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1.
New Phytol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39091140

ABSTRACT

Chloroplasts play a crucial role in plant defense against pathogens, making them primary targets for pathogen effectors that suppress host immunity. This study characterizes the Plasmopara viticola CRN-like effector, PvCRN20, which interacts with DEG5 in the cytoplasm but not with its interacting protein, DEG8, which is located in the chloroplast. By transiently overexpressing in tobacco leaves, we show that PvCRN20 could inhibit INF1- and Bax-triggered cell death. Constitutive expression of PvCRN20 suppresses the accumulation of reactive oxygen species (ROS) and promotes pathogen colonization. PvCRN20 reduces DEG5 entry into chloroplasts, thereby disrupting DEG5 and DEG8 interactions in chloroplasts. Overexpression of VvDEG5 and VvDEG8 induces ROS accumulation and enhances grapevine resistance to P. viticola, whereas knockout of VvDEG8 represses ROS production and promotes P. viticola colonization. Consistently, ectopic expression of VvDEG5 and VvDEG8 in tobacco promotes chloroplast-derived ROS accumulation, whereas co-expression of PvCRN20 counteracted this promotion by VvDEG5. Therefore, DEG5 is essential for the virulence function of PvCRN20. Although PvCRN20 is located in both the nucleus and cytoplasm, only cytoplasmic PvCRN20 suppresses plant immunity and promotes pathogen infection. Our results reveal that PvCRN20 dampens plant defenses by repressing the chloroplast import of DEG5, thus reducing host ROS accumulation and facilitating pathogen colonization.

2.
Immun Inflamm Dis ; 12(8): e1361, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39092772

ABSTRACT

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17ß-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. METHODS: Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. RESULTS: The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. CONCLUSION: E2 promoted the progression of TMJOA.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Estradiol , Osteoarthritis , Animals , Rats , Estradiol/pharmacology , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Osteoarthritis/metabolism , Osteoarthritis/pathology , Osteoarthritis/genetics , Disease Progression , Synoviocytes/metabolism , Synoviocytes/drug effects , Synoviocytes/pathology , Rats, Sprague-Dawley , Disease Models, Animal , Temporomandibular Joint/pathology , Temporomandibular Joint/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Cells, Cultured , Male , Adenosine/metabolism , Adenosine/analogs & derivatives , Cell Proliferation/drug effects
3.
J Med Virol ; 96(7): e29795, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39007429

ABSTRACT

Despite increased risk of severe acute respiratory syndrome coronavirus 2 infections and higher rates of COVID-19-related complications, racialized and Indigenous communities in Canada have lower immunization uptake compared to White individuals. However, there is woeful lack of data on predictors of COVID-19 vaccine mistrust (VM) that accounts for diverse social and cultural contexts within specific racialized and Indigenous communities. Therefore, we sought to characterize COVID-19 VM among Arab, Asian, Black, and Indigenous communities in Canada. An online survey was administered to a nationally representative, ethnically diverse panel of participants in October 2023. Arabic, Asian, Indigenous, and Black respondents were enriched in the sampling panel. Data were collected on demographics, COVID-19 VM, experience of racial discrimination, health literacy, and conspiracy beliefs. We used descriptive and regression analyses to determine the extent and predictors of COVID-19 VM among racialized and Indigenous individuals. All racialized respondents had higher VM score compared to White participants. Among 4220 respondents, we observed highest VM among Black individuals (12.18; ±4.24), followed by Arabic (12.12; ±4.60), Indigenous (11.84; ±5.18), Asian (10.61; ±4.28), and White (9.58; ±5.00) participants. In the hierarchical linear regression analyses, Black participants, women, everyday racial discrimination, and major experience of discrimination were positively associated with COVID-19 VM. Effects of racial discrimination were mediated by addition of conspiracy beliefs to the model. Racialized and Indigenous communities experience varying levels of COVID-19 VM and carry specific predictors and mediators to development of VM. This underscores the intricate interaction between race, gender, discrimination, and VM that need to be considered in future vaccination campaigns.


