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1.
Nature ; 612(7939): 232-235, 2022 12.
Article in English | MEDLINE | ID: mdl-36477130

ABSTRACT

It is generally believed that long-duration gamma-ray bursts (GRBs) are associated with massive star core collapse1, whereas short-duration GRBs are associated with mergers of compact star binaries2. However, growing observations3-6 have suggested that oddball GRBs do exist, and several criteria (prompt emission properties, supernova/kilonova associations and host galaxy properties) rather than burst duration only are needed to classify GRBs physically7. A previously reported long-duration burst, GRB 060614 (ref. 3), could be viewed as a short GRB with extended emission if it were observed at a larger distance8 and was associated with a kilonova-like feature9. As a result, it belongs to the type I (compact star merger) GRB category and is probably of binary neutron star (NS) merger origin. Here we report a peculiar long-duration burst, GRB 211211A, whose prompt emission properties in many aspects differ from all known type I GRBs, yet its multiband observations suggest a non-massive-star origin. In particular, substantial excess emission in both optical and near-infrared wavelengths has been discovered (see also ref. 10), which resembles kilonova emission, as observed in some type I GRBs. These observations point towards a new progenitor type of GRBs. A scenario invoking a white dwarf (WD)-NS merger with a post-merger magnetar engine provides a self-consistent interpretation for all the observations, including prompt gamma rays, early X-ray afterglow, as well as the engine-fed11,12 kilonova emission.


Subject(s)
Gamma Rays
2.
Cancer Sci ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38889220

ABSTRACT

RNA-binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.

3.
Radiology ; 311(2): e232178, 2024 May.
Article in English | MEDLINE | ID: mdl-38742970

ABSTRACT

Background Accurate characterization of suspicious small renal masses is crucial for optimized management. Deep learning (DL) algorithms may assist with this effort. Purpose To develop and validate a DL algorithm for identifying benign small renal masses at contrast-enhanced multiphase CT. Materials and Methods Surgically resected renal masses measuring 3 cm or less in diameter at contrast-enhanced CT were included. The DL algorithm was developed by using retrospective data from one hospital between 2009 and 2021, with patients randomly allocated in a training and internal test set ratio of 8:2. Between 2013 and 2021, external testing was performed on data from five independent hospitals. A prospective test set was obtained between 2021 and 2022 from one hospital. Algorithm performance was evaluated by using the area under the receiver operating characteristic curve (AUC) and compared with the results of seven clinicians using the DeLong test. Results A total of 1703 patients (mean age, 56 years ± 12 [SD]; 619 female) with a single renal mass per patient were evaluated. The retrospective data set included 1063 lesions (874 in training set, 189 internal test set); the multicenter external test set included 537 lesions (12.3%, 66 benign) with 89 subcentimeter (≤1 cm) lesions (16.6%); and the prospective test set included 103 lesions (13.6%, 14 benign) with 20 (19.4%) subcentimeter lesions. The DL algorithm performance was comparable with that of urological radiologists: for the external test set, AUC was 0.80 (95% CI: 0.75, 0.85) versus 0.84 (95% CI: 0.78, 0.88) (P = .61); for the prospective test set, AUC was 0.87 (95% CI: 0.79, 0.93) versus 0.92 (95% CI: 0.86, 0.96) (P = .70). For subcentimeter lesions in the external test set, the algorithm and urological radiologists had similar AUC of 0.74 (95% CI: 0.63, 0.83) and 0.81 (95% CI: 0.68, 0.92) (P = .78), respectively. Conclusion The multiphase CT-based DL algorithm showed comparable performance with that of radiologists for identifying benign small renal masses, including lesions of 1 cm or less. Published under a CC BY 4.0 license. Supplemental material is available for this article.


Subject(s)
Contrast Media , Deep Learning , Kidney Neoplasms , Tomography, X-Ray Computed , Humans , Female , Male , Middle Aged , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Retrospective Studies , Tomography, X-Ray Computed/methods , Prospective Studies , Radiographic Image Interpretation, Computer-Assisted/methods , Aged , Algorithms , Kidney/diagnostic imaging , Adult
4.
J Virol ; 97(10): e0093823, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37792003

ABSTRACT

IMPORTANCE: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines.


