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1.
Chemosphere ; 360: 142398, 2024 May 22.
Article En | MEDLINE | ID: mdl-38789053

Both thermal and environmental processes are significant factors influencing the existing characteristics, e.g., congener distributions, and existing levels, of polychlorinated naphthalenes (PCNs) in the environment. Soil plays an important role in the life cycle of PCNs, but degradation of PCNs in soils has never been reported. In this study, we collected surface soil samples from 13 cities in the Yangtze River Delta, which is one of the most crowded areas of China and analyzed the samples for 75 PCNs. The long-range transportation from polluted areas was the major source for PCNs in remote areas, but the PCN profiles in remote areas reported in our previous studies were different from those in human settlement in this study, indicating there is a transformation of PCNs after emissions from anthropogenic activities. Two experiments were then designed to reveal the degradation mechanisms, including influencing factors, products, and pathways, of PCNs in surface soils. Based on the experiments, we found that the major factor driving the losses of PCNs in surface soils was volatilization, followed by photo irradiation and microbial metabolism. Under photo-irradiation, the PCN structures would be destroyed through a process of dechlorination followed by oxidation. In addition, the dechlorination pathways of PCNs have been established and found to be significantly influenced by the structure-related parameters.

2.
Chem Asian J ; 19(7): e202301147, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38334040

Fluorescent mechanophores can indicate the deformation or damage in polymers. The development of mechanophores with multi-triggered response is of great interest. Herein, Diels-Alder (DA) adducts are incorporated into linear poly(methyl acrylate) PMA-BA and network poly(hexyl methacrylate) (PHMA) as mechanophores to detect the stress caused by ultrasound, freezing, and compression. The DA mechanophores undergo retro-DA reaction to release 9-styrylanthracene chromophore upon applying force, resulting in cyan fluorescence. The dissociation ratio of the DA mechanophore after pulsed ultrasonication of PMA-BA solution for 240 minutes is estimated to be 52 % by absorption spectra and 1H NMR. Additionally, the rate constant of mechanical cleavage is calculated to be 1.2×10-4 min-1⋅kDa-1 with the decrease in molecular weight from 69 to 22 kDa measured by gel permeation chromatography. Freezing of PHMA gels as well as compression of PHMA bulk samples turn-on the DA mechanophores, revealing the microscale fracture. Photon upconversion responses toward various force stimuli are also achieved in both polymer solutions and bulk samples by doping platinum octaethylporphyrin (PtOEP) or palladium meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) sensitizers with multiple excitation wavelengths.

3.
Ecotoxicol Environ Saf ; 272: 116080, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38350215

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.


Mercury , Metals, Heavy , Male , Humans , United States , Prostate-Specific Antigen , Cadmium , Nutrition Surveys , Zinc
4.
Int J Neurosci ; : 1-13, 2024 Jan 02.
Article En | MEDLINE | ID: mdl-38164693

INTRODUCTION: The metabotropic glutamate receptor 4 (mGlu4, GRM4) exhibits significant expression within the central nervous system (CNS) and has been implicated to be correlated with a poor prognosis. OBJECTIVE: This study was aimed to elucidate the relationship between the expression profile of GRM4 and the prognosis of glioma patients. METHODS: RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and China Glioma Genome Atlas (CGGA) repositories were used to evaluate the potential relationship. The value of clinical prognostic about GRM4 was assessed using clinical survival data from CGGA and TCGA. The GEPIA database was used to select genes like GRM4. PPI network was constructed by the database of (STRING), GO and KEGG analyses were performed. TargetScan, TarBase, miRDB, and starBase were used to explore miRNAs that could regulate GRM4 expression. EWAS Data Hub, MethSurv, and MEXPRESS were used for the analysis and relationship between DNA methylation and GRM4 expression and prognosis in glioma. TIMER2.0 and CAMOIP databases were used to assess the association between immune cell infiltration and GRM4. Human GBM cell lines were used to validate the function of GRM4. RESULTS: Our study shows that GRM4 is under expressed among gliomas and accompanied by poorer OS. Multivariate analysis showed that low mRNA expression of GRM4 was an independent factor of prognostic for shorter OS in all glioma patients. MiR-1262 affects the malignant phenotype of gliomas through GRM4. Methylation of DNA plays an important role in the instruction of GRM4 expression, the methylation level of GRM4 in glioma tissue is higher in comparison to normal tissue, and the higher methylation level was accompanied with the worse prognosis. Further analysis showed that GRM4 mRNA expression in GBM linked negatively with common lymphoid progenitor, Macrophage M1, Macrophage, and T cell CD4+ Th2, but not with the tumor purity. Overexpression of GRM4 prevents the migration of human GBM cell lines in vitro. CONCLUSION: GRM4 may have a substantial impact on the infiltration of immune cells and serve as a valuable prognostic biomarker in gliomas.

