SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

RNA 5-Methylcytosine Facilitates the Maternal-to-Zygotic Transition by Preventing Maternal mRNA Decay.

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.

Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.

The regulatory role of N(6)-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in pre-mRNA splicing remains an enigma. Here we show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 (SRp20) while blocking SRSF10 (SRp38) mRNA binding. Transcriptome assay with PAR-CLIP-seq analysis revealed that YTHDC1-regulated exon-inclusion patterns were similar to those of SRSF3 but opposite of SRSF10. In vitro pull-down assay illustrated a competitive binding of SRSF3 and SRSF10 to YTHDC1. Moreover, YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 depletion, can be restored by reconstitution with wild-type, but not m(6)A-binding-defective, YTHDC1. Our findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs.

The multiple mediating effects of self-efficacy and resilience on the relationship between social support and procrastination among vocational college students: a cross-sectional study.

BACKGROUND: Previous research has revealed a negative association between social support and procrastination. However, few studies have investigated the mechanism underlying this relationship among vocational college students. OBJECTIVE: Based on the social cognitive theory, this study was intended to investigate the multiple mediating effects of self-efficacy and resilience on the relationship between social support and procrastination among vocational college students. METHODS: This study employed a cross-sectional design involving a sample of 1,379 students from a vocational college in China. Data were collected using the General Procrastination Scale, the Multidimensional Scale of Perceived Social Support, the General Self-Efficacy Scale, and the Resilience Scale-14. The PROCESS macro for SPSS was used to examine the multiple mediation model. RESULTS: Our findings indicate significant negative correlations between social support, self-efficacy, resilience, and procrastination. The multiple mediation analysis showed that social support did not have a significant direct impact on procrastination. Instead, the relationship between social support and procrastination was fully mediated by self-efficacy (indirect effect: -0.017; 95% CI: -0.032, -0.004) and resilience (indirect effect: -0.047; 95% CI: -0.072, -0.025), and sequentially mediated by both factors (indirect effect: -0.013; 95% CI: -0.020, -0.007). CONCLUSIONS: The results emphasise the importance of enhancing self-efficacy and resilience in initiatives aimed at preventing and intervening in case of procrastination among vocational college students. Additionally, strengthening social support may also be crucial to preventing or reducing procrastination among this population.

Efficacy of Mometasone Furoate Cream Sodium Alginate Skin Repair Mask in Atopic Dermatitis Treatment.

Objective: To observe the clinical effect of mometasone furoate cream sodium Alginate Skin Repair Mask in the treatment of atopic dermatitis (AD). By assessing the combined use of these two treatments, the study aims to address a gap in knowledge regarding the effectiveness and safety of adjuvant therapies for AD, particularly in the context of Alginate Skin Repair Mask. Methods: Eighty patients were enrolled, including 42 males and 38 females aged 20-47 years, with an average age of (32.52±5.57) years, from July 2021 to July 2022, and the patients were divided into a single group (n=40) and a combined group (n=40) by random number table method. The patients in the single group were treated with mometasone furoate cream alone, and the patients in the combination group were treated with Alginate Skin Repair Mask on the basis of the treatment of the patients in the single group. The outcome measurements included clinical treatment effect, condition change (SCORAD score), quality of life (DLQI score), adverse reactions and disease recurrence were compared between the two groups. Both groups received treatment for 1 month. After the treatment of the patients, they were followed up for a period of 3 months. Results: The total effective rate of the single group was 80.0% (32/40), and that of the combined group was 97.5% (39/40) (P < .05). After treatment, the skin lesion area score, skin lesion degree score, pruritus insomnia score, and SCORAD total score in the combined group were significantly lower than those in the single group (35.03±9.41 vs 44.03±12.04) (all P < .05). The DLQI score of the combined group after treatment was significantly lower than that of the single group (3.72±1.53 vs 6.98±2.16) (P < .05). The incidence of adverse reactions in the single group was 22.5% (9/40), and the disease recurrence rate was 32.5% (13/40), while the incidence of adverse reactions in the combination group was 2.5% (1/40). The disease recurrence rate was 7.5% (3/40), and the incidence of adverse reactions and disease recurrence rate in the combination group were significantly lower than those in the single group (7.314, 7.812). Conclusion: Mometasone furoate cream sodium Alginate Skin Repair Mask has an ideal clinical effect in the treatment of atopic dermatitis. Compared with single mometasone furoate cream, the combination of sodium Alginate Skin Repair Mask can further improve the patient's condition, improve the quality of life of the patient, and reduce the risk of adverse reactions and disease recurrence. The higher total effective rate in the combined group indicates that the addition of Alginate Skin Repair Mask to the treatment regimen resulted in improved outcomes for patients with atopic dermatitis (AD). This translates to better control of the disease, reduction in symptoms, and overall improvement in the patient's condition.  However, it is important for clinicians to be aware that the use of topical glucocorticoids like mometasone furoate cream can potentially lead to adverse reactions. Some documented adverse reactions associated with long-term use of topical glucocorticoids include acne-like eruption, telangiectasia (dilation of small blood vessels), and local skin atrophy. By addressing multiple aspects of AD management, including skin barrier repair, moisturization, and inflammation control, the combination of mometasone furoate cream and Alginate Skin Repair Mask provides a more comprehensive treatment approach. This comprehensive approach may contribute to the observed reduction in recurrence rate in the combination group compared to the single group, where only mometasone furoate cream was used.

