Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice.

BACKGROUND: Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage. METHODS: Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney. RESULTS: Cdk5 was found to be activated by HG stimulation both in vitro and in vivo. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of in vivo experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia. CONCLUSION: Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5.

High resolution imaging of acoustic orbital angular momentum wave based on orthogonal matching tracking.

The orbital angular momentum (OAM) wave has shown great potential for improving radar imaging and underwater communication performance due to its helical wavefront phase and infinite orthogonal modes. However, there are currently no known applications of this technology in underwater imaging. In this paper, we employed acoustic OAM wave for underwater imaging and established transceiver signal models using the uniform circular array. We concurrently achieved two-dimensional imaging of azimuth and elevation angles, which differs from radar imaging. We proposed a matching process for the echo signal in the modal domain, the OAM wave beam image's sidelobe decreased by 7.9 dB in the elevation direction and 6.1 dB in the azimuth direction compared to the plane wave, with the mainlobe decreased by 0.2° in the elevation direction and 0.4° in the azimuth direction. Furthermore, this paper introduced OAM wave high-resolution image reconstruction based on the orthogonal matching pursuit (OMP) algorithm. Finally, we implemented broadband acoustic OAM wave for underwater imaging and introduced an image reconstruction method based on the modal domain OMP algorithm. Simulation results demonstrate that the use of OAM wave in underwater imaging is feasible, and the proposed scheme can achieve high-resolution imaging.

Erratum: MiR-375 Has Contrasting Effects on Newcastle Disease Virus Growth Depending on the Target Gene : Erratum.

[This corrects the article DOI: 10.7150/ijbs.25106.].

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China.

Newcastle disease virus (NDV) threatens global poultry production, with genotype VII the most prevalent strain in China. However, little information is available regarding viral multiplication and pathogenicity based inoculation route. The objectives of this study were to sequence NDV VII isolates and to analyze their biological characteristics in detail. A total of 86 oral and cloacal swabs were collected from Shaanxi and Gansu provinces in northwest China. Identification of genotype VII NDV based on the M gene was performed by qPCR. Viral multiplication and pathogenicity were assessed as a function of route of infection. We observed increased morbidity and mortality using intravenous injection, whereas intranasal, intraocular, and cloacal infections resulted in slower progression and milder clinical disease, with viral proliferation obvious in different tissues. These results provide an important basis for the clinical control and prevention of NDV epidemics in poultry.

Application value of structured psychological nursing combined group health education in blood purification patients: Assisted by the purification of a nanofiber composite.

To explore the research value of structured psychological nursing combined with group health education in patients with blood purification. From May 2020 to March 2022, 96 pure-blood patients in the hospital were selected and divided into research group and control group according to simple random classification, with 48 patients in each group. The control group received routine nursing, and the study group conducted health education combined with structured psychological nursing on the basis of usual care. The disease cognitive ability, negative emotions, blood purification adequacy rate, nutritional status qualification rate and complication rate of the two groups before and after intervention were counted. (1) The number of disease points with unclear status in the study group after intervention was 10.39 ± 1.87, complications were 13.88 ± 2.27, lack of disease information was 12.36 ± 2.16, and unpredictability was 9.58 ± 1.38, which were lower than 13.12 ± 2.53, 17.56 ± 2.53, 15.83 ± 3.0411.67 ± 1.71; (2) After the intervention, the values of SDS of 40.77 ± 3.69 and SAS of 41.52 ± 4.06 were lower than those of 45.82 ± 5.01 and 46.35 ± 4.81 in the control group. (3) The blood adequacy rate of the study group was 91.67%, and the nutritional qualification rate was 93.75%, and the data of both groups were higher than that of 77.08% and 79.17% of the control group. (4) The incidence of complications in the study group was 4.17%, and the control group was 16.67%. Group health education and structured psychological care can effectively alleviate patients' negative emotions and deepen their awareness of diseases, thereby improving blood purification rate and nutrient absorption.

High quality AlN film assisted by graphene/sputtered AlN buffer layer for deep-ultraviolet-LED.

