Dynamic water migration and flavor analysis of sea cucumber in the process of Sichuan pepper seasoning soak.

Soaking in seasoning solution is the main process of sea cucumber seasoning. This study analyzed the dynamic changes in water migration and flavor substances in sea cucumbers during soaking in a Sichuan pepper solution. It was found that the sea cucumber experienced a process of water absorption followed by water loss during the 0-48 h soaking process. During this period, the flavor compounds in sea cucumbers showed different dynamic trends. A total of 46 volatiles were identified, of which 29 were key flavor compounds. Its flavor profiles tended to stabilize as soaking time increased. m-Xylene, d-Limonene, Eucalyptol, p-Xylene, Sabinene, Beta-Myrcene, and Beta-Phellandrene were the main characteristic substances contributing to the differences in sea cucumber flavor. Correlation analysis predicted the relationship between water migration and the dynamic shifts in flavor compounds. This study provides a crucial reference for future studies on the processing and flavor modulation of sea cucumber products.

Study on the adsorption and migration rule of Sichuan pepper characteristic volatile compounds during the cooking process in the sea cucumber body wall.

The natural flavor of sea cucumber is generally not easily accepted by consumers. In this study, the effect of different cooking conditions on the adsorption of the characteristic flavor of Sichuan pepper by sea cucumber was investigated by response surface methodology, and the optimal cooking conditions were identified. A total of 45 volatiles were identified based on gas chromatography-mass spectrometry, of which 27 were key flavor actives. Low-field nuclear magnetic resonance and textural analysis showed that the addition of Sichuan pepper during the cooking process affected the water migration and the textural properties of sea cucumbers. It was shown that the addition of Sichuan pepper could significantly improve the flavor and other quality characteristics of sea cucumber. This study has important practical guiding significance for the flavor improvement and product innovation of sea cucumber food.

Modified coconut shell biochars (MCSBCs): Fabrication and their adsorptions for Pb(II).

The modified coconut shell biochars (MCSBCs) were fabricated and their adsorptions for Pb(II) were evaluated, in which waste coconut shell was used as the raw material, both ZnCl2 and KMnO4 were applied as the inorganic modifiers. FT-IR spectra, TGA, SEM and BET techniques were utilized to characterize their properties. It was spotted that the thermal stability of UCSBC could arrive at 500 °C. The BET specific surface areas of both Zn- and Mn-modified MCSBCs (485.137, 476.734 m2/g) were highly decreased as compared with that of UCSBC (3528.78 m2/g). In contrast, the average pore diameters of both Zn- and Mn-modified MCSBCs (3.295, 3.803 nm) were smaller than that of UCSBC (3.814 nm). These findings reveal that the modification of CSBC didn't change its pore size. Their adsorptions for Pb(II) were performed and some controlling factors involving pH, contact time, starting concentration and temperature were explored. Moreover, the experiment data were fitted via linear and non-linear techniques. It was found that the Langmuir maximal adsorption amounts of un-modified coconut shell biochar (UCSBC), Zn-modified and Mn-modified MCSBCs for Pb(II) could reach 31.653, 86.547 and 93.666 mg/g, respectively. Two-parameter kinetic models exposed that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs obeyed both the Lagergren first-order (non-linear R2 = 0.990, 0.954, 0.953, respectively) and Avrami fractional-order (non-linear R2 = 0.989, 0.946, 0.945, respectively) kinetic models. Two-parameter and three-parameter isotherm models verified that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs followed the Langmuir (non-linear R2 = 0.992, 0.997, 0.993, respectively) as well as Sips (non-linear R2 = 0.992, 0.997, 0.992, respectively) isotherm models. The computation of thermodynamic parameters evidenced that the modification of UCSBC via KMnO4 and ZnCl2 can effectively rise its adsorption for Pb(II), exhibiting promising applications in the handling of metal-bearing water.

lncRNA CDKN2B-AS1 regulates collagen expression.

The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10- 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10- 25). The inflammatory "TNFA signaling via NFKB" gene set was downregulated the most (Padj=1 × 10- 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10- 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10- 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

Modular Synthesis of Polysubstituted α-Phosphorylated Arenes via the Catellani Strategy.