Subject(s)
Arabs , COVID-19 Vaccines , COVID-19 , Health Literacy , Indigenous Peoples , Racism , Humans , Female , Male , Adult , COVID-19/prevention & control , COVID-19/ethnology , Canada/epidemiology , COVID-19 Vaccines/administration & dosage , Middle Aged , Indigenous Peoples/statistics & numerical data , Trust , Young Adult , Surveys and Questionnaires , Health Knowledge, Attitudes, Practice , Aged , Asian People , Black People/statistics & numerical data , Black People/psychology , SARS-CoV-2/immunology , Vaccination/psychology , Vaccination/statistics & numerical data , Adolescent , Ethnicity
4.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39007682

ABSTRACT

Temperature is a crucial factor influencing the accuracy of the hydrostatic leveling system (HLS), necessitating a temperature compensation test for HLS. This paper investigates HLS temperature compensation through theoretical correction and experimental verification. The influence of temperature on the accuracy of hydrostatic level products is determined through temperature tests on 34 hydrostatic level products. The optimal temperature compensation formula is derived using the non-linear curve fitting method. The HLS is enhanced with a temperature compensation algorithm and temperature sensor, resulting in a new, high-precision, and high-stability hydrostatic leveling product with temperature compensation. Experimental findings reveal that the stability of the improved hydrostatic leveling product exceeds 30% compared to products on the market and surpasses 70% compared to the original products.

5.
Polymers (Basel) ; 16(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39000807

ABSTRACT

This study aimed to develop Janus-, cross-network-, and coaxial-structured piezoelectric-conductive polymer nanofibers through electrospinning to mimic the piezoelectricity of bone and facilitate the conduction of electrical signals in bone tissue repair. These nanofibers were constructed using the piezoelectric polymer polyvinylidene fluoride, and the conductive fillers reduced graphene oxide and polypyrrole. The influence of structural features on the electroactivity of the fibers was also explored. The morphology and components of the various structural samples were characterized using SEM, TEM, and FTIR. The electroactivity of the materials was assessed with a quasi-static d33 meter and the four-probe method. The results revealed that the piezoelectric-conductive phases were successfully integrated. The Janus-structured nanofibers demonstrated the best electroactivity, with a piezoelectric constant d33 of 24.5 pC/N and conductivity of 6.78 × 10-2 S/m. The tensile tests and MIP measurements showed that all samples had porosity levels exceeding 70%. The tensile strength of the Janus and cross-network structures exceeded that of the periosteum (3-4 MPa), with average pore sizes of 1194.36 and 2264.46 nm, respectively. These properties indicated good mechanical performance, allowing material support while preventing fibroblast invasion. The CCK-8 and ALP tests indicated that the Janus-structured samples were biocompatible and significantly promoted the proliferation of MC3T3-E1 cells.

6.
Front Endocrinol (Lausanne) ; 15: 1327849, 2024.
Article in English | MEDLINE | ID: mdl-39006363

ABSTRACT

Introduction: Previous observational studies have shown that polycystic ovary syndrome (PCOS) was associated with adverse pregnancy and perinatal outcomes. However, it remains controversial whether PCOS is an essential risk factor for these adverse pregnancy and perinatal outcomes. We aimed to use instrumental variables in a two-sample Mendelian randomization (MR) study to determine causality between PCOS and adverse pregnancy and perinatal outcomes. Materials and methods: Summary statistics were extracted from a recent genome-wide association study (GWAS) meta-analysis conducted in PCOS, which included 10,074 cases and 103,164 controls of European ancestry. Data on Adverse pregnancy and perinatal outcomes were summarized from the FinnGen database of European ancestry, which included more than 180,000 samples. The inverse variance weighted (IVW) method of MR was applied for the main outcome. To assess heterogeneity and pleiotropy, we conducted sensitivity analyses, including leave-one-out analysis, weighted median, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MR-Egger regression. Results: Two-sample MR analysis with the IVW method suggested that PCOS exerted causal effects on the risk of hypertensive disorders of pregnancy [odds ratio (OR) 1.170, 95% confidence interval (CI) 1.051-1.302, p = 0.004], in particular gestational hypertension (OR 1.083, 95% CI 1.007-1.164, p = 0.031), but not other pregnancy and perinatal diseases (all p > 0.05). Sensitivity analyses demonstrated pleiotropy only in pre-eclampsia or eclampsia (p = 0.0004), but not in other pregnancy and perinatal diseases (all p > 0.05). The results remained consistent after excluding two outliers (all p > 0.05). Conclusions: We confirmed a causal relationship between PCOS and hypertensive disorders of pregnancy, in particular gestational hypertension, but no association with any other adverse pregnancy or perinatal outcome. Therefore, we suggest that women with PCOS who are pregnant should have their blood pressure closely monitored.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Polycystic Ovary Syndrome , Pregnancy Outcome , Humans , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/epidemiology , Polycystic Ovary Syndrome/complications , Female , Pregnancy , Pregnancy Outcome/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/genetics , Pregnancy Complications/genetics , Pregnancy Complications/epidemiology , Risk Factors , Infant, Newborn , Polymorphism, Single Nucleotide
7.
Article in English | MEDLINE | ID: mdl-39010714