The advantages of van der Waals epitaxial nitrides have become a research hot topic. It is worth noting that graphene plays an important role in the research of epitaxial AlN epitaxial layer. In this work, we demonstrate a method to obtain high-quality and low-dislocation AlN epitaxial layer by combining graphene and sputtered AlN as the nucleation layer on the C-sapphire substrate via metal organic chemical vapor deposition, and successfully fabricated a 277 nm AlGaN-based deep ultraviolet light emitting diode (DUV-LED) based on the obtained AlN epitaxial layer. The presence of graphene promotes the stress release of AlN. Compared with the AlN epitaxial layer directly grown on graphene/sapphire substrate, the exist of sputtered AlN/graphene nucleation layer facilitates most of the threading dislocations in AlN can annihilate each other in the range of about 100 nm. Thus, as grown AlN epitaxial layer shows the decreasing of the screw dislocation from 2.31 × 109to 2.08 × 108cm-2significantly. We manufacture an DUV-LED with 277 nm emission wavelength by using high-quality AlN films, which shows that magnitude of the leakage current is only on the order of nanoamperes and the forward turn on voltage is 3.5 V at room temperature. This study provides a meaningful strategy to achieve high-quality AlN film and high-performance DUV-LED.

Identification of a new amino acid mutation in the HN protein of NDV involved in pathogenicity.

The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.

Flexible High-Stability Self-Variable-Voltage Monolithic Integrated System Achieved by High-Brightness LED for Information Transmission.

The emergence of visible light information transmission systems is profoundly affecting the future of the Internet of Things (IoT) technology. The complex sensing and driving circuits of the IoT have become the key factor to hinder signal conversion and processing. Herein, a high-performance self-variable-voltage light information transmission integrated system (SVV-LTS) is reported and its application potential in low-power, self-powered optical communication transmission systems is demonstrated. Diffusion-adsorption regulation growth method and laser induction technology are innovatively used to realize high-brightness light-emitting diode (LED) and flexible micro-supercapacitor (MSC) on graphene. Meanwhile, MSC realizes the dual functions of supplying power to the system, realizing pressure signal response, and converting pressure signals into electrical signals. Finally, the MSC as power, sensor and LED as signal transmitter are integrated into an SVV-LTS. The response time of SVV-LTS is 80 ms and the luminous wavelength fluctuation of the LED is stable at 1.2 nm. This study will provide a new approach to realize low-power optical communication transmission systems affecting the IoT technology.

Detection of acute myocarditis using T1 and T2 mapping cardiovascular magnetic resonance: A systematic review and meta-analysis.

OBJECTIVES: This study was aimed to systematically review the existing literature and explore more the diagnostic value of T1 and T2 mapping in acute myocarditis. METHODS: Studies were searched from five electronic databases. Sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) were calculated to present diagnostic performance. A meta-regression and subgroup analysis was performed based on validation (endomyocardial biopsy [EMB] vs. clinical criteria). RESULTS: A total of 10 studies were included, with 400 myocarditis patients and 266 controls. Native T1, T2, and extracellular volume (ECV) values were significantly increased in the myocarditis group. Pooled sensitivities for T1, T2 mapping, and ECV were 0.84 (0.78-0.88), 0.77 (0.69-0.83), and 0.69 (0.50-0.83), respectively. Pooled specificities were 0.86 (0.69-0.95), 0.83 (0.73-0.89), and 0.77 (0.63-0.87), respectively. The DORs were 32 (12-87), 16 (8-30), and 7 (4-14), respectively. The areas under the curve (AUC) of SROC were 0.87 (0.84-0.90), 0.86 (0.82-0.89), and 0.80 (0.76-0.83), respectively. In the meta-regression and subgroup analysis, significantly lower specificities of T1 and T2 mapping were observed in EMB studies (p < 0.01). CONCLUSION: The currently available evidence shows that T1 and T2 mapping including ECV alone offer comparably good diagnostic performance for the detection of acute myocarditis. The reason for the observed mismatch with EMB findings should be further investigated.

High-Quality Transferred GaN-Based Light-Emitting Diodes through Oxygen-Assisted Plasma Patterning of Graphene.

