Advances in natural and synthetic macromolecules with stem cells and extracellular vesicles for orthopedic disease treatment.

Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.

Predictive Value of CFIm25 Expression in Peripheral Blood Monocytes for Coronary Atherosclerosis.

Background: Cleavage factor Im25 (CFIm25) regulates cell function by affecting mRNA editing processes and plays diverse roles in various diseases. Studies have found that peripheral blood monocytes are valuable in diagnosing and prognosing coronary atherosclerosis. However, no studies have examined the predictive value of CFIm25 expression in peripheral blood monocytes for coronary atherosclerosis. Methods and Results: We collected the coronary angiography results of 267 patients and calculated the Gensini score to evaluate their degree of coronary atherosclerosis. We isolated peripheral blood monocytes and detected CFIm25 RNA expression. Based on their Gensini score, we divided the patients into negative (0, n = 46), mild lesion (≤ 8, n = 71), moderate lesion (8-23, n = 76), and severe lesion (≥ 23, n = 74) groups. Results showed that CFIm25 expression correlated negatively with the Gensini score and the number of involved coronary vessels. Univariate and multivariate binary logistic regression analyses showed that CFIm25 expression in peripheral blood monocytes was a protective factor for severe lesions, ≥ 50% stenosis, and three-vessel lesions. The areas under the receiver operating characteristic curve of CFIm25 expression for predicting lesions, severe lesions, ≥50% stenosis, and three-vessel lesions were 0.743, 0.735, 0.791, and 0.736, respectively. Conclusions: CFIm25 expression in peripheral blood monocytes correlates negatively with the degree of coronary atherosclerosis and helps predict the severity and number of coronary artery lesions.

Identification of adult resistant genes to stripe rust in wheat from southwestern China based on GWAS and WGCNA analysis.

KEY MESSAGE: In this study, genome-wide association studies combined with transcriptome data analysis were utilized to reveal potential candidate genes for stripe rust resistance in wheat, providing a basis for screening wheat varieties for stripe rust resistance. Wheat stripe rust, which is caused by the wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst) is one of the world's most devastating diseases of wheat. Genetic resistance is the most effective strategy for controlling diseases. Although wheat stripe rust resistance genes have been identified to date, only a few of them confer strong and broad-spectrum resistance. Here, the resistance of 335 wheat germplasm resources (mainly wheat landraces) from southwestern China to wheat stripe rust was evaluated at the adult stage. Combined genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) based on RNA sequencing from stripe rust resistant accession Y0337 and susceptible accession Y0402, five candidate resistance genes to wheat stripe rust (TraesCS1B02G170200, TraesCS2D02G181000, TraesCS4B02G117200, TraesCS6A02G189300, and TraesCS3A02G122300) were identified. The transcription level analyses showed that these five genes were significantly differentially expressed between resistant and susceptible accessions post inoculation with Pst at different times. These candidate genes could be experimentally transformed to validate and manipulate fungal resistance, which is beneficial for the development of the wheat cultivars resistant to stripe rust.

T-cell Immunoglobulin and Mucin Domain 3 in Circulating Monocytes as a Novel Biomarker for Coronary Artery Disease.

The diagnostic role of T-cell immunoglobulin and mucin domain 3 (Tim-3) expression levels in circulating monocytes in coronary artery disease (CAD) remains to be determined. Here, we enrolled of 265 patients and isolated circulating monocytes from the blood of all participants. We found that the Tim-3 expression levels in monocytes were lower in CAD patients than in the control group. Spearman correlation analysis verified that the Tim-3 levels in monocytes were negatively correlated with the Gensini score and the number of coronary vessels. Multivariate logistic regression analysis showed that the Tim-3 levels in circulating monocytes were negatively correlated with CAD, severe CAD, and three-vessel CAD. The ROC curve showed that Tim-3 possessed high diagnostic value for CAD, severe CAD, and three-vessel CAD, with CAD prediction being the most significant of these values. In conclusion, Tim-3 in circulating monocytes is a novel biomarker for CAD. T-cell immunoglobulin and mucin domain 3 (Tim-3) in circulating monocytes as a novel biomarker for coronary artery disease.