In this paper, we described a palladium/norbornene-catalyzed ortho-C-H phosphormethylation of aryl iodides using XCH2P(O)RR', offering a reliable method for the modular synthesis of polysubstituted α-phosphorylated arenes. Alkenylation, hydrogenation, cyanation, methylation, and arylation were all viable termination steps compatible with the reaction. This method demonstrates excellent functional group tolerance and can be extended to the late-stage modification of bioactive molecules. Furthermore, the synthetic transformations of the products demonstrate the practical utility of this reaction.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2.

BACKGROUND: G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K+ current (IK1) were recorded using whole-cell patch clamps. Isolated cardiomyocytes were stained with Fluo-3/AM dye, and intracellular Ca2+ handling was examined by CCD camera. A mouse model of AF was established by Ang-II (angiotensin II) infusion. RESULTS: Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile, IK1 current was increased and Ca2+ handling was impaired in isolated atrial myocytes of SPX-KO mice. GALR2-cKO mice, but not GALR1-cKO and GALR3-cKO mice, had a higher incidence of AF, which was associated with higher IK1 current and intracellular Ca2+ overload. The phosphorylation level of CREB (cyclic AMP responsive element binding protein 1) was upregulated in atrial tissues of SPX-KO and GALR2-cKO mice. Chromatin immunoprecipitation confirmed the recruitment of p-CREB to the proximal promoter regions of KCNJ2 and SLN. Finally, spexin treatment suppressed CREB signaling, decreased IK1 current and decreased intracellular Ca2+ overload, which thus reduced the inducibility of AF in Ang-II-infused mice. CONCLUSIONS: Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

Development of 3D printed electrospun vascular graft loaded with tetramethylpyrazine for reducing thrombosis and restraining aneurysmal dilatation.

Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.

Study on the mechanism of miRNAs on liver injury in the condition of Protoscocephalus alveolarus transhepatic portal vein infection.

OBJECTIVE: To explore the role of miRNA in liver damage caused by Echinococcus multilocularis infection. METHODS: Six female C57BL mice were randomly divided into two groups, the control group and the infection group. Mice in the control group were injected with 100 µL PBS through the hepatic portal vein, and mice in the infection group were infected with E. multilocularis via the hepatic portal vein to establish a mouse model of infection. Small RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 E. multilocularis after 3 months of infection, screen out miRNAs related to liver damage, and verify by RT-PCR. RESULTS: Seventy-one differentially expressed miRNAs were found in the liver in comparison with control, and a total of 36 mouse miRNAs with |FC| >0.585 were screened out, respectively. In addition, Targetscan (V5.0) and miRanda (v3.3a) software were used to predict differential miRNAs target genes and functional enrichment of target genes. Functional annotation showed that "cytokine-cytokine interaction," "positive regulation of cytokine production," "inflammatory response," and "leukocyte activation" were enriched in the liver of E. multilocularis-infected mice. Moreover, the pathways "human cytomegalovirus infection," "cysteine and methionine metabolism," "Notch signaling pathway," and "ferroptosis" were involved in liver disease. Furthermore, four miRNAs (mmu-miR-30e-3p, mmu-miR-203-3p, mmu-miR-125b-5p, and mmu-miR-30c-2-3p) related to liver injury were screened and verified. CONCLUSION: This study revealed that the expression profiling of miRNAs in the livers was changed after E. multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.

The detection methods currently available for protein aggregation in neurological diseases.

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

Characterization of radial artery perforation patterns using optical coherence tomography.

