Aim This study aimed to assess the therapeutic potential of ACT001, a micheliolide derivative, in the treatment of acute lung injury ( ALI) induced by sepsis and investigate its pharmacological mechanisms. Methods At the animal level, an ALI model was established in mice through intraperitoneal injection of li-popolysaccharide (LPS). Subsequently, ACT001 was administered to the ALI-afflicted mice. The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate, lung inflammation, and pulmonary edema. At the cellular level, RAW264. 7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001. The study examined inflammatory response and oxidative stress levels, and proteomics analysis was conducted to investigate the underlying molecular mechanisms. Results At the animal level, ACT001 can improve the survival of mice with ALI, reduce lung inflammation, and reduce the levels of inflammatory cytokines in serum. At the cellular level, ACT001 promotes the polarization of RAW264. 7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-II related pathways, inhibiting the production of NO and related inflammatory cytokines while increasing SOD content and scavenging ROS. Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity, mainly by inhibiting the STAT1/ CIITA/ MHC-II pathway. ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.

Objective　To investigate the imaging characteristics and main clinical manifestations of patients with respiratory and/or cardiac arrest after medullary infarction (MI).Methods　The study included patients with respiratory and/or cardiac arrest after MI,who were hospitalized in the Department of Neurology of Huanhu hospital between 2016 and 2021.The patients were divided into groups and analyzed according to the infarct location and infarct size shown by MRI-DWI,the degree of vascular stenosis shown by MRA and the main clinical manifestations.Results　The study enrolled a total of 28 patients, including 19 patients with lateral medullary infarction (LMI) and 9 patients with medial medullary infarction (MMI).For LMI patients,from head to tail,there were 4 cases with upper MI,11 cases with middle MI,and 4 cases with lower MI.On the axial plane,there were 4 cases in the middle,14 cases in the dorsal,and 1 case through the middle and dorsal.Among the 28 patients,50% were large area MI (DWI high signal≥1/3 of the total area of medulla oblongata) and medium area MI (1/4 of the total area of medulla oblongata≤DWI high signal<1/3 of the total area of medulla oblongata).Sixteen cases completed brain MRA examination,of which 12 cases were moderate and severe vascular stenosis.Among the 28 patients,16 cases were complicated with infarction in other parts,of which 9 cases were complicated with cerebellar infarction.The main clinical symptoms were dizziness and dysarthria.For the 19 LMI patients,dizziness was the main complaint in 16,dysarthria in 16,dysphagia in 10,limb weakness in 7.For the 9 MMI patients,dizziness was the main complaint in 6,dysarthria in 8,dysphagia in 3,limb weakness in 7.Conclusion　LMI is the main type of respiratory and/or cardiac arrest after MI,and it is more common in patients with dorsal medulla oblongata in the middle part.The proportion of patients with medium and large area MI is relatively high.Most patients have moderate and severe vascular stenosis and often complicated with cerebellar infarction.The main complaints were dizziness and dysarthria.LMI was more prone to dysphagia and MMI to limb weakness.

Keloid is a fibrous proliferative disease of the skin, and its pathological essence is excessive wound healing caused by excessive fibrosis. Its pathological mechanism is complex and unclear. At present, it is believed that the cellular mechanism of keloids mainly involves inflammatory cells and fibrosis-related cells, as well as cytokines such as growth factors, interleukins, tumor necrosis factor, and matrix metalloproteinase; the molecular mechanism mainly involves TGF-p/Smad pathway, NF-Mo- lecular mechanisms such as kB pathway, STAT3 signaling pathway, MAPK signaling pathway, and focal adhesion kinase. This article reviews the latest research progress on the pathological mechanism of keloids from the perspectives of cells, cytokines, and molecular signaling pathways.

