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1.
Am J Cancer Res ; 14(3): 1419-1432, 2024.
Article in English | MEDLINE | ID: mdl-38590411

ABSTRACT

The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.

2.
Transl Oncol ; 44: 101942, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38555741

ABSTRACT

Cisplatin resistance plays a significant role in the dismal prognosis and progression of muscle-invasive bladder cancer (MIBC). However, the strategies to predict prognosis and cisplatin resistance are inefficient, and it remains unclear whether cisplatin resistance is associated with tumor immunity. In this study, we integrated the transcriptional data from cisplatin-resistant cell lines and a TCGA-MIBC cohort to establish cisplatin-resistance-related cluster classification and a cisplatin-resistance-related gene risk score (CRRGRS). Kaplan-Meier survival curves showed that compared with those in low CRRGRS group, MIBC patients belonging to high CRRGRS group had worse prognosis in TCGA-MIBC cohort and external GEO cohorts. Meanwhile, CRRGRS was able to help forecast chemotherapy and immunotherapy response of MIBC patients in the TGCA cohort and IMvigor210 cohort. Moreover, compared with the low CRRGRS group, the high CRRGS group possessed a relatively immunosuppressive "cold tumor" phenotype with a higher tumor immune dysfunction and exclusion (TIDE) score, ESTIMATE score, stromal score and immune score and a lower immunophenoscore (IPS) score. The upregulated expression levels of immune checkpoint genes, including PD-1, PD-L1 and CTLA4, in the high CRRGRS group also further indicated that a relative immunosuppressive tumor microenvironment may exist in MIBC patients belonging to high CRRGRS group. In addition, we integrated CRRGRS and clinical characteristics with prognostic value to develop a nomogram, which could help forecast overall survival of MIBC patients. Furthermore, DIAPH3 was identified as a regulator of proliferation and cisplatin resistance in MIBC. The expression of DIAPH3 was increased in cisplatin-resistant cell lines and chemotherapy-unsensitive people. Further mechanism exploration revealed that DIAPH3 facilitated tumor proliferation and cisplatin resistance by regulating the NF-kB and epithelial-mesenchymal transition (EMT) pathways. In conclusion, the comprehensive investigations of CRRGRS increased the understanding of cisplatin resistance and provided promising insights to restrain tumor growth and overcome chemoresistance by targeting DIAPH3.

3.
Angew Chem Int Ed Engl ; 63(17): e202320214, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38418405

ABSTRACT

Geminal (gem-) disubstitution in heterocyclic monomers is an effective strategy to enhance polymer chemical recyclability by lowering their ceiling temperatures. However, the effects of specific substitution patterns on the monomer's reactivity and the resulting polymer's properties are largely unexplored. Here we show that, by systematically installing gem-dimethyl groups onto ϵ-caprolactam (monomer of nylon 6) from the α to ϵ positions, both the redesigned lactam monomer's reactivity and the resulting gem-nylon 6's properties are highly sensitive to the substitution position, with the monomers ranging from non-polymerizable to polymerizable and the gem-nylon properties ranging from inferior to far superior to the parent nylon 6. Remarkably, the nylon 6 with the gem-dimethyls substituted at the γ position is amorphous and optically transparent, with a higher Tg (by 30 °C), yield stress (by 1.5 MPa), ductility (by 3×), and lower depolymerization temperature (by 60 °C) than conventional nylon 6.

4.
Bioresour Technol ; 395: 130395, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38301939

ABSTRACT

Currently, levan is attracting attention due to its promising applications in the food and biomedical fields. Levansucrase synthesizes levan by polymerizing the fructosyl unit in sucrose. However, a large amount of the byproduct glucose is produced during this process. In this paper, an engineered oleaginous yeast (Yarrowia lipolytica) strain was constructed using a surface display plasmid containing the LevS gene of Gluconobacter sp. MP2116. The levansucrase activity of the engineered yeast strain reached 327.8 U/g of cell dry weight. The maximal levan concentration (58.9 g/l) was achieved within 156 h in the 5-liter fermentation. Over 81.2 % of the sucrose was enzymolyzed by the levansucrase, and the byproduct glucose was converted to 21.8 g/l biomass with an intracellular oil content of 25.5 % (w/w). The obtained oil was comprised of 91.3 % long-chain fatty acids (C16-C18). This study provides new insight for levan production and comprehensive utilization of the byproduct in levan biosynthesis.