BACKGROUND: The characterization of radial artery perforation (RAP) patterns using optical coherence tomography (OCT) has not been well established. This study aimed to identify the characteristic RAP patterns in patients diagnosed through post-procedural OCT examination. METHODS: This retrospective study included 1936 consecutive patients who underwent radial artery (RA) OCT following OCT-guided transradial coronary intervention (TRI) from January 2016 to July 2022. Data regarding RAP characteristics were collected through OCT, including the perforation site as well as dimensions such as the length, width, and arc. Furthermore, RAP types were classified as small or large perforations, with a cut-off arc value of ≤90°. RESULTS: RAP, as identified by RA angiography (RAA) during TRI and on post-procedural OCT, was found in 16 out of 1936 patients (0.83 %). RA OCT imaging showed that the median distance between the RA ostium and the perforation site, the perforation length, width, and arc were 30.6 (14.4-42.2) mm, 1.55 (1.03-1.92) mm, 0.74 (0.60-1.14) mm, and 42.5 (25.0-58.1) °, respectively. Small perforations (arc ≤90°) were observed in 14 out of the 16 (87.5 %) patients with RAP. Post-procedural RAA revealed that 15 out of the 16 (93.7 %) patients with RAP had sealed perforations, with the remaining patient requiring external compression. CONCLUSIONS: Our findings demonstrated that RAP is uncommon during TRI, with clearly defined characteristic patterns on OCT. Most RAPs are small and tend to spontaneous seal through catheter tamponade.

A Meta-Analysis of the Prevalence of Children Goiter in High Water Iodine Areas of China.

Although there are now a large number of studies confirming that high iodine levels can cause goiter, there is controversy and a lack of quantitative data. A systematic search of PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database for literature on high iodine and goiter in children was performed with a time limit from January 2013 to October 2023. After screening the literature based on the inclusion criteria, extracting the literature data, and evaluating the risk of bias of the included studies, a single-arm meta-analysis was performed using R 4.0.4 software. Twenty-three studies with a total of 50,980 subjects were included. Meta-analysis showed that the prevalence of goiter among children in water-borne iodine-excess areas was 6.0% [95% CI (4.3%, 7.6%)], and subgroup analyses showed that the prevalence of goiter in children with water iodine 100.1-150 µg/L, 150.1-300 µg/L, and > 300 µg/L was 7.5% [95% CI (0.0%, 15.8%)], 5.5% [95% CI (3.1%, 8.0%)], and 10.2% [95% CI (6.7%, 13.6%)], respectively, and the difference was statistically significant (P < 0.01); The prevalence of goiter among children in the northern China (5.8% [95% CI (4.1%, 7.5%)]) was higher than that in the southern China (3.5% [95% CI (1.0%, 6.0%)]) (P < 0.01); the prevalence of goiter in children with urinary iodine levels 100-199 µg/L, 200-299 µg/L, and ≥ 300 µg/L was 2.4% [95% CI (1.9%, 2.9%)], 3.3% [95% CI (1.9%, 4.8%)], and 7.3% [95% CI (4.4%, 9.9%)], respectively, the difference was statistically significant (P < 0.01); the prevalence of goiter in children aged 8, 9, 10, 11, and 12 years old was 5.1% [95% CI (3.9%, 6.4%)], 8.0% [95% CI (4.0%, 11.9%)], 6.2% [95% CI (3.9%, 8.5%)], 5.5% [95% CI (0.0%, 13.2%)], and 5.4% [95% CI (0.0%, 15.1%)], and when age ≥ 9 years, the relationship between goiter prevalence and age showed a trend toward decreasing with age, but the relationship between different age was no statistical difference in the prevalence of goiter between ages. urinary iodine. The prevalence of goiter in children was higher in areas with high water iodine; the prevalence of goiter in children in the north was significantly higher than that in the south; the prevalence of goiter in children tends to increase with increased urinary iodine levels.