S1 nuclease (from Aspergillus oryzae) is a specific enzyme to degrade single stranded DNA or RNA molecules. It has been reported to be able to convert superhelical circular DNA molecules into open circle or linear forms under certain conditions, but this function has not been well explored. In order to use the action of S1 nuclease to linearize circular DNA and develop a novel way of cloning microcircular DNAs, the pUC19 was used to investigate the relationship between the linearization efficiency of S1 nuclease and the amount of enzyme used. By this way the optimal conditions for linearization of circular DNAs by S1 nuclease would be determined. 0.3u to 17u S1 nuclease per 100ng pUC19 DNA was added into a 25 microL system, respectively, to perform the reaction. The effectiveness of enzyme digestion was realized by electrophoresis in a 1.2% agarose gel. The results showed that along with the increase in enzyme amount from 0.3u to 17u a gradual decrease in the superhelical form, a gradual increase in the linear form and then in the circular form was obvious. The conversion from superhelical form to linear and circular form was directly related to the enzyme amount used. A higher proportion of linear DNA molecules was achieved by using 5 to 17u S1 nuclease per 100ng DNA. Besides, electrophoretic mobility of the S1 nuclease-linearized pUC19 was the same as that of the linear form produced by restriction enzyme digestion. According to the result of phiX174 digested by S1 nuclease it has been proposed that the enzyme cleaves first randomly on one site of one strand, thus converting the superhelical molecules into open circle form, and then on the same site of the complementary strand to produce the linear form. Therefore, the S1 nuclease-linearized DNA molecules are intact in the sense of their length and can be used for cloning. The plasmid-like DNA pC3 from cucumber mitochondria is a double stranded circular DNA molecule with about 550bp and the smallest known plasmid-like DNA in eukaryotic mitochondria. Many attempts have been made to linearize the molecule by using restriction enzymes but failed. Therefore, S1 nuclease was used to linearize pC3 based on the results obtained with pUC19. The linearized pC3 DNA molecules formed a very sharp band in a 2.5% agarose gel after electrophoresis. They were then recovered from the gel, added an "A" tail and ligated with T-vector. After transformation into E. coli JM109 cells, the positive clones were, screened by the blue-white selection. The insert was then cut using restriction enzymes EcoRI and Pst I. The result of electrophoresis shows that the electrophoretic mobility of the insert is just the same as that predicted. A 32 P-labled probe was synthesized using pC3 as the template and Southern blot analysis was carried out. The result shows that the inserted DNA is hybridized to the probe, which indicates that the cloned DNA fragment is from pC3. The sequence information of the insert shows that the plasmid-like DNA pC3 was 537bp in length. The nucleotide sequence was deposited in the GenBank (the accession number is AF522195).
Blotting, Southern ; Cloning, Molecular ; methods ; DNA, Circular ; genetics ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Molecular Sequence Data ; Single-Strand Specific DNA and RNA Endonucleases ; genetics ; metabolism

Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with collision-induced dissociation (CID) was used to study the fragmentation characteristics of six unusual nucleotide diphosphate sugars. The results indicated the major fragment of the six unusual nucleoside sugars observed in the ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H] together with fragment ions resulting from the loss of water and phosphate moiety, respectively. Furthermore, 4-position substituted change of unusual sugar rings affected the stability of two important characteristic fragment ions of [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).
Molecular Structure ; Nucleoside Diphosphate Sugars ; chemical synthesis ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods

Ribosomal RNAs are important because they catalyze the synthesis of peptides and proteins. Comparative studies of the secondary structure of 18S rRNA have revealed the basic locations of its many length-conserved and length-variable regions. In recent years, many more sequences of 18S rDNA with unusual lengths have been documented in GenBank. These data make it possible to recognize the diversity of the secondary and tertiary structures of 18S rRNAs and to identify the length-conserved parts of 18S rDNAs. The longest 18S rDNA sequences of almost every known eukaryotic phylum were included in this study. We illustrated the bioinformatics-based structure to show that, the regions that are more length-variable, regions that are less length-variable, the splicing sites for introns, and the sites of A-minor interactions are mostly distributed in different parts of the 18S rRNA. Additionally, this study revealed that some length-variable regions or insertion positions could be quite close to the functional part of the 18S rRNA of Foraminifera organisms. The tertiary structure as well as the secondary structure of 18S rRNA can be more diverse than what was previously supposed. Besides revealing how this interesting gene evolves, it can help to remove ambiguity from the alignment of eukaryotic 18S rDNAs and to improve the performance of 18S rDNA in phylogenetic reconstruction. Six nucleotides shared by Archaea and Eukaryota but rarely by Bacteria are also reported here for the first time, which might further support the supposed origin of eukaryote from archaeans.
Animals ; Base Sequence ; Drosophila melanogaster ; genetics ; Eukaryota ; classification ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; RNA, Ribosomal, 16S ; chemistry ; genetics ; RNA, Ribosomal, 18S ; chemistry ; classification ; genetics ; Sequence Alignment ; Sequence Analysis, RNA ; Thermus thermophilus ; genetics

Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Knockdown Techniques ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; Humans ; Microtubule-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Pancreatic Neoplasms ; enzymology ; metabolism ; pathology ; Protein Binding