Hydrogel-based treatments for spinal cord injuries.

Spinal cord injury (SCI) is characterized by damage resulting in dysfunction of the spinal cord. Hydrogels are common biomaterials that play an important role in the treatment of SCI. Hydrogels are biocompatible, and some have electrical conductivity that are compatible with spinal cord tissues. Hydrogels have a high drug-carrying capacity, allowing them to be used for SCI treatment through the loading of various types of active substances, drugs, or cells. We first discuss the basic anatomy and physiology of the human spinal cord and briefly discuss SCI and its treatment. Then, we describe different treatment strategies for SCI. We further discuss the crosslinking methods and classification of hydrogels and detail hydrogel biomaterials prepared using different processing methods for the treatment of SCI. Finally, we analyze the future applications and limitations of hydrogels for SCI. The development of biomaterials opens up new possibilities and options for the treatment of SCI. Thus, our findings will inspire scholars in related fields and promote the development of hydrogel therapy for SCI.

Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.

BACKGROUND: The value of human leukocyte antigen (HLA; also known as major histocompatibility complex) class I expression for the prediction of breast cancer survival outcomes remains unclear. We conducted a meta-analysis to explore the prognostic significance of this expression. MATERIALS AND METHODS: We searched electronic databases to identify reports on associations of HLA class I protein or mRNA expression with survival outcomes and clinicopathological factors in the breast cancer context. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to conduct a quantitative meta-analysis. RESULTS: The sample comprised eight studies involving 3590 patients. Only the classical HLA class Ia (HLA-ABC) molecules studies were included in this meta-analysis. Elevated HLA class I protein expression was found to be significantly related to better disease-free survival (DFS) (HR 0.58, 95% CI 0.35-0.95, P = 0.03), particularly among patients with triple-negative breast cancer (TNBC) (HR 0.31, 95% CI 0.18-0.52, P < 0.001), but not to overall survival. It was also associated with estrogen receptor (ER) negativity (OR 1.71, 95% CI 1.24-2.35, P = 0.001), progesterone receptor (PR) negativity (OR 1.49, 95% CI 1.22-1.81, P < 0.001), human epidermal growth factor receptor 2 (HER2) positivity (OR 1.51, 95% CI 1.18-1.94, P = 0.001), TNBC (OR 1.68, 95% CI 1.15-2.45, P < 0.01), high Ki-67 indices (OR 2.06, 95% CI 1.62-2.61, P < 0.001), and high nuclear grades (OR 2.67, 95% CI 2.17-3.29, P < 0.001). CONCLUSION: This meta-analysis demonstrated that enhanced HLA class I protein expression is significantly associated with the better DFS of patients with breast cancer, especially TNBC, as well as with ER and PR negativity, HER2 positivity, TNBC, and high Ki-67 indices and nuclear grades. The immune target HLA class I may serve as a prognostic indicator for breast cancer.

Full-length RNA sequencing reveals the mechanisms by which an TSWV-HCRV complex suppresses plant basal resistance.