A novel brick for bispecific antibody construction.

In recent years, the development of bispecific antibodies (bsAbs) has become a major trend in the biopharmaceutical industry. By simultaneously engaging two molecular targets, bsAbs have exhibited unique mechanisms of action that could lead to clinical benefits unattainable by conventional monoclonal antibodies. The type of structure used to construct a bsAb directly influences the distance, angle, degree of freedom, and affinity between the two antibody binding sites and the interaction between the two antigens or the cells where the antigens are located, which have been bound by the antibody. Consequently, the structure of the bsAb is one of the most vital factors affecting its function. Herein, we reported for the first time a novel basic module bsAb format, VFV (Variable domain-Fab-Variable domain). And then, the feasibility of the VFV format was demonstrated by constructing a series of engager-like basic module bsAbs. Next, a series of VFV bsAbs containing Fc (VFV-Ig), Fab (VFV-Fab), or Hinge (VFV-Hinge) were developed based on Hxb module, and all of them had adequate purity and activity. Finally, a T cell engager bsAb with the potential to overcome on-target off-tumor activity was constructed according to the structural characteristics of VFV, which validated that the VFV module can be used as a new brick for the construction of various bsAbs. In a word, the successful construction of this bsAb format for the first time not only enriches the arsenal of the bsAb format, but also provides inspiration for the construction of new bsAbs. Nevertheless, we are fully aware that as a proof-of-concept study, this paper has many shortcomings, and there is still a lot of work to be done to determine whether VFV can serve as a platform for drug development.

Relationship between Antithrombin III Activity and Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

We aimed to explore the role of antithrombin III (AT-III) activity in diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and chronic bronchitis, and its relationship with all-cause mortality of AECOPD patients. We performed univariate and multivariate Cox regression analyses of the factors determining all-cause mortality. We recruited 279 patients with AECOPD and 91 with chronic bronchitis. On admission, patients with AECOPD had lower AT-III activity (80.7 vs. 86.35%, p = 0.002) and higher neutrophil percentages (70.12 vs. 66.40%, p = 0.02) than those with chronic bronchitis. The patients who died were older (78 vs. 73 years, p < 0.001); had higher CRP (39.05 vs. 5.65 mg/L, p < 0.001), D-dimer (1.72 vs. 0.46 mg/L, p < 0.001), FIB (3.56 vs. 3.05 g/L, p = 0.01) levels; and exhibited lower AT-III activity (71.29 vs. 82.94%, p < 0.001) than the survivors. The AT-III area under the receiver operating characteristic curve for predicting COPD all-cause mortality was 0.75 (p < 0.001), optimal cutoff point 79.75%, sensitivity 86.8%, and specificity 57.1%. Multivariate Cox regression analyses showed that increased levels of CRP (HR = 1.005, p = 0.02), D-dimer (HR = 1.17, p = 0.01), WBC count (HR = 1.11, p = 0.002), and reduced AT-III activity (HR = 0.97, p = 0.02) were independent prognostic factors for all-cause mortality. Patients with AT-III ≤ 79.75% were 4.52 times (p = 0.001) more likely to die than those with AT-III > 79.75%. AT-III activity was lower in patients with AECOPD than in those with chronic bronchitis and is potentially useful as an independent predictor of all-cause mortality in patients with AECOPD: reduced AT-III activity and increased CRP and D-dimer levels indicate a higher risk of all-cause mortality.