5.
Ibrain ; 9(3): 290-297, 2023.
Article En | MEDLINE | ID: mdl-37786755

This study aimed to determine the values of the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate used in the procedural sedation of endoscopic retrograde cholangiopancreatography (ERCP). Sixty patients who fulfilled the inclusion and exclusion criteria of this study were selected. Sufentanil was administered intravenously and remimazolam besylate was administered 2 min later. ERCP treatment was feasible when the modified alertness/sedation (MOAA/S) score was ≤2. If choking or movement occurred during duodenoscope placement, it was considered as a positive reaction. The dose was increased in the next patient; otherwise, it was considered as a negative reaction, and the dose was reduced in the next patient. The ED50 and ED95 values and 95% confidence interval (CI) of remimazolam besylate were calculated by Probit regression analysis. All 60 patients completed the trial. The ED50 and ED95 values of remimazolam besylate were 0.196 and 0.239 mg/kg, respectively, for the procedural sedation of ERCP. The time of MOAA/S score ≤ 2 was (82.58 ± 21.70) s, and the mean time of awakening was (9.03 ± 5.64) min. Transient hypotension was observed in two patients without medical intervention. The ED50 and ED95 values of remimazolam besylate used in the procedural sedation of ERCP were 0.196 and 0.239 mg/kg, and the dose of the medications has definite efficacy and good safety.

6.
J Colloid Interface Sci ; 652(Pt A): 1085-1091, 2023 Dec 15.
Article En | MEDLINE | ID: mdl-37651924

Solid-state Li metal batteries (SSLMBs) are famous for superior security and excellent energy density. Nevertheless, the poor interfacial contact between solid lithium and electrode is one key problem in the development of SSLMBs, resulting in high impedance and growth of lithium dendrites along the grain boundaries. Herein, an innovative and accessible approach has been applied to SSLMBs, which introduces an ion-electron mixing (IEM) interface on the surface of Li1.3Al0.3Ti1.7(PO4)3 (LATP). The IEM interlayer generates LixSn/LiI of fast lithium-ion conductor through an in-situ reaction. The existence of LiI would promote the quick transmission of Li+ at the interface and inhibit the electronic conduction, thus restraining the growth of lithium dendrites. The batteries with IEM@LATP electrolyte could stably cycle more than 1000 h at high current density of 0.1 mA cm-2. Even increasing the current density to 3.0 mA cm-2, the batteries still could work normally. This novel and viable approach offers a robust basis for the practical application of SSLMBs and has some general applicability to other solid-state batteries.

7.
Arch Esp Urol ; 76(4): 270-282, 2023 Jun.
Article En | MEDLINE | ID: mdl-37455526

BACKGROUND: Prostaglandin E2 receptor 3 (PTGER3, EP3) is essential for many malignancies growth and metastasis. The role of PTGER3 in kidney renal clear cell carcinoma (KIRC) was assessed in terms of its prognosis and its association with immune infiltration. METHODS: Transcriptomic expression profiles of PTGER3 were acquired from The Cancer Genome Atlas (TCGA) database. Comparative analysis was performed to evaluate the disparity in PTGER3 expression between KIRC and normal tissues. The discriminative potential of PTGER3 as a distinguishing determinant was assessed through receiver operating characteristic (ROC) curves. Prognostic factors were evaluated employing COX regression and logistic models. Furthermore, the impact of PTGER3 on survival was ascertained utilizing the Kaplan-Meier method. A protein-protein interaction (PPI) network was constructed utilizing the STRING database. To investigate the correlation between immune infiltration levels and PTGER3 expression, a single-sample Gene Set Enrichment Analysis (GSEA) method was employed, employing the Gene Set Variation Analysis (GSVA) package and the Tumor Immune Estimation Resource (TIMER) database. RESULTS: Bioinformatics analysis unveiled a significant downregulation of PTGER3 expression in KIRC tissues compared to paraneoplastic tissues (p < 0.001). Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) experiments demonstrated a reduction in PTGER3 expression in 786-O cells in contrast to paraneoplastic tissues (p < 0.01). The ROC curve, employing PTGER3 as a potential diagnostic biomarker, exhibited a substantial area under the curve (AUC) value of 0.929. According to the Kaplan-Meier survival analysis, reduced PTGER3 expression increased the chance of negative overall survival (OS) (p = 0.019). A PPI network was constructed, elucidating the interaction patterns between PTGER3 and the top 10 co-expressed genes. An examination of gene enrichment and immune infiltration levels found a link between PTGER3 transcription and immune infiltration levels. Notably, high B cell counts and low Mast cell counts were connected to a poor prognosis in KIRC patients. CONCLUSIONS: The expression of PTGER3 was found to be diminished in KIRC in comparison to paracancerous tissue. This observation exhibited a correlation with both prognosis and immune cell infiltration. As a result, our findings suggest that PTGER3 could be considered a promising biomarker to forecast KIRC prognosis and as a possible target for immunotherapy.


