Explore the vast range of titles available.

Osmotic stress severely affects plant growth and development, resulting in massive loss of crop quality and quantity worldwide. The 70-kDa heat shock proteins (HSP70s) are highly conserved molecular chaperones that play essential roles in cellular processes including abiotic stress responses. However, whether and how plastid-targeted heat shock cognate 70 kDa protein (cpHSC70-1) participates in plant osmotic stress response remain elusive. Here, we report that the expression of cpHSC70-1 is significantly induced upon osmotic stress treatment. Phenotypic analyses reveal that the plants with cpHSC70-1 deficiency are sensitive to osmotic stress and the plants overexpressing cpHSC70-1 exhibit enhanced tolerance to osmotic stress. Consistently, the expression of the stress-responsive genes is lower in cphsc70-1 mutant but higher in 35S:: cpHSC70-1 lines than that in wild-type plants when challenged with osmotic stress. Further, the cphsc70-1 plants have less APX and SOD activity, and thus more ROS accumulation than the wild type when treated with mannitol, but the opposite is observed in the overexpression lines. Overall, our data reveal that cpHSC70-1 is induced and functions positively in plant response to osmotic stress by promoting the expression of the stress-responsive genes and reducing ROS accumulation.

This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07–0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P  = 0.046) and grade II–IV aGVHD (42.9 vs. 12.2%, P  = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival ( P  = 0.514), disease-free survival ( P  = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae , Apis mellifera , Bos taurus , Drosophila melanogaster , Danio rerio , Fugu rubripes , Gallus gallus , Homo sapiens , Monodelphis domestica , Macaca mulatta , Mus musculus , Pan troglodytes , Rattus norvegicus , Tetraodon nigroviridis , Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher ( p  < 0.01) than that in the ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus. The study also involved predicting miR-375 target genes. GO and KEGG enrichment analyses of these predicted target genes revealed that miR-375 is involved in 182 biological processes, affects 186 cellular components, and participates in 184 molecular functions. In terms of pathway enrichment, miR-375 was linked to nine pathways, including the Hippo, Wnt, and mTOR signaling pathways. This study has validated the interaction between miR-375 and its target gene FZD4, which can be recognized and bound to produce effects. These findings lead to the inference that miR-375 may play a crucial regulatory role in sheep reproduction through the Hippo pathway and Wnt pathway, laying a foundation for further exploration of miR-375’s role in this domain.

Abstract Background: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. Methods: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45+ BM cells were enriched with human CD45 microbeads. The CD45+ cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. Results: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. Conclusions: This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.

Background BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells. Methods This study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45 + BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis. Results We compared the heterogeneity of CD45 + BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT + NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1β hi Mφ, S100A9 hi Mφ, interferon-responsive Mφ, CD16 hi Mφ, MARCO hi Mφ, and S100A11 hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell–cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy. Conclusion Taken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.

Background The U-box gene encodes a ubiquitin ligase that contain U-box domain. The plant U-box gene (PUB) plays an important role in the response to stresses, but few reports about PUBs in cotton were available. Therefore research on PUBs is of great importance and a necessity when studying the mechanisms of stress- tolerance in cotton. Results In this study, we identified 93, 96, 185 and 208 PUBs from four sequenced cotton species G. raimondii (D 5 ), G. arboreum (A 2 ), G. hirsutum (AD 1 ) and G. barbadense (AD2), respectively. Prediction analysis of subcellular localization showed that the PUBs in cotton were widely localized in cells, but primarily in the nucleus. The PUBs in cotton were classified into six subfamilies (A-F) on the basis of phylogenetic analysis, which was testified by the analysis of conserved motifs and exon-intron structures. Chromosomal localization analysis showed that cotton PUBs were unevenly anchored on all chromosomes, varying from 1 to 14 per chromosome. Through multiple sequence alignment analysis, 3 tandem duplications and 28 segmental duplications in cotton genome D 5 , 2 tandem duplications and 25 segmental duplications in A 2 , and 143 homologous gene pairs in A 2 and D 5 were found; however no tandem duplications in A 2 or D 5 were found. Additionally, 105, 14 and 17 homologous gene pairs were found in the intra-subgenome of At and Dt, At sub-genome and Dt sub-genome of G. hirsutum , respectively. Functional analysis of GhPUB85A and GhPUB45D showed that these genes positively responded to abiotic stresses, but the expression patterns were different. In addition, although the expression levels of these two homologous genes were similar, their contributions were different when responding to stresses, specifically showing different responses to abiotic stresses and functional differences between the two subgenomes of G. hirsutum . Conclusions This study reported the genome-wide identification, structure, evolution and expression analysis of PUBs in cotton, and the results showed that the PUBs were highly conserved throughout the evolutionary history of cotton. All PUB genes were involved in the response to abiotic stresses (including salt, drought, hot and cold) to varying degrees.

