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1.
Angew Chem Int Ed Engl ; : e202407339, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714494

ABSTRACT

Two-electron oxidative addition is one of the most important elementary reactions for d-block transition metals but it is uncommon for f-block elements. Here, we report the first examples of intermolecular oxidative addition of E-H (E = C, N) bonds to uranium(II) centers. The transient U(II) species was formed in-situ by reducing a heterometallic cluster featuring U(IV)-Pd(0) bonds with potassium-graphite (KC8). Oxidative addition of C-H or N-H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1-adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two- or four-electron processes. This study demonstrates that the intermolecular two-electron oxidative addition reactions are viable for actinide elements.

2.
Neurol Sci ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722503

ABSTRACT

BACKGROUND: There is insufficient data on severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) infection in Chinese patients with multiple sclerosis (pwMS). This study aims to explore the manifestation of pwMS during the Coronavirus disease 2019 (COVID-19) pandemic and the effect of SARS-CoV-2 infection on the prognosis of MS in northern China. METHODS: In this cross-sectional study, an online self-administered questionnaire and telephone interviews were conducted among pwMS of northern China. Clinical correlation of SARS-CoV-2 infection since the onset of the COVID-19 pandemic in northern China was analyzed. RESULTS: 164 patients with an average age of 38.9 ± 12.2 years were included, of which 57.3% had a disease course ≤ 5 years. 33.5% of the patients were COVID-19 vaccinated. 87.2% received disease-modifying therapy (DMT), and the average immunotherapy duration was 1.9 ± 1.6 years. 83.5% were SARS-CoV-2 infected, 14.6% reported worsening of their original condition after infection, and 5.1% had a relapse of MS. Shorter disease course was independently related to infection risk (P = 0.046), whereas increasing age was related to aggravated behavioral symptoms (P = 0.008). However, gender, vaccination, and DMT were not associated with susceptibility or poor prognosis. CONCLUSION: A shorter disease course is independently associated with an increased risk of SARS-CoV-2 infection, and age is associated with worsening disability. It seems to be safe and necessary to use DMT during the pandemic, however, the use of B cell-depletion agents should be approached with caution.

3.
BMC Public Health ; 24(1): 1238, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711042

ABSTRACT

BACKGROUND: We conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs). METHODS: A thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data. RESULTS: The results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99-1.09). We found that passive smoking (OR 1.12, 95% CI 1.03-1.20), rather than active smoking (OR 1.00, 95% CI 0.93-1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0-1 year old children (OR 1.21, 95% CI 0.94-1.56), followed by 0-4 years old children (OR 1.12, 95% CI 0.97-1.28) and 5-9 years old children (OR 1.11, 95% CI 0.95-1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80-1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07-1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00-1.38). CONCLUSIONS: Maternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.


Subject(s)
Alcohol Drinking , Brain Neoplasms , Caffeine , Observational Studies as Topic , Prenatal Exposure Delayed Effects , Humans , Pregnancy , Female , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Brain Neoplasms/epidemiology , Brain Neoplasms/chemically induced , Brain Neoplasms/etiology , Child , Child, Preschool , Caffeine/adverse effects , Infant , Infant, Newborn , Smoking/epidemiology , Smoking/adverse effects , Risk Factors , Beverages/adverse effects
4.
Nat Commun ; 15(1): 3153, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605030

ABSTRACT

Although the motor cortex has been found to be modulated by sensory or cognitive sequences, the linkage between multiple movement elements and sequence-related responses is not yet understood. Here, we recorded neuronal activity from the motor cortex with implanted micro-electrode arrays and single electrodes while monkeys performed a double-reach task that was instructed by simultaneously presented memorized cues. We found that there existed a substantial multiplicative component jointly tuned to impending and subsequent reaches during preparation, then the coding mechanism transferred to an additive manner during execution. This multiplicative joint coding, which also spontaneously emerged in recurrent neural networks trained for double reach, enriches neural patterns for sequential movement, and might explain the linear readout of elemental movements.


