Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.

JMJD3 regulate H3K27me3 modification via interacting directly with TET1 to affect spermatogonia self-renewal and proliferation.

BACKGROUND: In epigenetic modification, histone modification and DNA methylation coordinate the regulation of spermatogonium. Not only can methylcytosine dioxygenase 1 (TET1) function as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine, it can also form complexes with other proteins to regulate gene expression. H3K27me3, one of the common histone modifications, is involved in the regulation of stem cell maintenance and tumorigenesis by inhibiting gene transcription. METHODS: we examined JMJD3 at both mRNA and protein levels and performed Chip-seq sequencing of H3K27me3 in TET1 overexpressing cells to search for target genes and signaling pathways of its action. RESULTS: This study has found that JMJD3 plays a leading role in spermatogonia self-renewal and proliferation: at one extreme, the expression of the self-renewal gene GFRA1 and the proliferation-promoting gene PCNA was upregulated following the overexpression of JMJD3 in spermatogonia; at the other end of the spectrum, the expression of differentiation-promoting gene DAZL was down-regulated. Furthermore, the fact that TET1 and JMJD3 can form a protein complex to interact with H3K27me3 has also been fully proven. Then, through analyzing the sequencing results of CHIP-Seq, we found that TET1 targeted Pramel3 when it interacted with H3K27me3. Besides, TET1 overexpression not only reduced H3K27me3 deposition at Pramel3, but promoted its transcriptional activation as well, and the up-regulation of Pramel3 expression was verified in JMJD3-overexpressing spermatogonia. CONCLUSION: In summary, our study identified a novel link between TET1 and H3K27me3 and established a Tet1-JMJD3-H3K27me3-Pramel3 axis to regulate spermatogonia self-renewal and proliferation. Judging from the evidence offered above, we can safely conclude that this study provides new ideas for further research regarding the mechanism of spermatogenesis and spermatogenesis disorders on an apparent spectrum.

The pore-rhizosheath shapes maize root architecture by enhancing root distribution in macropores.

Pores and old root-channels are preferentially used by roots to allow them to penetrate hard soils. However, there are few studies that have accounted for the effects of pore-rhizosheath on root growth. In this study, we developed an approach by adding the synthetic root exudates using a porous stainless tube with 0.1-mm micropores through a peristaltic pump to reproduce the rhizosheath around the artificial pore, and investigated the effects of pores with and without rhizosheaths on maize root growth in a dense soil. The results indicated that the artificial rhizosheath was about 2.69 mm wide in the region surrounding the pores. The rhizosheath had a higher content of organic carbon, total nitrogen, and abundance of Actinobacteria than that of the bulk soil. Compared with the artificial macropores, the artificial root-pores with a rhizosheath increased the opportunities for root utilisation of the pores space, promoting steeper and deeper root growth. It is concluded that the pore-rhizosheath has a significant impact on root architecture by enhancing root distribution in macropores.

Achieving widely distributed feature matches using flattened-affine-SIFT algorithm for fisheye images.

Performing correction first is the most common methods to address feature matching issues for fisheye images, but corrections often result in significant loss of scene details or stretching of images, leaving peripheral regions without matches. In this paper, we propose a novel approach, named flattened-affine-SIFT, to find widely distributed feature matches between stereo fisheye images. Firstly, we establish a new imaging model that integrates a scalable model and a hemisphere model. Utilizing the extensibility of the imaging model, we design a flattened array model to reduce the distortion of fisheye images. Additionally, the affine transformation is performed on the flattened simulation images, which are computed using the differential expansion and the optimal rigidity transformation. Then feature matches are extracted and matched from the simulated images. Experiments on indoor and outdoor fisheye images show that the proposed algorithm can find a large number of reliable feature matches. Moreover, these matches tend to be dispersed over the entire effective image, including peripheral regions with dramatic distortion.