Subject(s)
Caliciviridae Infections , Epitopes , Genotype , Norovirus , Viral Vaccines , Virion , Animals , Humans , Mice , Caliciviridae Infections/immunology , Caliciviridae Infections/prevention & control , Caliciviridae Infections/virology , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Immunization , Norovirus/chemistry , Norovirus/classification , Norovirus/genetics , Norovirus/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics , Viral Vaccines/immunology , Chimera/genetics , Chimera/immunology , Capsid Proteins/chemistry , Capsid Proteins/genetics , Capsid Proteins/immunology , Virion/chemistry , Virion/genetics , Virion/immunology
5.
Microb Pathog ; 188: 106560, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38272327

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.


Subject(s)
Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , Proteolysis , Inflammatory Bowel Diseases/therapy , Intestines , Intestinal Mucosa , Dysbiosis
6.
BMC Cardiovasc Disord ; 24(1): 119, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383333

ABSTRACT

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.


Subject(s)
Hydrogels , Myocardial Infarction , Humans , Rats , Mice , Animals , Swine , Rabbits , Sheep , Hydrogels/therapeutic use , Quality of Life , Myocardial Infarction/drug therapy , Heart , Injections
7.
Exp Parasitol ; 256: 108671, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38081528

ABSTRACT

Legumains belonging to C_13 peptidase family of proteins, and are ubiquitously disseminated among all vertebrate and invertebrate organisms, and have been implicated in innumerable biological and cellular functionality. Herein, we characterized and evaluated immunoregulatory characteristics of Legumain-1 from Fasciola gigantica (Fg-LGMN-1) during its interaction with host immune cells. The isopropyl-ß-d-thiogalactopyranoside (IPTG) stimulated RFg-LGMN-1 protein was positively detected by rat serum containing anti-RFg-LGMN-1 polyclonal antibodies. Furthermore, the uptake of RFg-LGMN-1 by goat monocytes was successfully confirmed using Immunofluorescence Assay (IFA). The immunohistochemical analysis revealed the native localization of LGMN-1 protein on the periphery and internal structures such as suckers, pharynx, and genital pore of the adult parasite, thereby validating its presence in excretory-secretory (ES) products of F. gigantica. The RFg-LGMN-1 co-incubated with concanavalin-A (Con-A) stimulated the increase of interleukin 2 (IL-2), IL-10, and IL-17 in monocytes derived from peripheral blood mononuclear cells (PBMCs) in the concentration-dependent manner. However, the IL-4 cytokine in response to the RFg-LGMN-1 protein declined. These results illuminated the role of LGMN-1 during the parasite-host interface. Our findings elaborated additional evidence that Legumain protein play a role in the manipulating host immune responses during parasite infections. However, further evaluation of RFg-LGMN-1 protein in context of its immunomodulatory roles should be conducted to enhance our understandings of the mechanisms employed by F. gigantica to evade host immune responses.


Subject(s)
Fasciola , Fascioliasis , Animals , Rats , Monocytes , Leukocytes, Mononuclear/metabolism , Goats , Immunity
8.
BMC Anesthesiol ; 24(1): 130, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580909

ABSTRACT

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.


Subject(s)
Cardiac Surgical Procedures , Hypotension , Shock, Septic , Humans , Critical Illness , Cardiac Surgical Procedures/adverse effects , Hypotension/diagnosis , Hypotension/complications , Lactates
9.
Article in English | MEDLINE | ID: mdl-38971179

ABSTRACT

BACKGROUND: Third molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PURPOSE: The study purpose was to measure and compare differences in pain, swelling, trismus, wound healing, and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. STUDY DESIGN, SETTING, SAMPLE: This study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. PREDICTOR VARIABLE: The predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiological saline) side. MAIN OUTCOME VARIABLE: The primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening, were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. COVARIATES: The covariates included age, sex, and operation time. ANALYSES: The Shapiro‒Wilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P < .05. RESULTS: The study included 60 patients (mean age: 25.81 ± 4.91; 23 (38%) males, 37 (62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < .001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < .001), maximal incisional opening (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P < .001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P < .001), and swelling (6.86 ± 0.70 mm, 7.15 ± 0.80 mm, day 3, P = .006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ± 2.14, day 3, P < .001). CONCLUSION AND RELEVANCE: The application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative QOL.