Subject(s)
Macaca , Motor Cortex , Animals , Motor Cortex/physiology , Neurons/physiology , Movement/physiology , Cues , Psychomotor Performance/physiology
5.
J Affect Disord ; 356: 483-491, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38640979

ABSTRACT

OBJECTIVES: A reliable, user-friendly, and multidimensional prediction tool can help to identify children at high risk for ADHD and facilitate early recognition and family management of ADHD. We aimed to develop and validate a risk nomogram for ADHD in children aged 3-17 years in the United States based on clinical manifestations and complex environments. METHODS: A total of 141,356 cases were collected for the prediction model. Another 54,444 cases from a new data set were utilized for performing independent external validation. The LASSO regression was used to control possible variables. A final risk nomogram for ADHD was established based on logistic regression, and the discrimination and calibration of the established nomogram were evaluated by bootstrapping with 1000 resamples. RESULTS: A final risk nomogram for ADHD was established based on 13 independent predictors, including behavioral problems, learning disabilities, age, intellectual disabilities, anxiety symptoms, gender, premature birth, maternal age at childbirth, parent-child interaction patterns, etc. The C-index of this model was 0.887 in the training set, and 0.862 in the validation set. Internal and external validation proved that the model was reliable. CONCLUSIONS: A nomogram, a statistical prediction tool that assesses individualized ADHD risk for children is helpful for the early identification of children at high risk for ADHD and the construction of a conceptual model of society-family-school collaborative diagnosis, treatment, and management of ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Nomograms , Humans , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/epidemiology , Child , Female , Male , Adolescent , Child, Preschool , Risk Factors , Reproducibility of Results , United States , Logistic Models , Risk Assessment/statistics & numerical data
6.
Chem Commun (Camb) ; 60(21): 2966-2969, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38376444

ABSTRACT

The monomeric and dimeric uranium azide complexes {[(CH3)2NCH2CH2NPiPr2]2U(N3)2} (2) and {[(CH3)2NCH2CH2NPiPr2]2U(N3)2}2 (3) were synthesized by treating complex 1 with NaN3 at 60 and -20 °C, respectively. A temperature-induced single-crystal to single-crystal transformation of 3 to 2 was observed. The reduction of either 2 or 3 with KC8 yields a uranium nitride complex {[(CH3)2NCH2CH2NPiPr2]4U2(µ-N)2} (4).

7.
Curr Med Chem ; 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38310388

ABSTRACT

AIMS: We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD). BACKGROUND: STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD. OBJECTIVE: The objective of this study is to investigate the molecular subtypes and prognostic model for STAD. METHODS: A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature. RESULTS: We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGASTAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets. CONCLUSION: This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

8.
Sci Total Environ ; 914: 169973, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38211854

ABSTRACT

Soil moisture is a critical variable that quantifies precipitation, floods, droughts, irrigation, and other factors with regard to decision-making and risk evaluation. An accurate prediction of soil moisture dynamics is important for soil and environmental management. However, the complex topographic condition and land use in hilly and mountainous areas make it a challenge to monitor and predict soil moisture dynamics in these areas. In this study, the determinants of soil moisture variability were determined by structural equation modeling, and then an attempt was made to estimate the spatial distribution of soil moisture content on steep hillslope using the state-space method. Herein, soil moisture at different depths (0-10, 10-20, and 20-30 cm) was monitored by portable time-domain reflectometer (TDR) along this hillslope (100 m × 180 m). It showed that the spatial variability of soil moisture decreased with increasing soil wetness, primarily in the topsoil (0-10 cm). Soil moisture was correlated with elevation (r = 0.28, 0.50, and 0.28), capillary porosity (r = 0.06, 0.37, and 0.28), soil texture (r for Clay: 0.20, 0.24, and 0.16; r for Sand: -0.25, -0.18, and -0.28), organic carbon (r = -0.31, -0.08, and 0.10) and land use (r = -0.01, 0.28, and 0.24) under different conditions (dry, moderate, and wet). Among these determinants, elevation made direct contributions to soil moisture variation, especially under moderate conditions, while land use made its impacts by altering soil texture. It is encouraging that the state-space approach yielded precise and cost-effective predictions of soil moisture dynamics along this steep hillslope since it gives the minimum root-mean-square error (RMSE) and Akaike information criterion (AIC). Moreover, soil organic carbon (AIC = -4.497, RMSE = 0.104, R2 = 0.899), rock fragment contents (AIC = -4.366, RMSE = 0.111, R2 = 0.878), and elevation (AIC = -3.693, RMSE = 0.156, R2 = 0.629) effectively anticipated the spatial distribution of soil moisture under dry, moderate, and wet conditions, respectively. This study confirms the efficacy of the state-space approach as a valuable tool for soil moisture prediction in areas characterized by complex and spatially heterogeneous conditions.