Background BM-MSCs play an important role in cancer development through the release of cytokines or exosomes. Studies have shown that extracellular exosomes derived from BM-MSCs are a key pro-invasive factor. However, how BM-MSC-exos influence AML cell proliferation, invasion and chemoresistance remains poorly understood. Methods We isolated exosomes from BM-MSCs and used electron microscopy, particle size separation and western blots to identify the exosomes. The invasion of leukemia cells was observed with a transwell assay. The stemness traits and chemoresistance of the leukemia cells were detected by FCM, colony formation and CCK-8 assays. TCGA database was used to investigate the prognostic relevance of S100A4 and its potential role in AML. Results In this study, we found that BM-MSC-exos increased the metastatic potential, maintained the stemness and contributed to the chemoresistance of leukemia cells. Mechanistically, BM-MSC-exos promoted the proliferation, invasion and chemoresistance of leukemia cells via upregulation of S100A4. Downregulating S100A4 clearly suppressed the proliferation, invasion, and chemoresistance of leukemia cells after treatment with BM-MSC-exos. Bioinformatic analysis with data in TCGA database showed that S100A4 was associated with poor prognosis in AML patients, and functional enrichment revealed its involvement in the processes of cell–cell adhesion and cytokine regulation. Conclusions S100A4 is vital in the BM-MSC-exo-driven proliferation, invasion and chemoresistance of leukemia cells and may serve as a potential target for leukemia therapy.

Background DNA methylation is an important epigenetic mode of genomic DNA modification and plays a vital role in maintaining epigenetic content and regulating gene expression. Cytosine-5 DNA methyltransferase ( C5-MTase) are the key enzymes in the process of DNA methylation. However, there is no systematic analysis of the C5-MTase in cotton so far, and the function of DNMT2 genes has not been studied. Methods In this study, the whole genome of cotton C5-MTase coding genes was identified and analyzed using a bioinformatics method based on information from the cotton genome, and the function of GhDMT6 was further validated by VIGS experiments and subcellular localization analysis. Results 33 C5-MTases were identified from three cotton genomes, and were divided into four subfamilies by systematic evolutionary analysis. After the protein domain alignment of C5-MTases in cotton, 6 highly conserved motifs were found in the C-terminus of 33 proteins involved in methylation modification, which indicated that C5-MTases had a basic catalytic methylation function. These proteins were divided into four classes based on the N-terminal difference, of which DNMT2 lacks the N-terminal regulatory domain. The expression of C5-MTases in different parts of cotton was different under different stress treatments, which indicated the functional diversity of cotton C5-MTase gene family. Among the C5-MTases , the GhDMT6 had a obvious up-regulated expression. After silencing GhDMT6 with VIGS, the phenotype of cotton seedlings under different stress treatments showed a significant difference. Compared with cotton seedlings that did not silence GhDMT6 , cotton seedlings silencing GhDMT6 showed significant stress resistance. Conclusion The results show that C5-MTases plays an important role in cotton stress response, which is beneficial to further explore the function of DNMT2 subfamily genes.

