cu2O/Cu and Cu7S4. Thermodynamic and in situ Raman spectra revealed that the optimized adsorption of the HCOO* intermediate on S-Cu2O/Cu was regulated and the H2 pathway (surface H) was suppressed by S-doping. Meanwhile, Cu7S4/Cu nanoflowers created abundant boundaries for ECR and strengthened the CO2 adsorption by inducing Cu. These findings provide a new perspective on synthetic methods for various electrocatalytic reduction processes.

Fascin-1 Promotes Cell Metastasis through Epithelial-Mesenchymal Transition in Canine Mammary Tumor Cell Lines.

Canine mammary tumors (CMTs) are the most common type of tumor in female dogs. In this study, we obtained a metastatic key protein, Fascin-1, by comparing the proteomics data of in situ tumor and metastatic cell lines from the same individual. However, the role of Fascin-1 in the CMT cell line is still unclear. Firstly, proteomics was used to analyze the differential expression of Fascin-1 between the CMT cell lines CHMm and CHMp. Then, the overexpression (CHMm-OE and CHMp-OE) and knockdown (CHMm-KD and CHMp-KD) cell lines were established by lentivirus transduction. Finally, the differentially expressed proteins (DEPs) in CHMm and CHMm-OE cells were identified through proteomics. The results showed that the CHMm cells isolated from CMT abdominal metastases exhibited minimal expression of Fascin-1. The migration, adhesion, and invasion ability of CHMm-OE and CHMp-OE cells increased, while the migration, adhesion, and invasion ability of CHMm-KD and CHMp-KD cells decreased. The overexpression of Fascin-1 can upregulate the Tetraspanin 4 (TSPAN4) protein in CHMm cells and increase the number of migrations. In conclusion, re-expressed Fascin-1 could promote cell EMT and increase lamellipodia formation, resulting in the enhancement of CHMm cell migration, adhesion, and invasion in vitro. This may be beneficial to improve female dogs' prognosis of CMT.

MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

Vertebrate fatty acyl desaturase with Δ4 activity.

Biosynthesis of the highly biologically active long-chain polyunsaturated fatty acids, arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids, in vertebrates requires the introduction of up to three double bonds catalyzed by fatty acyl desaturases (Fad). Synthesis of ARA is achieved by Δ6 desaturation of 182n - 6 to produce 183n - 6 that is elongated to 203n - 6 followed by Δ5 desaturation. Synthesis of EPA from 183n - 3 requires the same enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further elongations, a second Δ6 desaturation and a peroxisomal chain shortening step. This paper describes cDNAs, fad1 and fad2, isolated from the herbivorous, marine teleost fish (Siganus canaliculatus) with high similarity to mammalian Fad proteins. Functional characterization of the cDNAs by heterologous expression in the yeast Saccharomyces cerevisiae showed that Fad1 was a bifunctional Δ6/Δ5 Fad. Previously, functional dual specificity in vertebrates had been demonstrated for a zebrafish Danio rerio Fad and baboon Fad, so the present report suggests bifunctionality may be more widespread in vertebrates. However, Fad2 conferred on the yeast the ability to convert 225n - 3 to DHA indicating that this S. canaliculatus gene encoded an enzyme having Δ4 Fad activity. This is a unique report of a Fad with Δ4 activity in any vertebrate species and indicates that there are two possible mechanisms for DHA biosynthesis, a direct route involving elongation of EPA to 225n - 3 followed by Δ4 desaturation, as well as the more complicated pathway as described above.

Tailoring a local acid-like microenvironment for efficient neutral hydrogen evolution.

Electrochemical hydrogen evolution reaction in neutral media is listed as the most difficult challenges of energy catalysis due to the sluggish kinetics. Herein, the Ir-HxWO3 catalyst is readily synthesized and exhibits enhanced performance for neutral hydrogen evolution reaction. HxWO3 support is functioned as proton sponge to create a local acid-like microenvironment around Ir metal sites by spontaneous injection of protons to WO3, as evidenced by spectroscopy and electrochemical analysis. Rationalize revitalized lattice-hydrogen species located in the interface are coupled with Had atoms on metallic Ir surfaces via thermodynamically favorable Volmer-Tafel steps, and thereby a fast kinetics. Elaborated Ir-HxWO3 demonstrates acid-like activity with a low overpotential of 20 mV at 10 mA cm-2 and low Tafel slope of 28 mV dec-1, which are even comparable to those in acidic environment. The concept exemplified in this work offer the possibilities for tailoring local reaction microenvironment to regulate catalytic activity and pathway.

A diagnostic scoring model of ENKTCL in the nose-Waldeyer's ring based on logistic regression: Differential diagnosis from DLBCL.

Objective: To establish a logistic regression model based on CT and MRI imaging features and Epstein-Barr (EB) virus nucleic acid to develop a diagnostic score model to differentiate extranodal NK/T nasal type (ENKTCL) from diffuse large B cell lymphoma (DLBCL). Methods: This study population was obtained from two independent hospitals. A total of 89 patients with ENKTCL (n = 36) or DLBCL (n = 53) from January 2013 to May 2021 were analyzed retrospectively as the training cohort, and 61 patients (ENKTCL=27; DLBCL=34) from Jun 2021 to Dec 2022 were enrolled as the validation cohort. All patients underwent CT/MR enhanced examination and EB virus nucleic acid test within 2 weeks before surgery. Clinical features, imaging features and EB virus nucleic acid results were analyzed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors of ENKTCL and establish a predictive model. Independent predictors were weighted with scores based on regression coefficients. A receiver operating characteristic (ROC) curve was created to determine the diagnostic ability of the predictive model and score model. Results: We searched for significant clinical characteristics, imaging characteristics and EB virus nucleic acid and constructed the scoring system via multivariate logistic regression and converted regression coefficients to weighted scores. The independent predictors for ENKTCL diagnosis in multivariate logistic regression analysis, including site of disease (nose), edge of lesion (blurred), T2WI (high signal), gyrus like changes, EB virus nucleic acid (positive), and the weighted score of regression coefficient was 2, 3, 4, 3, 4 points. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. The AUC of the scoring model in the training cohort were 0.925 (95% CI, 0.906-0.990) and the cutoff point was 5 points. In the validation cohort, the AUC was 0.959 (95% CI, 0.915-1.000) and the cutoff value was 6 points. Four score ranges were as follows: 0-6 points for very low probability of ENKTCL, 7-9 points for low probability; 10-11 points for middle probability; 12-16 points for very high probability. Conclusion: The diagnostic score model of ENKTCL based on Logistic regression model which combined with imaging features and EB virus nucleic acid. The scoring system was convenient, practical and could significantly improve the diagnostic accuracy of ENKTCL and the differential diagnosis of ENKTCL from DLBCL.