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1.
Antonie Van Leeuwenhoek ; 117(1): 101, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008162

ABSTRACT

Two novel Gram-stain-negative, aerobic, and non-motile strains, designated FZY0004T and YYF002T, were isolated from an agar-degrading co-culture, which was obtained from seawater of the intertidal zone of Yancheng City, the Yellow Sea of China. Strain FZY0004T optimally grew at 28 °C, pH 7.0, and 2-6% NaCl, while strain YYF002T optimally grew at 28 °C, pH 7.5, and 2-4% NaCl. Strain FZY0004T possessed Q-9 as the major respiratory quinone, and its major fatty acids (> 10%) were summed feature 8 (C18:1 ω7c), C16:0, and summed feature 3 (C16:1 ω7c/C16:1 ω6c). The polar lipids identified in strain FZY0004T were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and several unidentified phospholipids (PL) and lipids (L). On the other hand, strain YYF002T had MK-6 as the predominant respiratory quinone and its major fatty acids consisted of iso-C15:0, iso-C15:1 G, and iso-C15:0 3-OH. The polar lipids identified in strain YYF002T were aminolipid (AL), PE, and several unidentified lipids. Strain FZY0004T shared 99.5% 16S rRNA gene sequence similarity and 90.1% average nucleotide identity (ANI) with T. povalilytica Zumi 95T, and strain YYF002T shared 99.2% 16S rRNA gene sequence similarity and 88.2% ANI with W. poriferorum JCM 12885T. The genomic DNA G + C contents of strains FZY0004T and YYF002T were 54.5% and 33.5%, respectively. The phylogenetic, phenotypic, and physiological characteristics permitted the distinction of the two strains from their neighbors, and we thus propose the names Thalassospira aquimaris sp. nov. (type strain FZY0004T = JCM 35895T = MCCC 1K08380T) and Winogradskyella marincola sp. nov. (type strain YYF002T = JCM 35950T = MCCC 1K08382T).


Subject(s)
Agar , DNA, Bacterial , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Seawater , RNA, Ribosomal, 16S/genetics , Seawater/microbiology , DNA, Bacterial/genetics , Agar/metabolism , Fatty Acids/metabolism , Base Composition , Bacterial Typing Techniques , China , Phospholipids/metabolism , Coculture Techniques , Sequence Analysis, DNA
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 324-328, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953255

ABSTRACT

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.


Subject(s)
Anxiety , Depression , Humans , Surveys and Questionnaires , Depression/epidemiology , Depression/diagnosis , Female , Anxiety/epidemiology , Male , Adult , Athletic Injuries/psychology , Athletic Injuries/epidemiology , China/epidemiology , Middle Aged , Young Adult
3.
Article in English | MEDLINE | ID: mdl-38953650

ABSTRACT

BACKGROUND AND IMPORTANCE: The surgical management of rostral disc herniations at L5-S1 poses challenges for conventional endoscopic approaches, particularly in patients who have had previous lumbar surgery. We present a full endoscopic transpedicular discectomy (FETD), whereby a pediculotomy is created to pass an endoscope through the pedicle for intracanal access. This addresses anatomic obstacles and potential complications associated with other endoscopic and minimally invasive or open techniques. To date, this is the only article to highlight this approach with a case report and intraoperative video. CLINICAL PRESENTATION: A 76-year-old man with a history of L3-S1 laminectomy presented with left leg pain and a near-complete left foot drop. An MRI revealed a left paracentral rostrally migrated disc herniation arising from L5-S1 with impingement of the exiting left L5 nerve root at the inferomedial aspect of the pedicle of L5. The patient consented to the FETD procedure. Using sequential reamers of increasing diameter and a high-speed burr, a superolateral to inferomedial pediculotomy was performed. This approach allowed us to target the pathology at the point of maximum compression without traversing the prior operative field. A transforaminal endoscopic approach was not possible with the iliac crest obstructing rostral angulation. The disc was successfully removed without any intraoperative complications, and after surgery, the patient's radiculopathy resolved without any radiographic evidence of instability. CONCLUSION: FETD is a unique approach that demonstrates the versatility of endoscopic spine surgery, offering advantages over conventional approaches particularly for rostral disc herniations at L5-S1 in the setting of prior lumbar surgery.

4.
J Nanobiotechnology ; 22(1): 382, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951872

ABSTRACT

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.