Carcinoma, Renal Cell , Kidney Neoplasms , Receptors, Prostaglandin E, EP3 Subtype , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Humans , Receptors, Prostaglandin E, EP3 Subtype/metabolism , Reverse Transcription , Reverse Transcriptase Polymerase Chain Reaction , Prognosis , Biomarkers
8.
Arch. esp. urol. (Ed. impr.) ; 76(4): 270-282, 28 june 2023. ilus, tab, graf
Article En | IBECS | ID: ibc-223192

Background: Prostaglandin E2 receptor 3 (PTGER3, EP3) is essential for many malignancies growth and metastasis. The role of PTGER3 in kidney renal clear cell carcinoma (KIRC) was assessed in terms of its prognosis and its association with immune infiltration. Methods: Transcriptomic expression profiles of PTGER3 were acquired from The Cancer Genome Atlas (TCGA) database. Comparative analysis was performed to evaluate the disparity in PTGER3 expression between KIRC and normal tissues. The discriminative potential of PTGER3 as a distinguishing determinant was assessed through receiver operating characteristic (ROC) curves. Prognostic factors were evaluated employing COX regression and logistic models. Furthermore, the impact of PTGER3 on survival was ascertained utilizing the Kaplan–Meier method. A protein-protein interaction (PPI) network was constructed utilizing the STRING database. To investigate the correlation between immune infiltration levels and PTGER3 expression, a single-sample Gene Set Enrichment Analysis (GSEA) method was employed, employing the Gene Set Variation Analysis (GSVA) package and the Tumor Immune Estimation Resource (TIMER) database. Results: Bioinformatics analysis unveiled a significant downregulation of PTGER3 expression in KIRC tissues compared to paraneoplastic tissues (p < 0.001). Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) experiments demonstrated a reduction in PTGER3 expression in 786-O cells in contrast to paraneoplastic tissues (p < 0.01). The ROC curve, employing PTGER3 as a potential diagnostic biomarker, exhibited a substantial area under the curve (AUC) value of 0.929. According to the Kaplan–Meier survival analysis, reduced PTGER3 expression increased the chance of negative overall survival (OS) (p = 0.019). A PPI network was constructed, elucidating the interaction patterns between PTGER3 and the top 10 co-expressed genes (AU)


Humans , Male , Female , Middle Aged , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Receptors, Prostaglandin E, EP3 Subtype , Neoplasm Staging , Antineoplastic Agents, Immunological , Prognosis
9.
Mol Med ; 29(1): 64, 2023 05 14.
Article En | MEDLINE | ID: mdl-37183261

BACKGROUND: Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients. METHODS: The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples. RESULTS: The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas. CONCLUSION: Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.