Blockade of HMGB1 Reduces Inflammation and Pruritus in Atopic Dermatitis by Inhibiting Skin Fibroblasts Activation.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsed eczema and serious pruritus. High-mobility group box 1 protein (HMGB1) is a nuclear-binding protein and serves as an alarmin to promote inflammatory responses. METHODS: In this study, we established an AD mouse model by topical use of MC903 on ears and then used a specific HMGB1-binding peptide cIY8 and a HMGB1 inhibitor of glycyrrhizin to investigate HMGB1 on fibroblast activation in the pathogenesis of AD-like symptoms. RESULTS: Topical use of cIY8 and oral use of glycyrrhizin significantly improved the MC903-induced AD-like symptoms and pathological changes of the ears and scratching behavior in an AD mouse model; cIY8 treatment inhibited the higher mRNAs of IL-1α, IL-4, IL-5, IL-13, and IL-31 in the ears. In human fibroblasts, HMGB1 caused nuclear translocation of NF-kB, and the nuclear translocation could be inhibited by pre-treatment of HMGB1 with cIY8, suggesting that NF-κB signaling pathway participates in the HMGB1-induced inflammation of AD in fibroblasts and that cIY8 effectively impedes the function of HMGB1. Glycyrrhizin inhibited the Ca2+ signaling induced by ionomycin in mouse primary fibroblasts. The fibroblast-related proteins of α-SMA, Hsp47, and vimentin and the pruritus-related proteins of IL-33 and periostin were increased in the ears of the AD mouse model, the ratio of EdU incorporation became higher in mouse fibroblasts treated with MC903, and the higher proliferation and inflammatory responses of the fibroblasts could be reversed by glycyrrhizin treatment. CONCLUSIONS: Fibroblast activation by HMGB1 is one of the critical processes in the development of inflammation and pruritus in the AD mouse model. The specific HMGB1-binding peptide cIY8 and the HMGB1 inhibitor glycyrrhizin inactivate skin fibroblasts to alleviate the inflammation and pruritus in the AD mouse model. Peptide cIY8 may be topically used to treat AD patients in the future.

miR-124-3p improves mitochondrial function of renal tubular epithelial cells in db/db mice.

Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus (DM) and the main cause of end-stage renal failure. However, the pathogenesis of DKD is complicated. In this study, we found that miR-124-3p plays a key role in regulating renal mitochondrial function and explored its possible mechanism in DKD progression by performing a series of in vitro and in vivo experiments. Decreased expression of miR-124-3p was found in db/db mice compared to db/m mice. Moreover, miR-124-3p down-regulated FOXQ1 by targeting FOXQ1 mRNA 3'-UTR in NRK-52E cells. Also, an increase in FOXQ1 and down-regulation of Sirt4 were found in db/db mouse kidney and renal tubular epithelial cells cultured with high glucose and high lipid. Overexpression of FOXQ1 could further down-regulate the expression of Sirt4 and aggravate the damage of mitochondria. Conversely, the knockdown of the FOXQ1 gene induced Sirt4 expression and partially restored mitochondrial function. To verify the effects of miR-124-3p on Sirt4 and mitochondria, we found that miR-124-3p mimics could up-regulate Sirt4 and inhibit ROS production and MitoSOX, thus restoring the number and morphology of mitochondria. These results showed that under high-glucose and high-lipid conditions, the down-regulation of miR-124-3p induces FOXQ1 in renal tubular epithelial cells, which in turn suppresses Sirt4 and leads to mitochondrial dysfunction, promoting the development of DKD.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention　- A Subanalysis of the PANDA III Trial.

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined.Methods and Results: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Circular RNAs: emerging players in brain aging and neurodegenerative diseases.

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.

Let-7a-5p abrogates progression of papillary thyroid carcinoma cells by decreasing nuclear receptor subfamily 6 group a member 1-mediated lipogenesis.

Increasing evidence shows that microRNAs (miRNAs) contribute vital roles in papillary thyroid carcinoma (PTC) carcinogenesis, proliferation, invasion, and so on. As the most common endocrine malignancy, there still have largely unknown molecular events. First, our analysis and open access database information indicates that the downregulation of let-7a-5p accelerates PTC progression. Next, lentivirus mediates the overexpression of let-7a-5p PTC cells, and found let-7a-5p suppressed cancer cells proliferation and invasion. Interestingly, bioinformatics analysis hints NR6A1 is the potential target gene of let-7a-5p. The regulation was validated by luciferase and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PTC tissue and the clinic tumors. Moreover, let-7a-5p regulated NR6A1 involved in PTC cells lipogensis in vitro and in vivo. Finally, let-7a-5p abrogates PCT xenograft tumors growth, NR6A1 expression and lipogenesis. Taken together, our data indicates that let-7a-5p suppresses PCT progression through decreased lipogenesis, the related let-7a-5p/NR6A1axis might be promising candidate targets for PTC treatment.