Serological evidence of bovine viral diarrhea virus and peste des petits ruminants virus infection in alpacas (Vicugna pacos) in Shanxi Province, northern China.

Bovine viral diarrhea virus (BVDV) and peste des petits ruminants virus (PPRV) are two important pathogens associated with a variety of disease syndromes that result in substantial financial losses in animal husbandry. This study was performed to assess the seroprevalence of antibodies to BVDV and PPRV among alpacas raised in Shanxi Province of northern China. Serum samples were obtained from 246 alpacas in Taiyuan (n=182), Xinzhou (n=31), and Jinzhong cities (n=33) of Shanxi Province, and serological testing was carried out using the competitive enzyme-linked immunosorbent assay. Overall seroprevalence to BVDV was 3.25% (95% CI 1.03-5.47), and seropositive alpacas were found only in Taiyuan City. The overall PPRV seroprevalence in alpacas was 28.86% (95% CI 23.20-34.52). While no PPRV-seropositive alpacas were found in Xinzhou City, the seroprevalence of PPRV was 90.91% (95% CI 81.10-100.72) in Jinzhong City and 22.53% (95% CI 16.46-28.60) in Taiyuan City, respectively, which showed a statistically significant difference. To our knowledge, the present work is the first report on seroprevalence of BVDV and PPRV in alpacas in China, which provides baseline information for the control of infection.

Transcripts of antibacterial peptides in chicken erythrocytes infected with Marek's disease virus.

BACKGROUND: Chicken erythrocytes are involved in immunity through binding of toll-like receptors (TLRs) with their ligands to activate downstream signaling and lead to cytokine production in erythrocytes. Some avian ß-defensins (AvBDs) are constitutively expressed in tissues and some others can be induced by various bacteria and viruses. However, the expression of AvBDs in erythrocytes has not yet been studied extensively. RESULTS: The transcripts of eight AvBDs (AvBD1 to AvBD7, and AvBD9) and liver-expressed antimicrobial peptide-2 (LEAP-2) were found in normal chicken erythrocytes. The expression levels of AvBD2, 4 and 7 were significantly increased (P < 0.01), whereas the levels of AvBD1, 6 and 9 were significantly decreased (P < 0.01) after Marek's disease virus (MDV) infection. The mRNA expression level of LEAP-2 was not significantly changed after MDV infection. Highest viral nucleic acid (VNA) of MDV in the feather tips among the tested time points was found at 14 days post-infection (d.p.i.). In addition, 35 MD5-related gene segments were detected in the erythrocytes at 14 d.p.i. by transcriptome sequencing. CONCLUSIONS: These results suggest that the AvBDs in chicken erythrocytes may participate in MDV-induced host immune responses.

Protective effects of zinc and N-acetyl-L-cysteine supplementation against cadmium induced erythrocyte cytotoxicity in Arbor Acres broiler chickens (Gallus gallus domesticus).