ABSTRACT

PURPOSE: (1) To determine the prevalence, magnitude and distribution pattern of acetabular rim ossification in patients with femoroacetabular impingement syndrome (FAIS) and (2) to determine the association between acetabular rim ossification and rotational abnormalities of the hip. METHODS: Patients underwent hip arthroscopic surgery for FAIS at our institute between January 2021 and May 2022 were retrospectively reviewed. Patients were included if preoperative computed tomography (CT) images of the operated hip and ipsilateral distal femur were available for the measurement of femoral and acetabular anteversion. The presence and size of acetabular rim ossification were evaluated on coronal CT sections for the superior half of the acetabulum on each clockface location. The associations between acetabular rim ossification and radiographic parameters of hip rotational morphology were examined. RESULTS: A total of 214 hips were included. Acetabular rim ossification was found in 167 hips (78%) and the most common locations were 10 and 11 o'clock. Patients presenting with acetabular rim ossification had a mean size of 4.6 ± 1.6 mm. It was the largest at 9 o'clock position (4.9 ± 2.2 mm), with a decreasing trend in size from posterior to anterior. Logistics regression analysis found age was associated with the occurrence of posterior ossification (p = 0.002). Linear regression analysis found age (p = 0.049) and male sex (p < 0.001) were significantly correlated with the size of ossification. Patients with increased cranial combined anteversion had larger posterior ossification than patients with normal and decreased cranial combined anteversion (4.2 ± 2.9 vs. 3.1 ± 2.5 mm, p = 0.016; 4.2 ± 2.9 vs. 2.5 ± 2.4 mm, p = 0.005). CONCLUSION: Increased combined anteversion is associated with greater posterior acetabular rim ossification. The presence and size of acetabular rim ossification are positively associated with older age and male sex. LEVEL OF EVIDENCE: Level III.

8.
Article in English | MEDLINE | ID: mdl-38958272

ABSTRACT

OBJECTIVE: To determine whether virtual reality (VR)-based dynamic standing balance training improves three elements of sensory integration and investigate whether VR-based dynamic standing balance training results in improved outcomes, especially regarding balance and gait, compared to the standard training method. DESIGN: This single-blinded, randomized, controlled trial involved 30 patients with hemiplegia. The experimental (EG, n = 15) and control (CG, n = 15) groups received VR augmented-standing balance training or standard standing balance training, respectively, for 20 minutes, 5 days a week, for 3 weeks. The patients were assessed for primary (Sensory Organization Test [SOT] and the Berg balance scale [BBS]) and secondary (the functional reaching test and timed up-and-go test [TUG]) outcomes before and after training. RESULTS: From preintervention to postintervention, the BBS score (F = 26.295, p < 0.05), TUG score (F = 18.12, p < 0.05), mean score of conditions 2 (F = 4.36, p < 0.05) and 6 (F = 5.61, p < 0.05), and composite score of the SOT (F = 5.385, p < 0.05) in both groups were significantly improved. However, there was no significant difference between EG and CG (time*group p > 0.05). CONCLUSION: VR combined with standing balance training improved sensory integration, postural control, balance, and gait ability in patients with hemiplegia, reducing fall risk. However, outcomes were comparable to general balance training regarding balance and gait.