Subject(s)
Exosomes , MicroRNAs , Myocardial Reperfusion Injury , NF-kappa B , Rats, Sprague-Dawley , Signal Transduction , Animals , MicroRNAs/metabolism , MicroRNAs/genetics , Myocardial Reperfusion Injury/metabolism , Exosomes/metabolism , NF-kappa B/metabolism , Rats , Male , Milk/chemistry , Myocardium/metabolism , Cardiotonic Agents/pharmacology , Myocytes, Cardiac/metabolism
5.
ACS Nano ; 18(26): 17304-17313, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38904507

ABSTRACT

Recently, aqueous iron ion batteries (AIIBs) using iron metal anodes have gained traction in the battery community as low-cost and sustainable solutions for green energy storage. However, the development of AIIBs is significantly hindered by the limited capacity of existing cathode materials and the poor intercalation kinetic of Fe2+. Herein, we propose a H+ and Fe2+ co-intercalation electrochemistry in AIIBs to boost the capacity and rate capability of cathode materials such as iron hexacyanoferrate (FeHCF) and Na4Fe3(PO4)2(P2O7) (NFPP). This is achieved through an electrochemical activation step during which a FeOOH nanowire layer is formed in situ on the cathode. This layer facilitates H+ co-intercalation in AIIBs, resulting in a high specific capacity of 151 mAh g-1 and 93% capacity retention over 500 cycles for activated FeHCF cathodes. We found that this activation process can also be applied to other cathode chemistries, such as NFPP, where we found that the cathode capacity is doubled as a result of this process. Overall, the proposed H+/Fe2+ co-insertion electrochemistry expands the range of applications for AIBBs, in particular as a sustainable solution for storing renewable energy.

6.
Acta Psychol (Amst) ; 248: 104354, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38878476

ABSTRACT

PURPOSE: Based on social exchange theory and social cognition theory, this paper studies the effect of work-related identity discrepancy on proactive behavior of close-leadership employees through hierarchical regression analysis and examines the mediating effect of face-pressure and the moderating effect of benevolent leadership. METHODS: This work surveyed 516 employees by questionnaire. The first round of survey mainly investigated employees in Changsha City, and the second round of survey mainly investigated employees' work-related identity discrepancy, face-pressure, benevolent leadership and proactive behavior in >10 regions. By tracking and matching, 396 valid questionnaires were finally obtained. Spss 22.0 was used to describe all the study variables; Mplus 7.0 is used to carry out a confirmatory factor analysis and a multi-path regression model. RESULTS: The difference in work-related identity discrepancy had a significant negative impact on proactive behavior. Face-pressure partially mediated the relationship between work-related identity discrepancy and proactive behavior. Benevolent leadership moderated the indirect relationship between work-related identity discrepancy, proactive behavior and face-pressure. We hope that the findings and discussions from this study will spark further exploration and practical application of enterprise management theories. CONCLUSION: In the context of leadership change, employee identity differences in perception can affect employee proactive behavior, especially for some close-leadership employees. Face-pressure in traditional Chinese culture has a prominent place. Managers should strive to foster an open and inclusive organizational atmosphere that promotes interaction and communication among employees, reduces the impact of negative factors like face pressure, and thereby stimulates employees' work initiative and innovative spirit. This enriches and deepens our understanding within the fields of organizational behavior and cross-cultural management.

7.
Int Immunopharmacol ; 138: 112513, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38917520

ABSTRACT

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

8.
J Transl Med ; 22(1): 428, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711158

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis. METHODS: Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed. RESULTS: Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD. CONCLUSIONS: This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms.


Subject(s)
Adenocarcinoma of Lung , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Lung Neoplasms , DNA Methylation/genetics , Humans , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Prognosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Gene Expression Profiling , CpG Islands/genetics , Female , Neoplasm Staging , Male , Middle Aged , Genome, Human , Aged
9.
Biotechnol Lett ; 46(4): 699-711, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38733437

ABSTRACT

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.


Subject(s)
Epichlorohydrin , Hydrolases , Epichlorohydrin/chemistry , Epichlorohydrin/metabolism , Hydrolases/genetics , Hydrolases/metabolism , Hydrolases/chemistry , Kinetics , Stereoisomerism , Escherichia coli/genetics , Escherichia coli/enzymology , Protein Engineering/methods , alpha-Chlorohydrin/analogs & derivatives
10.
Metallomics ; 16(5)2024 05 02.
Article in English | MEDLINE | ID: mdl-38744662