Subject(s)
Hexosyltransferases , Yarrowia , Yarrowia/genetics , Yarrowia/metabolism , Glucose , Fructans/metabolism , Sucrose/metabolism
5.
Cancer Med ; 12(19): 19889-19903, 2023 10.
Article in English | MEDLINE | ID: mdl-37747077

ABSTRACT

BACKGROUND: RCC1 functions as a pivotal guanine nucleotide exchange factor and was reported to be involved in mitosis, the assembly of the nuclear envelope, nucleocytoplasmic transport in cell physiological processes. Recent studies reported that RCC1 could regulate immunological pathways and promote the growth of some malignant solid tumors. However, the prognostic value and exact function of RCC1 remain unknown in patients with clear cell renal cell carcinoma (cRCC). METHODS: The UALCAN and KM plotter portals were used to analyze the expression profile and related tumor prognosis of RCC1 in ccRCC using data from TCGA. The expression profile of RCC1 was also confirmed in clinical samples using qRT-PCR, western blotting, and immunohistochemistry. The role of RCC1 on ccRCC cells in vitro was confirmed by a series of functional assays. Animal experiments were performed to verify the suppressive effect of RCC1 knockdown on tumor growth in vivo. The correlation of RCC1 expression with that of EZH2 was explored in clinical samples using IHC. The interaction between RCC1 and EZH2 was further verified using a CO-IP assay and a protein stability assay. RESULTS: RCC1 was upregulated in ccRCC tissues compared with normal tissues in TCGA dataset and paired clinical samples. RCC1 promoted ccRCC progression by accelerating the cell cycle and suppressing apoptosis. In addition, RCC1 could bind EZH2 and regulate its expression at the posttranscriptional level. RCC1 and EZH2 expression showed a strong correlation in clinical samples. Further investigation proved that RCC1 regulated EZH2 protein stability through the ubiquitin-proteasome pathway. CONCLUSIONS: RCC1 could be a potential therapeutic target in ccRCC. The RCC1/EZH2 axis takes part in the development of ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Humans , Carcinoma, Renal Cell/pathology , Cell Proliferation , Cell Cycle/genetics , Prognosis , Apoptosis , Kidney Neoplasms/pathology , Cell Line, Tumor , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Nuclear Proteins , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Guanine Nucleotide Exchange Factors/genetics
6.
Mol Cell Probes ; 71: 101924, 2023 10.
Article in English | MEDLINE | ID: mdl-37536457

ABSTRACT

BACKGROUND: Cancer stem cells (CSCs) are different from regular cancer cells because of their self-renewal feature and differentiation potential, which establishes the backbone of the vital role of CSCs in the progress and drug resistance of hepatocellular carcinoma (HCC). The objective of this study was to evaluate the effects of blood exosome-derived miRNA-30d-5p on the stemness and gemcitabine resistance of HCC cells and the underlying mechanisms. METHODS: The expression data of HCC-related miRNAs and mRNAs were downloaded from TCGA database and analyzed for differences. Employing the databases of starBase, TargetScan, miRDB, and mirDIP, we conducted target gene prediction upstream of mRNA. The expression of miRNA-30d-5p and SOCS3 mRNA was assayed by qRT-PCR, and the binding between them was validated by dual luciferase assay. CCK-8 was employed to evaluate cell viability and the IC50 value of gemcitabine. Cells were subjected to a sphere-forming assay to assess their ability to form spheres. Western blot was applied to evaluate the levels of cell surface marker proteins (Nanog, CD133, and Oct4) and exosome markers (CD9, CD81, and FLOT1). RESULTS: Bioinformatics analysis found that SOCS3 expression was down-regulated in HCC. qRT-PCR showed that SOCS3 expression was notably lower in HCC cell lines than in normal liver cell WRL68. At the cellular functional level, SOCS3 overexpression inhibited the viability, sphere-forming ability, stemness, and gemcitabine resistance of HCC cells. Bioinformatics analysis demonstrated that miRNA-30d-5p was the upstream regulator of SOCS3 and highly expressed in HCC tissues and cells. Dual luciferase assay demonstrated that miRNA-30d-5p could bind SOCS3. Rescue experiments showed that upregulating SOCS3 could reverse the effects of miRNA-30d-5p overexpression on the viability, sphere-forming ability, and gemcitabine sensitivity of HCC cells. CONCLUSIONS: Blood exosome-derived miRNA-30d-5p promoted the stemness and gemcitabine resistance of HCC cells by repressing SOCS3 expression. Hence, the miRNA-30d-5p/SOCS3 axis might be a therapeutic target for chemotherapy resistance and a feasible marker for the prognosis of HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Exosomes , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Exosomes/genetics , Exosomes/metabolism , Gemcitabine , Gene Expression Regulation, Neoplastic , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics
7.
Angew Chem Int Ed Engl ; 62(34): e202307697, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37395559

