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1.
J Virol ; 98(7): e0043324, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38888346

ABSTRACT

The cellular endosomal sorting complex required for transport (ESCRT) system comprises five distinct components and is involved in many different physiological processes. Recent studies have shown that different viruses rely upon the host ESCRT system for viral infection. However, whether this system is involved in white spot syndrome virus (WSSV) infection remains unclear. Here, we identified 24 homologs of ESCRT subunits in kuruma shrimp, Marsupenaeus japonicus, and found that some key components were strongly upregulated in shrimp after WSSV infection. Knockdown of key components of the ESCRT system using RNA interference inhibited virus replication, suggesting that the ESCRT system is beneficial for WSSV infection. We further focused on TSG101, a crucial member of the ESCRT-I family that plays a central role in recognizing cargo and activating the ESCRT-II and ESCRT-III complexes. TSG101 colocalized with WSSV in hemocytes. The addition of N16 (a TSG101 inhibitor) markedly decreased WSSV replication. TSG101 and ALIX of the ESCRT system interact with WSSV envelope proteins. The host proteins TSG101, RAB5, and RAB7, the viral protein VP28, and DNA were detected in endosomes isolated from hemocytes of WSSV-infected shrimp. Knockdown of Rab5 and Rab7 expression reduced viral replication. Taken together, these results suggest that the ESCRT system is hijacked by WSSV for transport through the early to late endosome pathway. Our work identified a novel requirement for the intracellular trafficking and infection of WSSV, and provided novel therapeutic targets for the prevention and control of WSSV in shrimp aquaculture. IMPORTANCE: Viruses utilize the ESCRT machinery in a variety of strategies for their replication and infection. This study revealed that the interaction of ESCRT complexes with WSSV envelope proteins plays a crucial role in WSSV infection in shrimp. The ESCRT system is conserved in the shrimp Marsupenaeus japonicus, and 24 homologs of the ESCRT system were identified in the shrimp. WSSV exploits the ESCRT system for transport and propagation via the interaction of envelope proteins with host TSG101 and ALIX in an endosome pathway-dependent manner. Understanding the underlying mechanisms of WSSV infection is important for disease control and breeding in shrimp aquaculture.


Subject(s)
DNA-Binding Proteins , Endosomal Sorting Complexes Required for Transport , Penaeidae , Virus Replication , White spot syndrome virus 1 , Animals , White spot syndrome virus 1/physiology , White spot syndrome virus 1/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism , Penaeidae/virology , Penaeidae/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Endosomes/metabolism , Endosomes/virology , Hemocytes/virology , Hemocytes/metabolism , Host-Pathogen Interactions , Viral Envelope Proteins/metabolism , Viral Envelope Proteins/genetics , RNA Interference
2.
Proc Natl Acad Sci U S A ; 119(15): e2116844119, 2022 04 12.
Article in English | MEDLINE | ID: mdl-35377811

ABSTRACT

In pathological or artificial conditions, memory can be formed as silenced engrams that are unavailable for retrieval by presenting conditioned stimuli but can be artificially switched into the latent state so that natural recall is allowed. However, it remains unclear whether such different states of engrams bear any physiological significance and can be switched through physiological mechanisms. Here, we show that an acute social reward experience switches the silent memory engram into the latent state. Conversely, an acute social stress causes transient forgetting via turning a latent memory engram into a silent state. Such emotion-driven bidirectional switching between latent and silent states of engrams is mediated through regulation of Rac1 activity­dependent reversible forgetting in the hippocampus, as stress-activated Rac1 suppresses retrieval, while reward recovers silenced memory under amnesia by inhibiting Rac1. Thus, data presented reveal hippocampal Rac1 activity as the basis for emotion-mediated switching between latent and silent engrams to achieve emotion-driven behavioral flexibility.