Immunoprotective effect and mechanism of rEg.P29 against CD4 + T cell-deficient mice with Echinococcus multilocularis infection.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by infection with the larval stage of Echinococcus multilocularis and a major challenge to human public health. Vaccines are the most effective way to prevent and control infectious diseases. We previously revealed that the Echinocuccus granulosus recombinant protein P29 is a good vaccine candidate against E. granulosus. However, the protective and immunological mechanism of rEg.P29 against E. multilocularis remain unclear. In this study, CD4 + T cell-deficient mice are transferred with spleen CD4 + T cells isolated from wild-type mice and subjected to rEg.P29 immunization, and then these immunized mice are infected with E. multilocularis. The cyst inhibition rate is calculated by weighing the body and cyst weights. The level of antibody is detected by ELISA. Flow cytometry is used to detect the level of IFN-γ production by CD4 + T and CD8 + T cells. The cytokines in culture supernatant are detected by ELISA. The expressions of CD44 and CD62L on memory T cells are determined by flow cytometry. The results show the cyst inhibition rate is 41.52% after adoptive transfer of CD4 + T cells. Furthermore, the levels of IgG, IgM, IgA and IgE in serum are significantly increased compared with those in the PBS group. The IFN-γ-secretion by CD8 + T cells and the level of IFN-γ in culture supernatant are obviously increased; and the number of CD4 + T cells is increased, but the number of IFN-γ producing CD4 + T cells has no significant difference compared with PBS group. In addition, the number of CD44 +CD62L ‒CD8 + memory T cells in the spleen is significantly increased, while the number of CD44 ‒CD62L + CD8 + memory T cells is not significantly altered. Collectively, rEg.P29 can alleviate E. multilocularis infection by inducing humoral immune responses and CD8 + T cell responses.

Comparative Proteomic and Metabonomic Profiling of Buds with Different Flowering Capabilities Reveal Novel Regulatory Mechanisms of Flowering in Apple.

Flower bud formation in the apple tree life cycle is associated with multiple biological processes. To explore the physiological and molecular mechanisms underlying the protein and metabolite changes in buds with different flowering capabilities, axillary buds with no flowering (Ab), long-shoot buds with a low flowering rate (Lb), and spur buds with a higher flowering rate than the Lb (Sb) were analyzed using a Tandem Mass Tag™ proteomic technique in combination with nLC-MS/MS analyses. We identified 471 (88 up- and 383 down-regulated), 459 (176 up- and 283 down-regulated), and 548 (387 up- and 161 down-regulated) differentially expressed proteins in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively, that were involved in carbohydrate, amino acid and lipid transport, and metabolism. Additionally, 110 (91 increased and 19 decreased), 89 (71 increased and 18 decreased), and 99 (37 increased and 62 decreased) metabolites having significantly different levels were identified in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively. The identified metabolites were related to amino acids and their isoforms, sugars and polyols, and organic acids, and occurred at significantly greater levels in the Sbs than the other buds. Thus, flower bud formation is a complex process that involves various biochemical materials and signals, such as carbohydrates, amino acids and their isoforms, and organic acids.

Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-ß production.

OBJECTIVE: FAS-mediated apoptosis of hepatocytes and aberrant TGF-ß signaling are major drivers of liver fibrosis. Decreased miRNA let-7 expression in the livers of patients and animals with fibrosis suggests a mechanistic link of let-7 to hepatic fibrogenesis. METHODS: Using transient transfection we tested the effects of let-7 overexpression and TET3 siRNA knockdown on FAS and TGF-ß1 expression and FAS-mediated apoptosis in human and mouse primary hepatocytes. We assessed the therapeutic activity of let-7 miRNA delivered via adeno-associated viral vectors in mouse models of carbon tetrachloride (CCl4)-induced and bile duct ligation (BDL)-induced liver fibrosis. RESULTS: Let-7 decreased TGF-ß1 production from hepatocytes through a negative feedback loop involving TET3. On the other hand, let-7 post-transcriptionally inhibits FAS expression, thereby suppressing hepatocyte apoptosis. Hepatic-specific delivery of let-7 miRNA mitigated liver fibrosis in both CCl4 and BDL mouse models. CONCLUSIONS: Let-7 is a crucial node in the signaling networks that govern liver fibrosis progression. Let-7 and/or its derivatives may be used as therapeutic agents for liver fibrosis.

Activation and induction of antigen-specific T follicular helper cells play a critical role in recombinant SARS-CoV-2 RBD vaccine-induced humoral responses.

