Plasmodium vivax tryptophan-rich antigen reduces type I collagen secretion via the NF-κBp65 pathway in splenic fibroblasts.

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.

Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane.

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.

Breaking the Trade-Off Between Polymer Dielectric Constant and Loss via Aluminum Oxo Macrocycle Dopants for High-Performance Neuromorphic Electronics.

The dielectric layer is crucial in regulating the overall performance of field-effect transistors (FETs), the key component in central processing units, sensors, and displays. Despite considerable efforts being devoted to developing high-permittivity (k) dielectrics, limited progress is made due to the inherent trade-off between dielectric constant and loss. Here, a solution is presented by designing a monodispersed disk-shaped Ce-Al-O-macrocycle as a dopant in polymer dielectrics. The molecule features a central Ce(III) core connected with eight Al atoms through sixteen bridging hydroxyls and eight 3-aminophenyl peripheries. The incorporation of this macrocycle in polymer dielectrics results in an up to sevenfold increase in dielectric constants and up to 89% reduction in dielectric loss at low frequencies. Moreover, the leakage-current densities decrease, and the breakdown strengths are improved by 63%. Relying on the above merits, FETs bearing cluster-doped polymer dielectrics give near three-orders source-drain current increments while maintaining low-level leakage/off currents, resulting in much higher charge-carrier mobilities (up to 2.45 cm2  V-1  s-1 ) and on/off ratios. This cluster-doping strategy is generalizable and shows great promise for ultralow-power photoelectric synapses and neuromorphic retinas. This work successfully breaks the trade-off between dielectric constant and loss and offers a unique design for polymer composite dielectrics.

Systematic analysis of the cuprotosis in tumor microenvironment and prognosis of gastric cancer.

Cuprotosis is a new programmed cell death related to cancer. However, the characteristics of cuprotosis in gastric cancer (GC) remain unknown. Ten cuprotosis molecules from 1544 GC patients were used to identify three GC molecular genotypes. Cluster A was characterized by the best clinical outcome and was significantly enriched in metabolic signaling pathways. Cluster B exhibited elevated immune activation, high immune stroma scores and was significantly enriched in tumor immune signaling pathways. Cluster C was characterized by severe immunosuppression and poor response to immunotherapy. Notably, the citrate cycle, cell cycle, and p53 signaling pathways were enriched in the differentially expressed genes among the three subtypes, which were critical signaling pathways for cell death. We also developed a cuprotosis signature risk score that could accurately predict the survival, immunity, and subtype of GC. This study presents a systematic analysis of cuprotosis molecules and provides new immunotherapeutic targets for GC patients.

E2F1-mediated KDM4A-AS1 up-regulation promotes EMT of hepatocellular carcinoma cells by recruiting ILF3 to stabilize AURKA mRNA.

Hepatocellular carcinoma (HCC) is a gastrointestinal tumor with high clinical incidence. Long non-coding RNAs (lncRNAs) play vital roles in modulating the growth and epithelial-mesenchymal transition (EMT) of HCC. However, the underlying mechanism of lncRNA KDM4A antisense RNA 1 (KDM4A-AS1) in HCC remains elusive. In our study, the role of KDM4A-AS1 in HCC was systematically investigated. The levels of KDM4A-AS1, interleukin enhancer-binding factor 3 (ILF3), Aurora kinase A (AURKA), and E2F transcription factor 1 (E2F1) were determined by RT-qPCR or western blot. ChIP and dual luciferase reporter experiments were performed to detect the binding relationship between E2F1 and KDM4A-AS1 promoter sequence. RIP and RNA-pull down confirmed the interaction of ILF3 with KDM4A-AS1/AURKA. Cellular functions were analyzed by MTT, flow cytometry, wound healing and transwell assays. IHC was performed to detect Ki67 in vivo. We found that KDM4A-AS1 was increased in HCC tissues and cells. Elevated KDM4A-AS1 level was correlated to poor prognosis of HCC. Knockdown of KDM4A-AS1 inhibited the proliferation, migration, invasion and EMT of HCC cells. ILF3 bound to KDM4A-AS1 and AURKA. KDM4A-AS1 maintained the stability of AURKA mRNA by recruiting ILF3. E2F1 transcriptionally activated KDM4A-AS1. Overexpressed KDM4A-AS1 reversed the contribution of E2F1 depletion to AURKA expression and EMT in HCC cells. KDM4A-AS1 promoted tumor formation in vivo through the PI3K/AKT pathway. These results revealed that E2F1 transcriptionally activated KDM4A-AS1 to regulate HCC progression via the PI3K/AKT pathway. E2F1 and KDM4A-AS1 may serve as good prognostic targets for HCC treatment.