Subject(s)
CA1 Region, Hippocampal , Mental Recall , Social Behavior , rac1 GTP-Binding Protein , Animals , CA1 Region, Hippocampal/enzymology , Cues , Mental Recall/physiology , Mice , Neurons/enzymology , Reward , rac1 GTP-Binding Protein/metabolism
3.
Anal Chem ; 96(11): 4632-4638, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38457631

ABSTRACT

Superoxide anion (O2•-) plays a pivotal role in the generation of other reactive oxygen species within the body and is closely linked to epilepsy. Despite this connection, achieving precise imaging of O2•- during epilepsy pathology remains a formidable challenge. Herein, we develop an activatable molecular probe, CL-SA, to track the fluctuation of the level of O2•- in epilepsy through simultaneous fluorescence imaging and chemiluminescence sensing. The developed probe CL-SA demonstrated its efficacy in imaging of O2•- in neuronal cells, showcasing its dual optical imaging capability for O2•- in vitro. Furthermore, CL-SA was successfully used to observe aberrantly expressed O2•- in a mouse model of epilepsy. Overall, CL-SA provides us with a valuable tool for chemical and biomedical studies of O2•-, promoting the investigation of O2•- fluctuations in epilepsy, as well as providing a reliable means to explore the diagnosis and therapy of epilepsy.


Subject(s)
Molecular Probes , Superoxides , Mice , Animals , Humans , Reactive Oxygen Species , Hep G2 Cells , Optical Imaging/methods , Fluorescent Dyes/chemistry
4.
BMC Plant Biol ; 24(1): 705, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054416

ABSTRACT

BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.


Subject(s)
Droughts , Gene Expression Regulation, Plant , Plant Proteins , Transcription Factors , Triticum , Transcription Factors/metabolism , Transcription Factors/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Triticum/genetics , Triticum/physiology , Triticum/metabolism , Stress, Physiological/genetics , Adaptation, Physiological/genetics , Genes, Plant , Drought Resistance
5.
Opt Express ; 32(11): 19517-19530, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859085

ABSTRACT

We study the excitations of dark solitons in a nonlinear optical fiber with the second- and fourth-order dispersion, and find the emergence of striped dark solitons (SDSs) and some multi-dark-soliton bound states. The SDSs can exhibit time-domain oscillating structures on a plane wave, and they have two types: the ones with or without the total phase step, while the multi-dark-soliton bound states exhibit different numbers of amplitude humps. By the modified linear stability analysis, we regard the SDSs as the results of the competition between periodicity and localization, and analytically give their existence condition, oscillation frequency, and propagation stability, which show good agreements with numerical results. We also provide a possible interpretation of the formation of the existing striped bright solitons (SBSs), and find that SBS will become the pure-quartic soliton when its periodicity and localization carry equal weight. Our results provide the theoretical support for the experimental observation of striped solitons in nonlinear fibers, and our method can also guide the discovery of striped solitons in other physical systems.

6.
Inflamm Res ; 73(3): 345-362, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38157008

ABSTRACT

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.


Subject(s)
Colitis , Saponins , Rats , Mice , Animals , Pyruvate Carboxylase/metabolism , NF-kappa B/metabolism , Lipopolysaccharides/pharmacology , Molecular Docking Simulation , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Inflammation/metabolism , Saponins/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Macrophages/metabolism , Dextran Sulfate/adverse effects , Dextran Sulfate/metabolism , Mice, Inbred C57BL , Disease Models, Animal
7.
Eur J Clin Microbiol Infect Dis ; 43(2): 249-257, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38030860