ABSTRACT

Herein, we report a one-pot method for enantioselective C-H allylation of pyridines at C3 via tandem borane and palladium catalysis. This method involves borane-catalyzed pyridine hydroboration to generate dihydropyridines, then palladium-catalyzed enantioselective allylation of the dihydropyridines with allylic esters, and finally air oxidation of the allylated dihydropyridines to afford the products. This method enables the introduction of an allylic group at C3 with excellent regio- and enantioselectivities.

8.
Int J Mol Sci ; 24(8)2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37108666

ABSTRACT

The tumor microenvironment (TME) plays an important part in the initiation and development of clear cell renal cell carcinoma (ccRCC). However, an understanding of the immune infiltration in TME is still unknown. Our study aims to explore the correlation between the TME and the clinical features, as well as the prognosis of ccRCC. In the present study, ESTIMATE and CIBERSORT computational methods were applied to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal fractions in the ccRCC form The Cancer Genome Atlas (TCGA) database. Then, we sought to find out those immune cell types and genes which may play a significant role and validated them in the GEO database. Furthermore, an immunohistochemical analysis of our external validation dataset was used to detect SAA1 and PDL1 expression in the ccRCC cancer tissues and corresponding normal tissues. Statistical analysis was performed to study the relationship between SAA1 and clinical characteristics, as well as PDL1 expression. Furthermore, a ccRCC cell model with SAA1 knockdown was constructed, which was used for cell proliferation and the migration test. The intersection analysis of the univariate COX and PPI analysis were performed to imply Serum Amyloid A1 (SAA1) as a predictive factor. The expression of SAA1 was significantly negatively correlated to OS and positively correlated to the clinical TMN stage system. The genes in the high-expression SAA1 group were basically enriched in immune-related activities. The proportion of mast cells resting was negatively correlated with SAA1 expression, indicating that SAA1 may be involved in the maintenance of the immune status for the TME. Moreover, the PDL1 expression was positively related to the SAA1 expression and negatively correlated with the patients' prognosis. Further experiments revealed that the knockdown of SAA1 inhibited ccRCC development through suppressing cell proliferation and migration. SAA1 may be a novel marker for the prognosis prediction of ccRCC patients and may play a vital role in the TME by mast cell resting and PDL1 expression. SAA1 has the potential to become a therapeutic target and indicator for immune target therapy in ccRCC treatment.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Tumor Microenvironment/genetics , Prognosis , Cell Proliferation , Kidney Neoplasms/genetics , Biomarkers , Serum Amyloid A Protein/genetics
9.
Medicina (Kaunas) ; 59(4)2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37109674