10.
BMC Oral Health ; 24(1): 758, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956625

ABSTRACT

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.


Subject(s)
Cone-Beam Computed Tomography , Dental Implants , Finite Element Analysis , Incisor , Maxilla , Orthodontic Anchorage Procedures , Periodontal Ligament , Tooth Movement Techniques , Humans , Tooth Movement Techniques/methods , Tooth Movement Techniques/instrumentation , Orthodontic Anchorage Procedures/instrumentation , Orthodontic Anchorage Procedures/methods , Periodontal Ligament/diagnostic imaging , Imaging, Three-Dimensional/methods , Cuspid/diagnostic imaging , Orthodontic Appliance Design , Dental Stress Analysis , Biomechanical Phenomena , Orthodontic Appliances, Removable
11.
J Cell Mol Med ; 28(5): e18010, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37927242

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a common malignancy originating from oral mucosal tissue. OSCC cells employ immune evasion strategies to avoid immune attacks, but research on inhibiting immune evasion and delaying OSCC progression is limited. This study aimed to investigate how SLC3A2 downregulation mediates immune evasion and promotes metastasis in OSCC through bioinformatics analysis and cell experiments. Gene enrichment analysis was performed using human double sulphur death-related genes from the GSEA database. Differentially expressed genes were selected from the GEO database. Diagnostic models were constructed and validated using gene expression datasets. Immune infiltration and function were analysed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Cell experiments were conducted to evaluate the impact of SLC3A2 on immune response in OSCC. Ten double sulphur death-related genes were identified, with SLC3A2 and SLC7A11 being enriched in tongue squamous cell carcinoma-related diseases. Differential expression analysis revealed five genes (SLC3A2, SLC7A11, RPN1, GYS1 and NDUFS1) of diagnostic significance. GO analysis showed enrichment in amino acid import and transmembrane transport, while KEGG pathway analysis highlighted enrichment in ferroptosis, diabetic cardiomyopathy, and Starch and sucrose metabolism. Experimental verification confirmed higher SLC3A2 expression in OSCC cells. Overexpression of SLC3A2 inhibited cell proliferation and reduced PD-1 and CTLA-4 expression. Reduced SLC3A2 expression in OSCC promotes immune evasion and tumour progression by impairing T lymphocyte function. This study provides insights into targeted regulation of SLC3A2 expression for immune response-based therapies in OSCC.

12.
Antimicrob Agents Chemother ; 67(11): e0081223, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37877694

ABSTRACT

Type II toxin-antitoxin systems are highly prevalent in bacterial genomes and play crucial roles in the general stress response. Previously, we demonstrated that the type II antitoxin PfMqsA regulates biofilm formation through the global regulator AgtR in Pseudomonas fluorescens. Here, we found that both the C-terminal DNA-binding domain of PfMqsA and AgtR are involved in bacterial antibiotic susceptibility. Electrophoretic mobility shift assay (EMSA) analyses revealed that AgtR, rather than PfMqsA, binds to the intergenic region of emhABC-emhR, in which emhABC encodes an resistance-nodulation-cell division efflux pump and emhR encodes a repressor. Through quantitative real-time reverse-transcription PCR and EMSA analysis, we showed that AgtR directly activates the expression of the emhR by binding to the DNA motif [5´-CTAAGAAATATACTTAC-3´], leading to repression of the emhABC. Furthermore, we demonstrated that PfMqsA modulates the expression of EmhABC and EmhR. These findings enhance our understanding of the mechanism by which antitoxin PfMqsA contributes to antibiotic susceptibility.