ABSTRACT

PURPOSE: The objective of this multicenter study was to compare the diagnostic performance of lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) to detect the Dynamiker Aspergillus Galactomannan levels in serum and bronchoalveolar lavage fluid (BALF) samples for I. METHODS: We registered 310 clinically suspected Aspergillus infection patients from December 2021 to February 2023 and classified them into subgroups as the "IA group" and "non-IA group" based on the latest EORTC/MSG guidelines. The immunoassays were analyzed by LFA and ELISA respectively. RESULTS: Galactomannan was examined using LFA, and serum and BALF samples demonstrated sensitivities of 82.57% and 89.47%, specificities of 90.76% and 92.00%, PPVs of 89.11% and 96.23%, and NPVs of 85.04% and 79.31%, respectively. Galactomannan was observed using two assays in serum and BALF samples and showed PPAs of 95.11% and 93.33%, NPAs of 89.19% and 96.30%, and TPAs of 92.47% and 94.25%, respectively. The ROC curve demonstrated that LFA had optimum diagnostic value when the index value (I value) = 0.5, the sensitivity was 84.94%, and the specificity was 90.97%. CONCLUSION: Compared to the ELISA method, the LFA has shown excellent performance for the diagnosis of IA in serum and BALF sample and can be used as an assay for the early diagnosis of patients with IA. The dynamic change in galactomannan levels may be useful for assessing treatment response.


Subject(s)
Aspergillosis , Galactose/analogs & derivatives , Invasive Fungal Infections , Humans , Sensitivity and Specificity , Aspergillosis/diagnosis , Aspergillus , Mannans/analysis , Bronchoalveolar Lavage Fluid/microbiology
8.
Scand J Gastroenterol ; 59(2): 133-141, 2024.
Article in English | MEDLINE | ID: mdl-37752679

ABSTRACT

BACKGROUND: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. METHODS: A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. RESULTS: 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(ß = - 0.349, p = 0.035). CONCLUSION: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.


Subject(s)
Pancreaticoduodenectomy , Stomach , Humans , Pancreaticoduodenectomy/adverse effects , Length of Stay , Gastric Emptying , Postoperative Complications/prevention & control , Postoperative Complications/etiology
9.
Fish Shellfish Immunol ; 151: 109679, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38844185

ABSTRACT

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) typically composing of eight subunits (CSN1-8) mediates the process of deneddylation and deubiquitination. The fifth subunit of COP9 signalosome, CSN5, has special characteristics compared with the other seven subunits, and plays vital roles in the deneddylation activity and diverse cellular processes. However, the role of CSN5 in antiviral immunity is not clear. In this study, we identified 8 subunits (CSN1-8) of COP9 signalosome in shrimp Marsupenaeus japonicus. CSN1-6 were existed in all tested tissues, but CSN7-CSN8 were not detected in hepatopancreas. After WSSV challenged, the expression level of Csn1 to Csn4, and Csn6 to Csn8 were highly decreased, but the expression level of Csn5 was conspicuously increased in shrimp challenged by white spot syndrome virus (WSSV). The CSN5 was recombinantly expressed in Escherichia coli and its polyclonal antibody was prepared. The expression level of CSN5 was conspicuously increased at RNA and protein levels in the shrimp challenged by WSSV. After knockdown of Csn5 by RNA interference, the WSSV replication was obviously increased in shrimp. When injected the recombinant protein of CSN5 with the membrane penetrating peptide into shrimp, WSSV replication was inhibited and the survival rate of shrimp was significantly improved compared with control. We further analyzed the expression of antimicrobial peptides (AMPs) in Csn5-RNAi shrimp, and the results showed that the expression of several AMPs was declined significantly. These results indicate that CSN5 inhibits replication of WSSV via regulating expression of AMPs in shrimp, and the recombinant CSN5 might be used in shrimp aquaculture for the white spot syndrome disease control.


Subject(s)
Arthropod Proteins , COP9 Signalosome Complex , Immunity, Innate , Penaeidae , White spot syndrome virus 1 , Animals , Penaeidae/genetics , Penaeidae/immunology , COP9 Signalosome Complex/genetics , COP9 Signalosome Complex/immunology , White spot syndrome virus 1/physiology , Arthropod Proteins/genetics , Arthropod Proteins/immunology , Arthropod Proteins/chemistry , Immunity, Innate/genetics , Gene Expression Regulation/immunology , Gene Expression Profiling/veterinary , Sequence Alignment/veterinary , Phylogeny
10.
Chaos ; 34(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38416671