Symptom profiles in patients receiving maintenance hemodialysis and their association with quality of life: a longitudinal study.

PURPOSE: Many patients receiving maintenance hemodialysis experience one or multiple symptoms. Using a latent profile analysis to identify symptom profiles may provide insights for person-centered symptom management strategies. METHODS: This is a longitudinal study based on data from patients receiving maintenance hemodialysis at three hospitals in Shanghai, China. Of the 448 patients who completed the surveys at baseline (T1), 309 completed the 12-month follow-up survey (T2). Symptoms and quality of life were measured by the Chinese version of Kidney Disease Quality of Life 36 Short Form. The optimal classification of symptoms was identified using latent profile analysis. RESULTS: Five symptom profiles were identified: High (9.2%), Fatigue and Gastrointestinal (7.1%), Fatigue and Skin (10.7%), Skin (23.2%), and Low (49.8%). The high-symptom profile and the-fatigue-and-skin-symptom profile were associated with a lower level of physical functioning, a higher burden of kidney disease, and more negative effects of kidney disease than the low symptom profile at T1 and T2. Multivariate regression analysis showed that the high-symptom profile predicted a poorer physical functioning at T2, and the-fatigue-and-skin-symptom profile predicted a poorer physical functioning and higher burden of kidney disease at T2. CONCLUSION: Patients receiving maintenance hemodialysis reported unique symptom experiences which could be classified into different profiles. Patients reporting an overall high level of symptoms or a high level of fatigue and skin symptoms were more likely to have a poorer quality of life.

The association of lymphocyte with hypothyroidism in obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder. Numerous investigations have found a strong inherent relationship between OSA and hypothyroidism. Studies suggest that lymphocytes may be involved in the development of hypothyroidism in patients with OSA. This study aimed to assess the association between lymphocytes and hypothyroidism in OSA patients. PATIENTS AND METHODS: This study involved 920 patients with OSA who underwent nocturnal sleep monitoring, thyroid function testing, and routine blood tests. In patients with OSA, logistic regression analysis indicated independent predictors of hypothyroidism. The cutoff level of lymphocyte count was determined using a receiver operating characteristic (ROC) analysis to predict the occurrence of hypothyroidism in individuals with OSA. RESULTS: This study comprised 920 OSA patients (617 males and 303 women), 879 with normal thyroid function, and 41 with hypothyroidism, with a hypothyroidism incidence of 4.46%. In the entire OSA population and male OSA patients, the number of lymphocytes was significantly higher in the hypothyroid group than in the control group (p = 0.002 and 0.020, respectively). In addition, among the OSA population younger than 60 years old and patients with mild to moderate OSA, lymphocytes were found to be considerably more in the hypothyroid group than in the euthyroid group. Lymphocyte count, ESS, and sex were all independent predictors of hypothyroidism development in OSA patients. According to ROC curve analysis, the risk of hypothyroidism increases with increasing lymphocyte count in the total patient population, with an optimal diagnostic cutoff point of 2.5 (× 10*9/L). CONCLUSIONS: The prevalence of hypothyroidism in patients with OSA increases as the number of lymphocytes increases. Lymphocyte count can be used as an independent predictor of the occurrence of hypothyroidism, and it has a diagnostic value for OSA combined with hypothyroidism.

First Report of Nigrospora sphaerica causing Leaf Spot on Rhododendron simsii in China.