Viruses deploy numerous strategies to infect plants, typically by forming complexes with another virus, leading to more efficient infection. However, the detailed plant responses to viral infection and the underlying mechanisms of co-infection remain unclear. Previously, we found that tomato spotted wilt orthotospovirus (TSWV) and Hippeastrum chlorotic ringspot orthotospovirus (HCRV) could infect plants in the field by forming a complex. In this study, we found that TSWV infected tobacco (Nicotiana benthamiana) plants in cooperation with HCRV, leading to a more efficient infection rate of both viruses. We then used the in-depth full-length transcriptome to analyze the responses of N. benthamiana to complex infection by TSWV-HCRV (TH). We found that infection with individual TSWV and HCRV triggered plant defense responses, including the jasmonic acid signaling pathway, autophagy, and secondary metabolism. However, TH co-infection could not trigger and even suppress some genes that are involved in these basal resistance responses, suggesting that co-infection is advantageous for the virus and not for the plants. Typically, the TH complex inhibits NbPR1 expression to suppress tobacco resistance. Moreover, the TH complex could alter the expression of microRNAs (miRNAs), especially novel-m0782-3p and miR1992-3p, which directly interact with NbSAM and NbWRKY6 and suppress their expression in tobacco, leading to downregulation of NbPR1 and loss of resistance in tobacco to TSWV and HCRV viruses. Overall, our results elucidated the co-infection mechanisms of TH in tobacco by deploying the miRNA of plants to suppress plant basal resistance and contributed to developing a novel strategy to control crop disease caused by this virus complex.

A meta-analysis of short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer.

OBJECTIVES: This meta-analysis aimed to compare the short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer. METHODS: The databases PubMed, Embase, Scopus, Cochrane Library, Web of Science, ScienceDirect, and major scientific websites were screened up to January 2023. Randomized controlled trials and observational studies comparing fluorescence navigation-assisted and fluorescence-free navigation-assisted hepatectomy for liver cancer were included. Our meta-analysis comprises overall results and 2 subgroup analyses based on surgery type (laparoscopy and laparotomy). These estimates are presented as mean differences (MD) or odds ratio (OR) estimates with 95% CIs. RESULTS: We analyzed 16 studies that included 1260 patients with liver cancer. Our results showed that fluorescent navigation-assisted hepatectomy were significantly more shorter than fluorescence-free navigation-assisted hepatectomy in the following parameters: operative time [MD = -16.19; 95% CI: -32.27 to -0.11; p = 0.050], blood loss [MD = -107.90; 95% CI: -160.46 to -55.35; p < 0.001], blood transfusion [OR = 0.5; 95% CI: 0.35 to 0.72; p = 0.0002], hospital stay [MD = -1.60; 95% CI: -2.33 to -0.87; p < 0.001], and postoperative complications [OR = 0.59; 95% CI: 0.42 to 0.82; p = 0.002], The one-year disease-free survival rate [OR = 2.87; 95% CI: 1.64 to 5.02; p = 0.0002] was higher in the fluorescent navigation-assisted hepatectomy group. CONCLUSIONS: Indocyanine green fluorescence imaging has good clinical value and can improve the short-term and long-term results of hepatectomy for liver cancer.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

First Report of Lasiodiplodia theobromae Causing Stem Brown Rot of Loquat in China.

