Genotype-phenotype association and functional analysis of hnRNPA1 mutations in amyotrophic lateral sclerosis.

BACKGROUND: Pathogenic variants in hnRNPA1 have been reported in amyotrophic lateral sclerosis (ALS) patients. However, studies on hnRNPA1 mutant spectrum and pathogenicity of variants were rare. METHODS: We performed whole exome sequencing of ALS-associated genes and subsequent verification of rare variants in hnRNPA1 in our ALS patients. The hnRNPA1 mutations reported in literature were reviewed and combined with our results to determine the genotype-phenotype relationship. Functional analysis of the novel variant p.G195A was performed in vitro by transfection of mutant hnRNPA1 into 293T cell. RESULTS: Among 207 ALS patients recruited, 3 rare hnRNPA1 variants were identified (mutant frequency 1.45%), including two recurrent mutations (p.P340S and p.G283R), and a novel rare variant p.G195A. In combination with previous reports, there are 27 ALS patients with 15 hnRNPA1 mutations identified. Disease onset age was 47.90 ± 1.52 years with predominant limb onset. The p.P340S mutation caused flail arm syndrome (FAS) in two independent families with extended life expectancy. The newly identified p.G195A mutation, lying at the start of the PrLD ("prion-like" domain)/LCD (low-complexity domain), causes local structural changes in 3D protein prediction. Upon sodium arsenite exposure, mutant hnRNPA1 retained in the nucleus but deficit of cytoplasmic G3BP1-positive stress granule clearance was observed. This is different from the p.P340S mutation which caused both cytoplasmic translocation and stress granule formation. No cytoplasmic TDP-43 translocation was observed. CONCLUSION: Mutations in hnRNPA1 are overall minor in ALS patients. The p.P340S mutation is associated with manifestation of FAS. Mutations in LCD of hnRNPA1 cause stress granule misprocessing.

Effects of oral probiotics on inflammation and intestinal function in adult patients after appendectomy: Randomized controlled trial.

BACKGROUND: Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation. Oral probiotics are one of the postoperative treatments for rapid rehabilitation. However, there is a lack of prospective studies on this topic after appendectomy. AIM: To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy. METHODS: This was a prospective, randomized trial. A total of 60 emergency patients were randomly divided into a control group (n = 30) and a probiotic group (n = 30). Patients in the control group started to drink some water the first day after surgery, and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery. The indices of inflammation and postoperative conditions were recorded, and the data were analyzed with RStudio 4.3.2 software. RESULTS: A total of 60 participants were included. Compared with those in the control group, the C-reactive protein (CRP), interleukin 6 and procalcitonin (PCT) levels were significantly lower in the probiotic group at 2 d after surgery (P = 2.224e-05, P = 0.037, and P = 0.002, respectively, all P < 0.05). This trend persisted at day 5 post-surgery, with CRP and PCT levels remaining significantly lower in the probiotic group (P = 0.001 and P = 0.043, both P < 0.05). Furthermore, probiotics resulted in a shorter time to first flatus and a greater percentage of gram-negative bacilli in the feces (P = 0.035, P = 0.028, both P < 0.05). CONCLUSION: Postoperative oral administration of probiotics may modulate the gut microbiota, benefit the recovery of the early inflammatory response, and subsequently enhance recovery after appendectomy.

Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7.

OBJECTIVE: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it. METHODS: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex. RESULTS: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01). CONCLUSIONS: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.

Transcriptomics and metabolomics of blood, urine and ovarian follicular fluid of yak at induced estrus stage.

To gain a deeper understanding of the metabolic differences within and outside the body, as well as changes in transcription levels following estrus in yaks, we conducted transcriptome and metabolome analyses on female yaks in both estrus and non-estrus states. The metabolome analysis identified 114, 13, and 91 distinct metabolites in urine, blood, and follicular fluid, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted an enrichment of pathways related to amino acid and lipid metabolism across all three body fluids. Our transcriptome analysis revealed 122 differentially expressed genes within microRNA (miRNA) and 640 within long non-coding RNA (lncRNA). Functional enrichment analysis of lncRNA and miRNA indicated their involvement in cell signaling, disease resistance, and immunity pathways. We constructed a regulatory network composed of 10 lncRNAs, 4 miRNAs, and 30 mRNAs, based on the targeted regulation relationships of the differentially expressed genes. In conclusion, the accumulation of metabolites such as amino acids, steroids, and organic acids, along with the expression changes of key genes like miR-129 during yak estrus, provide initial insights into the estrus mechanism in yaks.

Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke.

