The tripartite motif (TRIM) protein family is an E3 ubiquitin ligase family. Recent reports have indicated that some TRIM proteins have antiviral functions, especially against retroviruses. However, most studies mainly focus on the relationship between TRIM21 and interferon or other antiviral effectors. The effect of TRIM21 on virus-encoded proteins remains unclear. In this study, we screened candidate interacting proteins of HBV DNA polymerase (Pol) by FLAG affinity purification and mass spectrometry assay and identified TRIM21 as its regulator. We used a coimmunoprecipitation (co-IP) assay to demonstrate that TRIM21 interacted with the TP domain of HBV DNA Pol. In addition, TRIM21 promoted the ubiquitination and degradation of HBV DNA Pol using its RING domain, which has E3 ubiquitin ligase activity. Lys260 and Lys283 of HBV DNA Pol were identified as targets for ubiquitination mediated by TRIM21. Finally, we uncovered that TRIM21 degrades HBV DNA Pol to restrict HBV DNA replication, and its SPRY domain is critical for this activity. Taken together, our results indicate that TRIM21 suppresses HBV DNA replication mainly by promoting the ubiquitination of HBV DNA Pol, which may provide a new potential target for the treatment of HBV.

No abstract available

The yellow nutsedge (Cyperus esculentus L. 1753) is an unconventional oil plant with oil-rich tubers, and a potential alternative for traditional oil crops. Here, we reported the first high-quality and chromosome-level genome assembly of the yellow nutsedge generated by combining PacBio HiFi long reads, Novaseq short reads, and Hi-C data. The final genome size is 225.6 Mb with an N50 of 4.3 Mb. More than 222.9 Mb scaffolds were anchored to 54 pseudochromosomes with a BUSCO score of 96.0%. We identified 76.5 Mb (33.9%) repetitive sequences across the genome. A total of 23,613 protein-coding genes were predicted in this genome, of which 22,847 (96.8%) were functionally annotated. A whole-genome duplication event was found after the divergence of Carex littledalei and Rhynchospora breviuscula, indicating the rich genetic resources of this species for adaptive evolution. Several significantly enriched GO terms were related to invasiveness of the yellow nutsedge, which may explain its plastic adaptability. In addition, several enriched Kyoto Encyclopedia of Genes and Genomes pathways and expanded gene families were closely related with substances in tubers, partially explaining the genomic basis of characteristics of this oil-rich tuber.

Anaerobic fungi are effective fibre-degrading microorganisms in the digestive tract of horses. However, our understanding of their diversity and community structure is limited, especially in different parts of the gastrointestinal tract.

Spinal cord injury (SCI) could lead to severe disabilities in motor and sensory functions, and cause a heavy burden on patient physiology and psychology due to lack of specific repair measures so far. ANXA7 is an annexin with Ca2+ -dependent GTPase activity, which were mainly expressed in neuron in spinal cord and downregulated significantly after SCI in mice. In our study, GTPase activity activation of ANXA7 plays the protective role in neuron after OGD/R through inhibiting neuron apoptosis, which mediated by enhancing autophagy via mTOR/TFEB pathway. We also discovered that ANXA7 has significant interaction with neural-specific lysosomal-associated membrane protein LAMP5, which together with ANXA7 regulates autophagy and apoptosis. Asp411 mutation of ANXA7 obviously impaired the interaction of ANXA7 and LAMP5 compared with the wild type. Furthermore, it was found that activation of ANXA7 could help to stabilize the protein expression of LAMP5. Overexpression of LAMP5 could attenuate the destruction of lysosomal acidic environment, inhibition of autophagy and activation of apoptosis caused by ANXA7 downregulation after OGD/R. We verified that injecting ANXA7 overexpression lentivirus and activation of ANXA7 both have significant repair effects on SCI mice by using CatWalk assay and immunohistochemistry staining. In summary, our findings clarify the new role of ANXA7 and LAMP5 in SCI, provided a new specific target of neuronal repair and discovered new molecular mechanisms of ANXA7 to regulate autophagy and apoptosis. Targeting ANXA7 may be a prospective therapeutic strategy for SCI in future.

Evidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood.

Antioxidant proteins perform significant functions in disease control and delaying aging which can prevent free radicals from damaging organisms. Accurate identification of antioxidant proteins has important implications for the development of new drugs and the treatment of related diseases, as they play a critical role in the control or prevention of cancer and aging-related conditions. Since experimental identification techniques are time-consuming and expensive, many computational methods have been proposed to identify antioxidant proteins. Although the accuracy of these methods is acceptable, there are still some challenges. In this study, we developed a computational model called ANPrAod to identify antioxidant proteins based on a support vector machine. In order to eliminate potential redundant features and improve prediction accuracy, 673 amino acid reduction alphabets were calculated by us to find the optimal feature representation scheme. The final model could produce an overall accuracy of 87.53% with the ROC of 0.7266 in five-fold cross-validation, which was better than the existing methods. The results of the independent dataset also demonstrated the excellent robustness and reliability of ANPrAod, which could be a promising tool for antioxidant protein identification and contribute to hypothesis-driven experimental design.

Understanding the tabletability change of materials after granulation is critical for the formulation and process design in tablet development. In this paper, a material library consisting of 30 pharmaceutical materials was used to summarize the pattern of change of tabletability during high shear wet granulation and tableting (HSWGT). Each powdered material and the corresponding granules were characterized by 19 physical properties and nine compression behavior classification system (CBCS) parameters. Principal component analysis (PCA) was used to compare the physical properties and compression behaviors of ungranulated powders and granules. A new index, namely the relative change of tabletability (CoTr), was proposed to quantify the tabletability change, and its advantages over the reworking potential were demonstrated. On the basis of CoTr values, the tabletability change classification system (TCCS) was established. It was found that approximately 40% of materials in the material library presented a loss of tabletability (i.e., Type I), 50% of materials had nearly unchanged tabletability (i.e., Type II), and 10% of materials suffered from increased tabletability (i.e., Type III). With the help of tensile strength (TS) vs. compression pressure curves implemented on both powders and granules, a data fusion method and the PLS2 algorithm were further applied to identify the differences in material properties requirements for direct compression (DC) and HSWGT. Results indicated that increasing the plasticity or porosity of the starting materials was beneficial to acquiring high TS of tablets made by HSWGT. In conclusion, the presented TCCS provided a means for the initial risk assessment of materials in tablet formulation design and the data modeling method helped to predict the impact of formulation ingredients on the strength of compacts.

Argonaute 2 (AGO2), the only protein with catalytic activity in the human Argonaute family, is considered as a key component of RNA interference (RNAi) pathway. Here we performed a yeast two-hybrid screen using the human Argonaute 2 PIWI domain as bait to screen for new AGO2-interacting proteins and explored the specific mechanism through a series of molecular biology and biochemistry experiments.

Maintaining the integrity of the blood-spinal cord barrier is critical for the recovery of spinal cord injury. Ferroptosis contributes to the pathogenesis of spinal cord injury. We hypothesized that ferroptosis is involved in disruption of the blood-spinal cord barrier. In this study, we administered the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal cord injury in rats. Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord injury. Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein. Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury, as shown by the immunofluorescence of an endothelial cell marker (rat endothelium cell antigen-1, RECA-1) and ferroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Liproxstatin-1 reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Furthermore, inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment. In summary, liproxstatin-1 improved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-spinal cord barrier integrity.

On the basis of mouse I-Ab-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization of Apoe-/- mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development. Finally, P6-specific T cell clones were generated and adoptive transfer of T cell clones into recipients fed an HFD led to significant increase in aortic plaque coverage when compared to control animals receiving a MOG35-55-specific T cell line. Recipient mice not fed an HFD, however, did not exhibit such enhancement, indicating that an inflammatory environment facilitated the atherogenic activity of P6-specific T cells. That P6 is identical to or cross-reacts with a naturally processed peptide of ApoB-100 is evidenced by the ability of P6 to stimulate the proliferation of T cells in the lymph node of mice primed by full-length human ApoB-100. By identifying an atherogenic T cell epitope of ApoB-100 and establishing specific T cell clones, our studies open up new and hitherto unavailable avenues to study the nature of atherogenic T cells and their functions in the atherosclerotic disease process.