Cadmium (Cd) is one of the most toxic metals released into the environment. Here, we investigated the protective role of Zn2+ and/or N-acetyl-L-cysteine (NAC) against Cd cytotoxicity in the erythrocytes of Arbor Acres (AA) broiler chickens. Four hundred one-day-old AA chickens were divided into 12 groups for in vitro and in vivo studies. Zn2+ and/or NAC was given to the Cd exposed AA chickens to assess their protective roles. This was accomplished by investigating nuclear morphological abnormalities, oxidative stress (SOD, CAT, GPx, GSH and T-AOC), cell apoptosis, ROS accumulation and mitochondrial membrane potential (MMP). Results showed that Cd led to dose- and time-dependent cytotoxicity in the erythrocytes of AA chickens characterized by morphological abnormalities, nucleus damage, increased apoptosis rate and antioxidants depletion. Zn2+ or NAC significantly decreased the erythrocyte apoptosis, ROS production and mitochondrial membrane depolarization caused by Cd. SOD, CAT, GPx, GSH and T-AOC activities significantly decreased both in serum and erythrocytes of Cd exposed AA chickens. The supplementation with Zn2+ or NAC alleviated Cd induced oxidative stress through promoting SOD or GPx/GSH activities respectively. NAC presented a better role in reducing apoptosis, improving antioxidant activities more than Zn2+ in vitro. The combined use of Zn2+ and NAC enhanced cytoprotection in Cd exposed erythrocytes of AA chickens compared to Zn2+ or NAC alone. In conclusion, Zn2+ and NAC exerted remarkable protective roles in Cd exposed erythrocytes of AA chickens by inhibiting cell apoptosis and oxidative stress, and this provides a promising approach to antagonize Cd poisoning in poultry.

Effect of Fluoride on Endocytosis and Surface Marker Expression Levels of Mouse B Cells In Vitro.

BACKGROUND/AIMS: To clarify the effect of fluoride on splenic B cells, the endocytosis and surface marker expression levels of mouse splenic B cells were detected in vitro by flow cytometry. METHODS: Cells were stimulated with 10 µg/mL lipopolysaccharide (LPS) and varying concentrations of Sodium Fluoride (NaF) (0, 50 µM, 100 µM, 500 µM, 1000 µM). RESULTS: The results demonstrated that the endocytic capacity of B cells was enhanced by NaF at 50µM. NaF significantly enhanced CD80 expression at 50 µM and decreased CD86 expression at 500 µM. CD40 and CD138 expression on B cells were down-regulated at varying high concentrations of NaF. CONCLUSION: our results showed that the endocytic capacity, expression levels of CD40 and CD80 of B cells changed significantly at lower concentrations, whereas expression levels of CD138 and CD86 changed significantly at higher concentrations, suggesting that fluoride could inhibit immune function in animals.

The PCV3 Cap Virus-like Particle Vaccine with the Chimeric PCV2-Neutralizing Epitope Gene Is Effective in Mice.

Porcine circovirus type 3 (PCV3) infection can cause symptoms similar to those of porcine circovirus type 2 (PCV2) infection, and coinfections with both PCV2 and PCV3 are observed in the swine industry. Consequently, developing chimeric vaccines is essential to prevent and control porcine circovirus infections. In this study, we used both E. coli and mammalian expression systems to express PCV3 Cap (Cap3) and a chimeric gene containing the PCV2-neutralizing epitope within the PCV3 Cap (Cap3-Cap2E), which were assembled into virus-like particle (VLP) vaccines. We found that Cap3 lacking nuclear localization signal (NLS) could not form VLPs, while Cap3 with a His-tag successfully assembled into VLPs. Additionally, the chimeric of PCV2-neutralizing epitopes did not interfere with the assembly process of VLPs. Various immunization approaches revealed that pCap3-Cap2E VLP vaccines were capable of activating high PCV3 Cap-specific antibody levels and effectively neutralizing both PCV3 and PCV2. Furthermore, pCap3-Cap2E VLPs demonstrated a potent ability to activate cellular immunity, protecting against PCV3 infection and preventing lung damage in mice. In conclusion, this study successfully developed a PCV3 Cap VLP vaccine incorporating chimeric PCV2-neutralizing epitope genes, providing new perspectives for PCV3 vaccine development.

Sumoylation activates the transcriptional activity of Pax-6, an important transcription factor for eye and brain development.