AIMS: We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke. METHODS: We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT-PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA. RESULTS: EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post-MCAO. EA also downregulated the expression of pro-inflammatory cytokines, including Tnf-α, Il-6, Il-1ß, and Ccl-2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect. CONCLUSION: EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Suggesting Dictyostelium as a Model for Disease-Related Protein Studies through Myosin II Polymerization Pathway.

Dictyostelium myosin II displays remarkable dynamism within the cell, continually undergoing polymerization and depolymerization processes. Under low-ion conditions, it assumes a folded structure like muscle myosins and forms thick filaments through polymerization. In our study, we presented intermediate structures observed during the early stages of polymerization of purified myosin via negative staining electron microscopy, immediately crosslinked with glutaraldehyde at the onset of polymerization. We identified folded monomers, dimers, and tetramers in the process. Our findings suggest that Dictyostelium myosin II follows a polymerization pathway in vitro akin to muscle myosin, with folded monomers forming folded parallel and antiparallel dimers that subsequently associate to create folded tetramers. These folded tetramers eventually unfold and associate with other tetramers to produce long filaments. Furthermore, our research revealed that ATP influences filament size, reducing it regardless of the status of RLC phosphorylation while significantly increasing the critical polymerization concentrations from 0.2 to 9 nM. In addition, we demonstrate the morphology of fully matured Dictyostelium myosin II filaments.

Coupling effect of solidification and consolidation on characteristics of the dredged silt.

Dehydration with a plate and frame filter press is a common method for treating dredged silt from rivers and lakes. The silt is often conditioned by the addition of solidifying materials before plate and frame press filtration and, therefore, is subjected to the coupling effect of solidification and consolidation. In this study, consolidation tests of the silt with cement were carried out and compared with the silt after only solidification or only consolidation in terms of moisture content, unconfined compressive strength, and leaching concentration. The test results showed that the moisture content of the silt can be reduced to less than 60% under the coupling action of solidification and consolidation, which was 22% and 4% lower than with solidification only or consolidation only, respectively. The effect of consolidation improved the solidification process; the unconfined compressive strength increased rapidly in the early stage of curing and was 30-150% higher than that of solidified silt. The coupling effects of solidification and consolidation on the leaching concentrations of Ni and Cr in silt were the most significant, and the lowest leaching concentrations were 60% and 90% lower than those of solidified only and consolidated only silt, respectively.

Whole-genome resequencing of major populations revealed domestication-related genes in yaks.

BACKGROUND: The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. MATERIAL AND METHOD: Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. RESULTS: By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). CONCLUSIONS: We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.

Circular RNA mapping reveals CircCWC22 as a MiR-3059-x sponge in yak fat deposition by regulating HMGCL.

The regulatory mechanisms and functions of circular RNAs (circRNAs) in yak intramuscular fat (IMF) deposition remain unclear. This study aimed to investigate yak circRNAs with high and low IMF content using high-throughput sequencing. A total of 270 differentially expressed circRNAs were identified, of which 129 were upregulated and 141 were downregulated. Among these circRNAs, circCWC22, derived from the yak CWC22 gene, was further studied to understand its functions and regulatory mechanisms. Sequencing and RNase R processing confirmed the circular nature of circCWC22. By constructing a circRNA-miRNA-mRNA co-expression network, the potential regulatory pathway of circCWC22/miR-3059-x/HMGCL was identified. To investigate the roles of circCWC22, miR-3059-x, and HMGCL in the deposition of yak intramuscular preadipocytes (YIMAs), CCK-8, EdU, BODIPY, triglyceride content, and qRT-PCR analyses were performed. The results demonstrated that circCWC22, miR-3059-x, and HMGCL promoted the differentiation and inhibited the proliferation of YIMAs. Using the dual-luciferase reporter system and qRT-PCR, we confirmed that circCWC22 adsorbed miR-3059-x, and HMGCL was identified as a target gene of miR-3059-x. In conclusion, this study uncovered a large number of potential circRNAs involved in IMF deposition and highlighted the significant role of circCWC22 in yak IMF deposition via the circCWC22/miR-3059-x/HMGCL axis.

IMF deposition ceRNA network analysis and functional study of HIF1a in yak.

The concentration of intramuscular fat (IMF) is a crucial determinant of yak meat quality. However, the molecular mechanisms that regulate IMF in yak remain largely elusive. In our study, we conducted transcriptome sequencing on the longissimus dorsi muscle tissues of yaks with varying IMF contents. We then filtered differentially expressed genes (DEGs), microRNAs (DEMs), and long non-coding RNAs (DELs) to elucidate potential regulatory pathways of adipogenesis in yaks. Overall, our research sheds light on an array of potential mRNAs and noncoding RNAs implicated in IMF deposition and elaborates on the role of HIF1α in yaks. These findings contribute valuable insights that can serve as a guide for further research into the molecular mechanisms governing IMF deposition.