9.
World J Gastroenterol ; 30(23): 3005-3015, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38946876

ABSTRACT

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem in China, ranking fifth for incidence and third for mortality. Knowledge of the invasive depth of the tumor is vital to treatment decisions. AIM: To evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) for preoperative T staging in patients with GC by comparing with multi-detector computed tomography (MDCT). METHODS: This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023. Patients underwent DCEUS, including ultrasonography (US) and intravenous contrast-enhanced ultrasonography (CEUS), and MDCT examinations for the assessment of preoperative T staging. Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual. The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard. RESULTS: A total of 229 patients with GC (80 T1, 33 T2, 59 T3 and 57 T4) were included. Overall accuracies were 86.9% for DCEUS and 61.1% for MDCT (P < 0.001). DCEUS was superior to MDCT for T1 (92.5% vs 70.0%, P < 0.001), T2 (72.7% vs 51.5%, P = 0.041), T3 (86.4% vs 45.8%, P < 0.001) and T4 (87.7% vs 70.2%, P = 0.022) staging of GC. CONCLUSION: DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT, and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.


Subject(s)
Contrast Media , Multidetector Computed Tomography , Neoplasm Staging , Stomach Neoplasms , Ultrasonography , Humans , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Middle Aged , Male , Female , Contrast Media/administration & dosage , Prospective Studies , Aged , Ultrasonography/methods , Ultrasonography/statistics & numerical data , Multidetector Computed Tomography/methods , Adult , China/epidemiology , Gastroscopy/methods , Stomach/diagnostic imaging , Stomach/pathology , Stomach/surgery , Aged, 80 and over
10.
Macromolecules ; 57(12): 5561-5577, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38948183

ABSTRACT

Traditional π-conjugated luminescent macromolecules typically suffer from aggregation-caused quenching (ACQ) and high cytotoxicity, and they require complex synthetic processes. In contrast, nonconventional luminescent macromolecules (NCLMs) with nonconjugated structures possess excellent biocompatibility, ease of preparation, unique luminescence behavior, and emerging applications in optoelectronics, biology, and medicine. NCLMs are currently believed to produce inherent luminescence due to through-space conjugation of overlapping electron orbitals in solid/aggregate states. However, as experimental facts continue to exceed expectations or even overturn some previous assumptions, there is still controversy about the detailed luminous mechanism of NCLMs, and extensive studies are needed to further explore the mechanism. This Perspective highlights recent progress in NCLMs and classifies and summarizes these advances from the viewpoint of molecular design, mechanism exploration, applications, and challenges and prospects. The aim is to provide guidance and inspiration for the huge fundamental and practical potential of NCLMs.

11.
Ecotoxicol Environ Saf ; 282: 116703, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38986335

ABSTRACT

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

12.
Biotechnol J ; 19(7): e2400115, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38987223

ABSTRACT

The nonconventional methylotrophic yeast Komagataella phaffii is widely applied in the production of industrial enzymes, pharmaceutical proteins, and various high-value chemicals. The development of robust and versatile genome editing tools for K. phaffii is crucial for the design of increasingly advanced cell factories. Here, we first developed a base editing method for K. phaffii based on the CRISPR-nCas9 system. We engineered 24 different base editor constructs, using a variety of promoters and cytidine deaminases (CDAs). The optimal base editor (PAOX2*-KpA3A-nCas9-KpUGI-DAS1TT) comprised a truncated AOX2 promoter (PAOX2*), a K. phaffii codon-optimized human APOBEC3A CDA (KpA3A), human codon-optimized nCas9 (D10A), and a K. phaffii codon-optimized uracil glycosylase inhibitor (KpUGI). This optimal base editor efficiently performed C-to-T editing in K. phaffii, with single-, double-, and triple-locus editing efficiencies of up to 96.0%, 65.0%, and 5.0%, respectively, within a 7-nucleotide window from C-18 to C-12. To expand the targetable genomic region, we also replaced nCas9 in the optimal base editor with nSpG and nSpRy, and achieved 50.0%-60.0% C-to-T editing efficiency for NGN-protospacer adjacent motif (PAM) sites and 20.0%-93.2% C-to-T editing efficiency for NRN-PAM sites, respectively. Therefore, these constructed base editors have emerged as powerful tools for gene function research, metabolic engineering, genetic improvement, and functional genomics research in K. phaffii.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Saccharomycetales , Gene Editing/methods , Saccharomycetales/genetics , CRISPR-Cas Systems/genetics , Humans , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , Promoter Regions, Genetic/genetics , Proteins
13.
Theranostics ; 14(10): 3927-3944, 2024.
Article in English | MEDLINE | ID: mdl-38994017