9.
J Neurooncol ; 165(1): 79-90, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37819535

ABSTRACT

BACKGROUND: The efficacy of current immunotherapeutic strategies for patients with glioblastoma multiforme (GBM) remains unsatisfactory. The purpose of this study was to investigate the correlation between tumor necrosis factor alpha-induced protein 2 (TNFAIP2) and immunogenic cell death (ICD) in GBM, and to examine the effect of TNFAIP2 knockdown and anti-PD-1 combination treatment in a mouse glioma model. METHODS: The CGGA and TCGA databases were used to explore the possible function of TNFAIP2 in GBM. Multiplex immunohistochemistry (mIHC) staining was performed to detect the immune infiltration of tissues. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) were utilized to detect the release of damage-associated molecular patterns (DAMPs) and the activation of the immune response. A mouse glioma model was applied to examine the induction of immune response. RESULTS: In vitro and in vivo studies demonstrated that TNFAIP2 knockdown increased the surface exposure of calreticulin (CALR), heat shock protein 70 kDa (HSP70), and heat shock protein 90 kDa (HSP90) in GBM cell lines, thereby inducing immunogenic cell death (ICD). Importantly, the study found that TNFAIP2 knockdown in combination with anti-PD-1 therapy significantly improved the overall survival of glioma in a mouse model. CONCLUSIONS: TNFAIP2 knockdown induces ICD by downregulating TNFAIP2 in GBM. In addition, TNFAIP2 knockdown sensitized glioma to anti-PD-1 therapy. Hence, targeting TNFAIP2 alone or in combination with anti-PD-1 therapy may be a potential strategy for GBM treatment through ICD.


Subject(s)
Glioblastoma , Glioma , Animals , Mice , Humans , Glioblastoma/pathology , Immunogenic Cell Death , Glioma/pathology , Cell Line , Disease Models, Animal , Cell Line, Tumor , Cytokines
10.
Int J Mol Sci ; 24(18)2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37762084

ABSTRACT

Clostridium butyricum, a new probiotic in recent years, can produce butyric acid and short-chain fatty acids. It has the characteristics of strong acid and alkali resistance, high temperature resistance, and strong resistance to most antibiotics, and has more advantages than other probiotics. However, the action mechanism of C. butyricum on Eriocheir sinensis is still unclear and needs further study. In this study, when C. butyricum was added to the basic diet, the number of living bacteria was 0, 1 × 106 and 1 × 108 CFU/g, respectively. The E. sinensis were randomly divided into three groups: (blank control group, experimental group 1 (1 × 106 CFU/g) and experimental group 2 (1 × 108 CFU/g)). They were fed an experimental diet for 28 days. The effects of C. butyricum on E. sinensis were studied by detecting the differences in non-specific immune indexes, intestinal microflora, and metabolites between serum and hepatopancreas. The results showed that C. butyricum could improve the antioxidant ability of E. sinensis serum and hepatopancreas, protect intestinal tissues, and promote the absorption of nutrients. At the same time, it can enhance the microbial diversity and richness of the E. sinensis gut flora. LC-MS metabolomics was used to detect the metabolism of intestinal flora. It was found that C. butyricum could up-regulate lysophosphatidylcholine in the intestine. Through the KEGG enrichment pathway, it was found that significantly different metabolites were mainly concentrated in six metabolic pathways. The purine metabolism and alanine, aspartate, and glutamate metabolism pathways showed a downward trend, indicating that the addition of C. butyricum to feed could reduce purine metabolism, promote the water-salt balance of the organism's cells, and reduce inflammation. In this study, it was found that the addition of certain concentrations of C. butyricum to feed could improve the antioxidant ability of E. sinensis, improve the intestinal flora environment, and promote the growth of beneficial bacteria in the gut. This can promote the body's metabolism, which is more conducive to its growth.