Brain Neoplasms , Glioma , Humans , Hippo Signaling Pathway , CRISPR-Cas Systems/genetics , Genes, Lethal , Glioma/genetics , Oncogenes , Brain Neoplasms/genetics
10.
ACS Appl Mater Interfaces ; 15(8): 11033-11041, 2023 Mar 01.
Article En | MEDLINE | ID: mdl-36802470

Developing fluorescent motifs capable of displaying mechano- and thermo-stimuli reversibly and ratiometrically is appealing for monitoring the deformation or temperature to which polymers are subjected. Here, a series of excimer-type chromophores Sin-Py (n = 1-3) consisting of two pyrenes linked with oligosilanes of one to three silicon atoms is developed as the fluorescent motif incorporated in a polymer. The fluorescence of Sin-Py is steered with the linker length where Si2-Py and Si3-Py with disilane and trisilane linkers display prominent excimer emission accompanied by pyrene monomer emission. Covalent incorporation of Si2-Py and Si3-Py in polyurethane gives fluorescent polymers PU-Si2-Py and PU-Si3-Py, respectively, where intramolecular pyrene excimers and corresponding combined emission of excimer and monomer are obtained. Polymer films of PU-Si2-Py and PU-Si3-Py display instant and reversible ratiometric fluorescence change during the uniaxial tensile test. The mechanochromic response arises from the reversible suppression of excimer formation during the mechanically induced separation of the pyrene moieties and relaxation. Furthermore, PU-Si2-Py and PU-Si3-Py show thermochromic response toward temperature, and the inflection point from the ratiometric emission as a function of temperature gives an indication of the glass transition temperature (Tg) of the polymers. The design of the excimer-based mechanophore with oligosilane provides a generally implementable way to develop mechano- and thermo-dual-responsive polymers.

11.
J Biochem Mol Toxicol ; 37(4): e23308, 2023 Apr.
Article En | MEDLINE | ID: mdl-36644951

YTH domain-containing protein 2 (YTHDC2), a member of N6-methyladenosine (m6A) readers, has been reported to be closely associated with multiple cancer types. However, very little is known about the YTHDC2 gene and its involvement in prostate cancer. YTHDC2 protein expression level was analyzed and correlated to clinical outcomes in prostate cancer patients who underwent prostatectomy in Guizhou Provincial People's Hospital. The YTHDC2 expression level was also detected in prostate cancer cell lines and an immortalized prostate epithelial cell line BPH-1 and RWPE1 by quantitative real-time reverse transcription polymerase chain reaction. Furthermore, we established stable cell lines (DU145 and PC-3) transfected with either empty vector or the full-length YTHDC2 gene and conducted cell function assays in vitro. Fisher's exact test and Pearson χ2 test were employed, Kaplan-Meier method was used for the survival analysis. Of 32 patient samples who enrolled in this study, YTHDC2 was significantly upregulated in prostate cancer (PCa) patients with higher Gleason scores and serum prostate-specific antigen levels. YTHDC2 expression was significantly elevated in all PCa cell lines compared to BPH-1 and RWPE1 (all p < 0.05). Functionally, the enforced expression of YTHDC2 markedly promoted cell growth, migration, and invasion efficacies in prostate cancer cells. Our data indicate that YTHDC2 upregulation may be potentially associated with the prognosis of prostate cancer patients.


Prostatic Hyperplasia , Prostatic Neoplasms , Male , Humans , Prostatic Hyperplasia/metabolism , Cell Line, Tumor , Prostatic Neoplasms/metabolism , Prostate/metabolism , Prostate/surgery , Prostatectomy/methods , RNA Helicases/metabolism
12.
Am J Reprod Immunol ; 89(6): e13528, 2023 06.
Article En | MEDLINE | ID: mdl-35148017

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that has caused fatal infectious diseases and global spread. This novel coronavirus attacks target cells through the interaction of spike protein and angiotensin-converting enzyme II (ACE2), leading to different clinical symptoms. However, for a successful pregnancy, a well-established in-uterine environment includes a specific immune environment, and multi-interactions between specific cell types are prerequisites. The immune-related changes in patients infected with novel coronavirus could interfere with the immune microenvironment in the uterus, leading to fetal loss. We first reviewed the intrauterine environment in the normal development process and the possible pregnancy outcome in the infection state. Then, we summarized the immune response induced by SARS-CoV-2 in patients and analyzed the changes in ACE2 expression in the female reproductive system. Finally, the present observational evidence of infection in pregnant women was also reviewed.