The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM.

Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug interactions. In the kidneys, OATs facilitate the elimination of metabolic waste products and xenobiotics. However, their transport activities can lead to the accumulation of certain toxic compounds within cells, causing kidney damage. Moreover, OATs are important drug targets, because their inhibition modulates the elimination or retention of substrates linked to diseases. Despite extensive research on OATs, the molecular basis of their substrate and inhibitor binding remains poorly understood. Here we report the cryo-EM structures of rat OAT1 (also known as SLC22A6) and its complexes with para-aminohippuric acid and probenecid at 2.1, 2.8 and 2.9 Å resolution, respectively. Our findings reveal a highly conserved substrate binding mechanism for SLC22 transporters, wherein four aromatic residues form a cage to accommodate the polyspecific binding of diverse compounds.

Development Trend in Composition Optimization, Microstructure Manipulation, and Strengthening Methods of Die Steels under Lightweight and Integrated Die Casting.

In the general environment of lightweight automobiles, the integrated die-casting technology proposed by Tesla has become the general mode to better achieve weight reduction in automobiles. The die-casting mold required by integrated die-casting technology has the characteristics of large scale and complexity. Hence, higher requirements are put forward for the comprehensive performance of the die steel. Despite the stagnation in the progress of conventional strengthening methods, enhancing the performance of die steel has become increasingly challenging. Indeed, it necessitates exploring novel die steel and optimizing heat treatment and reinforcement technologies. This article summarizes and analyzes the development status of die steel and corresponding heat treatment and microstructure manipulation as well as strengthening methods and elaborates on an excellent nano-strengthening technology. Furthermore, this review will aid researchers in establishing a comprehensive understanding of the development status of die steel and the processes utilized for its strengthening. It will also assist them in developing die steel with improved comprehensive performance to meet the high demand for mold steel in the integrated die-casting technology of the new era.

Effects of initial temperature and moisture content on heat generation during degradation of municipal solid waste.

Heat generation from degradation of organic matter in municipal solid waste (MSW) often leads to increased landfill temperature. However, it is difficult to measure environmental heat loss in laboratory and field tests; therefore, little research has been conducted to evaluate heat generation during waste degradation under different initial temperatures and moisture contents. In this study, tests were conducted to investigate the effects of initial temperature and moisture content on heat generation during waste degradation. A simple formula for calculating heat generation was proposed. Within 200 h, the waste temperature decreased by about 70%, and lower initial moisture contents were associated with greater temperature decreases. The smallest temperature decrease of 47% and the greatest heat generation occurred when the initial temperature was 40 °C. The initial moisture content increased from 30% to 60% and the heat generation increased from 5% to 36%. The heat generation per unit mass of organic matter during the aerobic and anaerobic stages were 19.44-23.77 and 0.27-0.50 MJ·kg-1, respectively, indicating that the proposed formula for calculation of heat generated from waste degradation was reasonable. The results presented herein provide theoretical support for the prediction of heat generation and the recycling of heat resources in MSW landfill sites.

Transcriptomic analysis of yak longissimus dorsi muscle identifies genes associated with tenderness.

Meat tenderness is an important sensory index when consumers choose meat products, which determines the value of meat products and consumers' buying intentions. Yak meat is rich in nutrition and unique in flavor, which is favored by consumers. However, its meat has the deficiencies of low tenderness and poor taste, which has a negative impact on the value of its meat products and customer satisfaction. To identify the genes affecting the yak meat tenderness, we used RNA-seq to analyze the longissimus dorsi muscle of yaks with different tenderness, screened a total of 1120 differentially expressed genes (DEGs). Meanwhile, 23 pathways were significantly enriched. By further analysis, we identified eight genes related to yak meat tenderness (WNT5A, ARID5B, SERPINE1 KLHL40, RUNX1, MAFF, RFX7 and ARID5A). Notably, SERPINE1 was involved in the significant enrichment pathways of 'complement and coagulation cascade pathway', 'HIF-1 signaling pathway' and 'AGE-RAGE signaling pathway in diabetic complications' which can regulate meat tenderness. This implies that SERPINE1 may play an important regulatory role among them. The DEGs associated with yak meat quality screened in this work will be helpful to identify potential biomarkers related to meat tenderness.

Epigenomics Analysis of the Suppression Role of SIRT1 via H3K9 Deacetylation in Preadipocyte Differentiation.