Flax is an important crop for oil and fiber, however, no high-density genetic maps have been reported for this species. Specific length amplified fragment sequencing (SLAF-seq) is a high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. In this study, SLAF-seq was employed to develop SNP markers in an F2 population to construct a high-density genetic map for flax. In total, 196.29 million paired-end reads were obtained. The average sequencing depth was 25.08 in male parent, 32.17 in the female parent, and 9.64 in each F2 progeny. In total, 389,288 polymorphic SLAFs were detected, from which 260,380 polymorphic SNPs were developed. After filtering, 4,638 SNPs were found suitable for genetic map construction. The final genetic map included 4,145 SNP markers on 15 linkage groups and was 2,632.94 cM in length, with an average distance of 0.64 cM between adjacent markers. To our knowledge, this map is the densest SNP-based genetic map for flax. The SNP markers and genetic map reported in here will serve as a foundation for the fine mapping of quantitative trait loci (QTLs), map-based gene cloning and marker assisted selection (MAS) for flax.

This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks.

The MYB transcription factor family can regulate biological processes such as ABA signal transduction to cope with drought stress, but its evolutionary mechanism and the diverse pathways of response to drought stress in different species are rarely reported. In this study, a total of 4791 MYB family members were identified in 908,757 amino acid sequences from 12 model plants or crops using bioinformatics methods. It was observed that the number of MYB family members had a linear relationship with the chromosome ploidy of species. A phylogenetic analysis showed that the MYB family members evolved in subfamily clusters. In response to drought stress, the pathways of MYB transcription factor families exhibited species-specific diversity, with closely related species demonstrating a higher resemblance. This study provides abundant references for drought resistance research and the breeding of wheat, soybean, and other plants.

Povidone-iodine (PVI) is principally used as an antimicrobial agent. It has been found that 0.5% PVI can attenuate congestion, edema and pain induced by pressure sores. Thus this study aimed to assess the effects of 0.5% PVI on acute skin wounds. Four full-thickness excisional wounds were generated on the dorsal skin of male Sprague-Dawley rats with a 10-mm sterile punch. Two wounds were left untreated and the other two were dressed with gauze with 0.5% PVI for 1 hour per day for the first 5 days after injury. 10-mm full-thickness excisional wounds were also generated on the dorsal skin of rats treated with 10 mg/kg SB431542 and all wounds were treated with 0.5% PVI for 5 days. PVI treatment enhanced wound healing via promotion of expression of α SMA and TGF β, neovascularization and re-epithelialization. Interleukin 6 was reduced following PVI treatment. Inhibition of TGF β abolished the effect of PVI treatment on wound closure. These data show that topical application of 0.5% PVI could promote acute skin wound healing though increased expression of TGF β leading to enhanced formation of granulation tissue, even in the absence of obvious infection.

Cardiopulmonary bypass (CPB) results in severe lung injury via inflammation and endothelial injury. The aim of this study was to evaluate the effect of endothelial colony-forming cells (ECFCs) on lung injury in rats subjected to CPB.

We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection. We found that HBV-miR-3 expression gradually increased in a dose- and time-dependent manner in HBV-infected HepG2-NTCP cells. HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes, thereby enhancing the IFN-induced anti-HBV effect. In addition, HBV-miR-3 in exosomes facilitated the M1 polarization of macrophages. Furthermore, exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR. In short, these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways, which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.

Argatroban is a synthetic thrombin inhibitor approved by U.S. Food and Drug Administration for the treatment of thrombosis. However, whether it plays a role in the repair of spinal cord injury is unknown. In this study, we established a rat model of T10 moderate spinal cord injury using an NYU Impactor Moder III and performed intraperitoneal injection of argatroban for 3 consecutive days. Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord. RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway, which is involved in astrogliosis and glial scar formation. Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway. Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord. Taken together, these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway, thereby promoting the recovery of neurological function after spinal cord injury.

Nafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action.

Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.