Involvement of miR-495 overexpression in the pathogenesis of bronchopulmonary dysplasia in preterm infants via the targeting of NEDD4L-ENaC pathway.

Background: Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication causing morbidity and mortality in preterm infants. A key histopathological feature of BPD is late lung growth retardation, in which the process of alveolarization is hindered and the mechanism of which is unclear. Emerging evidence indicates that microRNAs (miRNAs) promote the development of BPD via the inhibition of their target genes. MiR-495 has been reported to be involved in various lung diseases. However, the physiological function of miR-495 in BPD has not yet been fully understood. Methods: Differentially expressed miRNAs in peripheral blood of patients with BPD were compared with those of normal controls. A dual-luciferase reporter assay was performed to identify the target genes of miR-495. A BPD neonatal rat model was established by injecting lipopolysaccharide (LPS) in the amniotic sac of pregnant rats. The morphology of the lungs was observed using hematoxylin and eosin (HE) staining. The expression of miR-495, neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L), and epithelial Na+ channel (ENaC) was tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot analysis, and immunofluorescent (IF) staining. Results: The expression of miR-495 was significantly increased in the peripheral blood samples of premature infants with BPD and verified using qRT-PCR. NEDD4L was proven to be the target gene of miR-495. Additionally, miR-495 expression was also increased in the lungs of rat pups with BPD at postnatal day (P) 3 compared with the control group. qRT-PCR and Western blot results showed that NEDD4L expression was decreased while ENaC expression was increased at the transcriptional and translational levels. IF staining results showed that NEDD4L level was decreased while ENaC level was increased in the LPS-induced BPD rat model, which was consistent with abnormal changes in alveolar structure. Conclusions: The aberrant overexpression of miR-495 may contribute to the development of BPD by targeting NEDD4L-ENaC pathway, implying an imbalance in lung fluid clearance.

Overview of the preparation method, structure and function, and application of natural peptides and polypeptides.

Natural polypeptides, a kind of molecular polymer with obvious biological activity, are widely existing in nature. They participate in various physiological activities of living organisms and play an important role in promoting human health. They are also widely applied in medicine, food, and cosmetic industries. By searching literature from Pubmed, Google Scholar, Web of Science, Springer Link and Elsevier, this work presents an overview of the preparation methods, the relationship between structure and function, and the application of natural polypeptides. The preparation methods mainly include solvent extraction, enzymatic decomposition, microbiological fermentation, chemical synthesis, genetic engineering recombination, and using cell free system. Natural polypeptide's physiological function mainly includes antioxidative, antibacterial, antihypertensive. This review could provide scientific basis for the research and development of natural polypeptide.

Vaginal foreign bodies in children: a single-center retrospective 10-year analysis.

OBJECTIVE: To evaluate the clinical features and outcome in girls with a vaginal foreign body. METHODS: The clinical data of 97 girls with a vaginal foreign body were collected between 2010 and 2020. The descriptive analysis was used to summarize the clinical characteristics. RESULTS: The patients were aged between 1.5 and 14.8 years, and the age of peak incidence was shown to be 3-10 years, which accounted for 88% of the cases. Blood-stained vaginal discharge or vaginal bleeding was the most common symptom (48%). The most common foreign bodies were small hard objects (57%), followed by bits of cloth or toilet tissue (22%). The patient whose foreign object was a disk battery had the most severe symptoms. When an injury of the vaginal mucosal was suspected, antibiotics were used to prevent infection, with full recovery of all patients without any additional treatment after removal of the foreign object. CONCLUSION: If there is no damage to the vaginal mucosa, no additional treatment is needed after the foreign body is removed. When a vaginal foreign body is suspected to be a battery, emergency surgery is needed to prevent further damage.