Sirtuin 1 (SIRT1) overexpression significantly inhibits lipid deposition during yak intramuscular preadipocyte (YIMA) differentiation; however, the regulatory mechanism remains unknown. We elucidated the role of SIRT1 in YIMA differentiation using lentivirus-mediated downregulation technology and conducted mRNA-seq and ChIP-seq assays using H3K9ac antibodies after SIRT1 overexpression in order to reveal SIRT1 targets during YIMA adipogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed in order to identify the functional annotation of common genes. In addition, a potential target of SIRT1 was selected to verify its effects on the differentiation and proliferation of YIMAs. SIRT1 interfered with lipid deposition and promoted YIMA differentiation. In total, 143,518 specific peaks were identified after SIRT1 overexpression, where genes associated with downregulation peaks were enriched in transcription, gene expression, lipid-related processes, and classical lipid-related pathways. The H3K9ac signal in the whole genome promoter region (2 kb upstream and downstream of the transcription start site (TSS)) was weakened, and the peaks were distributed across all gene functional regions. Genes that lost signals in their TSS region or gene body region were enriched in both biological processes and pathways associated with lipogenesis. The ChIP-seq results revealed 714 common differential genes in mRNA-seq, which were enriched in "MAPK signaling", "lipid and atherosclerosis", "mTOR signaling", and "FoxO signaling" pathways. A total of 445 genes were downregulated in both their H3K9ac signals and mRNA expression, and one of their most significantly enriched pathways was FoxO signaling. Nine genes (FBP2, FPGT, HSD17B11, KCNJ15, MAP3K20, SLC5A3, TRIM23, ZCCHC10, and ZMYM1) lost the H3K9ac signal in their TSS regions and had low mRNA expression, and three genes (KCNJ15, TGM3, and TRIM54) had low expression but lost their H3K9ac signal in the gene body region. The interference of TRIM23 significantly inhibited fat deposition during preadipocyte differentiation and promoted cell proliferation by increasing S-phase cell numbers. The present study provides new insights into the molecular mechanism of intramuscular fat content deposition and the epigenetic role of SIRT1 in adipocyte differentiation.

The Role of Lithium in the Aging Precipitation Process of Al-Zn-Mg-Cu Alloys and Its Effect on the Properties.

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties.

Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS: Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

Identification and cross-validation of autophagy-related genes in cardioembolic stroke.

Objective: Cardioembolic stroke (CE stroke, also known as cardiogenic cerebral embolism, CCE) has the highest recurrence rate and fatality rate among all subtypes of ischemic stroke, the pathogenesis of which was unclear. Autophagy plays an essential role in the development of CE stroke. We aim to identify the potential autophagy-related molecular markers of CE stroke and uncover the potential therapeutic targets through bioinformatics analysis. Methods: The mRNA expression profile dataset GSE58294 was obtained from the GEO database. The potential autophagy-related differentially expressed (DE) genes of CE stroke were screened by R software. Protein-protein interactions (PPIs), correlation analysis, and gene ontology (GO) enrichment analysis were applied to the autophagy-related DE genes. GSE66724, GSE41177, and GSE22255 were introduced for the verification of the autophagy-related DE genes in CE stroke, and the differences in values were re-calculated by Student's t-test. Results: A total of 41 autophagy-related DE genes (37 upregulated genes and four downregulated genes) were identified between 23 cardioembolic stroke patients (≤3 h, prior to treatment) and 23 healthy controls. The KEGG and GO enrichment analysis of autophagy-related DE genes indicated several enriched terms related to autophagy, apoptosis, and ER stress. The PPI results demonstrated the interactions between these autophagy-related genes. Moreover, several hub genes, especially for CE stroke, were identified and re-calculated by Student's t-test. Conclusion: We identified 41 potential autophagy-related genes associated with CE stroke through bioinformatics analysis. SERPINA1, WDFY3, ERN1, RHEB, and BCL2L1 were identified as the most significant DE genes that may affect the development of CE stroke by regulating autophagy. CXCR4 was identified as a hub gene of all types of strokes. ARNT, MAPK1, ATG12, ATG16L2, ATG2B, and BECN1 were identified as particular hub genes for CE stroke. These results may provide insight into the role of autophagy in CE stroke and contribute to the discovery of potential therapeutic targets for CE stroke treatment.

Parvularcula maris sp. nov., an algicidal bacterium isolated from seawater.

A taxonomic study was carried out on strain BGMRC 0090T, which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090T belonged to the genus Parvularcula, with highest sequence similarity to Parvularcula lutaonensis CC-MMS-1T (98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090T and five strains of the genus Parvularcula with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090T was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090T contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C18 : 1ω7c/ω6c) and C16 : 0. Based on the polyphasic evidence presented in this paper, strain BGMRC 0090T is concluded to represent a novel species of the genus Parvularcula, for which the name Parvularcula maris sp. nov. is proposed. The type strain is BGMRC 0090T (= KCTC 92591T=MCCC 1K08100T).