ABSTRACT

We study the small mass limit in mean field theory for an interacting particle system with non-Gaussian Lévy noise. When the Lévy noise has a finite second moment, we obtain the limit equation with convergence rate ε+1/εN, by taking first the mean field limit N→∞ and then the small mass limit ε→0. If the order of the two limits is exchanged, the limit equation remains the same but has a different convergence rate ε+1/N. However, when the Lévy noise is α-stable, which has an infinite second moment, we can only obtain the limit equation by taking first the small mass limit and then the mean field limit, with the convergence rate 1/Nα-1+1/Np2+εp/α where p∈(1,α). This provides an effectively limit model for an interacting particle system under a non-Gaussian Lévy fluctuation, with rigorous error estimates.

11.
New Microbiol ; 46(4): 340-347, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38252044

ABSTRACT

Gram-negative bacteria are increasingly recognized as the sauce of severe infections. In recent years, epidemiological data has indicated that the drug resistance rate of Gram-negative bacteria has significantly increased. We analyzed the epidemiological surveillance data of gram-negative bacteria in Shaoxing City in 2021 by retrospectively collecting drug susceptibility data of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Burkholderia cepacian from thirteen tertiary hospitals. A total of 24,142 strains were collected from thirteen hospitals. The isolation rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, P. mirabilis, E. cloacae, and B. cepacian were 29.25%, 18.83%, 11.03%, 8.43%, 3.80%, 3.12%, and 0.75%, respectively. Among them, 2.86% were carbapenem-resistant E. coli, 12.98% were CRKP, 31.27% were CRPA, and 34.77% were CRAB. Carbapenem-resistant Enterobacterales were more sensitive to ceftazidime-avibactam and polymyxin. The drug resistance rates of P. aeruginosa and A. baumannii to polymyxin were 0 and 1.3%, but the resistance rates to ceftazidime-avibactam were 10.5% and 26.0%, respectively. Based on results from epidemiological data, CRKP had a high isolation rate and non-fermenting bacteria had a high resistance rate to ceftazidime-avibactam. All hospitals should strengthen monitoring and enact continuous intervention to reduce the generation and spread of drug-resistant bacteria.


Subject(s)
Escherichia coli , Gram-Negative Bacteria , Humans , Retrospective Studies , Tertiary Care Centers , Carbapenems , Polymyxins
12.
Adv Skin Wound Care ; 37(6): 1-7, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38767429

ABSTRACT

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.


Subject(s)
Acellular Dermis , Calcaneus , Heel , Skin Transplantation , Soft Tissue Injuries , Wound Healing , Humans , Male , Female , Calcaneus/injuries , Calcaneus/surgery , Adult , Heel/injuries , Heel/surgery , Skin Transplantation/methods , Middle Aged , Wound Healing/physiology , Soft Tissue Injuries/surgery , Fractures, Bone/surgery
13.
J Transl Med ; 21(1): 670, 2023 09 27.
Article in English | MEDLINE | ID: mdl-37759298