COVID-19 , Humans , Female , Pregnancy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2 , Peptidyl-Dipeptidase A/metabolism , Pregnancy Outcome
13.
Reprod Sci ; 30(6): 1927-1937, 2023 06.
Article En | MEDLINE | ID: mdl-36512190

To explore the differences in clinicopathological characteristics and prognosis between seromucinous borderline ovarian tumors (SMBOTs) and mucinous borderline ovarian tumors (MBOTs). Ninety-one patients with SMBOTs and MBOTs who underwent surgery at the Obstetrics and Gynecology Hospital of Fudan University from July 2006 to January 2015 were included. The median onset age of patients with SMBOTs (29 years, 20-77) was younger than that of patients with MBOTs (37 years, 16-71). SMBOTs were more likely to be exogenous and show bilateral ovarian involvement and had a smaller average tumor size of 10.63 cm, while MBOTs were more prone to endogenous growth and show unilateral involvement and had a larger average tumor size of 18.55 cm (p < 0.05). Compared with MBOTs, SMBOTs were characterized by the expression of Mullerian differentiation markers (p < 0.05). Recurrence occurred in 15.8% patients with SMBOT and 9.1% patients with MBOT. One case of SMBOT (2.6%) and one case of MBOT (2.3%) progressed to malignancy during follow-up, but no disease-related death was observed. Age less than 40 years was a risk factor for recurrence, while the effect of fertility-sparing surgery (FSS) on recurrence requires a larger sample size to be validated. The clinical characteristics of SMBOTs and MBOTs are similar but also quite different. High expression of Mullerian differentiation markers in SMBOT may indicate a better response to hormone therapy. Repeated FSS should be performed with caution and fully informed because of the risk of recurrence and progression to malignancy.


Obstetrics , Ovarian Neoplasms , Adult , Female , Humans , Pregnancy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Prognosis , Retrospective Studies , Risk Factors
14.
Childs Nerv Syst ; 39(4): 909-914, 2023 04.
Article En | MEDLINE | ID: mdl-36456749

PURPOSE: Retrospective analysis of clinical and epidemiological characteristics of central nervous system (CNS)tumors in Uyghur children from a single center in Xinjiang. METHODS: Between January 2013 and December 2021, 243 children (0-17 years old) with a clear pathological type of CNS tumor are collected and analyzed for tumor size, grade, and category, as well as their relationship with the child's gender, age, and region of origin according to the 2021 edition of the new WHO CNS tumor classification. OUTCOME: The 243 cases of CNS tumors in Uyghur children are predominantly from rural areas, with 144 cases (59.26%) of supratentorial tumors and 129 cases (53.09%) of low-grade tumors. With an overall male-to-female ratio of 1.43:1, a peak age of incidence of 6 to 8 years. CONCLUDING: The present study is based on a 9-year analysis of pediatric CNS data from a single center, and the center is the largest tertiary hospital in Xinjiang with large numbers of admitted patients, which may reflect some extent the clinical characteristics and epidemiological features characteristics of pediatric CNS tumors in Uyghur in Xinjiang.


Central Nervous System Neoplasms , Child , Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Adolescent , Retrospective Studies , Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/pathology , Incidence , Hospitalization
15.
Oxid Med Cell Longev ; 2022: 3611540, 2022.
Article En | MEDLINE | ID: mdl-36111167

Background: The expression of ZFP36 in previous study was reduced in prostate cancer (PCa) tissues as compared to benign prostate tissues, indicating the potential of ZFP36 as an auxiliary marker for PCa. Further evaluation was conducted in clinical samples for in vitro and in vivo experiments, to prove the potential possibility that ZFP36 dysregulation participated in the malignant phenotype of PCa, to determine its potential mechanism for tumor regulation, and to provide a new theoretical basis for gene therapy of PCa. Methods: First, the expression of ZFP36 in prostate tissue and PCa tissue was explored, and the relationship between ZFP36 and clinical features of PCa patients was illustrated. Subsequently, the impact of ZFP36 on the biology of PCa cells and relevant downstream pathways of ZFP36's biological impact on PCa were elucidated. Finally, whether oxidative stress mediated the regulation of ZFP36 in PCa was verified by the determination of oxidative stress-related indicators and bioinformatics analysis. Results: The downregulation of ZFP36 in PCa tissue had a positive correlation with high Gleason scores, advanced pathological stage, and biochemical recurrence. ZFP36 was identified as an independent prognostic factor for PCa patients' BCR-free survival (P = 0.022) by survival analysis. Following a subsequent experiment of function gain and loss, ZFP36 inhibited the proliferation, invasion, and migration in DU145 and 22RV1 cells and inhibits tumor growth in the mouse model. Additionally, high-throughput sequencing screened out CDK6 as the downstream target gene of ZFP36. Western blot/Q-PCR demonstrated that overexpression of ZFP36 could reduce the expression of CDK6 at both cellular and animal levels, and the dual-luciferase experiment and RIP experiment proved that CDK6 was the downstream target of ZFP36, indicating that CDK6 was a downstream target of ZFP36, which mediated tumor cell growth by blocking cell cycle at the G1 stage. Furthermore, ZFP36 inhibited oxidative stress in PCa cells. Conclusions: In PCa, ZFP36 might be a tumor suppressor that regulated growth, invasion, and migration of PCa cells. The lately discovered ZFP36-CDK6 axis demonstrated the molecular mechanism of PCa progression to a certain extent which might act as a new possible therapeutic target of PCa therapy.