Two-dimensional (2D) release layers are commonly used to realize flexible nitride films. Here, high-quality, large-area, and transferable nitride films can be precisely controlled grown on O2-plasma-assisted patterned graphene. The first-principles calculation indicates that the patterned graphene introduced by O2 plasma changes the original wettability of sapphire and the growth behavior of Al atoms is related with layer number of graphene, which is consistent with experimental results. The as-fabricated violet GaN-based light-emitting diodes (LEDs) show high stability and high light output power (LOP). This work provides a general rule for the growth of high-quality and transferable III-nitride films on graphene from the atomic scale and provide actual demonstration in LED. The advantages of the proposed new growth method can supply new ways for electronic and optoelectronic flexible devices of group III nitride semiconductors.

Comparative biology of two genetically closely related Newcastle disease virus strains with strongly contrasting pathogenicity.

A lentogenic strain of Newcastle disease virus (NDV) with an intracerebral pathogenicity index (ICPI) of 0.36 was derived by the passage of a mesogenic NDV isolate with an original ICPI of 1.04. Animal experiments showed that the original strain caused much severer clinical signs and mortality than the derived strain in chickens. To elucidate the molecular reason for this virulence change, the complete viral genomes of the original and derived strains were sequenced. Molecular analysis showed that both viruses contained the same fusion (F) protein with a cleavage site (Fcs) motif that is usually associated with velogenic viruses. Molecular comparison revealed five amino acid (aa) differences in nucleoprotein (NP) (aa 426), hemagglutinin-neuraminidase (HN) (aas 215 and 430), and large protein (L) (aas 1694 and 1767), accompanied by the changes of relevant biological activities in membrane fusion and replication. Thus, we believe that the virulence changes may induced by these mutations. Our findings make a foundation for more in-depth investigations of the molecular mechanism underlying virulence.

Evasion of Host Antiviral Innate Immunity by Paramyxovirus Accessory Proteins.

For efficient replication, viruses have developed multiple strategies to evade host antiviral innate immunity. Paramyxoviruses are a large family of enveloped RNA viruses that comprises diverse human and animal pathogens which jeopardize global public health and the economy. The accessory proteins expressed from the P gene by RNA editing or overlapping open reading frames (ORFs) are major viral immune evasion factors antagonizing type I interferon (IFN-I) production and other antiviral innate immune responses. However, the antagonistic mechanisms against antiviral innate immunity by accessory proteins differ among viruses. Here, we summarize the current understandings of immune evasion mechanisms by paramyxovirus accessory proteins, specifically how accessory proteins directly or indirectly target the adaptors in the antiviral innate immune signaling pathway to facilitate virus replication. Additionally, some cellular responses, which are also involved in viral replication, will be briefly summarized.

Identification of Newcastle disease virus P-gene editing using next-generation sequencing.

Avian paramyxoviruses 1 has the ability to edit its P gene to generate three amino-coterminal proteins (P, V and W), but its kinetic change is unclear. In this study, next-generation sequencing (NGS) was used to analyze the P-gene editing of Newcastle disease virus (NDV). Transcriptome analysis of chicken embryonic tissues and bursa of fabricius showed the P-gene editing frequencies were 45.46-52.70%. To investigate the rules of P-gene editing along time, the ratio of PVW was determined by PCR based deep sequencing at multiple time points in cells infected with velogenic and lentogenic strain respectively. The results confirmed similar editing frequencies with transcriptome data and the PVW ratios were stable along time among different NDVs, but had a greater V-gene transcript on velogenic strain infection (P<0.001), which were different from previous reports. Also, it was shown that the number of inserted G residues in P-derived transcripts was not limited to +9G, and +10G transcripts were identified. These results confirmed the NDV P-gene editing frequencies and provided a novel point of view on NDV P-gene editing with NDV virulence.

Screening and mechanistic study of key sites of the hemagglutinin-neuraminidase protein related to the virulence of Newcastle disease virus.