Subject(s)
Clostridium butyricum , Gastrointestinal Microbiome , Antioxidants , Butyric Acid , Purines
11.
Med Oncol ; 40(11): 310, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773553

ABSTRACT

Breast cancer is a prevalent malignant tumor, posing a significant threat to women's health globally due to its increasing incidence and tendency to affect younger patients. Protein tyrosine phosphatases (PTPs) are a class of enzymes that have emerged as potential targets for various tumors, including breast cancer, because they can modulate oncogenic tyrosine kinases, which are both tumor-suppressive and oncogenic. The regulation of tyrosine phosphorylation levels is crucial for cell proliferation and differentiation. Although the clinical biomarker potential of PTPs is not fully explored, there is evidence to suggest that they may serve as clinical biomarkers and therapeutic targets for breast cancer. We found that increased expression levels of PTPN11 and PTPN3 were associated with a higher risk of death in patients with breast cancer, while PTPN11 and PTPN18 are significantly associated with overall survival in patients with estrogen receptor-positive (ER+) breast cancer. Meanwhile, PTPN11 expression was found to be negatively associated with survival in patients with ER+ breast cancer. Furthermore, PTPN11 exposes a metabolic vulnerability to breast cancer metastasis via dysregulated ceramide metabolism. Therefore, we speculate that PTPN11 has the potential to serve as a therapeutic target for breast cancer by regulating lipid metabolism reprogramming.


Subject(s)
Breast Neoplasms , Neoplasms, Second Primary , Humans , Female , Breast Neoplasms/genetics , Protein-Tyrosine Kinases , Lipid Metabolism , Ceramides , Tyrosine , Protein Tyrosine Phosphatases, Non-Receptor , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Melanoma, Cutaneous Malignant
12.
Transl Pediatr ; 12(7): 1305-1318, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37575903

ABSTRACT

Background: To establish and independently validate nomograms for predicting singleton preterm birth (PTB) risk based on a large sample size comprising data from two independent datasets. Methods: This cohort study used data from 50 states and the District of Columbia in the National Vital Statistics System (NVSS) database between January 2016 and December 2020. Multivariate logistic regression analysis was used to confirm the independent risk factors for PTB. Statistically significant variables were incorporated into the logistic regression models to establish PTB prediction nomograms. The models were developed using the United States (US)-derived data and were independently validated using data from US Territories. Results: A total of 16,294,529 mother-newborn pairs from the US were included in the training set, and 54,708 mother-newborn pairs from the US Territories were included in the validation set. In all, 4 nomograms were built: 1 to predict PTB probability, and another 3 to predict moderately and late PTB probability, very PTB probability, and extremely PTB probability, respectively. Hypertensive eclampsia and infertility treatment were found to be the top 2 contributors to PTB. Conclusions: We developed and validated nomograms to predict the individualized probability of PTB, which could be useful to physicians for improved early identification of PTB and in making individualized clinical decisions.

13.
Microbiol Spectr ; 11(4): e0521022, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37289056

ABSTRACT

Listeria monocytogenes is an important pathogen which easily contaminates food and causes fatal systemic infections in human. Bacteriocins have received much attention regarding their natural methods of controlling health-related pathogens. Here, we investigated and characterized a novel two-component bacteriocin named acidicin P from Pediococcus acidilactici LAC5-17. Acidicin P showed obvious antimicrobial activity to L. monocytogenes. Through a sequence similarity network analysis for two-component bacteriocin precursors mined in the RefSeq database, acidicin P was observed to belong to an unusual group of two-component bacteriocins. Acidicin P contains two peptides designated Adpα and Adpß which are assessed to interact with each other and form a helical dimer structure which can be inserted into the lipid bilayer of target cell membrane. We demonstrate that A5, N7, and G9 in the A5xxxG9 motif of Adpα and S16, R19, and G20 in the S16xxxG20 motif of Adpß played crucial roles in stabilizing the helix-helix interaction of Adpα and Adpß and were essential for the antilisterial activity of acidicin P by site-directed mutagenesis. A positive residue, R14, in Adpα and a negative residue, D12, in Adpß are also important for acidicin P to fight against L. monocytogenes. These key residues are supposed to form hydrogen bonding, which is crucial for the interaction of Adpα and Adpß. Furthermore, acidicin P induces severe permeabilization and depolarization of the cytoplasmic membrane and causes dramatic changes in L. monocytogenes cell morphology and ultrastructure. Acidicin P has the potential to be applied to inhibit L. monocytogenes efficiently both in the food industry and medical treatments. IMPORTANCE L. monocytogenes can cause widespread food contamination and severe human listeriosis, which amount to a large proportion of the public health and economic burdens. Today, L. monocytogenes is usually treated with chemical compounds in the food industry or antibiotics for human listeriosis. Natural and safe antilisterial agents are urgently required. Bacteriocins are natural antimicrobial peptides that have comparable narrow antimicrobial spectra and are attractive potentials for precision therapy for pathogen infection. In this work, we discover a novel two-component bacteriocin designated acidicin P, which shows obvious antilisterial activity. We also identify the key residues in both peptides of acidicin P and demonstrate that acidicin P is inserted into the target cell membrane and disrupts the cell envelop to inhibit the growth of L. monocytogenes. We believe that acidicin P is a promising lead for further development as an antilisterial drug.