Loquat (Rhaphiolepis biabas, heterotypic synonym: Eriobotrya japonica) is an important edible and medicinal plant that is widely cultivated on 133 thousand hectares (recorded in 2022) in China. A stem brown rot was observed on young and old trees in Mengzi city (23°23' N; 103°23' E), Yunnan Province, southwest China, during October 2014 and September 2021. Incidence ranged from 20% of trees in surrounding plantations to 50% incidence of a 160 tree orchard that was the focal point of the disease survey. Circular brown lesions occurred initially on the stems and gradually covered all the epidermis of the stem, leading to irregular dents within the bark that developed a dark brown powdery appearance (Fig.1A). Larger lesions affected vascular tissues, causing diseased trees to wither and die. Diseased tissues were surface-disinfected in a 5% sodium hypochlorite solution for 3 min, rinsed three times with sterile distilled water, placed on potato dextrose agar (PDA), and incubated in the dark at 28°C. Twenty samples were collected for tissue isolation, and 11 isolates were single-spored on water agar. In culture, the colonies on PDA were white to dark-gray, velvet, with dense hyphae, diameter 7.64 cm after 5 days. After 18 days, spherical or subglobose pycnidia were developed and semi-buried in medium, their walls were thicker and dark-brown, which were black particles surrounded by gray-black hyphae. Conidiogenous cells were hyaline, cylindrical, holoblastic, slightly swollen at the base, with rounded apex. Conidia were initially hyaline and aseptate with elliptic or ovate shape, becoming dark brown with a single septate and developing longitudinal striations along thick walls at maturity. Conidia dimensions varied from 8.0 to 12.2 × 3.8 to 6.1µm (n=50) (Fig.1D). The morphological characteristics of eleven isolates were consistent with the description of Lasiodiplodia theobromae (Alves et al. 2008). Further confirmation was also determined by sequencing the internal transcribed spacer (ITS), ß-tubulin genes, partial translation elongation factor-1α (TEF-1α) (White et al. 1990, Carbone et al. 1999, Glass et al.1995). The isolate LSB-1 was selected for DNA sequence analysis. Based on BLASTn analysis, ITS sequences (OM617921) had 98.3% similarity with L. theobromae CBS164.96 (accession AY640255), CBS124.13(accession DQ458890), CAA006 (accession DQ458891) and CBS111530 (accession EF622074), ß-tubulin sequences (OM643838) showed 99.1% similarity with L. theobromae accessions EU673110. The TEF-1α (OM643839) had 99.0% identity with L. theobromae accession EF633054. The isolate LSB-1 clustered on the same clade with other L. theobromae. Pathogenicity testing of isolate LSB-1, LSB-2, LSB-3 was conducted by inoculating the stems of l-year-old seedlings growing in pots. The epidermis at the inoculation site, 15-20 cm below the crown, was wiped with 75% alcohol cotton ball, washed three times with sterile water, and then punctured (5mm diameter) with sterile inoculation needle. A 5mm block of each isolate cultured on PDA for seven days was attached to the inoculation site. Controls were inoculated with sterile PDA blocks. The inoculation area was covered with polyethylene cling film. All inoculated seedlings were kept in controlled greenhouse at 27°C with 80% relative humidity under natural daylight conditions, and watered weekly. Each treatment was repeated three times. Eight days after inoculation, all diseased plants showed dark brown discoloration at the point of inoculation (Fig. 1G) with the bark at the inoculation site gradually raising as the disease progressed. Thirty days after inoculation, all inoculated seedlings produced typical symptoms, whereas the control seedlings remained healthy. Fungal isolates were only recovered from symptomatic stems and were morphologically identical to L. theobromae, completing Koch's postulates. According to the relevant literature, Lasiodiplodia theobromae has a broad host range, causing numerous diseases, including canker and dieback of branch (Aguilera-Cogley et al., 2021), panicle blight (Mahadevakumar et al, 2022), root rot (Abd-El Ghani and Fatouh, 2005), fruit rot(Freire et al., 2011) in diverse geographical regions. To our knowledge, this is the first report of L. theobromae causing stem brown rot of loquat in China and provides a foundation for further study of the epidemiology and integrated management of this disease.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-kBs pathway

Introduction: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. Methods: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1β (IL-1β). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. Results: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. Conclusion: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment (AU)

Sacubitril/valsartan attenuates myocardial ischemia/reperfusion injury via inhibition of the GSK3ß/NF-κB pathway in cardiomyocytes.

In ischemia/reperfusion (I/R) injury, both inflammation and apoptosis play a vital role, and the inhibition of excessive inflammation and apoptosis show substantial clinical potential in the treatment of I/R disease. The role of sacubitril/valsartan (SAC/VAL)-a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI)-in inflammation regulation and apoptosis in the context of I/R injury needs to be further explored. In this study, we investigate the short- and long-term effects of SAC/VAL administration in treating adult murine I/R injury both in vivo and in vitro. Our results verified that the application of SAC/VAL could reduce infarct size and suppress apoptosis and the inflammatory response in the acute phase post I/R. Long-term application of SAC/VAL for four weeks significantly improved ventricular function and reversed pathological ventricular remodeling. Mechanistically, SAC/VAL treatment induces the inhibition of the GSK3ß-mediated NF-κB pathway through synergistically blocking angiotensin 1 receptor (AT1R) and activating natriuretic peptide receptor (NPR). In summary, we reported the therapeutic role of SAC/VAL in regulating the GSK3ß/NF-κB signaling pathway to suppress the inflammatory response and apoptosis, thereby reducing cardiac dysfunction and remodeling post I/R.