Pax-6 is an evolutionarily conserved transcription factor regulating brain and eye development. Four Pax-6 isoforms have been reported previously. Although the longer Pax-6 isoforms (p46 and p48) bear two DNA-binding domains, the paired domain (PD) and the homeodomain (HD), the shorter Pax-6 isoform p32 contains only the HD for DNA binding. Although a third domain, the proline-, serine- and threonine-enriched activation (PST) domain, in the C termini of all Pax-6 isoforms mediates their transcriptional modulation via phosphorylation, how p32 Pax-6 could regulate target genes remains to be elucidated. In the present study, we show that sumoylation at K91 is required for p32 Pax-6 to bind to a HD-specific site and regulate expression of target genes. First, in vitro-synthesized p32 Pax-6 alone cannot bind the P3 sequence, which contains the HD recognition site, unless it is preincubated with nuclear extracts precleared by anti-Pax-6 but not by anti-small ubiquitin-related modifier 1 (anti-SUMO1) antibody. Second, in vitro-synthesized p32 Pax-6 can be sumoylated by SUMO1, and the sumoylated p32 Pax-6 then can bind to the P3 sequence. Third, Pax-6 and SUMO1 are colocalized in the embryonic optic and lens vesicles and can be coimmunoprecipitated. Finally, SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm, and sumoylation significantly enhances the DNA-binding ability of p32 Pax-6 and positively regulates gene expression. Together, our results demonstrate that sumoylation activates p32 Pax-6 in both DNA-binding and transcriptional activities. In addition, our studies demonstrate that p32 and p46 Pax-6 possess differential DNA-binding and regulatory activities.

Rapid quantitative detection of Brucella melitensis by a label-free impedance immunosensor based on a gold nanoparticle-modified screen-printed carbon electrode.

A rapid and simple method for quantitative monitoring of Brucella melitensis using electrochemical impedance spectroscopy (EIS) is reported for the first time. The label-free immunosensors were fabricated by immobilizing Brucella melitensis antibody on the surface of gold nanoparticle-modified screen-printed carbon electrodes (GNP-SPCEs). Cyclic voltammetry (CV) and EIS were used to characterize the Brucella melitensis antigen interaction on the surface of GNP-SPCEs with antibody. A general electronic equivalent model of an electrochemical cell was introduced for interpretation of the impedance components of the system. The results showed that the change in electron-transfer resistance (Rct) was significantly different due to the binding of Brucella melitensis cells. A linear relationship between the Rct variation and logarithmic value of the cell concentration was found from 4 × 10(4) to 4 × 10(6) CFU/mL in pure culture. The label-free impedance biosensor was able to detect as low as 1 × 10(4) and 4 × 10(5) CFU/mL of Brucella melitensis in pure culture and milk samples, respectively, in less than 1.5 h. Moreover, a good selectivity versus Escherichia coli O157:H7 and Staphylococcus aureus cells was obtained for our developed immunosensor demonstrating its specificity towards only Brucella melitensis.

[Involvement of Wnt/ß-catenin signaling in the osteogenesis of bone marrow mesenchymal stem cells induced by drynaria total flavonoids].

OBJECTIVE: To explore the effects of the expression of Wnt/ß-catenin signaling factor mRNA during drynaria total flavonoids on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: The BMSCs were isolated from SD rats by whole bone marrow culture method and purified by passage. And the P3 BMSCs were intervened with 100 µg/ml drynaria total flavonoids. At Day 21, mineralized staining was performed. At Days 7, 14, 21 and 28 post-intervention, the activity of alkaline phosphatase (ALP) was detected and polymerase chain reaction (PCR) used to detect the expressions of Wnt/ß-catenin signaling pathway related factors ß-catenin, LEF-1 and cycline D mRNA. RESULTS: At each time point post-intervention, comparing the ALP activity in cell supernatant between two group, the drynaria total flavonoids group was higher than the blank control group (7 d: 11.10 ± 0.08 vs 1.61 ± 0.14; 14 d: 24.62 ± 0.34 vs 1.64 ± 0.04; 21 d: 18.41 ± 0.06 vs 1.53 ± 0.04; 28 d: 14.9 ± 0.14 vs 1.52 ± 0.04; all P < 0.01). At Day 21, upon staining with alizarin red, the drynaria total flavonoids group was positive while the blank control group negative. At Day 14, the expression of ß-catenin mRNA was higher in the drynaria total flavonoids group higher than that in the blank control group (0.357 ± 0.063 vs 0.174 ± 0.013, P < 0.05). At Day 7, the expressions of LEF-1 and cycline D mRNA were higher in the drynaria total flavonoids group than those in the blank control group (LEF-1 0.0611 ± 0.0002 vs 0.0345 ± 0.0131; cycline D 0.1510 ± 0.0255 vs 0.0718 ± 0.0294, all P < 0.05). CONCLUSION: Drynaria total flavonoids induce BMSCs to differentiate into osteoblasts. And it is accompanied with the altered expression of Wnt/ß-catenin signaling pathway related factor mRNA.