Elevated serum leptin levels are associated with lower renal function among middle-aged and elderly adults in Taiwan, a community-based, cross-sectional study.

Background: Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail. Methods: The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia. Results: In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (ß=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia. Conclusion: According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Trifluoromethyl-substituted 3,5-bis(arylidene)-4-piperidones as potential anti-hepatoma and anti-inflammation agents by inhibiting NF-кB activation.

Some methoxy-, hydroxyl-, pyridyl-, or fluoro-substituted 3,5-bis(arylidene)-4-piperidones (BAPs) could reduce inflammation and promote hepatoma cell apoptosis by inhibiting activation of NF-κB, especially after introduction of trifluoromethyl. Herein, a series of trifluoromethyl-substituted BAPs (4-30) were synthesised and the biological activities were evaluated. We successfully found the most potential 16, which contains three trifluoromethyl substituents and exhibits the best anti-tumour and anti-inflammatory activities. Preliminary mechanism research revealed that 16 could promote HepG2 cell apoptosis in a dose-dependent manner by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax, C-caspase-3. Meanwhile, 16 inhibited activation of NF-κB by directly inhibiting the phosphorylation of p65 and IκBα induced by LPS, together with indirectly inhibiting MAPK pathway, thereby exhibiting both anti-hepatoma and anti-inflammatory activities. Molecular docking confirmed that 16 could bind to the active sites of Bcl-2, p65, and p38 reasonably. The above results suggested that 16 has enormous potential to be developed as a multifunctional agent for the clinical treatment of liver cancers and inflammatory diseases.

[Biocontrol effect and mechanism of Bacillus laterosporus Bl13 against early blight disease of tomato]. / 侧孢芽孢杆菌Bl13å¯¹ç•ªèŒ„æ—©ç–«ç— é˜²æ²»æ•ˆæžœåŠæœºåˆ¶.

Bacillus laterosporus Bl13 has good antagonistic effect on the pathogen of tomato early blight (TEB) disease. A pot experiment was conducted to investigate the effect and mechanism of B. laterosporus Bl13 against TEB disease by measuring biological traits such as plant height, stem diameter, disease index of TEB, activity of plant defense enzyme in leaves, and microbial diversity and community composition in root area. The results showed that B. laterosporus Bl13 could significantly reduce the disease index of TEB disease incidence, increase the activity of defensive enzymes including polyphenol oxidase (PPO) and peroxidase (POD) in leaves, and reduce the effects of the disease on the aboveground and root growth of tomato. Meanwhile, B. laterosporus Bl13 improved soil microbial community structure in the root zone, by significantly increasing the relative abundance of plant growth-promoting bacteria (Bacillus and Pseudomonas) and decreasing that of Olpidium and Haematonectria. The results showed that B. laterosporus Bl13 could enhance plant resistance against TEB disease through improving the activity of defensive enzymes in tomato leaves and increasing the number of beneficial microbes in the root zone.

Simultaneous coronary thrombosis with multisite myocardial infarction and complex malignant arrhythmia: A case report.

INTRODUCTION: Acute myocardial infarction with simultaneous coronary thrombosis has been rarely reported. This combination induces various arrhythmias and is a high-risk factor for cardiogenic shock. PATIENT CONCERNS: A 65-year-old man presented with sweating and a 3-h abrupt persistent back pain that radiated to the anterior. DIAGNOSIS: Multisite myocardial infarction, coronary thrombosis with and complex malignant arrhythmia INTERVENTIONS:: Prompt intervention includes cardiac pacing, percutaneous coronary intervention (PCI), thrombus aspiration and intra-aortic balloon pump (IABP). OUTCOMES: The patient was successfully rescued after PCI and thrombus aspiration. CONCLUSIONS: Recognition of dynamic electrocardiographic changes enhances our understanding of the pathogenesis of myocardial infarction.