Analysis of the miRNA expression profile involved in the tomato spotted wilt orthotospovirus-pepper interaction.

MicroRNAs (miRNAs) are a class of about 22 nucleotide endogenous non-coding small RNAs that play important roles in plant development and defense responses to biotic and abiotic stress. Tomato spotted wilt orthotospovirus (TSWV) is among the most devastating plant viruses worldwide, causing leaf spotting and wilting symptoms in many plants. In this study, high-throughput sequencing technology was used to identify miRNAs in peppers that were regulated by TSWV infection, and bioinformatics techniques were used to analyze the function of these miRNAs and their target genes. The sequencing results showed that, in the pepper plants infected by TSWV, a total of 101 miRNAs were differentially expressed, and several differentially expressed miRNAs were verified by the qRT-PCR method. Based on the GO function and KEGG pathway enrichment analysis, the functions of these miRNAs and their target genes were predicted. These target genes play a regulatory role in pathways such as plant-pathogen interactions and plant hormone signal transduction. Our results provide information about pepper miRNAs and will help to further understand the mechanism of TSWV-host interactions.

Extracellular vesicle-derived miR-511-3p from hypoxia preconditioned adipose mesenchymal stem cells ameliorates spinal cord injury through the TRAF6/S1P axis.

Extracellular vesicle (EV) from hypoxic adipose tissue-derived mesenchymal stem cells (AD-MSCs) play critical roles in spinal cord injury (SCI) by transferring miRNAs to target cells through fusion with the cell membrane. However, the role of miR-511-3p within the AD-MSCs -derived EV in SCI is largely unknown. Western blotting results demonstrated the secretion of EVs derived from AD-MSCs under hypoxia (Hyp-EVs) was more than those under normoxia (Nor-EVs), and miR-511-3p expression was more enriched in Hyp-EVs. PC12 cells were stimulated with lipopolysaccharide (LPS) to induce cell damage. AD-MSCs were transfected with miR-511-3p mimic or miR-511-3p inhibitor to induce EVs-miR-511-3p overexpression or silencing. Cells treated with Hyp-EVs-miR-511-3p mimic reduced LPS-induced apoptosis, alleviated inflammation and promoted proliferation, while cells treated with Hyp-EVs-miR-511-3p inhibitor aggravated LPS-induced apoptosis and inflammation, and suppressed proliferation. Luciferase reporter gene assay revealed tumor necrosis factor receptor-associated factor 6 (TRAF6) was a target downstream gene of miR-511-3p. A series of gain- and loss-of-function experiments verified that TRAF6 could antagonize the effects of Hyp-EVs-miR-511-3p on inflammation, cell apoptosis and viability. Furthermore, cells treated with CYM5541, an agonist of sphingosine-1-phosphate receptor 3 (S1PR3), reversed the inhibitory effect of Hyp-EVs-miR-511-3p mimic on S1PR3 expression, inflammation and cell apoptosis. Finally, intravenously injection of Hyp-EVs-miR-511-3p mimic into SCI model rats obviously reduced inflammation and promoted neurological function recovery. In conclusion, EVs-derived miR-511-3p from hypoxia preconditioned AD-MSCs ameliorates SCI via TRAF6/S1P/NF-κB pathway, which indicates that miR-511-3p may be a potential therapeutic target for SCI.

Use of deep sequencing to profile small RNAs derived from tomato spotted wilt orthotospovirus and hippeastrum chlorotic ringspot orthotospovirus in infected Capsicum annuum.