Rhododendron simsii (indoor azalea) is widely cultivated for its high ornamental value (Xu et al. 2021). In April to May 2023, a leaf spot disease occurred in a field study at the Baili Azalea Forest Area (27°12'N, 105°48'E), Guizhou Province, China. About 500 plants were investigated, and the results showed that the incidence of leaf spot was 20 ~ 30%. To study this disease, 10 plants showing severe symptoms were collected. Initially, the symptoms were round or irregularly shaped brown spots (1 to 10 mm). With time, the spots enlarged and merged. Symptomatic leaves were washed with sterile distilled water, and 5 × 5 mm pieces of the infected tissues were removed. After surface sterilization (30 s with 75% ethanol, 2 min with 3% NaOCl, then washed three times with sterilized distilled water), the leaf pieces were dried and placed on potato dextrose agar (PDA) and incubated at 25℃ for 5 days. Fungal colonies developed from leaf tissues, and the germinated spores were transferred onto PDA for further purification and morphological observation. Three isolates (GUBJ23, GUBJ24, and GUBJ12) with similar morphology were obtained from five affected leaves. The representative strain GUBJ23 was selected for further study. On PDA the mycelium was initially white but with sporulation turned gray and then black. Black, single-celled conidia, spherical to sub-spherical, from 11.80 to 21.39 × 13.38 to 21.83 µm (n = 50) in diameter were borne singly on hyaline vesicles at the tips of conidiophores. These morphological characteristics were similar to those of Nigrospora sphaerica (Wang et al. 2017). To confirm the identification, primer pairs for the internal transcribed spacer (ITS) region (ITS5/ITS4), ß-tubulin (TUB2) (Bt-2a/Bt-2b), and the translation elongation factor 1-alpha (TEF1-α) (EF1-728F/EF1-986R), were used for PCR amplification of DNA from strain GUBJ23 (Carbone and Kohn 1999; Glass et al. 1995; White et al. 1990). The resulting sequences were deposited in GenBank with accession numbers OR818025 (ITS), OR835150 (TUB2), and OR835147 (TEF1-α). BLAST searches of the sequences revealed 99.80% identity (503/504 bp) of the ITS sequence, 100.00% identity (395/395 bp) of the TUB2 sequence, and 100.00% identity of the TEF1-α sequence (241/241 bp) with N. sphaerica LC7294 (accessions KX985932, KY019602, and KY019397, respectively.) Based on a combined dataset of ITS, TEF1-α, and TUB2 sequences, a phylogenetic tree was constructed using the maximum likelihood method and confirmed that isolates GUBJ23, GUBJ24, and GUBJ12 were N. sphaerica (Wang et al. 2017). Leaves of three healthy R. simsii plants were spray-inoculated with a spore suspension (105 conidia/mL), and an additional three plants were sprayed with sterile water. These plants were incubated at 25℃ in 75% relative humidity. After 5 to 7 days of inoculation, 0.5 to 1.8 mm spots appeared on the leaves. At 10 to 14 days after inoculation, grayish brown, semicircular or irregular lesions appeared on the leaves, usually with a diameter of 0.8 to 3 mm. The symptoms were like symptoms seen on naturally infected leaves, while the control leaves remained asymptomatic. The pathogen was re-isolated from diseased leaves and identified by morphological characterization and molecular analyses (ITS, TUB and TEF1-α), and the reisolated pathogen was identical to N. sphaerica. Thus completing Koch's postulates. According to previous research, N. sphaerica is a widely distributed phytopathogenic fungus that has a wide host range (Wang et al. 2017). This study is the first to identify N. sphaerica as the cause of leaf spot disease in R. simsii. Given the popularity of R. simsii as a pot plant and landscape shrub in Asia and othr regions, the occurrence of leaf spot disease seriously affects its ornamental and economic value. Therefore, it is crucial to establish and implement effective disease management practices to reduce impact of the disease.

First report of Diaporthe eres causing leaf spot on Rhododendron latoucheae Franch. in China.