ABSTRACT

Iron-sulfur (Fe-S) clusters are an essential and ubiquitous class of protein-bound prosthetic centers that are involved in a broad range of biological processes (e.g. respiration, photosynthesis, DNA replication and repair and gene regulation) performing a wide range of functions including electron transfer, enzyme catalysis, and sensing. In a general manner, Fe-S clusters can gain or lose electrons through redox reactions, and are highly sensitive to oxidation, notably by small molecules such as oxygen and nitric oxide. The [2Fe-2S] and [4Fe-4S] clusters, the most common Fe-S cofactors, are typically coordinated by four amino acid side chains from the protein, usually cysteine thiolates, but other residues (e.g. histidine, aspartic acid) can also be found. While diversity in cluster coordination ensures the functional variety of the Fe-S clusters, the lack of conserved motifs makes new Fe-S protein identification challenging especially when the Fe-S cluster is also shared between two proteins as observed in several dimeric transcriptional regulators and in the mitoribosome. Thanks to the recent development of in cellulo, in vitro, and in silico approaches, new Fe-S proteins are still regularly identified, highlighting the functional diversity of this class of proteins. In this review, we will present three main functions of the Fe-S clusters and explain the difficulties encountered to identify Fe-S proteins and methods that have been employed to overcome these issues.


Subject(s)
Iron-Sulfur Proteins , Iron-Sulfur Proteins/metabolism , Iron-Sulfur Proteins/chemistry , Iron-Sulfur Proteins/genetics , Oxidation-Reduction
11.
ACS Appl Mater Interfaces ; 16(22): 29153-29161, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38770559

ABSTRACT

While polymer fabrics are integral to a wide range of applications, their vulnerability to mechanical damage limits their sustainability and practicality. Addressing this challenge, our study introduces a versatile strategy to develop photohealable fabrics, utilizing a composite of polystyrene (PS) and an azobenzene-containing polymer (PAzo). This combination leverages the structural stability of PS to compensate for the mechanical weaknesses of PAzo, forming the fiber structures. Key to our approach is the reversible trans-cis photoisomerization of azobenzene groups within the PAzo under UV light exposure, enabling controlled morphological alterations in the PS/PAzo blend fibers. The transition of PAzo sections from a solid to a liquid state at a low glass transition temperature (Tg ∼ 13.7 °C) is followed by solidification under visible light, thus stabilizing the altered fiber structures. In this study, we explore various PS/PAzo blend ratios to optimize surface roughness and mechanical properties. Additionally, we demonstrate the capability of these fibers for photoinduced self-healing. When damaged fabrics are clamped and subjected to UV irradiation for 20 min and pressed for 24 h, the mobility of the cis-form PAzo sections facilitates healing while retaining the overall fabric structure. This innovative approach not only addresses the critical issue of durability in polymer fabrics but also offers a sustainable and practical solution, paving the way for its application in smart clothing and advanced fabric-based materials.

12.
Phys Rev Lett ; 132(19): 196402, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38804933

ABSTRACT

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

13.
Heliyon ; 10(9): e30640, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38774102

ABSTRACT

The skeletal muscle is the largest organ in mammals and is the primary motor function organ of the body. Our previous research has shown that long non-coding RNAs (lncRNAs) are significant in the epigenetic control of skeletal muscle development. Here, we observed progressive upregulation of lncRNA 4930581F22Rik expression during skeletal muscle differentiation. Knockdown of lncRNA 4930581F22Rik hindered skeletal muscle differentiation and resulted in the inhibition of the myogenic markers MyHC and MEF2C. Furthermore, we found that lncRNA 4930581F22Rik regulates myogenesis via the ERK/MAPK signaling pathway, and this effect could be attenuated by the ERK-specific inhibitor PD0325901. Additionally, in vivo mice injury model results revealed that lncRNA 4930581F22Rik is involved in skeletal muscle regeneration. These results establish a theoretical basis for understanding the contribution of lncRNAs in skeletal muscle development and regeneration.

14.
In Vivo ; 38(3): 1079-1093, 2024.
Article in English | MEDLINE | ID: mdl-38688627

ABSTRACT

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Quetiapine Fumarate , Xenograft Model Antitumor Assays , Animals , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/radiotherapy , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Mice , Humans , Quetiapine Fumarate/pharmacology , Quetiapine Fumarate/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Apoptosis/drug effects , Disease Progression , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Male
15.
Cancer Med ; 13(8): e7200, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38634194

ABSTRACT

BACKGROUND: Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. METHODS: We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. RESULTS: This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). CONCLUSIONS: In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , alpha-Fetoproteins , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Lymphatic Metastasis , Neoplasm Recurrence, Local , Prognosis , RNA, Long Noncoding/genetics , RNA, Small Nucleolar
16.
J Med Chem ; 67(10): 8309-8322, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38669059