Cervical sagittal balance plays a pivotal role in spine surgeries as it has a significant impact on the clinical outcomes in cervical spine surgery. Image processing techniques have significantly improved the accuracy and precision of cervical surgical techniques. This study aims to investigate the effects of T1 slope (T1s) on the disappearance of cervical lordosis after posterior cervical double-door laminoplasty using medical informatics and radiographic measures. To do so, we determined and measured the loss of T1s and cervical lordosis during the postoperative follow-up period in patients with double-door posterior cervical laminoplasty. Patients (n = 40) who underwent posterior cervical double-door laminoplasty participated in this study. For all patients, the difference between the preoperative T1s (angle between the upper edge of T1 and the horizontal line) and preoperative and postoperative cervical lordosis (Cobb method) was estimated, and the linear relationship between the two was statistically analyzed to observe the influence of preoperative T1s on postoperative cervical lordosis disappearance. The average preoperative T1s was 23.54°, and the average preoperative cervical lordosis angle was 8.50°. After 1–20 months of follow-up (mean = 9.53 months), the average postoperative cervical lordosis was 8.50°, and the average loss of cervical lordosis was 0.22°. Twenty cases had different degrees of lordosis angle loss after the operation, with an average loss of 9.31°. All patients were divided into groups A and B, according to a mean value of T1s = 23.54°, of which T1S > 23.54° was group A and T1s < 23.54 was group B. Cervical lordosis was quantified by the C2–C7 Cobb angle. The Cobb angle difference of cervical lordosis was measured before and after the operation, and its correlation with preoperative T1s was assessed. The preoperative Cobb angle and cervical curvature changes in the two groups were statistically compared, and the difference between the two groups was statistically significant (p < 0.05). The group with a T1s > 23.54° had greater loss of preoperative Cobb angle and cervical curvature. In group A, the mean preoperative cervical disability index (NDI) was 32.4 ± 3.4, and the mean postoperative NDI score was 16.5 ± 2.1. The mean preoperative VAS scores of neck pain and neck pain were 5.41 ± 1.1 and 5.55 ± 0.3, respectively, and the improvement in neck pain was −0.2%. The mean preoperative NDI in group B was 30.1 ± 2.9, and the mean postoperative NDI score was 11.5 ± 3.1. The mean VAS score for preoperative neck pain was 5.11 ± 1.2, that for postoperative neck pain was 4.18 ± 0.7, and that for neck pain improved by 18%. There was a significant difference between the two groups (p < 0.05). The disappearance of cervical lordosis after posterior cervical double-door laminoplasty is an important cause of postoperative cervical spine pain. The T1s is meaningful for predicting the loss of postoperative curvature in patients undergoing posterior cervical double-door laminoplasty. This is especially true for patients with good preoperative cervical curvature without ankylosis and kyphosis but with a wide T1s.

In the western Henan agricultural area, Duhu (Dupo♂ × Hu sheep♀) hybrid lambs are the primary breed of local meat sheep, predominantly raised in large-scale indoor feeding systems, although many farmers still rely on grazing. However, limited research exists on the meat quality of Duhu lambs under both grazing and indoor feeding systems. This study examined how grazing and indoor feeding affect the nutritional quality, flavor, amino acid profile, and fatty acid composition of 7-month-old Duhu lamb meat. Grazed lamb meat exhibited significantly (p < 0.05) higher moisture, protein content, hardness, adhesiveness, springiness, rubberiness, chewiness, and resilience than indoor-fed lamb. Regarding aroma, ammonia, oxidized compounds, and inorganic sulfides were more pronounced and stable in grazed lamb meat. Flavor analysis showed stronger bitter, salty, and sweet profiles in grazed lamb meat, whereas the sour flavor was more pronounced in indoor-fed meat. Among the volatile flavor compounds, 26 organic compounds were identified in grazed lamb meat compared with 12 in indoor-fed meat, with 1 compound common. Additionally, 16 amino acids were found in both feeding systems, with amino acid levels significantly higher (p < 0.01) in indoor-fed lamb. In total, 25 fatty acids were detected in grazed lamb meat, whereas 15 were found in indoor-fed meat, with 11 showing significantly different levels (p < 0.05). Indoor-fed lamb meat exhibited a considerably higher saturated fatty acid content (p < 0.05) compared to grazed lamb meat, while the n-3 polyunsaturated fatty acid content was significantly lower (p < 0.05).