Rhododendron latoucheae Franch. is an evergreen shrub with charming fragrance and large and abundant flowers that make it highly attractive as an ornamental species. The species is distribution in southwest China covers several different habitats and environments (Zhang, et al. 2022). From May to July in 2023, symptoms of leaf spot were observed on R. latoucheae over a wide portion of the Baili Azalea Forest Area (27°10' to 27°20'N, 105°04' to 106°04'E), Guizhou Province, China. About 500 plants were surveyed, and the incidence of leaf spot on R. latoucheae leaves was 12%, significantly reducing their ornamental and economic value. The affected leaves had irregular, grey white lesions with a clear blackish brown boundary and faint black conidiomata in a brown center. To isolate the pathogen, 15 symptomatic leaves were collected from 10 plants. A few black dots were picked from the lesions with a sterilized needle, plated on water agar, and incubated at 25°C for 24 h to observe spore germination (Choi et al. 1999). Then the germinated spores were transferred onto PDA for further purification and morphological observation. Three single-spore isolates (GULJ1-L7, GULJ1-L8, and GULJ1-L9) identical in morphology were obtained. The isolate GULJ 1-L7 was used for further study. Colonies on PDA irregular grew white felty aerial mycelium, becoming white felted aerial mycelium in the centre and grey-brown mycelium at the marginal area on the upper surface, while the lower surface presents alternating white, tan and taupe. Colony with conidiomata irregularly distributed over agar surface. In the representative isolate, darkly pigmented pycnidia (flask-shaped) were produced over the colony surface on PDA after about 30 days, and oozed milky or yellowish mucilaginous drops. The fungus produced two types of conidia, α and ß. Regular α conidia were 5.15-10.29 × 1.54-3.33 µm (n = 50), hyaline, elongated, biguttulate and non-septate. Beta conidia were 20.34-31.91 × 1.01-1.90 µm (n = 50), aseptate, hyaline, smooth, spindle shaped, slightly curved to bent. The morphological features were consistent with the description of Diaporthe eres (Pereira, et al. 2022). The pathogen was confirmed to be D. eres by amplification and sequencing of the internal transcribed spacer region (ITS), the partial ß-tubulin (TUB), the partial translation elongation factor 1-alpha (TEF) genes and the calmodulin (CAL) using primers ITS1/ITS4, Bt-2a/Bt-2b, EF1-728F/EF1-986R, and CAL-228F/CAL-737R, respectively (Tao et al. 2020). Sequences from PCR amplification were deposited in GenBank with accession numbers OR740563 (ITS), OR754301 (TUB), OR754298 (TEF), and OR754295 (CAL) respectively. BLAST searches of the sequences revealed 99.07% (533/538 nt), 100% (490/490 nt), 99.69% (317/318 nt) and 98.95% (376/380 nt) homology with those of D. eres AR5193T from GenBank (KJ210529.1, KJ420799.1, KJ210550.1 and KJ434999.1), respectively. Phylogenetic analysis (MEGA 7.0) using the maximum-likelihood method placed the isolate GULJ1-L7 in a well-supported cluster with D. eres CBS 138694T. The pathogen was thus identified as D. eres based on the morphological characterization and molecular analyses (Feng, et al. 2013; Tao, et al. 2020). The pathogenicity of GULJ1-L7 was tested through a pot assay. Due to the difficulty of artificial planting wild R. latoucheae, we conducted a pot essay to detect the pathogenicity of GULJ1-L7 using a closely related Rhododendron delavayi Franch. Ten healthy R. delavayi plants were scratched with a sterilized needle (0.45 mm in diameter) on three leaves per plant. Plants were inoculated by spraying α and ß spore mixture suspension (106 spores ml-1) of GULJ1-L7 onto leaves until runoff, and the control leaves were sprayed with sterile water. The plants were maintained at 25°C and 75% relative humidity in a growth chamber. The pathogenicity test was repeated three times. After 14 days, the treated leaves developed brown lesions similar to those in the field, whereas the control had no symptoms. The same fungus was reisolated from the infected leaves and identified based on a morphological characterization and molecular analyses. These results fulfilled Koch's postulates. To our knowledge, this is the first report of leaf spot on R. latoucheae caused by D. eres in China. The fungal pathogen identification will provide valuable information for prevention and management of leaf spot disease associated with R. latoucheae.

Identification of Susceptibility Genes Underlying Bovine Respiratory Disease in Xinjiang Brown Cattle Based on DNA Methylation.

DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Insights into the Molecular Mechanism of Formaldehyde Inhibition of [FeFe]-Hydrogenases.

[FeFe]-hydrogenases are efficient H2 converting biocatalysts that are inhibited by formaldehyde (HCHO). The molecular mechanism of this inhibition has so far not been experimentally solved. Here, we obtained high-resolution crystal structures of the HCHO-treated [FeFe]-hydrogenase CpI from Clostridium pasteurianum, showing HCHO reacts with the secondary amine base of the catalytic cofactor and the cysteine C299 of the proton transfer pathway which both are very important for catalytic turnover. Kinetic assays via protein film electrochemistry show the CpI variant C299D is significantly less inhibited by HCHO, corroborating the structural results. By combining our data from protein crystallography, site-directed mutagenesis and protein film electrochemistry, a reaction mechanism involving the cofactor's amine base, the thiol group of C299 and HCHO can be deduced. In addition to the specific case of [FeFe]-hydrogenases, our study provides additional insights into the reactions between HCHO and protein molecules.

Agar-Derived Slope-Dominated Carbon Anode with Puparium Like Nano-Morphology for Cost-Effective SIBs.