Virus-derived small RNAs are one of the key factors of RNA silencing in plant defence against viruses. We obtained virus-derived small interfering RNA profiles from Tomato spotted wilt orthotospovirus and Hippeastrum chlorotic ringspot orthotospovirus infected Capsicum annuum XX19 and XY11 by deep sequencing one day after inoculation. The vsiRNAs data were mapped to the TSWV and HCRV genomes, and the results showed that the vsiRNAs measured 19-24 nucleotides in length. Most of the vsiRNAs were mapped to the S segment of the viral genome. For XX19 and XY11 infected with HCRV, the distribution range of vsiRNAs in S RNA was 52.06-55.20%, while for XX19 and XY11 infected with TSWV, the distribution range of vsiRNAs in S RNA was 87.76-89.07%. The first base at the 5' end of the siRNA from TSWV and HCRV was primarily biased towards A, U, or C. Compared with mock-inoculated XX19 and XY11, the expression level of CaRDR1 was upregulated in TSWV- and HCRV-inoculated XX19 and XY11. CaAGO2 and CaAGO5 were upregulated in XY11 against HCRV infection, and CaRDR2 was downregulated in TSWV-infected XY11 and XX19. The profile of HCRV and TSWV vsiRNA verified in this study could be useful for selecting key vsiRNA such as those in disease-resistant varieties by artificially synthesizing amiRNA.

Outcomes of atrial fibrillation in patients with COVID-19 pneumonia: A systematic review and meta-analysis.

BACKGROUND: Recently, emerging evidence has suggested that atrial fibrillation (AF) has an epidemiological correlation with coronavirus disease 2019 (COVID-19). However, the clinical outcomes of AF in COVID-19 remain inconsistent and inconclusive. The aim of this study was to provide a comprehensive description of the impact of AF on the prognosis of patients with COVID-19 pneumonia. METHODS: Three electronic databases (PubMed, Embase, and Web of Science) were searched for eligible studies as of March 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations between AF (preexisting and new-onset) and in-hospital mortality, post-discharge mortality, and ventilator use. RESULTS: A total of 36 individual studies were incorporated into our meta-analysis. The combined results revealed that preexisting AF was associated with increased in-hospital mortality (pooled OR: 2.07; 95% CI: 1.60-2.67; p < 0.001), post-discharge mortality (pooled OR: 2.69; 95% CI: 1.24-5.83; p < 0.05), and ventilator utilization (pooled OR: 4.53; 95% CI: 1.33-15.38; p < 0.05) in patients with COVID-19. In addition, our data demonstrated that new-onset AF during severe acute respiratory syndrome coronavirus 2 infection was significantly correlated with increased mortality (pooled OR: 2.38; 95% CI: 2.04-2.77; p < 0.001). CONCLUSIONS: The presence of AF is correlated with adverse outcomes in patients with COVID-19 pneumonia, which deserves increased attention and should be managed appropriately to prevent adverse outcomes.

Iso-suillin-induced DNA damage leading to cell cycle arrest and apoptosis arised from p53 phosphorylation in A549 cells.

Extensive investigations have revealed that iso-suillin, a secondary metabolite isolated from Suillus flavus, could induce cell cycle arrest and apoptosis in human chronic myeloid leukemia K562 cells, human hepatocellular carcinoma SMMC-7721 cell line, and human small cell lung cancer H446 cell line in vitro. In the present study, human lung cancer A549 cells were used to reveal the mechanism of iso-suillin's effects on lung adenocarcinoma, which were detected both in vitro and in vivo. Results showed that iso-suillin potently inhibited A549 cell proliferation through an early G1 arrest. Iso-suillin also induced A549 cell apoptosis in vitro. Phosphorylation of p53 at serines 15 and 20 may be one of the pivotal factors for cell cycle arrest and apoptosis after treatment of iso-suillin in A549 cells. Moreover, in an A549 xenograft model, tumor growth and progression could be inhibited by iso-suillin. Body weight change and some vital organs toxicity was also roughly examined, no significant toxic effects of iso-suillin were shown (at a dose of 5 mg/kg for each administration). The in vitro and in vivo anti-tumor effects implied that iso-suillin may act as a tumor growth inhibitor, and its induction of p53 phosphorylation is pivotal for cell cycle arrest and apoptosis in A549 cells.