ABSTRACT

BACKGROUND: Gastric cancer (GC) is a fatal cancer with unclear pathogenesis. In this study, we explored the function and potential mechanisms of intercellular adhesion molecule 2 (ICAM2) in the development and advancement of GC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to quantify ICAM2 expression in harvested GC tissues and cultured cell lines. Immunohistochemical analyses were conducted on a GC tissue microarray to quantify ICAM2 expression and explore its implication on the prognosis of GC patients. In vitro experiments were carried out to reveal the biological functions of ICAM2 in GC cell lines. Further, in vivo experiments were conducted using xenograft models to assess the impact of ICAM2 on GC development and metastasis. Western blot, immunofluorescence, immunoprecipitation, luciferase assay, chromatin immunoprecipitation, and ubiquitination analysis were employed to investigate the underlying mechanisms. RESULTS: ICAM2 expression was downregulated in GC, positively correlating with advanced T stage, distant metastasis, advanced clinical stage, vessel invasion, and shorter patient survival time. ICAM2 overexpression suppressed the proliferation, migration, invasion, metastasis of GC cells as well as their ability to form tumors, whereas ICAM2 knockdown yielded opposite results. Erythroblast transformation-specific-related gene (ERG) as a transcription factor promoted the transcription of ICAM2 by binding to the crucial response element localized within its promoter region. Further analysis revealed that ICAM2 reduced radixin (RDX) protein stability and expression. In these cells, ICAM2 bound to the RDX protein to promote the ubiquitination and degradation of RDX via NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L), and this post-translational modification resulted in the inhibition of GC. CONCLUSIONS: In summary, this study demonstrates that ICAM2, which is induced by ERG, suppresses GC progression by enhancing the ubiquitination and degradation of RDX in a NEDD4L-dependent manner. Therefore, these results suggest that ICAM2 is a potential prognostic marker and a therapeutic target for GC.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Prospective Studies , Ubiquitination , Cell Adhesion Molecules , Transcriptional Regulator ERG
14.
Exp Eye Res ; 233: 109536, 2023 08.
Article in English | MEDLINE | ID: mdl-37336468

ABSTRACT

Climatic droplet keratopathy (CDK) is characterized by an increased number of oil-like deposits on the most anterior corneal layers, which affect vision and can cause blindness. Environmental ultraviolet radiation (UVR) exposure is a major risk factor, but the underlying mechanism of CDK pathogenesis is unclear. Increasing evidence has demonstrated that miRNAs participate in the cross-talk with oxidative stress. We aimed to explore whether certain miRNAs are involved in the pathogenesis of CDK. We performed miRNA sequencing of tears from patients with CDK and healthy individuals from Tacheng region of Xinjiang and conducted bioinformatic analysis of key miRNAs. We also evaluated viability, migration, and apoptosis of human corneal epithelial cells (HCECs) subjected to UVR treatment. miR-1273h-5p expression was abnormally downregulated in the tears of patients with CDK. miR-1273h-5p promoted cell proliferation and migration and inhibited UVR-induced mitochondrial apoptosis. miR-1273h-5p protected HCECs against UVR-induced oxidative damage by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial apoptosis via the activation of the Nrf2 pathway. Thus, our results suggest that miR-1273h-5p protects the corneal epithelium against UVR-induced oxidative stress damage.


Subject(s)
Epithelium, Corneal , MicroRNAs , Humans , Epithelium, Corneal/metabolism , Ultraviolet Rays/adverse effects , MicroRNAs/genetics , MicroRNAs/metabolism , Oxidative Stress , Apoptosis
15.
J Biochem Mol Toxicol ; 37(6): e23346, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36988443

ABSTRACT

The protection of the blood-brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR-3064-5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR-3064-5p in exosomes secreted by DCs (DCs-exo). An SAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL-IF staining. We found that overexpression of miR-3064-5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin-3, ZO-1), whereas knockdown of miR-3064-5p exerted the opposite effect. Dual-LUC assay confirmed that miR-3064-5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL-6, IL-1ß, IFN-γ, and TGF-ß1) levels and apoptosis. The results of the co-IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs-exo reduced brain edema, upregulated miR-3064-5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs-exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR-3064-5p enhanced the protective effect of DCs-exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR-3064-5p to ameliorate BBB damage after SAH. Mechanistically, miR-3064-5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway.


Subject(s)
MicroRNAs , Sirtuins , Subarachnoid Hemorrhage , Rats , Animals , Blood-Brain Barrier/metabolism , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/metabolism , Rats, Sprague-Dawley , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/pharmacology , Proprotein Convertase 9/therapeutic use , MicroRNAs/genetics , MicroRNAs/metabolism , Tight Junction Proteins/genetics , Tight Junction Proteins/metabolism , Sirtuins/genetics , Sirtuins/metabolism , Dendritic Cells/metabolism
16.
Environ Res ; 223: 115441, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36758917