The microstructure of hard carbons (HCs) including interlayer distance and lateral ab direction and pore size distribution plays a key role in regulating the sodium ions storage performance. Herein, by employing the gelatinous agar as a model precursor, series P-doping HCs (P-HC-x, x = 1, 2, 3, 4) are facilely prepared in batches via controllably regulating its crosslinking state by phytic acid (PA) at a low carbonization temperature of 750 °C, in which PA plays three roles (acid, flame retardant, and P-doping precursor) in promoting the final structure of P-HC-x. Among those, the puparium like P-HC-2 with expanded carbon interlayer distance of 3.91 Å and shortened lateral ab direction of 9.4 nm delivers a high reversible capacity of 394 mAh g-1 at 0.1 A g-1 with high increased slope capacity of 363 mAh g-1 as well as an ultrafast charge-discharge feature and a superlong cycle life. Pairing with the Na3 V2 (PO4 )3 cathode, the fabricated sodium-ion full cells exhibit the 132 mAh g-1 reversible capacity at 0.1 A g-1 , and 86% capacity retention after 100 cycles. This work successfully develops slope-dominated high-performance carbon anode, which will provide new insights for the microstructure regulation and design of other precursor-derivedHCs.

HK3 stimulates immune cell infiltration to promote glioma deterioration.

BACKGROUND: Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions between neoplastic cells and the surrounding microenvironment can generate an immunosuppressive TME, which can accelerate the malignant progression of glioma. Therefore, it is crucial to explore associations between energy metabolism and the immunosuppressive TME and to identify new biomarkers for glioma prognosis. METHODS: In our work, we analyzed the co-expression relationship between glycolytic genes and immune checkpoints based on the transcriptomic data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) and found the correlation between HK3 expression and glioma tumor immune status. To investigate the biological role of HK3 in glioma, we performed bioinformatics analysis and established a mouse glioblastoma (GBM) xenograft model. RESULTS: Our study showed that HK3 significantly stimulated immune cell infiltration into the glioma TME. Tissue samples with higher HK3 expressive level showed increasing levels of immune cells infiltration, including M2 macrophages, neutrophils, and various subtypes of activated memory CD4+ T cells. Furthermore, HK3 expression was significantly increasing along with the elevated tumor grade, had a higher level in the mesenchymal subtype compared with those in other subtypes of GBM and could independently predict poor outcomes of GBM patients. CONCLUSION: The present work mainly concentrated on the biological role of HK3 in glioma and offered a novel insight of HK3 regulating the activation of immune cells in the glioma microenvironment. These findings could provide a new theoretical evidence for understanding the metabolic molecular within the glioma microenvironment and identifying new therapeutic targets.

Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. This study explored the mechanism of miR-181a-5p in the inflammatory response in COPD mice. COPD mouse models were established by cigarette smoke (CS) exposure following pretreatment with recombinant adeno-associated virus (rAAv)-miR-181a-5p, si-HMGB1 (high mobility group box 1), and NF-κB pathway inhibitor PDTC, respectively. Pathological changes of lung tissues were determined by HE staining. Bronchoalveolar lavage fluid was collected to count total cells, neutrophils, and lymphocytes using a Countess II automatic cell counter. Expressions of neutrophil elastase (NE) and inflammatory factors (TNF-α, IL-6, IL-8, and IFN-γ) were detected by ELISA. Binding relationship between miR-181a-5p and HMGB1 was predicted on starBase and validated by dual-luciferase assay. miR-181a-5p expression was detected by RT-qPCR, and expressions of HMGB1, IκBα, and p-IκBα were detected by western blot. The expression level of miR-181a-5p was lower in lung tissues. miR-181a-5p overexpression alleviated inflammatory response and pathological changes of lung tissues in COPD mice, with decreased pulmonary inflammation scores, total cells, neutrophils, and lymphocytes and expressions of NE and inflammatory factors. HMGB1 expression level was increased in COPD mice. miR-181a-5p targeted HMGB1. si-HMGB1 relieved inflammatory responses in COPD mice. NF-κB was activated in COPD mice, evidenced by degraded IκBα and increased p-IκBα levels. si-HMGB1 significantly restrained the activation of NF-κB pathway. Briefly, miR-181a-5p targets HMGB1 to inhibit the NF-κB pathway, thus alleviating the inflammatory response in COPD mice.

Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review.

BACKGROUND: Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization. CASE PRESENTATION: The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation. CONCLUSIONS: Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.