Subject(s)
Antitoxins , Pseudomonas fluorescens , Pseudomonas fluorescens/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
13.
Environ Microbiol ; 25(7): 1363-1373, 2023 07.
Article in English | MEDLINE | ID: mdl-36916068

ABSTRACT

Global climate change mostly impacts river ecosystems by affecting microbial biodiversity and ecological functions. Considering the high functional redundancy of microorganisms, the unknown relationship between biodiversity and ecosystem functions obstructs river ecological research, especially under the influence of increasing weather extremes, such as in intermittent rivers and ephemeral streams (IRES). Herein, dry-wet alternation experiments were conducted in artificial stream channels for 25 and 90 days of drought, both followed by 20 days of rewetting. The dynamic recovery of microbial biodiversity and ecosystem functions (represented by ecosystem metabolism and denitrification rate) were determined to analyse biodiversity-ecosystem-function (BEF) relationships after different drought durations. There was a significant difference between bacterial and eukaryotic biodiversity recovery after drought. Eukaryotic biodiversity was more sensitive to drought duration than bacterial, and the eukaryotic network was more stable under dry-wet alternations. Based on the establishment of partial least squares path models, we found that eukaryotic biodiversity has a stronger effect on ecosystem functions than bacteria after long-term drought. Indeed, this work represents a significant step forward for further research on the ecosystem functions of IRES, especially emphasizing the importance of eukaryotic biodiversity in the BEF relationship.


Subject(s)
Ecosystem , Eukaryota , Droughts , Biodiversity , Rivers , Bacteria/genetics
14.
PLoS Pathog ; 17(7): e1009745, 2021 07.
Article in English | MEDLINE | ID: mdl-34252166

ABSTRACT

Norovirus (NoV) is the major pathogen causing the outbreaks of the viral gastroenteritis across the world. Among the various genotypes of NoV, GII.4 is the most predominant over the past decades. GII.4 NoVs interact with the histo-blood group antigens (HBGAs) to invade the host cell, and it is believed that the receptor HBGAs may play important roles in selecting the predominate variants by the nature during the evolution of GII.4 NoVs. However, the evolution-induced changes in the HBGA-binding affinity for the GII.4 NoV variants and the mechanism behind the evolution of the NoV-HBGA interactions remain elusive. In the present work, the virus-like particles (VLPs) of the representative GII.4 NoV stains epidemic in the past decades were expressed by using the Hansenula polymorpha yeast expression platform constructed by our laboratory, and then the enzyme linked immunosorbent assay (ELISA)-based HBGA-binding assays as well as the molecular dynamics (MD) simulations combined with the molecular mechanics/generalized born surface area (MMGBSA) calculations were performed to investigate the interactions between various GII.4 strains and different types of HBGAs. The HBGA-binding assays show that for all the studied types of HBGAs, the evolution of GII.4 NoVs results in the increased NoV-HBGA binding affinities, where the early epidemic strains have the lower binding activity and the newly epidemic strains exhibit relative stronger binding intensity. Based on the MD simulation and MMGBSA calculation results, a physical mechanism that accounts for the increased HBGA-binding affinity was proposed. The evolution-involved residue mutations cause the conformational rearrangements of loop-2 (residues 390-396), which result in the narrowing of the receptor-binding pocket and thus tighten the binding of the receptor HBGAs. Our experimental and computational studies are helpful for better understanding the mechanism behind the evolution-induced increasing of HBGA-binding affinity, which may provide useful information for the drug and vaccine designs against GII.4 NoVs.


