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.

Rational Synthesis of Functionalized Covalent Organic Frameworks via Four-Component Reaction.

The construction of function-oriented covalent organic frameworks (COFs) remains a challenge as it requires simultaneous consideration of diversified structures, robust linkage, and tailorable functionalities. Herein, we report the rational synthesis of functionalized COFs via a four-component reaction strategy. Through the four-component Debus-Radziszewski reaction, 11 N-substituted imidazole-based COFs with diversified structures were facilely constructed from readily available building blocks. By forming the N-substituted imidazole linkage, these synthesized COFs displayed ultrastability toward strong acids and base. Moreover, the four components reaction allows the rational synthesis of COFs with tailorable functionalities. As an example, the phosphonate-functionalized COF (LZU-530) was rationally constructed for the efficient adsorption of uranium(VI). The uranium(VI) uptake of LZU-530 reaches up to 95 mg·g-1 in 2 M HNO3, which is the highest uptake of the existing organic porous materials under such harsh conditions. Our results highlight the use of multicomponent reaction for the rational synthesis of robust and functionalized COFs toward targeted applications.

Supracluster Assembly of Archimedean Cages with 72 Hydrogen Bonds for the Aldol Addition Reaction.

Clusters that can be experimentally precisely characterized and theoretically accurately calculated are essential to understanding the relationship between material structure and function. Here, we propose the concept of "supraclusters", which aim to connect "supramolecules" and "suprananoparticles" as well as reveal the unique assembly behavior of "supraclusters" with nanoparticle size at the molecular level. The implementation of supraclusters is full of challenges due to the difficulty in satisfying the ordered connectivity of clusters due to their abundant and dispersed hydrogen bonding sites. By solvothermal synthesis under a high catechol (H2 CATs) content, we successfully isolated a series of triangular {Al6 M3 } cluster compounds possessing brucite-like structural features. Interestingly, eight {Al6 M3 } clusters form 72-fold strong hydrogen bonding truncatedhexahedron Archimedean {Al6 M3 }8 supracluster cage (abbreviated as H-tcu). Surprisingly, the solution stability of the H-tcu was further proved by electrospray ionization mass spectrometry (ESI-MS) characterization. Therefore, it is not difficult to explain the reason for assembly of H-tcu into edge-directed and vertex-directed isomers. These porous supraclusters can be obtained by scale-up synthesis and exhibit a noticeable catalysis effect towards the condensation of acetone and p-nitrobenzaldehyde. As an intermediate state of supramolecule and suprananoparticle, the supracluster assembly can enrich the cluster chemistry and bring new structural types.

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.

A Chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro.

Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing P. vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-term culture in vitro Conserved across all Plasmodium spp., merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the P. vivax merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients; hence, we incorporate the highly conserved and immunogenic C terminus of both P. vivax merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization of mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature P. vivax schizonts. In the immunized mice, an elevated antibody response was observed in the rPvMSP8+1-immunized group compared to that immunized with single-antigen components. In addition, we examined the growth inhibition of these antibodies against Plasmodium cynomolgi (Berok strain) parasites, which is phylogenetically close to P. vivax and sustains long-term culture in vitro Similarly, the chimeric anti-rPvMSP8+1 antibodies recognize P. cynomolgi MSP8 and MSP1-19 on mature schizonts and showed strong inhibition in vitro via growth inhibition assay. This study provides support for a new multiantigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against P. vivax malaria using sister species P. cynomolgi.

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.

Determination of Flavonoids Compounds of Three Species and Different Harvesting Periods in Crataegi folium Based on LC-MS/MS.