ABSTRACT

Two-dimensional La2Ti2O7 nanosheets with regular morphology and good dispersion were prepared by the hydrothermal method under a magnetic field. Zero-dimensional Pt quantum dots (Pt-QDs) were loaded on the La2Ti2O7 nanosheets. The electron-hole separation and carrier transfer in the Pt-loaded La2Ti2O7 nanosheets were significantly enhanced. The La2Ti2O7 nanosheets loaded with 3 wt% Pt-QDs exhibit the largest NO removal efficiency of 51% and less than 3.2 ppb NO2 intermediate pollutant in 30 min. The high photocatalytic ability was attributed to the surface plasmon resonance in Pt-QDs and the enhanced electron-hole separation. A large number of e-, h+, •OH and •O2- active species were formed on the surface of Pt-loaded La2Ti2O7 nanosheets under light irradiation. The conversion pathway from NO to NO3- was verified by the in situ diffuse reflectance infrared Fourier-transform spectroscopy and DFT calculation. This work supplies a feasible approach to responsive photocatalysts for efficient, stable, and selective NO removal avoiding the NO2 secondary pollutant.


Subject(s)
Quantum Dots , Quantum Dots/chemistry , Light , Nitrogen Dioxide , Titanium
17.
BMC Geriatr ; 23(1): 828, 2023 12 09.
Article in English | MEDLINE | ID: mdl-38066433

ABSTRACT

PURPOSE: Older individuals are priority coronavirus disease 2019 (COVID-19) vaccine recipients. Our aim was to investigate the prevalence of and factors influencing vaccine hesitancy in older individuals living in nursing homes and communities. METHODS: A self-administered COVID-19 vaccine hesitancy survey was conducted from September 2021 to December 2021 among people aged ≥ 60 years in eight nursing homes (382 participants) and the community (112 participants) in Taizhou, China. The response rate was 72.1% (382/530) for older adults in nursing homes and 68.7% (112/163) for older adults in the community. RESULTS: We found that 58.1% of the older individuals in nursing homes and 36.6% of those in the community were hesitant to receive the COVID-19 vaccine and that there was a statistically significant difference (P < 0.001). Multiple logistic regression results indicated that the main factors influencing hesitation among the older individuals in nursing homes were being male (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI): 1.01-2.76); their cognitive level, including having a high perceived risk of COVID-19 infection (OR = 3.06, 95% CI: 1.73-5.43) or the perception of low vaccine safety (OR = 3.08, 95% CI: 1.545- 6.145); anxiety (OR = 3.43, 95% CI: 1.96-5.99); and no previous influenza vaccination (OR = 1.82, 95% CI: 1.13-2.93); whereas those for older individuals in the community were comorbid chronic diseases (OR = 3.13, 95% CI: 1.11- 8.78) and community workers not recommending the vaccine (OR = 8.223, 95% CI: 1.77-38.27). CONCLUSION: The proportion of older individuals in nursing homes who were hesitant to receive the COVID-19 vaccine was significantly higher than for older individuals in the community. Targeted measures should be implemented to reduce vaccine hesitancy and improve vaccination rates in response to the special environment of nursing homes and the characteristics of this population.


Subject(s)
COVID-19 , Humans , Male , Aged , Female , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Vaccination , China/epidemiology , Nursing Homes
18.
BMC Musculoskelet Disord ; 24(1): 591, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37468856