ABSTRACT

Background and Objectives: Calcium-binding protein 39-like (CAB39L) has been reported to be downregulated and possessed diagnostic and prognostic values in several types of cancer. However, the clinical value and mechanism of CAB39L in kidney renal clear cell carcinoma (KIRC) remain unclear. Materials and Methods: Bioinformatics analysis was conducted using different databases including TCGA, UALCAN, GEPIA, LinkedOmics, STRING, and TIMER. One-way variance analysis and t-test were chosen to investigate the statistical differences of CAB39L expression in KIRC tissues with different clinical characteristics. The receiver operating characteristic (ROC) curve was chosen to assess the discriminatory capacity of CAB39L. Kaplan-Meier curves were employed for assessing the influence of CAB39L on the progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) of KIRC patients. The independent prognostic significance of clinical parameters for OS such as CAB39L expression in KIRC patients was estimated by Cox analysis. A series of in vitro functional experiments and Western blot (WB) and immunohistochemistry (IHC) were used to validate the relative protein expression and function of CAB39L. Results: The mRNA and protein levels of CAB39L were relatively downregulated in KIRC samples. Meanwhile, hypermethylation of the CAB39L promoter region was possibly associated with its low expression in KIRC. The ROC curve showed that the mRNA expression of CAB39L had a strong diagnostic value for both early and late KIRC. Kaplan-Meier survival curves indicated that a higher mRNA level of CAB39L predicted good PFS, DSS, and OS. The mRNA expression of CAB39L was an independent prognostic factor (hazard ratio = 0.6, p = 0.034) identified by multivariate Cox regression analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis exhibited that CAB39L was mainly associated with substance and energy metabolism. Finally, overexpression of CAB39L impaired the proliferation and metastasis of KIRC cells in vitro. Conclusions: CAB39L possesses prognostic and diagnostic capacity in KIRC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Prognosis , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Computational Biology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Biomarkers , Kidney
10.
Int J Mol Sci ; 24(7)2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37047824

ABSTRACT

DNA polymerase delta 1 catalytic subunit (POLD1) plays a vital role in genomic copy with high fidelity and DNA damage repair processes. However, the prognostic value of POLD1 and its relationship with tumor immunity in clear cell renal cell carcinoma (ccRCC) remains to be further explored. Transcriptional data sets and clinical information were obtained from the TCGA, ICGC, and GEO databases. Differentially expressed genes (DEGs) were derived from the comparison between the low and high POLD1 expression groups in the TCGA-KIRC cohort. KEGG and gene ontology (GO) analyses were performed for those DEGs to explore the potential influence of POLD1 on the biological behaviors of ccRCC. The prognostic clinical value and mutational characteristics of patients were described and analyzed according to the POLD1 expression levels. TIMER and TISIDB databases were utilized to comprehensively investigate the potential relevance between the POLD1 levels and the status of the immune cells, as well as the tumor infiltration of immune cells. In addition, RT-qPCR, Western blot, immunohistochemistry and several functional and animal experiments were performed for clinical, in vitro and in vivo validation. POLD1 was highly expressed in a variety of tumors including ccRCC, and further verified in a validation cohort of 60 ccRCC samples and in vitro cell line experiments. POLD1 expression levels in the ccRCC samples were associated with various clinical characteristics including pathologic tumor stage and histologic grade. ccRCC patients with high POLD1 expression have poor clinical outcomes and exhibit a higher rate of somatic mutations than those with low POLD1 expression. Cox regression analysis also showed that POLD1 could act as a potential independent prognostic biomarker. The DEGs associated with POLD1 were significantly enriched in the immunity-related pathways. Moreover, further immune infiltration analysis indicated that high POLD1 expression was associated with high NK CD56bright cells, Treg cells, and myeloid-derived suppressor cells' (MDSCs) infiltration scores, as well as their marker gene sets of immune cell status. Meanwhile, POLD1 exhibited resistance to various drugs when highly expressed. Finally, the knockdown of POLD1 inhibited the proliferation and migration, and promoted the apoptosis of ccRCC cells in vitro and in vivo, as well as influenced the activation of oncogenic signaling. Our current study demonstrated that POLD1 is a potential prognostic biomarker for ccRCC patients. It might create a tumor immunosuppressive microenvironment and inhibit the susceptibility to ferroptosis leading to a poor prognosis.


Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Animals , Carcinoma, Renal Cell/genetics , DNA Polymerase III , Prognosis , Cell Proliferation , Kidney Neoplasms/genetics , Biomarkers , Tumor Microenvironment
11.
Materials (Basel) ; 16(2)2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36676466

ABSTRACT

In this work, based on Y3Al5O12:Ce3+ (YAG:Ce3+) transparent ceramic and (Sr, Ca)AlSiN3:Eu2+ phosphors, novel green-light-emitting materials were systematically studied. YAG:Ce3+ transparent ceramics with different doping-concentrations, from 0% to 1% (Sr, Ca)AlSiN3:Eu2+ phosphors, were fabricated by dry pressing and vacuum sintering. The serial phosphor ceramics had 533 nm green-light emission when excited by 460 nm blue light. The PL, PLE, and chromaticity performances were measured, indicating that more of the green-light component was emitted with the increase in doping concentration. The addition of (Sr, Ca)AlSiN3:Eu2+ phosphor increased the green-light wavelength area and improved the quantum yield (QY) of the YAG:Ce3+ ceramic matrix. The phase composition, microstructure, crystal-field structure and phosphor distribution of (Sr, Ca)AlSiN3:Eu2+ phosphor-doped YAG:Ce3+ transparent ceramics were investigated, to explore the microscopic causes of the spectral changes. Impressively, (Sr, Ca)AlSiN3:Eu2+ phosphors were distributed homogeneously, and the pinning effect of phosphor caused the suppression of grain growth. The novel materials could provide an effective strategy for full-spectrum white lighting and displaying applications in the future.

12.
Medicina (Kaunas) ; 59(1)2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36676733

ABSTRACT

Primary urethral adenocarcinoma in females is an extremely rare malignancy with unclear origin and only a few retrospective cases have been reported. The controversy continues to exist over the origin of primary urethral adenocarcinoma from periurethral glands (which include the Skene's glands), urethritis glandularis or intestinal metaplasia. Herein, we report one case of a 49-year-old female with distal urethral adenocarcinoma who presented with obstructive voiding. Abdominal and pelvic CT scans and chest radiology were unremarkable. Biopsy of the mass confirmed urethral adenocarcinoma. The patient underwent partial ureterectomy and was disease-free at the 2-years follow-up period. We also present another extremely rare case of primary urethral adenocarcinoma with mucinous features in a 58-year-old female who initially complained of external urethral orifice itching with painless urethral bleeding and was treated with local excision. The patient has not received any neoadjuvant or adjuvant therapy, and experienced tumor recurrence, inguinal lymph nodes metastasis, and even local iliopsoas metastasis during over 10-years follow-up. In conclusion, our current study emphasizes the importance of imaging studies and biopsy in making an accurate preoperative diagnosis of this rare disease, and further highlights the role of multimodal therapy. A combination of radiotherapy, chemotherapy and surgery is recommended for the optimal local and distant disease control. Moreover, better medical compliance and regular follow-up are required in these patients.


Subject(s)
Adenocarcinoma , Urethral Neoplasms , Humans , Female , Middle Aged , Retrospective Studies , Neoplasm Recurrence, Local , Urethra , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Urethral Neoplasms/diagnosis , Urethral Neoplasms/surgery
13.
Huan Jing Ke Xue ; 44(1): 58-65, 2023 Jan 08.
Article in Chinese | MEDLINE | ID: mdl-36635795

ABSTRACT

A high-resolution emission inventory of anthropogenic active volatile organic compounds (VOCs) for the Yangtze River Delta (YRD) region was developed based on the local measurement of 41 cities in the region and the specific 4.4 database of EPA. The emission characteristics and composition of VOCs were analyzed. The ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAP) of VOCs were calculated. The results showed that the total emission of anthropogenic VOCs in the YRD in 2017 was 4.9×106 t. The emission contributions of process sources, industrial solvent sources, mobile sources, domestic sources, storage and transportation sources, agricultural sources, and waste treatment sources were 34.3%, 27.1%, 19.5%, 9.7%, 6.1%, 2.5%, and 0.4%, respectively. Aromatic hydrocarbons and alkanes were the main components of VOCs, accounting for 25% of the total VOCs emissions in the region. The contribution rates of OFP from process sources, industrial solvent sources, mobile sources, and domestic sources were 38.3%, 21.5%, 16.4%, and 13.2%, respectively, and the contribution rates of SOAP were 26.2%, 34.1%, 18.1%, and 17.9%, respectively, which was basically consistent with the main contribution sources of VOCs emissions. The emission characteristics of the key industries in each city were obviously different. The key urban agglomeration of VOCs emission was mainly petrochemical industries and equipment manufacturing, whereas the northern part of the region was mainly wood furniture and other coating industries. The results showed that propylene, m-xylene, p-xylene, and ethylene were the main contribution sources of ozone, whereas toluene, 1,2,4-trimethylene, m-xylene, and p-xylene were the main contribution sources of secondary organic aerosols. In the next stage, the fine management of VOCs can be transformed into the main industries based on chemical reaction activity, which can give priority to the governance of key industries such as the chemical industry, petrochemical, automobile manufacturing, textile, wood, and furniture and can formulate different governance paths according to urban characteristics.