ABSTRACT

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 1 , Drug Design , Liver Cirrhosis , Phosphodiesterase Inhibitors , Pyrimidines , Animals , Cyclic Nucleotide Phosphodiesterases, Type 1/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 1/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Humans , Rats , Phosphodiesterase Inhibitors/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/therapeutic use , Phosphodiesterase Inhibitors/chemistry , Male , Structure-Activity Relationship , Rats, Sprague-Dawley , Molecular Docking Simulation , Molecular Structure
17.
Med Phys ; 51(6): 4133-4142, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38578373

ABSTRACT

BACKGROUND: Pulmonary emphysema is a part of chronic obstructive pulmonary disease, which is an irreversible chronic respiratory disease. In order to avoid further damage to lung tissue, early diagnosis and treatment of pulmonary emphysema is essential. PURPOSE: Early pulmonary emphysema diagnosis is difficult with conventional radiographic imaging. Recently, x-ray phase contrast imaging has proved to be an effective and promising imaging strategy for soft tissue, due to its high sensitivity and multi-contrast. The aim of this study is to diagnose pulmonary emphysema early utilizing an x-ray Talbot-Lau interferometer (TLI). METHODS: We successfully established the mouse model of emphysema by porcine pancreatic elastase treatment, and then used the established x-ray TLI to perform imaging experiments on the mice with different treatment time. The traditional absorption CT and phase contrast CT were obtained simultaneously through TLI. The CT results and histopathology of mice lung in different treatment time were quantitatively analyzed. RESULTS: By imaging mice lungs, it can be found that phase contrast has higher sensitivity than absorption contrast in early pulmonary emphysema. The results show that the phase contrast signal could distinguish the pulmonary emphysema earlier than the conventional attenuation signal, which can be consistent with histological images. Through the quantitative analysis of pathological section and phase contrast CT, it can be found that there is a strong linear correlation. CONCLUSIONS: In this study, we quantitatively analyze mean linear intercept of histological sections and CT values of mice. The results show that the phase contrast signal has higher imaging sensitivity than the attenuation signal. X-ray TLI multi-contrast imaging is proved as a potential diagnostic method for early pulmonary emphysema in mice.


Subject(s)
Interferometry , Pulmonary Emphysema , Animals , Pulmonary Emphysema/diagnostic imaging , Mice , Interferometry/instrumentation , Tomography, X-Ray Computed , Lung/diagnostic imaging , Early Diagnosis , Mice, Inbred C57BL
18.
Spine J ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38685276

ABSTRACT

BACKGROUND CONTEXT: Transcranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. PURPOSE: To evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. DESIGN: We present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. PATIENT SAMPLE: Two hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Intraoperative neuromonitoring data was correlated to immediate post-operative neurologic examinations and chart review. METHODS: Baseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of pre-operative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. RESULTS: TaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three pre-existing motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. CONCLUSIONS: These findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery.

19.
J Immunother Cancer ; 12(4)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688579

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.


Subject(s)
Cytomegalovirus , Glioblastoma , Humans , Glioblastoma/immunology , Glioblastoma/virology , Glioblastoma/pathology , Mice , Cytomegalovirus/immunology , Animals , Cytomegalovirus Infections/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Brain Neoplasms/immunology , Tumor Microenvironment/immunology , RNA-Seq , Female , Male , Single-Cell Gene Expression Analysis
20.
Heliyon ; 10(5): e27075, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38444462

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) has emerged as a prominent global health concern, representing a substantial burden within the spectrum of chronic liver diseases. Despite its escalating prevalence, a definitive therapeutic strategy or efficacious pharmacological intervention for NAFLD has yet to receive official approval to date. While Fu Fang Qiyin granules have exhibited efficacy in addressing NAFLD, the intricacies of their underlying mechanism of action remain inadequately elucidated. In this study, we substantiated the ameliorative impact of Qiyin on highfat diet (HFD)induced NAFLD in rat models. The results of metabonomics showed that 108 potential biomarkers in serum and urine related to amino acid metabolism, energy metabolism, and pyrimidine metabolism, have returned to normal levels compared to the model group. Hepatic transcriptomics further indicated that Qiyin potentially confers protective effects against NAFLD by mediating liver inflammation and fibrosis through lumican (LUM) and decorin (DCN). In summation, our investigation provides compelling evidence affirming the therapeutic promise of Qiyin for NAFLD. It elucidates the underlying mechanistic pathways, furnishing a compelling rationale for its prospective clinical application.

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