The role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited. In this study, we expressed and purified recombinant SARS-CoV-2 RBD protein in Drosophila S2 cells for the first time and explored the mechanism of Tfh cells induced by RBD vaccine in humoral immune response. We mapped the dynamic of Tfh cell in lymph node and spleen following RBD vaccination and revealed the relationship between Tfh cells and humoral immune response induced by SARS-CoV-2 RBD vaccine through correlation analysis, blocking of IL-21 signaling pathway, and co-culture of Tfh with memory B cells. Recombinant RBD protein elicited a predominant Tfh1 and Tfh1-17 subset response and strong GC responses in spleen and lymph nodes, especially to enhanced vaccination. IL-21 secreted by Tfh cells affected the development and differentiation of B cells and played a key role in the humoral immune response. These observations will help us further understand the mechanism of protective immune response induced by COVID-19 vaccine and has guiding significance for the development of vaccines against newly emerging mutants.

Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder with high morbidity and mortality. The current study aims to explore the role of Cullin-associated and neddylation-dissociated protein 1 (CAND1) in the development of NAFLD and the underlying mechanisms. CAND1 is reduced in the liver of NAFLD male patients and high fat diet (HFD)-fed male mice. CAND1 alleviates palmitate (PA) induced lipid accumulation in vitro. Hepatocyte-specific knockout of CAND1 exacerbates HFD-induced liver injury in HFD-fed male mice, while hepatocyte-specific knockin of CAND1 ameliorates these pathological changes. Mechanistically, deficiency of CAND1 enhances the assembly of Cullin1, F-box only protein 42 (FBXO42) and acetyl-CoA acyltransferase 2 (ACAA2) complexes, and thus promotes the ubiquitinated degradation of ACAA2. ACAA2 overexpression abolishes the exacerbated effects of CAND1 deficiency on NAFLD. Additionally, androgen receptor binds to the -187 to -2000 promoter region of CAND1. Collectively, CAND1 mitigates NAFLD by inhibiting Cullin1/FBXO42 mediated ACAA2 degradation.

The selective regulation of immune responses by matrix metalloproteinase MMP14 in Ostrinia furnacalis.

Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and immune responses in insects, yet it remains unclear how MMPs affect the various immune processes against pathogenic infections and whether the responses vary among insects. In this study, we used the lepidopteran pest Ostrinia furnacalis larvae to address these questions by examining the changes of immune-related gene expression and antimicrobial activity after the knockdown of MMP14 and bacterial infections. We identified MMP14 in O. furnacalis using the rapid amplification of complementary DNA ends (RACE), and found that it was conserved and belonged to the MMP1 subfamily. Our functional investigations revealed that MMP14 is an infection-responsive gene, and its knockdown reduces phenoloxidase (PO) activity and Cecropin expression, while the expressions of Lysozyme, Attacin, Gloverin, and Moricin are enhanced after MMP14 knockdown. Further PO and lysozyme activity determinations showed consistent results with gene expression of these immune-related genes. Finally, the knockdown of MMP14 decreased larvae survival to bacterial infections. Taken together, our data indicate that MMP14 selectively regulates the immune responses, and is required to defend against bacterial infections in O. furnacalis larvae. Conserved MMPs may serve as a potential target for pest control using a combination of double-stranded RNA and bacterial infection.

Bioinformatics Analysis of Differentially Expressed Genes in Ischemic Cardiomyopathy Using GEO Database.

It was to analyze differentially expressed genes and their expression characteristics in ischemic cardiomyopathy (ICM) by bioinformatics and provide targets for drug therapy of ICM. For this purpose, the gene expression data of ICM in the gene expression omnibus (GEO) database were used, the differentially expressed genes between healthy myocardium and ICM myocardium were screened by R language, and then the differentially expressed genes were analyzed by protein-protein interaction (PPI), gene ontology (GO), and KEGG to select the key genes. Results showed that the useful genes of ICM were successfully screened in the GEO database, and KEGG pathway analysis was performed for the differentially expressed genes in ICM tissues, including the main pathways: viral carcinogenesis, energy metabolism, viral response, oxidative phosphorylation, influenza A, extracellular matrix receptor interaction, Epstein-Barr virus infection, chemokine receptor pathway, phagosome, proteasome, and protein digestion and absorption. PPI network analysis showed that C3, F5, FCGR3A, APOB, PENK, LUM, CHRDL1, FCGR3A, CIQB, and FMOD were critical genes. In conclusion, bioinformatics can screen out the key genes in ICM, which is helpful to understand the treatment of drug targets in ICM patients.