Angiogenesis, the expansion of preexisting blood vessels, is a complex process required for tumor growth and metastasis. Although current antiangiogenic strategies have shown promising results in several cancer types, identification of additional antiangiogenic targets is required to improve the therapeutic response. Herein, we show that the microtubule-binding protein CLIP-170 (cytoplasmic linker protein of 170 kDa) is highly expressed in breast tumor samples and correlates positively with blood vessel density. Depletion of CLIP-170 significantly impaired vascular endothelial tube formation and sprouting in vitro and inhibited breast tumor growth in mice by decreasing tumor vascularization. Our data further show that CLIP-170 is important for the migration but not the proliferation of vascular endothelial cells. In addition, CLIP-170 promotes the polarization of endothelial cells in response to the angiogenic stimulus. These findings thus demonstrate a critical role for CLIP-170 in tumor angiogenesis and suggest its potential as a novel antiangiogenic target.
Animals ; Breast Neoplasms ; blood supply ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Polarity ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Microtubule-Associated Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Microtubules ; metabolism ; Neoplasm Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Neovascularization, Pathologic ; RNA Interference ; RNA, Small Interfering ; metabolism ; Transplantation, Heterologous

Objective To make analysis and diagnosis on backhand twist technique used by player A, who is the leading men’s player of national table tennis team, so as to provide references for improving his backhand twist technique. Methods The three-dimensional kinematics test and analysis were used. The backhand twist techniques of player A and those of player B who has good backhand twist techniques were compared by quantitative data and picture analysis. Results At the stage of swinging racket backward, the racket swing amplitude, shoulder angle and wrist angle of player A were significantly smaller than those of player B. The roll angle of trunk of player A was significantly larger than that of player B. At the stage of swinging and hitting the ball, the shoulder angle, elbow angle of player A were significantly bigger than those of player B, while the increasing amplitude of shoulder angle and elbow angle, as well as the changing amplitude in roll angle of trunk of Lin Guoyuan were significantly smaller than those of player B. At the stage of swinging racket forward, the shoulder angle and elbow angle of player A were significantly bigger than those of player B. The increasing amplitude of shoulder angle and elbow angle, as well as the roll angle of trunk and its changing amplitude of player A were significantly smaller than those of player B. Conclusions The racket swing amplitude of player A was smaller, and the distance between the racket and the ball of player A was close at the end of swinging racket backward stage. During swinging and hitting the ball stage, the hitting point was far from the body, the shoulder joint was not stable enough to support, so that the wrist was used more. The center of gravity was not enough to force forward, and the outburst power was not concentrated. At swinging racket forward stage, player A’s braking was not active enough, which affected the stability of hitting the ball. At hitting the ball stage, the torsion of the trunk was smaller, and the waist power was not concentrated. On the basis of unaffecting the forehand outburst power, player A should slightly adjust his backhand twisting technique, or appropriately increase the the racket swing amplitude and torsion of the body. In the process of hitting the ball, the sequence of outburst power was the waist, the forearm and the wrist.

Objective:To investigate the CT imaging features of epidural hematoma (EDH) surrounding subdural effusion (satellite effusion sign) and its application value in diagnosis of EDH.Methods:A retrospective analysis of clinical and imaging data of 30 patients with EDH and 122 patients with acute subdural hematoma (SDH), admitted to our hospitals from December 2017 to February 2020, was performed. The frequencies of satellite effusion sign were compared in the two groups, and the differences between the correct diagnosis rate of traditional CT performance and the correct diagnosis rate of traditional CT performance+satellite effusion sign were compared in the two groups; the specific characteristics of satellite effusion sign was clarified and its relations with morphological characteristics and distribution of hematoma were analyzed.Results:Among 30 patients with acute EDH, the occurrence rate of satellite effusion sign was 63.3% (19/30); among 122 patients with acute SDH, the occurrence rate of satellite effusion sign was 2.5% (3/122); the difference was statistically significant ( χ2=67.248, P=0.000). Among the 30 patients with acute EDH, the correct diagnosis rate of traditional CT manifestation was 86.7% (26/30), and the correct diagnosis rate of traditional CT manifestation+satellite effusion sign was 93.3% (28/30), without statistically significance ( χ2=0.185, P=0.667). The length of the satellite effusion sign was (1.1±0.9) cm, ranged from 0.2 cm-3.1 cm; the width was (3.6±2.0) mm, ranged from 1.4 mm-7.5 mm. The incidence of satellite effusion sign in the frontotemporal EDH patients (73.9%) was significantly increased as compared with that in the occipitoparietal EDH patients (28.6%, P<0.05); that of patients with clinically diagnosed cerebral contusion, laceration, cerebral hernia or other severe to extremely severe craniocerebral injuries (22.2%) was significantly reduced as compared with that of patients with mild to moderate craniocerebral injuries (81.0%, P<0.05). Conclusion:Satellite effusion sign is an important new CT sign in the diagnosis of EDH, which is closely related to the locations of hematoma and severities of craniocerebral injury.