Subject(s)
Bacteriocins , Listeria monocytogenes , Listeriosis , Humans , Bacteriocins/pharmacology , Anti-Bacterial Agents/pharmacology , Listeriosis/drug therapy , Cell Membrane
14.
EClinicalMedicine ; 59: 101975, 2023 May.
Article in English | MEDLINE | ID: mdl-37180469

ABSTRACT

Background: Severe traumatic brain injury (sTBI) is extremely disabling and associated with high mortality. Early detection of patients at risk of short-term (≤14 days after injury) death and provision of timely treatment is critical. This study aimed to establish and independently validate a nomogram to estimate individualised short-term mortality for sTBI based on large-scale data from China. Methods: The data were from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry (between Dec 22, 2014, and Aug 1, 2017; registered at ClinicalTrials.gov, NCT02210221). This analysis included information of eligible patients with diagnosed sTBI from 52 centres (2631 cases). 1808 cases from 36 centres were enrolled in the training group (used to construct the nomogram) and 823 cases from 16 centres were enrolled in the validation group. Multivariate logistic regression was used to identify independent predictors of short-term mortality and establish the nomogram. The discrimination of the nomogram was evaluated using area under the receiver operating characteristic curves (AUC) and concordance indexes (C-index), the calibration was evaluated using calibration curves and Hosmer-Lemeshow tests (H-L tests). Decision curve analysis (DCA) was used to evaluate the net benefit of the model for patients. Findings: In the training group, multivariate logistic regression demonstrated that age (odds ratio [OR] 1.013, 95% confidence interval [CI] 1.003-1.022), Glasgow Coma Scale score (OR 33.997, 95% CI 14.657-78.856), Injury Severity Score (OR 1.020, 95% CI 1.009-1.032), abnormal pupil status (OR 1.738, 95% CI 1.178-2.565), midline shift (OR 2.266, 95% CI 1.378-3.727), and pre-hospital intubation (OR 2.059, 95% CI 1.472-2.879) were independent predictors for short-term death in patients with sTBI. A nomogram was built using the logistic regression prediction model. The AUC and C-index were 0.859 (95% CI 0.837-0.880). The calibration curve of the nomogram was close to the ideal reference line, and the H-L test p value was 0.504. DCA curve demonstrated significantly better net benefit with the model. Application of the nomogram in external validation group still showed good discrimination (AUC and C-index were 0.856, 95% CI 0.827-0.886), calibration, and clinical usefulness. Interpretation: A nomogram was developed for predicting the occurrence of short-term (≤14 days after injury) death in patients with sTBI. This can provide clinicians with an effective and accurate tool for the early prediction and timely management of sTBI, as well as support clinical decision-making around the withdrawal of life-sustaining therapy. This nomogram is based on Chinese large-scale data and is especially relevant to low- and middle-income countries. Funding: Shanghai Academic Research Leader (21XD1422400), Shanghai Medical and Health Development Foundation (20224Z0012).