Cyclin-Dependent Kinase 6 , Prostatic Neoplasms , Tristetraprolin , Animals , Cell Line, Tumor , Cyclin-Dependent Kinase 6/genetics , Cyclin-Dependent Kinase 6/metabolism , Humans , Male , Mice , Neoplasm Grading , Oxidative Stress , Prostatic Neoplasms/pathology , Tristetraprolin/genetics , Tristetraprolin/metabolism
16.
BMC Urol ; 22(1): 105, 2022 Jul 18.
Article En | MEDLINE | ID: mdl-35850713

BACKGROUND: The purpose of this study was to characterize the pathophysiological changes of hydronephrosis caused by ureteral calculi obstruction in a new rabbit ureteral calculi model by implanting flowable resin. METHODS: Forty New Zealand rabbits were randomly divided into two groups: the calculi group and the sham control group. In the calculi group (n = 20), rabbits were operated at left lower abdomen and the left ureter was exposed. Then flowable resin (flowable restorative dental materials) was injected into the left ureter using a 0.45 mm diameter intravenous infusion needle. Then light-cured for 40 s by means of a dental curing light to form calculi. In the sham control group, normal saline was injected into the ureter. Rabbits underwent X-ray and routine blood and urine tests preoperatively, as well as X-ray, CT, dissection, HE staining and routine blood and urine tests on 1, 3, 5 and 7 days postoperatively. Stone formation was assessed by X-ray and unenhanced CT scan after surgery. The pathophysiological changes were evaluated through dissection, HE staining and routine blood and urine tests. RESULTS: Ureteral calculi models were successfully constructed in 17 rabbits. In calculi group, high-density shadows were observed in the left lower abdomen on postoperative day 1st, 3rd, 5th and 7th by X-ray and CT scan. Dissection found obstruction formation of the left ureters, dilatation of the renal pelvis and upper ureter during 7 days after surgery. The renal long-diameters of the left ureters increased only on the 1st postoperative day. HE staining found ureteral and kidney damage after surgery. In calculi group and sham group,the serum creatinine, urea nitrogen, white blood cells and urine red blood cells were raised at day 1 after surgery. However, the indicators returned to normal at day 3, 5, and 7. CONCLUSIONS: This is a stable, less complicated operation and cost-effective ureteral calculi model by implanting flowable resin. And this novel model may allow us to further understand the pathophysiology changes caused by ureteral calculi obstruction.


Ureter , Ureteral Calculi , Ureteral Diseases , Ureteral Obstruction , Animals , Kidney Pelvis , Rabbits , Ureteral Calculi/complications , Ureteral Calculi/surgery , Ureteral Obstruction/complications , Ureteral Obstruction/surgery
17.
Brain Sci ; 12(6)2022 May 28.
Article En | MEDLINE | ID: mdl-35741587

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and normal tissues. Our study found considerable genetic and expression alterations in heterogeneity among lower-grade gliomas and normal brain tissues. There are two pyroptosis phenotypes in lower-grade glioma, and they exhibited differences in cell infiltration characteristics and clinical characters. Then, a PyroScore model using the lasso-cox method was constructed to measure the level of pyroptosis in each patient. PyroScore can refine the lower-grade glioma patients with a stratified prognosis and a distinct tumor immune microenvironment. Pyscore may also be an effective factor in predicting potential therapeutic benefits. In silico analysis showed that patients with a lower PyroScore are expected to be more sensitive to targeted therapy and immunotherapy. These findings may enhance our understanding of pyroptosis in lower-grade glioma and might help optimize risk stratification for the survival and personalized management of lower-grade glioma patients.