Inhibition of ERK1/2 phosphorylation attenuates spinal cord injury induced astrocyte activation and inflammation through negatively regulating aquaporin-4 in rats.

The extracellular signal-regulated kinase (ERK) pathway has been reported to play a pivotal role in mediating spinal cord injury (SCI) progression. The present study aimed to investigate the effects of phosphorylated ERK1/2 (p-ERK1/2) inhibition on SCI-induced astrocyte activation and inflammation and its possible mechanism in rats. Here, female Sprague-Dawley rats were randomly assigned to four groups: (1) Sham group, (2) SCI group, (3) TGN-020 group (aquaporin-4, AQP4, blocking agent), (4) PD98059 group (ERK blocking agent). A well SCI model was established by compressing the thoracic vertebra 10 level (weight 35 g, time 5 min) in rats. Western blotting and immunofluorescence staining were used to measure the expression of associated proteins after SCI. HE staining and Nissl staining were performed to detect the morphological changes of spinal cords and the number of surviving neurons following SCI, respectively. The Basso-Beattie-Bresnahan open-field rating scale was used to evaluate functional locomotor recovery following SCI in rats. Our results demonstrated that SCI significantly induced the upregulation of aquaporin-4, p-ERK1/2, glial fibrillary acidic protein, proliferating cell nuclear antigen, and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-1ß). However, treatment with TGN-020 or PD98059 could effectively inhibit astrocyte proliferation and proinflammatory cytokine release, preserve the number of surviving ventral horn neurons, and subsequently improve the locomotor function of rats after SCI. Interestingly, the SCI-induced elevation of AQP4 expression was downregulated by p-ERK1/2 inhibition, suggesting that blocking ERK1/2 phosphorylation could attenuate astrocyte activation and inflammatory processes through negative regulation of AQP4. Therefore, p-ERK1/2 blockade may be employed as a therapeutic target for SCI.

Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3'-Spiro[ß-lactam]-oxindoles.

Oxindoles and ß-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3'-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[ß-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.

Outcomes of new-onset atrial fibrillation in patients with sepsis: A systematic review and meta-analysis of 225,841 patients.

BACKGROUND: The outcomes of new-onset atrial fibrillation (AF) during sepsis are inconsistent and inconclusive. This meta-analysis aims to provide a comprehensive description of the impact of new-onset AF on the prognosis of sepsis. METHODS: Three electronic databases (PubMed, Embase, and the Cochrane Library) were searched for relevant studies. Meta-analysis was performed using odds ratios (OR) and 95% confidence intervals (CI) as effect measures. RESULTS: A total of 225,841 patients from 13 individual studies were incorporated to the meta-analysis. The summary results revealed that new-onset AF during sepsis was associated with increased odds of in-hospital mortality (pooled OR: 2.09; 95% CI: 1.53-2.86; p < 001), post-discharge mortality (pooled OR: 2.44; 95% CI: 1.81-3.29; p < .001), and stroke (pooled OR:1.88; 95% CI: 1.13-3.14; p < .05). Results also indicated that the incidence of new-onset AF varied from 1.9% for mild sepsis to 46.0% for septic shock. Furthermore, compared to those without AF, people with new-onset AF had longer ICU and hospital stays, as well as a higher recurrence of AF. CONCLUSIONS: New-onset AF is frequently associated with adverse outcomes in patients with sepsis. This is a clinical issue that warrants more attention and should be managed appropriately to prevent poor prognosis.