15.
Eur Urol Open Sci ; 50: 31-42, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37101770

ABSTRACT

Background: Circular RNAs (circRNAs) have been uncovered to be implicated in the malignant development of bladder cancer (BC). Objective: Herein, this work aimed to investigate the role and mechanism of circRNA ubiquitin-associated protein 2 (circUBAP2) in BC progression. Design setting and participants: Quantitative real-time polymerase chain reaction and Western blotting were used for the detection of genes and proteins. Outcome measurements and statistical analysis: In vitro functional experiments were conducted using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), Transwell, wound healing, and flow cytometry assays, respectively. A glycolysis analysis was conducted by assessing glucose uptake and lactate production. A murine xenograft model was established to perform in vivo experiments. The binding interaction between miR-496 and circUBAP2 or DNA topoisomerase 2-alpha (TOP2A) was verified using a dual-luciferase reporter assay. Results and limitations: CircUBAP2 was highly expressed in BC patients, and high circUBAP2 expression showed a shorter survival rate. Functionally, knockdown of circUBAP2 could suppress BC cell growth, migration, invasion, and aerobic glycolysis in vitro, as well as impede BC growth in nude mice. Mechanistically, circUBAP2 acted as a sponge for miR-496, which targeted TOP2A. Moreover, circUBAP2 could indirectly regulate TOP2A expression through sequestering miR-496. Furthermore, a series of rescue experiments showed that miR-496 inhibition reversed the anticancer action of circUBAP2 knockdown on BC cells. Moreover, miR-496 could attenuate BC cell malignant phenotypes and aerobic glycolysis, which were abolished by TOP2A overexpression. Conclusions: Silencing of circUBAP2 could suppress BC growth, invasion, migration, and aerobic glycolysis by the miR-496/TOP2A axis, suggesting a promising target for the molecular targeted therapies of BC. Patient summary: Circular RNA ubiquitin-associated protein 2 (circUBAP2) was found to be associated with poor prognosis in bladder cancer (BC). Knockdown of circUBAP2 might suppress BC growth, invasion, migration, and aerobic glycolysis, indicating that it may be a new target for the development of molecular targeted therapy for BC.

16.
Front Immunol ; 14: 1095740, 2023.
Article in English | MEDLINE | ID: mdl-36865557

ABSTRACT

Intestinal health is closely associated with overall animal health and performance and, consequently, influences the production efficiency and profit in feed and animal production systems. The gastrointestinal tract (GIT) is the main site of the nutrient digestive process and the largest immune organ in the host, and the gut microbiota colonizing the GIT plays a key role in maintaining intestinal health. Dietary fiber (DF) is a key factor in maintaining normal intestinal function. The biological functioning of DF is mainly achieved by microbial fermentation, which occurs mainly in the distal small and large intestine. Short-chain fatty acids (SCFAs), the main class of microbial fermentation metabolites, are the main energy supply for intestinal cells. SCFAs help to maintain normal intestinal function, induce immunomodulatory effects to prevent inflammation and microbial infection, and are vital for the maintenance of homeostasis. Moreover, because of its distinct characteristics (e.g. solubility), DF is able to alter the composition of the gut microbiota. Therefore, understanding the role that DF plays in modulating gut microbiota, and how it influences intestinal health, is essential. This review gives an overview of DF and its microbial fermentation process, and investigates the effect of DF on the alteration of gut microbiota composition in pigs. The effects of interaction between DF and the gut microbiota, particularly as they relate to SCFA production, on intestinal health are also illustrated.


Subject(s)
Gastrointestinal Microbiome , Swine , Animals , Intestines , Gastrointestinal Tract , Dietary Fiber , Nutrients
17.
J Environ Manage ; 337: 117717, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-36958284

ABSTRACT

Soil erosion is a common form of land degradation. The Coupled Model Intercomparison Project Phase 6 (CMIP6) provides a scenario framework for global socio-economic development and climate change by combining Shared Socioeconomic Pathways (SSP) and Representative Concentration Pathways (RCP). The soil erosion estimation under global climate change and land-use change scenarios provided by CMIP6 is valuable for representing future changes and hotspots. This study estimated the future changes in soil erosion in the Three Gorges Reservoir (TGR) area, China, which has suffered severe soil loss over an extended period, and vegetation restoration projects have been conducted since 1999. The scenarios provided by SSP1-2.6, SSP2-4.5, and SSP5-8.5 were coupled with the scenarios of regional vegetation restoration projects to reflect future land use changes (LUC) and climate change. The results showed that future soil erosion from 2020 to 2100 in the TGR area will experience a non-significant decreasing trend (with trend slopes of -0.013, -0.020, and-0.006 in SSP1-2.6, SSP2-4.5, and SSP5-8.5, respectively, with p > 0.05). However, with the R factors calculated by different methods, this decreasing trend becomes either insignificant or a significant increasing trend. SSP1-2.6 will experience the lowest soil erosion in 2100 owing to the large amount of forest increase in this scenario. Furthermore, as estimates, the grain-for-green policy (GGP) will reduce 89353.47, 92737.73 and 42916.52 ton soil erosion per year in SSP1-2.6, SSP2-4.5 and SSP3-8.5 by 2100, respectively. In the future, the GGP will become increasingly important for controlling soil loss in the TGR area owing to the increasing precipitation in all scenarios, which increases the risk of soil loss.