Crataegi folium have been used as medicinal and food materials worldwide due to its pharmacological activities. Although the leaves of Crataegus songorica (CS), Crataegus altaica (CA) and Crataegus kansuensis (CK) have rich resources in Xinjiang, China, they can not provide insights into edible and medicinal aspects. Few reports are available on the qualitative and quantitative analysis of flavonoids compounds of their leaves. Therefore, it is necessary to develop efficient methods to determine qualitative and quantitative flavonoids compounds in leaves of CS, CA and CK. In the study, 28 unique compounds were identified in CS versus CK by qualitative analysis. The validated quantitative method was employed to determine the content of eight flavonoids of the leaves of CS, CA and CK within 6 min. The total content of eight flavonoids was 7.8-15.1 mg/g, 0.1-9.1 mg/g and 4.8-10.7 mg/g in the leaves of CS, CA and CK respectively. Besides, the best harvesting periods of the three species were from 17th to 26th September for CS, from 30th September to 15th October for CA and CK. The validated and time-saving method was successfully implemented for the analysis of the content of eight flavonoids compounds in CS, CA and CK for the first time.

[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.

[Effect of long-term intake of ginseng extracts on gut microbiota in rats].

As a traditional Chinese medicine in China, ginseng has a wide range of medicinal and health value. At present, the nutritional value of ginseng as a medicinal food has been a hotspot in studies. Intestinal flora plays an important role in the organism, which has been confirmed by many researchers. In order to find out the effect of long-term intake of ginseng extracts on the gut microbiota structure of rats, MiSeq sequencing platform was applied in macro gene sequencing of cecal contents in the long-term use of ginseng extracts modelin rats. According to the findings, after long-term administration with ginseng extracts, probiotics such as Bifidobacterium, Lactobacillus, Allobaculum and Clostridium, in the intestinal flora of rats were significantly increased, suggesting that long-term intake of ginseng extracts could facilitate the growth of probiotics. Meanwhile, some pathogenic bacteria, such as Butyricimonas, Parabacteroides, Alistipes, Helicobacter, were significantly down-regulated, indicating that long-term intake of ginseng extracts may have a positive effect in inhibiting the colonization of pathogenic bacteria. In conclusion, this study provided an important basis for the research on the effect of long-term use of ginseng extracts on the intestinal flora of rats.

[Prediction of microRNA-296-5p target genes and its application in lung development].

OBJECTIVE: To predict the target genes of rno-microRNA-296-5p (miR-296) using bioinformatics software and databases, and to provide a theoretical basis for further studies of biological effects of miR-296 in fetal lung development. METHODS: PubMed and Google were used to search for all reported literature on miR-296. The miRBase database was used to determine the sequence and evolutionary conservatism of miR-296. The TargetScans database was used to predict the target genes of miR-296. The DAVID Bioinformatics Resources 6.8 database was used for the functional enrichment analysis of the target genes. The KEGG database was used to analyze the signaling pathways of target genes. RESULTS: miR-296 was reported to play important roles in many biological processes and have a high degree of sequence conservation among species. The target genes of miR-296 were involved in biological processes, cell components, and molecular function. Those target genes were significantly enriched in the mitogen-activated protein kinase signaling pathway, Wnt signaling pathway, and transforming growth factor-ß signaling pathway (p<0.05). CONCLUSIONS: The bioinformatics analysis of the target genes of miR-296 provides a basis for studying biological effects and mechanism of action of miR-296 in lung development.

Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation.

Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia-reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 µM) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.

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.

Altered cortical thickness and structural covariance networks in chronic low back pain.

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

Altered volume of the amygdala subregions in patients with chronic low back pain.

Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.

Microbiota regulates the TLR7 signaling pathway against respiratory tract influenza A virus infection.

Although intestinal flora are crucial in maintaining immune homeostasis of the intestine, the role of intestinal flora in immune responses at other mucosal surfaces remains less clear. Here, we show that intestinal flora composition critically regulates the toll-like receptor 7 (TLR7) signaling pathway following respiratory influenza virus infection. TLR7 ligands rescued the immune impairment in antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for TLR7, MyD88, IRAK4, TRAF6, and NF-κB at steady state. Significant changes in the composition of culturable commensal bacteria reduced the expression levels of components of the TLR7 signaling pathway. Our results reveal the importance of intestinal flora in regulating immunity in the respiratory mucosa through the upregulation of the TLR7 signaling pathway for the proper activation of inflammasomes.

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.

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.