Subject(s)
Air Pollutants , Ozone , Volatile Organic Compounds , Volatile Organic Compounds/analysis , Air Pollutants/analysis , Environmental Monitoring , Ozone/analysis , Solvents , Aerosols/analysis , China
14.
Animals (Basel) ; 13(2)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36670802

ABSTRACT

Our previous study reported that N-acetylcysteine (NAC) administration improved the function of intestinal absorption in piglets infected with porcine epidemic diarrhea virus (PEDV). However, the effects of NAC administration on the functions of other tissues and organs in PEDV-infected piglets have not been reported. In this study, the effects of NAC on the liver, spleen, lung, lymph node, and gastrocnemius muscle in PEDV-infected piglets were investigated. Thirty-two 7-day-old piglets with similar body weights were randomly divided into one of four groups: Control group, NAC group, PEDV group, and PEDV+NAC group (eight replicates per group and one pig per replicate). The trial had a 2 × 2 factorial design consisting of oral administration of 0 or 25 mg/kg body weight NAC and oral administration of 0 or 1.0 × 104.5 TCID50 PEDV. The trial lasted 12 days. All piglets were fed a milk replacer. On days 5-9 of the trial, piglets in the NAC and PEDV + NAC groups were orally administered NAC once a day; piglets in the control and PEDV groups were orally administered the same volume of saline. On day 9 of trial, piglets in the PEDV and PEDV+NAC groups were orally administrated 1.0 × 104.5 TCID50 PEDV, and the piglets in the control and NAC groups were orally administrated the same volume of saline. On day 12 of trial, samples, including of the liver, spleen, lung, lymph node, and gastrocnemius muscle, were collected. PEDV infection significantly increased catalase activity but significantly decreased the mRNA levels of Keap1, Nrf2, HMOX2, IFN-α, MX1, IL-10, TNF-α, S100A12, MMP3, MMP13, TGF-ß, and GJA1 in the spleens of piglets. NAC administration ameliorated abnormal changes in measured variables in the spleens of PEDV-infected piglets. In addition, NAC administration also enhanced the antioxidant capacity of the mesenteric lymph nodes and gastrocnemius muscles in PEDV-infected piglets. Collectively, these novel results revealed that NAC administration improved the redox and functional gene expression levels in the spleen, mesenteric lymph nodes, and gastrocnemius muscle in PEDV-infected piglets.

15.
Histol Histopathol ; 38(8): 917-928, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36458571

ABSTRACT

BACKGROUND: Bladder cancer is one of the most commonly diagnosed malignancies of the urinary system with relatively poor prognosis and insufficient treatment strategies. RFWD3 is an E3 ligase whose function is rarely investigated in malignant tumors. METHODS: A tissue microarray was used for evaluating RFWD3 expression in clinical samples and its correlation with tumor characteristics and patients' prognosis. RFWD3 knockdown and overexpression cell models were constructed for conducting loss-of-function and gain-of-function assays. qPCR and western blotting were used for detecting mRNA and protein levels of RFWD3, respectively. MTT assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were carried out to demonstrate the change of cell phenotypes upon RFWD3 knockdown. RESULTS: RFWD3 expression was relatively higher in bladder cancer tissues than in normal tissues, which is correlated with higher N stage and poorer prognosis of patients. Knockdown of RFWD3 in bladder cancer cells significantly inhibited cell proliferation, colony formation, promote cell apoptosis and restrained cell migration. Overexpression of RFWD3 induced the opposite effects. CONCLUSIONS: It was illustrated that RFWD3 possesses excellent tumor-promoting ability in bladder cancer. Accordingly, RFWD3 may be a promising therapeutic target in the targeted therapy of bladder cancer, which is worth further research.