18.
J Geriatr Cardiol ; 19(4): 284-291, 2022 Apr 28.
Article En | MEDLINE | ID: mdl-35572220

OBJECTIVE: To investigate the effects of Tongmai Yangxin Pill (TMYXP) combined with metoprolol tartrate or metoprolol alone for the treatment of premature ventricular complex (PVC) in patients with symptomatic frequent PVC. METHODS: A total of 584 patients with symptomatic frequent PVC were randomly assigned (in a 1:1 ratio) into two groups: study group [n = 292, TMYXP (40 pills twice/day, orally) combined with metoprolol tartrate (25 mg twice/day, orally)] and control group [n = 292, metoprolol tartrate (25 mg twice/day, orally) plus placebo pill (40 pills twice/day, orally)]. The total treatment period was eight weeks. RESULTS: After eight weeks of treatment, the total effective rate of reduction of PVC in the study group and the control group were 76.4% and 51.4%, respectively (P < 0.001). TMYXP combined with metoprolol tartrate demonstrated a significantly greater reduction of the frequency of PVCs compared with the metoprolol tartrate alone (-4537 times/24 h vs. -3013 times/24 h, P < 0.001). The study group also showed a better result compared with the control group with respect to PVC related symptoms. In terms of New York Heart Association classification improvement, the total effective rates were 21.9% in the study group and 12.4% in the control group ( P < 0.05). Both the study group and the control group exhibited improvements in echocardiographic indexes. Left ventricular ejection fraction was significantly improved in the study group compared with the control group ( P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. CONCLUSIONS: Compared with metoprolol tartrate alone, TMYXP combined with metoprolol tartrate could more effectively reduce the frequency of PVC and alleviated PVC related symptoms, and improve cardiac function in patients with symptomatic PVC.

19.
Comput Intell Neurosci ; 2022: 1514396, 2022.
Article En | MEDLINE | ID: mdl-35449745

Most of the existing region-matching algorithms need to match all regions, resulting in a waste of computing resources, increasing the cost of simulation technology and data redundancy, and resulting in the reduction of network data stream transmission efficiency. This paper presents a parallel region-matching knowledge recognition algorithm. Combined with the shortcomings of existing matching algorithms, a simulation technology is constructed to realize the parallel matching of multiple regions in HLA distributed simulation. The algorithm can realize the parallel matching calculation of multiple changed regions in one simulation. At the same time, the basic idea based on mobile intersection is adopted in the matching calculation, and the historical information before and after the region range is moved is used. The matching is limited to the moving interval, and the moving crossover theory is applied to the matching calculation to realize the relevant historical information before and after the region. Simulation results show that the parallel region-matching knowledge recognition algorithm can support HLA distributed simulation evaluation. In the matching calculation, the basic idea based on moving intersection is adopted, and the matching is limited to the moving interval by using the historical information before and after the region is moved, which reduces a large number of irrelevant calculations. Theoretical analysis and experimental results show that the algorithm is particularly suitable for the application needs of building large-scale distributed simulation based on multi-core computing platform.


Algorithms , Computer Simulation
20.
PLoS One ; 17(4): e0266413, 2022.
Article En | MEDLINE | ID: mdl-35363807

This paper explored how the government provides low-carbon subsidies for the manufacturers, retailers, and consumers in a secondary supply chain under cap-and-trade scheme. We calculated the best prices, emissions reductions, and the demands for common and low-carbon products when subsidizing each of the abovementioned market players. In particular, a comparative analysis of their equilibrium outcomes was made thereafter. The MATLAB simulation found that the optimal emissions reductions under the three subsidy modes were even and positively correlated to low-carbon subsidies, which, however, negatively correlated to the prices of both product types. Higher subsidies drove up demand for low-carbon products and dragged down that for common goods. But the prices of these products maintained the highest levels when consumers were subsidized; demand for common products was greater when subsidies went to retailers than to manufacturers or consumers, consequently generating the largest emissions and highest profits. When the subsidies were greater than [Formula: see text], all three subsidy modes saw a drop in total carbon emissions. That being so, the government should offer proper subsidies before seeing energy-saving progress.


Financing, Government , Government , Carbon , Commerce , Costs and Cost Analysis
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