Subject(s)
Blood Group Antigens/metabolism , Host-Parasite Interactions/physiology , Norovirus/metabolism , Humans , Molecular Docking Simulation , Norovirus/genetics , Virus Attachment
15.
BMC Cancer ; 23(1): 611, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37400785

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs), which are involved in various human malignancies, have emerged as promising biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in hepatocellular carcinoma (HCC) and identify novel biomarkers associated with HCC development and progression. METHODS: CircRNA expression profiles of HCC tissues were jointly analyzed to identify differentially expressed circRNAs. Overexpression plasmid and siRNA targeting candidate circRNAs were used in functional assays in vitro. CircRNA-miRNA interactions were predicted using miRNAs expressed in the miRNA-seq dataset GSE76903. To further screen downstream genes targeted by the miRNAs, survival analysis and qRT-PCR were conducted to evaluate their prognostic role in HCC and construct a ceRNA regulatory network. RESULTS: Three significantly upregulated circRNAs, hsa_circ_0002003, hsa_circ_0002454, and hsa_circ_0001394, and one significantly downregulated circRNA, hsa_circ_0003239, were identified and validated by qRT-PCR. Our in vitro data indicated that upregulation of hsa_circ_0002003 accelerated cell growth and metastasis. Mechanistically, DTYMK, DAP3, and STMN1, which were targeted by hsa-miR-1343-3p, were significantly downregulated in HCC cells when hsa_circ_0002003 was silenced and were significantly correlated with poor prognosis in patients with HCC. CONCLUSION: Hsa_circ_0002003 may play critical roles in HCC pathogenesis and serve as a potential prognostic biomarker for HCC. Targeting the hsa_circ_0002003/hsa-miR-1343-3p/STMN1 regulatory axis could be an effective therapeutic strategy in patients with HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , RNA, Circular/genetics , Up-Regulation , Liver Neoplasms/pathology , MicroRNAs/metabolism , Biomarkers/analysis
16.
Environ Sci Technol ; 57(8): 3323-3333, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36729963

ABSTRACT

Chemical sulfidation has been considered as an effective strategy to improve the reactivity of zero-valent iron (S-ZVI). However, sulfidation is a widespread biogeochemical process in nature, which inspired us to explore the biogenetic sulfidation of ZVI (BS-ZVI) with sulfate-reducing bacteria (SRB). BS-ZVI could degrade 96.3% of trichloroethylene (TCE) to acetylene, ethene, ethane, and dichloroethene, comparable to S-ZVI (97.0%) with the same S/Fe ratio (i.e., 0.1). However, S-ZVI (0.21 d-1) exhibited a faster degradation rate than BS-ZVI (0.17 d-1) based on pseudo-first-order kinetic fitting due to extracellular polymeric substances (EPSs) excreted from SRB. Organic components of EPSs, including polysaccharides, humic acid-like substances, and proteins in BS-ZVI, were detected with 3D-EEM spectroscopy and FT-IR analysis. The hemiacetal groups and redox-activated protein in EPS did not affect TCE degradation, while the acetylation degree of EPS increased with the concentration of ZVI and S/Fe, thus inhibiting the TCE degradation. A low concentration of HA-like substances attached to BS-ZVI materials promoted electron transport. However, EPS formed a protective layer on the surface of BS-ZVI materials, reducing its TCE reaction rate. Overall, this study showed a comparable performance enhancement of ZVI toward TCE degradation through biogenetic sulfidation and provided a new alternative method for the sulfidation of ZVI.


Subject(s)
Trichloroethylene , Water Pollutants, Chemical , Trichloroethylene/chemistry , Trichloroethylene/metabolism , Extracellular Polymeric Substance Matrix/metabolism , Iron/chemistry , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/chemistry
17.
Environ Sci Technol ; 57(41): 15487-15498, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37807898

ABSTRACT

Global climate change significantly increased the duration of droughts in intermittent rivers, impacting benthic microbial-mediated biogeochemical processes. However, the impact of prolonged droughts on the carbon contribution of intermittent rivers remains poorly understood. In this study, we investigated the potential effects of varying drought gradients (ranging from 20 to 130 days) on benthic biofilms community structure (algae, bacteria, and fungi) and their carbon metabolism functions (ecosystem metabolism and carbon dioxide (CO2) emission fluxes) using mesocosm experiments. Our findings indicate that longer drought durations lead to reduced alpha diversity and community heterogeneity, tighter interdomain networks, and an increased role of stochastic processes in community assembly, with a discernible threshold at around 60 days. Concurrently, the biofilm transforms into a carbon sink following a drought period of 60 days, as evidenced by the transformation of CO2 emission fluxes from 633.25 ± 194.69 to -349.61 ± 277.79 mg m-2 h-1. Additionally, the partial least-squares path model revealed that the resilience of algal communities and network stability may drive biofilm's transformation into a carbon sink, primarily through the heightened resilience of autotrophic metabolism. This study underscores the significance of the carbon contribution from intermittent rivers, as the shift in carbon metabolism functions with increasing droughts could lead to skewed estimations of current riverine carbon fluxes.