ABSTRACT

Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.


Subject(s)
Cell Cycle , Cytokinesis , Mice, Knockout , Myocardial Infarction , Myocytes, Cardiac , Ribosomes , Animals , Mice , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocytes, Cardiac/metabolism , Ribosomes/metabolism , Phosphoproteins/metabolism , Phosphoproteins/genetics , Nucleolin , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Retinoblastoma Protein/metabolism , Retinoblastoma Protein/genetics , Cell Proliferation , Male , Humans
14.
World J Gastrointest Oncol ; 16(6): 2757-2768, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994162

ABSTRACT

BACKGROUND: Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. AIM: To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. METHODS: High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. RESULTS: Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. CONCLUSION: Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

15.
Lung Cancer ; 194: 107884, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38991281

ABSTRACT

BACKGROUND: Neoadjuvant chemoimmunotherapy followed by surgery is recommended for resectable non-small-cell lung cancer (NSCLC). However, a considerable proportion of patients do not undergo surgery and opt for alternative treatments such as radiotherapy. The efficacy of radiotherapy in this context remains unclear. METHODS: This retrospective study analyzed data from patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by either surgery or radiotherapy. Propensity score matching (PSM) was used to balance the heterogeneity between the groups. Efficacy outcomes, safety profiles, and disease recurrence patterns were assessed. RESULTS: In total, 175 patients were included; 50 underwent radiotherapy, and 125 underwent surgery. Prior to matching, radiotherapy was inferior to surgery in terms of progression-free survival (PFS; Hazard ratio [HR], 2.23; P = 0.008). Following a 1:1 PSM adjustment, each group consisted of 40 patients. The median PFS was 30.8 months in the radiotherapy group and not reached in the surgery group (HR, 1.46; P = 0.390). The 12- and 24-month PFS rates were 90.4 % and 69.0 % for the radiotherapy group compared to 94.1 % and 73.9 % for the surgery group, respectively. Subgroup analyses after PSM showed that patients with stage IIIA disease tend to benefit more from surgery than those with stage IIIB disease (HR, 3.00; P = 0.074). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 62.5 % of patients in the radiotherapy group and 55.0 % in the surgery group, with no grade 5 TRAEs reported. The incidence of grade 3-4 treatment-related pneumonitis or pneumonia was 7.5 % and 2.5 % in the radiotherapy and surgery groups, respectively. CONCLUSION: Radiotherapy may be a viable alternative to surgery in patients with resectable NSCLC who do not undergo surgical resection after initial neoadjuvant chemoimmunotherapy, offering comparable efficacy and a manageable safety profile. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.