Prevalence of Porcine Circoviruses in Slaughterhouses in Central Shanxi Province, China.

Background: Porcine circovirus disease is currently the greatest threat to pig farming. Four main porcine circovirus genotypes are circulating worldwide. Objective: The study aimed to assess the prevalence of porcine circovirus genotypes in the central part of Shanxi province. Methods: We investigated the prevalence of porcine circovirus type 2 (PCV2), porcine circovirus type 3 (PCV3), and porcine circovirus type 4 (PCV4). Porcine circoviruses were analyzed by polymerase chain reaction (PCR) in the lung tissues of 180 pigs from 7 slaughterhouses in central Shanxi, China. Results: The prevalence of PCV2, PCV3, and PCV4 were 56.8, 80, and 9.4%, respectively, and the negative rate was 10% for all three pathogens. The co-infection with PCV2 + PCV3, PCV2 + PCV4, PCV3 + PCV4, and PCV2 + PCV3 + PCV4 were 47.2, 7.4, 7.4, and 5.6%, respectively. Among PCV4-positive samples, the positive rate of PCV4 + PCV2 was 52.9% (9/17), whereas that of PCV4 + PCV3 was 100% (17/17). On the other hand, PCV2 and PCV3 were detected in 57.1% (93/163) and in 78.5% (128/163) of PCV4-negative samples, respectively. Phylogenetic analysis demonstrated that PCV2, PCV3, and PCV4 were not in the same clade and were distant from each other. Conclusion: The high positive rates of PCV3, PCV2 + PCV3, and PCV3 + PCV4 suggest that PCV3 may play a decisive role in PCV2 and PCV4 infections. Therefore, further control of PCV3 is needed to reduce the spread of the virus.

Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway.

Depression is a mental health problem with typically high levels of distress and dysfunction, and 150 mg/L fluoride (F) can induce depression-like behavior. The development of depression is correlated with neuronal atrophy, insufficient secretion of monoamine neurotransmitters, extreme deviations from the normal microglial activation status, and immune-inflammatory response. Studies found that Se supplementation was related to the improvement of depression. In this study, we applied selenium nanoparticles (SeNPs) for F-induced depression disease mitigation by regulating the histopathology, metabolic index, genes, and protein expression related to the JAK2-STAT3 signaling pathway in vivo. Results showed that F and 2 mg Se/kg BW/day SeNPs lowered the dopamine (DA) content (P < 0.05), altered the microglial morphology, ramification index as well as solidity, and triggered the microglial neuroinflammatory response by increasing the p-STAT3 nuclear translocation (P < 0.01). Furthermore, F reduced the cortical Se content and the number of surviving neurons (P < 0.05), increasing the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 of the cortex (P < 0.01), accompanied by the depression-like behavior. Importantly, 1 mg Se/kg BW/day SeNPs alleviated the microglial ramification index as well as solidity changes and decreased the interleukin-1ß secretion induced by F by suppressing the p-STAT3 nuclear translocation (P < 0.01). Likewise, 1 mg Se/kg BW/day SeNPs restored the F-disturbed dopamine and noradrenaline secretion, increased the number of cortical surviving neurons, and reduced the vacuolation area, ultimately suppressing the occurrence of depression-like behavior through inhibiting the JAK2-STAT3 pathway activation. In conclusion, 1 mg Se/kg BW/day SeNPs have mitigation effects on the F-induced depression-like behavior. The mechanism of how SeNPs repair neural functions will benefit depression mitigation. This study also indicates that inhibiting the JAK/STAT pathway can be a promising novel treatment for depressive disorders.