[Expression of microRNA-495-5p in preterm infants with bronchopulmonary dysplasia: a bioinformatics analysis].

OBJECTIVE: To study the expression of microRNA-495-5p (miRNA-495-5p) in the serum of preterm infants with bronchopulmonary dysplasia (BPD) based on a bioinformatics analysis, and to provide a theoretical basis for further research on the association between miRNA-495-5p and BPD. METHODS: A total of 40 preterm infants who were admitted to the neonatal intensive care unit from January 2015 to December 2016 were enrolled. Among these infants, 20 with early clinical manifestations of BPD were enrolled as the BPD group, and 20 without such manifestations were enrolled as the control group. Peripheral blood samples were collected. The miRNA microarray technique was used to screen out differentially expressed miRNAs in serum between the two groups. RT-PCR was used for validation of results. TargetScan, miRDB, and miRWalk databases were used to predict the target genes of miRNA-495-5p. The DAVID database was used to perform gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the target genes. RESULTS: Compared with the control group, the BPD group had a significant increase in the expression of miRNA-495-5p in serum (P<0.05). A total of 117 target genes of miRNA-495-5p were predicted by the above three databases and they were involved in several molecular functions (including transcriptional regulatory activity, transcriptional activation activity, and transcription cofactor activity), biological processes (such as metabolic regulation, DNA-dependent transcriptional regulation, and vascular pattern), and cell components (including nucleoplasm, membrane components, and insoluble components) (P<0.05). As for signaling pathways, these genes were significantly enriched in the mTOR signaling pathway (P<0.05). CONCLUSIONS: MiRNA-495-5p may be involved in the development and progression of BPD by regulating angiogenesis, stem cell differentiation, apoptosis, and autophagy, which provides clues for further research on the role and functional mechanism of miRNA-495-5p in BPD.

[Nerve-sparing robot-assisted laparoscopic radical cystectomy: Clinical application and effect].

OBJECTIVE: To investigate the clinical feasibility and effect of nerve-sparing robot-assisted laparoscopic radical cystectomy (NSRA-LSRC). METHODS: We retrospectively reviewed the clinical data on 12 cases of NSRA-LSRC performed from March 2016 to May 2018. The patients were aged 45 to 65 years old and all potent before surgery, with a mean IIEF-5 score of >17. The surgical procedure involved excision of the bladder and prostate and dissection of the pelvic lymph nodes, with preservation of the bilateral neurovascular bundles, internal accessory pudendal artery and pubic bladder complex. All the patients were advised to take PDE5I postoperatively and followed up for the sexual function with the IIEF-5 scores. RESULTS: Surgical procedures were completed successfully, all with negative surgical margins. Postoperative pathology confirmed invasive high-grade urothelial carcinoma or carcinoma in situ in all the cases, including 11 cases in stage T2N0M0 or below and 1 case in stage T3aN0M0. There were no serious intraoperative or postoperative complications, nor recurrence or metastasis during the follow-up period of 12－36 (20.7 ± 8.0) months. The IIEF-5 scores of the patients at 3, 6 and 12 months after operation were 10.9 ± 6.9, 12.3 ± 6.9 and 14.1 ± 8.0, respectively. At 12 months, satisfactory sexual intercourse was achieved with the help of potency-enhancing medicine in 5 cases (41.7%), penile erection insufficient for sexual intercourse in 3 cases (25%), and no erection in 4 cases (33.3%). CONCLUSIONS: Nerve-sparing robot-assisted laparoscopic radical cystectomy can maximally preserve the sexual function of the patients with urinary bladder carcinoma.