Newcastle disease is a kind of avian infectious disease caused by Newcastle disease virus (NDV). The virulence of NDV is dependent mainly on the fusion (F) protein and hemagglutinin-neuraminidase (HN) protein. The genomes of 2 viruses, NDV-Blackbird and NDV-Dove, are 99.9% similar, while NDV-Blackbird is a velogenic virus, and NDV-Dove is a lentogenic virus. Further analysis revealed that the F proteins of the 2 strains were identical, and only 5 amino acid sites on the HN proteins were inconsistent. Five different HN mutant plasmids were constructed and analyzed in this study. The results showed that the mutation F110L caused a significant increase in fusion-promotion activity caused by an increase in neuraminidase activity. Because of the increase in receptor-binding activity caused by G116R, there was a significant increase in fusion-promotion activity. The mutation G54S resulted in a slight decrease in the fusion-promotion activity caused by a slight decrease in receptor-binding activity. The slight increase in the fusion-promotion activity caused by A469V was associated with a significant increase in neuraminidase activity. Therefore, the amino acids L110 and R116 played a key role in determining the virulence difference between NDV-Blackbird and NDV-Dove, which could lay a foundation for illuminating the virulence differences of NDV strains, as well as the development of attenuated vaccines.

MicroRNA gga-miR-455-5p suppresses Newcastle disease virus replication via targeting cellular suppressors of cytokine signaling 3.

Newcastle disease (ND) is an acute and contagious avian disease caused by Newcastle disease virus (NDV). MicroRNAs (miRNAs) play a significant role in host-pathogen interactions and the innate immune response. However, the role of miRNAs in the host response to NDV infection is not clearly understood. In this study, we showed that expression of the cellular miRNA gga-miR-455-5p was downregulated in vivo and in vitro in response to NDV infection. Next, we found that the transfection of chicken embryonic fibroblasts (CEFs) with gga-miR-455-5p suppressed NDV replication, while the blockade of endogenous gga-miR-455-5p expression with inhibitors enhanced NDV replication. In addition, gga-miR-455-5p enhanced the expression of type I interferon and the interferon-inducible genes (ISGs) OASL and Mx1 by targeting SOCS3, a negative regulator of type I IFN signaling. Altogether, these findings highlight the crucial role of gga-miR-455-5p in host defense against NDV by targeting the SOCS3 gene to inhibit NDV replication.

Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway.

Newcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity are not well-understood. The suppressor of cytokine signaling 3 (SOCS3) inhibits the type I interferon-dependent antiviral signaling pathway by utilizing a feedback loop. In this study, we analyzed the transcriptome data of the chicken embryo and BF infected with NDV and found significant upregulation of SOCS3. Next, we demonstrated that NDV infection and nonstructural V protein induced the up-regulation of SOCS3. Furthermore, we showed that overexpression of SOCS3 facilitated viral replication and reduced the expression of phosphorylation STAT1, MX1, and OASL, while inhibition of SOCS3 with siRNAs reduced virus replication and promoted the expression of phosphorylation STAT1, MX1, and OASL. Finally, we demonstrated that the MEK/ERK signaling pathway was involved in the expression of SOCS3 mediated by NDV infection and V protein transfection, and using specific inhibitor U0126 to block this signaling pathway attenuated SOCS3 expression and inhibited NDV replication through promoting the expression of type I interferon, OASL and MX1. Taken together, these data demonstrate that NDV infection and NDV nonstructural V protein activates the expression of SOCS3 at the mRNA and protein level through a mechanism dependent on the MEK/ERK signaling pathway, which benefits virus replication.

Insights into the chicken bursa of fabricius response to Newcastle disease virus at 48 and 72 hours post-infection through RNA-seq.

Newcastle disease virus (NDV) causes significant economic losses to the poultry industry worldwide. As a lymphoid organ, the bursa of Fabricius (BF) plays a pivotal role in destroying invading pathogens. Virulent NDV strains can cause rapid atrophy of the BF; however, there is limited knowledge regarding the BF innate immune response to NDV infection. In this study, we used the virulent NDV strain F48E9 to infect four-week-old chickens and found atrophy of the BF, with severe damage and high NDV viral loads after NDV infection in dying chickens. To better understand the interactions between the host and NDV, we compared the transcriptional profiles at 48 and 72 h following infection with the virulent NDV strain F48E9 using RNA-seq. We identified a total of 1498 differentially expressed genes (DEGs), which were enriched in a variety of biological processes and pathways according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The enriched pathways were associated with innate immune and inflammatory responses as well as metabolism-related signalling pathways. Excessive inflammatory and innate immune responses induced by the NDV strain may be related to severe BF damage. The global survey of changes in gene expression performed herein provides new insights into complicated molecular mechanisms underlying the interaction between NDV and chickens and will enable the use of new strategies to protect chickens against NDV.