RAP44 phage integrase-guided 50K genomic island integration in Riemerella anatipestifer.

Bacteriophages are viruses that infect bacteria. Bacteria and bacteriophages have been fighting for survival. Over time, the evolution of both populations has been affected. Pathogenic Flavobacteriaceae species including Riemerella anatipestifer mainly infects ducklings, geese, and turkeys. However, it does not infect humans, rats, or other mammals, and is a suitable and safe research object in the laboratory. Our previous study showed that there is a 10K genomic island in R. anatipestiferIn this study, we found another integrated 50K genomic islands and focused on the relationship between R. anatipestifer genomic islands and the RAP44 phage genome. The phage RAP44 genome was integrated into R. anatipestifer chromosome, and an evolutionary relationship was evident between them in our comparative analysis. Furthermore, the integrated defective RAP44 phage sequence had the function of integration, excision, and cyclization automatically. Integrases are important integration elements. The integrative function of integrase was verified in R. anatipestifer. The integrase with the attP site can be integrated stably at the attB locus of the R. anatipestifer genome. A recombinant strain can stably inherit and express the exogenous gene. By studying the integration between host bacterium and phage, we have provided evidence for the evolution of the genomes in R. anatipestifer.

The small heat shock protein alphaA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis.

The small heat shock protein alphaA-crystallin is a structural protein in the ocular lens. In addition, recent studies have also revealed that it is a molecular chaperone, an autokinase and a strong anti-apoptotic regulator. Besides its lenticular distribution, a previous study demonstrates that a detectable level of alphaA-crystallin is found in other tissues including thymus and spleen. In the present study, we have re-examined the distribution of alphaA-crystallin in various normal human and mouse tissues and found that the normal pancreas expresses a moderate level of alphaA-crystallin. Moreover, alphaA-crystallin is found significantly downregulated in 60 cases of pancreatic carcinoma of different types than it is in 11 normal human pancreas samples. In addition, we demonstrate that alphaA-crystallin can enhance the activity of the activating protein-1 (AP-1) through modulating the function of the MAP kinase, and also upregulates components of TGFbeta pathway. Finally, expression of alphaA-crystallin in a pancreatic cancer cell line, MiaPaCa, results in retarded cell migration. Together, these results suggest that alphaA-crystallin seems to negatively regulate pancreatic carcinogenesis.

Prevalence of porcine respiratory pathogens in slaughterhouses in Shanxi Province, China.

BACKGROUND: Porcine respiratory diseases remain the biggest challenge in pig-based food production and are a public health concern. Despite control measures, persistent outbreaks have been reported worldwide. OBJECTIVE: To establish an early detection mechanism for pig farm disease outbreaks based on slaughterhouse risk and environmental assessment. METHODS: We investigated the prevalence and risk factors of porcine respiratory disease-causing pathogens including Mycoplasma hyopneumoniae (MHP), porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS). Polymerase chain reaction (PCR) was used to analyse the lungs of 491 pigs from 19 slaughterhouses across 11 cities in Shanxi Province, China. RESULTS: PCR detected MHP, PCV2, PPRSV and HPS in 76.99%, 67.00%, 11.82% and 19.55% of the samples, respectively; 10.12% were negative for all four pathogens. Co-positivity rates for two and three pathogens were identified. The results confirmed significant correlations between PCV2 and MHP (p = .001, p < .05), HPS and PCV2 (p = .01, p < .05) and MHP and PRRSV (p = .01, p < .05). No significant correlation was observed between HPS and MHP (p = .067, p > .05). Positive MHP and PCV2 rates were low in areas with high vegetation coverage. The overall pathogen positivity rate was higher in both lower and higher temperature environments. CONCLUSIONS: Interactions among pathogens may increase disease severity. Furthermore, environmental assessment and pathogen surveillance within pig slaughterhouses can be an effective approach for early detection and mitigation of new disease threats before broad dissemination occurs among a herd.