ABSTRACT

PURPOSE: The purpose of this study was to introduce the surgical method of K-wire combined with screw in the treatment of Arbeitsgemeinschaftfür Osteosynthesefragen (AO) type B3.1 phalangeal fractures and to compare its clinical, radiological and functional outcomes with K-wire fixation. METHODS: This was a retrospective comparative study. From January 2015 to February 2022, we treated 86 patients with AO type B3.1 phalangeal fractures. A total of 71 patients were finally included in the statistical analysis. Thirty-nine patients received K-wires combined with screw, and 32 patients received simple K-wires. The follow-up time was at least 6 months. Outcome measures included general information, operative time, total active motion (TAM), pinch strength, radiological union time, pain assessed by visual analog scale (VAS), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, cost, and complications. RESULTS: The follow-up time was 6-12 months, with an average of 7.9 months. All patients achieved clinical and radiological union. Compared with the K-wire fixation group, the TAM, radiological union time and VAS score of the K-wire combined with screw group had obvious advantages. Compared with the opposite healthy hand, the grip strength of the two groups was similar, and there was no significant difference in the QuickDASH score. The incidence rate of complications in the K-wire combined with screw group (2/39) was lower than that in the K-wire fixation group (7/32). CONCLUSIONS: Compared with simple K-wire fixation, K-wire combined with screw in the treatment of AO type B3.1 phalangeal fractures is a safer and reliable surgical method. K-wire controls the rotation and plays a role similar to a "lock". The screw can exert pressure and fix it more firmly. It shortens the time of fracture healing and has a higher TAM and fewer postoperative complications.


Subject(s)
Fracture Fixation, Internal , Fractures, Bone , Humans , Retrospective Studies , Fracture Fixation, Internal/methods , Treatment Outcome , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Bone Screws , Bone Wires
19.
J Environ Manage ; 331: 117291, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36657200

ABSTRACT

The huge output of sewage sludge has caused a remarkable environmental burden. Sludge dewatering is considered as an important way to reduce the sludge volume. Five imidazole-based ionic liquids were used to improve the dewaterability of sewage sludge. 1-ethyl-3-methylimidazolium dihydrogen phosphate ([Emim][H2PO4]) was screened out as a potential conditioner of sludge due to its excellent dewatering performance and reusability. The solid content of sludge filter cake after treatment with [Emim][H2PO4] was about 10% higher than that of sludge treated by cationic polyacrylamides (CPAM). The intensification mechanism of ionic liquids to the improvement of sludge dewatering performance was studied. The presence of acidic ionic liquids [Emim][H2PO4] resulted the increase of zeta potential from -14.57 ± 0.81 mV to -5.60 ± 0.30 mV and led to the protonation of biopolymers. Acidic ionic liquids [Emim][H2PO4] inactivated the microorganism and led to a porous and unconsolidated structure of the solid sludge particles. All these effects were conducive to destroy the microstructure of sludge and release water. However, [Emim]Cl, [Bmim][OTf] and [Hmim][OTf] showed little effect on the protonation of ionizable functional groups at near-neutral environment. The dissolution of biopolymer decreased the zeta potential and strengthened the electrostatic repulsion. So, they showed weaker intensification effects than CPAM.


Subject(s)
Ionic Liquids , Sewage , Sewage/chemistry , Biopolymers , Hydrogen-Ion Concentration , Water/chemistry , Cations , Waste Disposal, Fluid/methods
20.
Chemistry ; 28(12): e202103901, 2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35028990

ABSTRACT

Covalent organic framework, as an emerging porous nano-frame structure with pre-designed structure and custom properties, has been demonstrated as a prospective electrode for rechargeable Li-ion batteries. For improving the reversible capacity and long-term cycle stability of COF materials, we propose a GQDs modified COF material (COF-GQDs) and apply it as the anode for LIBs for the first time. This COF-GQDs electrode delivers enhanced long-term cycling performance with a large capacity of ∼820 mAh g-1 after 300 cycles at 100 mA g-1 and an improved rate performance. The enhanced lithium-storage performance, in terms of obvious-shortened activation process and high reversible capacities, can be attributed to the modification of carboxyl GQDs, which would activate more active sites (activated C=C groups from benzene rings) for lithium-storage, and provide fast lithium-ion transportation kinetic. Besides, the decreased interphase resistance, enhanced electronic conductivity, and prevented aggregation of needle-flake COF structure, originated from the addition of GQDs, which lead to the enhanced improved cycling stability of the COF-GQDs electrode. This manuscript can promote the further exploration on the design of COF-related materials with modification of functionalized carbonaceous materials to achieve enhanced lithium-storage properties for next-generation energy storage.

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