Truncated chicken MDA5 enhances the immune response to inactivated NDV vaccine.

Melanoma Differentiation-Associated protein 5 (MDA5) is a cytoplasmic sensor for viral invasion and plays an important role in regulation of the immune response against Newcastle disease virus (NDV) in chickens. MDA5 was used as an adjuvant to enhance the humoral immune response against influenza virus. In the current study, truncated chicken MDA5 [1-483 aa, chMDA5(483aa)] expressed by recombinant adenovirus was administered to specific-pathogen-free (SPF) chickens to improve the immune response induced by inactivated NDV vaccine. A total of 156 SPF chickens were divided into six groups, and after two rounds of immunization, the humoral immune response, cell-mediated immune (CMI) response and the protective efficacy of the vaccines against NDV challenge were evaluated. The results showed that co-administration of chMDA5(483aa) expressed by adenovirus increased the NDV-specific antibody response by 1.7 times and chickens received chMDA5(483aa) also gained a higher level of CMI response. Consistently, the protective efficacy of the inactivated NDV vaccine against virulent NDV (vNDV) challenge was improved by co-administrate with chMDA5(483aa), as indicated by the reduced morbidity and pathological lesions, lower levels of viral load in organs and reduced virus shedding. Our study demonstrated that chMDA5(433aa) expressed by adenovirus could enhance the immune efficacy of inactivated NDV vaccine in chickens and could be a potential adjuvant candidate in developing chicken NDV vaccines.

MiR-375 Has Contrasting Effects on Newcastle Disease Virus Growth Depending on the Target Gene.

MicroRNAs regulate post-transcriptional gene expression via either translational repression or mRNA degradation. They have important roles in both viral infection and host anti-infection processes. We discovered that the miR-375 is significantly upregulated in Newcastle disease virus (NDV)-infected chicken embryonic visceral tissues using a small RNA sequencing approach. Further research revealed that the overexpression of miR-375 markedly decreases the replication of the velogenic NDV F48E9 and the lentogenic NDV La Sota by targeting the M gene of NDV in DF-1 cells. Interestingly, miR-375 has another target, ELAVL4, which regulates chicken fibrocyte cell cycle progression and decreases NDV proliferation. In addition, miR-375 can influence bystander cells by its secretion in culture medium. Our results indicated that miR-375 is an inhibitor of NDV, but can also enhance NDV growth by reducing the expression of its target ELAVL4. These results emphasize the complex roles of microRNAs in the regulation of viral infections.

High level expression of ISG12(1) promotes cell apoptosis via mitochondrial-dependent pathway and so as to hinder Newcastle disease virus replication.

Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV), poses a considerable risk for the poultry industry. A comprehensive understanding of the interaction between NDV and its host is therefore critical for control of this disease. Previously, we found that chicken ISG12(1) was among the significantly upregulated interferon-stimulated genes (ISGs) in embryos and the bursa of Fabricius of chickens infected by NDV, based on transcriptome sequencing. However, its antiviral effects and function were poorly understood. In this study, we aimed to determine the effects of chicken ISG12(1) on NDV replication. First, we confirmed that NDV infection stimulated high level expression of chicken ISG12(1) in vivo and in vitro based on RT-qPCR. Next, through overexpression and knockdown experiments, the antiviral activity of ISG12(1) was investigated. As expected, this protein was found to hinder NDV replication. In addition, we showed that ISG12(1) localized to the mitochondria; promoted the redistribution of Bax, a proapoptotic protein causing irreversible loss of mitochondrial function, from the cytoplasm to the mitochondria; and therefore induced cell apoptosis. In conclusion, elucidation of the role of chicken ISG12(1) in combatting NDV infection contributes to our understanding of the responses of poultry to viruses and may facilitate the generation of more efficient vaccines to control ND.