16.
Hortic Res ; 11(7): uhae142, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38988622

ABSTRACT

Chinese cherry (Prunus pseudocerasus) holds considerable importance as one of the primary stone fruit crops in China. However, artificially improving its traits and genetic analysis are challenging due to lack of high-quality genomic resources, which mainly result from difficulties associated with resolving its tetraploid and highly heterozygous genome. Herein, we assembled a chromosome-level, haplotype-resolved genome of the cultivar 'Zhuji Duanbing', comprising 993.69 Mb assembled into 32 pseudochromosomes using PacBio HiFi, Oxford Nanopore, and Hi-C. Intra-haplotype comparative analyses revealed extensive intra-genomic sequence and expression consistency. Phylogenetic and comparative genomic analyses demonstrated that P. pseudocerasus was a stable autotetraploid species, closely related to wild P. pusilliflora, with the two diverging ~18.34 million years ago. Similar to other Prunus species, P. pseudocerasus underwent a common whole-genome duplication event that occurred ~139.96 million years ago. Because of its low fruit firmness, P. pseudocerasus is unsuitable for long-distance transportation, thereby restricting its rapid development throughout China. At the ripe fruit stage, P. pseudocerasus cv. 'Zhuji Duanbing' was significantly less firm than P. avium cv. 'Heizhenzhu'. The difference in firmness is attributed to the degree of alteration in pectin, cellulose, and hemicellulose contents. In addition, comparative transcriptomic analyses identified GalAK-like and Stv1, two genes involved in pectin biosynthesis, which potentially caused the difference in firmness between 'Zhuji Duanbing' and 'Heizhenzhu'. Transient transformations of PpsGalAK-like and PpsStv1 increase protopectin content and thereby enhance fruit firmness. Our study lays a solid foundation for functional genomic studies and the enhancement of important horticultural traits in Chinese cherries.

17.
Chem Biodivers ; : e202401154, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39003590

ABSTRACT

A novel compound streptothiomycin F (1), and a new natural product, N-(5-nitropentyl)acetamide (2), were discovered alongside ten previously identified compounds (3-12) through solid fermentation of marine-derived Streptomyces sp. ZS-A31 based on rice. The chemical structures of compounds 1-2 were elucidated using 1D and 2D NMR, as well as HRESIMS data analysis. Evaluation of all isolated compounds for their antibiofilm and antibacterial activities against P. aeruginosa was carried out using microdilution and crystal violet staining methods. Results highlighted the weak potency of the known compounds lumichrome (3) and vanillic acid (7) in inhibiting biofilm formation.

18.
Front Pharmacol ; 15: 1423629, 2024.
Article in English | MEDLINE | ID: mdl-38989149

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a malignancy with high incidence in China. Due to the lack of effective molecular targets, the prognosis of ESCC patients is poor. It is urgent to explore the pathogenesis of ESCC to identify promising therapeutic targets. Metabolic reprogramming is an emerging hallmark of ESCC, providing a novel perspective for revealing the biological features of ESCC. In the hypoxic and nutrient-limited tumor microenvironment, ESCC cells have to reprogram their metabolic phenotypes to fulfill the demands of bioenergetics, biosynthesis and redox homostasis of ESCC cells. In this review, we summarized the metabolic reprogramming of ESCC cells that involves glucose metabolism, lipid metabolism, and amino acid metabolism and explore how reprogrammed metabolism provokes novel opportunities for biomarkers and potential therapeutic targets of ESCC.

19.
ERJ Open Res ; 10(4)2024 Jul.
Article in English | MEDLINE | ID: mdl-38957167

ABSTRACT

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

20.
Chemosphere ; 363: 142708, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971446

ABSTRACT

Bisphenol A (BPA), an endocrine-disrupting contaminant, is ubiquitous in the environment due to its presence in plastics, wastewater, and agricultural runoff. This study investigated the photodegradation behavior of BPA in coastal aquaculture waters near Qingdao, China. Lower salinity promoted BPA photodegradation, while higher salinity has an inhibitory effect, suggesting slower degradation in seawater compared to ultrapure water. Triplet-excited dissolved organic matter (3DOM*) was identified as the primary mediator of BPA degradation, with additional contributions from hydroxyl radicals (•OH), singlet oxygen (1O2), and halogen radicals (HRS). Alepocephalidae aquaculture water exhibited the fastest degradation rate, likely due to its high DOM and nitrate/nitrite (NO3-/NO2-) content, which are sources of 3DOM* and •OH. A positive correlation existed between NO3-/NO2- concentration and the BPA degradation rate. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis identified the primary BPA photodegradation products, formed mainly through oxidative degradation, hydroxyl substitution, nitration, and chlorination pathways. Elucidating these photodegradation mechanisms provides valuable insights into the environmental fate and potential ecological risks of BPA in aquaculture environments. This knowledge can inform strategies for marine environmental protection and the development of sustainable practices.

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