Subject(s)
Droughts , Ecosystem , Carbon Sequestration , Carbon Dioxide , Biodiversity , Biofilms , Climate Change
18.
Environ Sci Technol ; 57(4): 1828-1836, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36637413

ABSTRACT

Global climate changes have increased the duration and frequency of river flow interruption, affecting the physical and community structure of benthic biofilms. However, the dynamic responses of biofilm metabolism during the dry-wet transition remain poorly understood. Herein, the dynamic changes in biofilm metabolic activities were investigated through mesocosm experiments under short-term (25 day) and long-term drought (90 day), followed by a 20 day rewetting. The biofilm ecosystem metabolism, as measured by gross primary production and community respiration, was significantly inhibited and turned heterotrophic during the desiccation phase and then recovered, becoming autotrophic during the rewetting period regardless of the desiccation periods due to the high resilience of the autotrophic community. However, long-term drought decreased the recovery rate of the ecosystem metabolism and also caused irreparable damage to the biofilm carbon metabolism, measured using Biolog Eco Plates. Specifically, the recovery of the total carbon metabolic activity is related to the specific carbon source utilized by biofilm microorganisms, such as polymers, carbohydrates, and carboxylic acids. However, the divergent changes of amino acids caused the failure of the total carbon metabolism in long-term drought treatments to recover to the control level even after 20 days of rewetting. This research provides direct evidence that the increased duration of non-flow periods affects biofilm-mediated carbon biogeochemical processes.


Subject(s)
Desiccation , Ecosystem , Biofilms , Climate Change , Rivers , Carbon
19.
Environ Res ; 218: 114937, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36435489

ABSTRACT

The use of biochar materials as catalysts to activate persulfate (PS) for the degradation of antibiotics has attracted much attention. In this study, a carbonaceous material (Cu/Zn-SBC) was prepared from sewage sludge by hydrothermal modification. The efficiency of PS activation by Cu/Zn-SBC was investigated using tetracycline (TC) as the model antibiotic. In the Cu/Zn-SBC + PS system, the TC removal rate reached 90.13% at 10 min and exceeded 99% within 4 h. This not only met the requirement of removing large amounts of pollutants in a short time but also achieved the complete removal of pollutants in the subsequent time. Additionally, the Cu/Zn-SBC + PS system was found to be dominated by radical and nonradical pathways. Cu, hydroxyl and carboxyl groups on the surface of Cu/Zn-SBC promoted the production of free radicals and non-free radicals. Under several changes in reaction conditions and water environment factors, the TC removal rate remained above 85% within 10 min. Furthermore, the removal rate of TC was still 85.79% when Cu/Zn-SBC combined with PS was reused twice and 77.14% when reused four times. This study provides an ideal solution for the treatment of sewage sludge, and offers a stable and efficient material for removing antibiotics from wastewater.


Subject(s)
Anti-Bacterial Agents , Water Pollutants, Chemical , Sewage , Water Pollutants, Chemical/analysis , Charcoal , Tetracycline
20.
Cell Mol Biol Lett ; 28(1): 24, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36959535

ABSTRACT

BACKGROUND: Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. METHODS: Liquid chromatography-tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. RESULTS: DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. CONCLUSIONS: This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.


Subject(s)
Acute Lung Injury , Extracellular Vesicles , Sepsis , Animals , Mice , Acute Lung Injury/etiology , Acute Lung Injury/drug therapy , CD4-Positive T-Lymphocytes , Inflammation , Oxidative Stress , Sepsis/complications , T-Lymphocytes , Diacylglycerol Kinase/metabolism
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