Subject(s)
Conservation of Natural Resources , Soil Erosion , Conservation of Natural Resources/methods , Soil , Forests , China , Climate Change
18.
Urol Int ; 107(6): 632-645, 2023.
Article in English | MEDLINE | ID: mdl-36958293

ABSTRACT

INTRODUCTION: Circular RNAs (circRNAs) are related to the pathogenesis and progression of bladder cancer (BC). This research aimed to investigate the role and mechanism of hsa_circ_0008035 (circ_0008035) in BC progression. METHODS: Circ_0008035, microRNA (miR)-1,184, and Ras-related protein 2B (RAP2B) levels were examined in BC via quantitative real-time polymerase chain reaction and Western blotting. Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, caspase-3 assay kit, transwell, and tube formation assays were conducted to estimate the effects of circ_0008035 on the malignant phenotypes of BC tumors. The interaction between RNAs and genes was evaluated via a dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model of BC in nude mice was established to estimate the effect of circ_0008035 in BC in vivo. RESULTS: Circ_0008035 and RAP2B levels were upregulated, while miR-1184 abundance was downregulated in BC tissues and cells. Circ_0008035 knockdown constrained cell proliferation, migration, invasion and angiogenesis but promoted apoptosis in vitro. And circ_0008035 silencing curbed xenograft tumor growth in vivo. Circ_0008035 acted as a miRNA sponge for miR-1184. Circ_0008035 increased RAP2B expression by sponging miR-1184. MiR-1184 downregulation relieved the effects of circ_0008035 knockdown on BC progression. And RAP2B knockdown partly reversed the effects of miR-1184 overexpression on BC progression. CONCLUSION: Circ_0008035-mediated BC progression via regulating the miR-1184/RAP2B axis, providing a potential target for BC treatment.


Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Humans , Animals , Mice , Mice, Nude , Urinary Bladder Neoplasms/genetics , Urinary Bladder , Apoptosis , Bandages , Cell Proliferation , MicroRNAs/genetics , rap GTP-Binding Proteins
19.
Heliyon ; 9(1): e12361, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36685439

ABSTRACT

The segmentation of retinal vessel takes a crucial part in computer-aided diagnosis of diseases and eye disorders. However, the insufficient segmentation of the capillary vessels and weak anti-noise interference ability make such task more difficult. To solve this problem, we proposed a multi-scale residual attention network (MRANet) which is based on U-Net network. Firstly, to collect useful information about the blood vessels more effectively, we proposed a multi-level feature fusion block (MLF block). Then, different weights of each fused feature are learned by using attention blocks, which can retain more useful feature information while reducing the interference of redundant features. Thirdly, multi-scale residual connection block (MSR block) is constructed, which can better extract the image features. Finally, we use the DropBlock layer in the network to reduce the network parameters and alleviate network overfitting. Experiments show that based on DRIVE, the accuracy rate and the AUC performance value of our network are 0.9698 and 0.9899 respectively, and based on CHASE_DB1 dataset, they are 0.9755 and 0.9893 respectively. Our network has a better segmentation effect compared with other methods, which can ensure the continuity and completeness of blood vessel segmentation.

20.
Chemistry ; 29(23): e202204034, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-36628553

ABSTRACT

Exploiting effective non-noble metal electrocatalysts for oxygen reduction reaction (ORR) is crucial for fuel cells and metal-air batteries. Herein, we designed and fabricated Co nanoparticles confined in Mo/N co-doped polyhedral carbon frameworks (Co-NP/MNCF) derived from polyoxometalate-encapsuled metal-organic framework, which showed comparable ORR performance with commercial Pt/C and a larger diffusion-limited current density. Moreover, the Co-NP/MNCF also exhibited excellent ORR stability and methanol tolerance. These appealing performances can be attributed to the porosity regulation and heteroatom doping of metal-organic framework derived polyhedral carbon frameworks, which could be beneficial for the exposure of more active sites, the optimization of electronic structure and the mass transfer of electrolyte/electron/ion.

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