Subject(s)
Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder/pathology , Prognosis , Ubiquitin-Protein Ligases/genetics , Cell Proliferation/genetics , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, Neoplastic , Apoptosis
16.
Sci Total Environ ; 854: 158713, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36113791

ABSTRACT

Heavy metal exposure via food consumption is inadequately investigated and deserves considerable attention. We collected hundreds of food ingredients and daily meals and assessed their probabilistic health risk using a Monte Carlo simulation based on an ingestion rate investigation. The detected concentrations of four heavy metals (Cr, Cd, Pb, and Hg) in all daily meal samples were within the limits stipulated in the National Food Safety Standard (GB 2762-2017), while that for As level was excessive in 0.3 % of daily meal samples. The same results were also observed in most food ingredient samples, and a standard-exceeding ratio of 23 % of As was observed in aquatic food or products, especially seafood, which was with the highest concentration reaching 1.24 mg/kg. Combining the detected heavy metal amounts with the ingestion rate investigation, the hazard quotients (HQs) of As, Cr, Cd, Pb, and Hg in daily meals and food ingredients were all calculated as lower than 1 (no obvious harm), while the incremental lifetime cancer risk (ILCR) of As and Cr (>1 × 10-4), indicating that the residual As posed potential health effects to human health. It was noteworthy that the proportion of aquatic foods only accounted for 6.3 % of daily meals, but they occupied 41.1 % of the heavy metal exposure, which could be attributed to the high amounts of heavy metals in aquatic foods. This study not only provided basic data of heavy metal exposure and potential health risks through daily oral dietary intake, but also illuminated the contribution of different kinds of food ingredients. Specifically, the study highlighted the contamination of aquatic foods with As, especially seafood such as shellfish and bivalves.


Subject(s)
Food Ingredients , Mercury , Metals, Heavy , Humans , Cadmium , Rivers , Lead , Food Contamination/analysis , Metals, Heavy/analysis , Risk Assessment/methods , Mercury/analysis , Meals , Environmental Monitoring , China
17.
Front Bioeng Biotechnol ; 11: 1335071, 2023.
Article in English | MEDLINE | ID: mdl-38260744

ABSTRACT

Aiming at the shortcomings of most existing control strategies for lower limb rehabilitation robots that are difficult to guarantee trajectory tracking effect and active participation of the patient, this paper proposes a force/position-based velocity control (FPVC) strategy for the hybrid end-effector lower limb rehabilitation robot (HE-LRR) during active training. The configuration of HE-LRR is described and the inverse Jacobian analysis is carried out. Then, the FPVC strategy design is introduced in detail, including normal velocity planning and tangential velocity planning. The experimental platform for the HE-LRR system is presented. A series of experiments are conducted to validate the FPVC strategy's performance, including trajectory measurement experiments, force and velocity measurement experiments, and active participation experiments. Experimental studies show that the end effector possesses good following performance with the reference trajectory and the desired velocity, and the active participation of subjects can be adjusted by the control strategy parameters. The experiments have verified the rationality of the FPVC strategy, which can meet the requirements of trajectory tracking effect and active participation, indicating its good application prospects in the patient's robot-assisted active training.

18.
J Clin Med ; 11(22)2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36431168

ABSTRACT

OBJECTIVE: Venous thromboembolism (VTE) is a life threating complication in intensive care units (ICUs). This study aimed to pool the prevalence of VTE and examined the risk factors of VTE in intensive care patients worldwide. METHODS: A systematic search in PubMed, EMBASE and Web of Science databases was performed. Studies reported that the data on the prevalence of VTE or relevant information were synthesized using a random-effects model. RESULTS: A total of 42 studies reporting on 27,344 patients were included. The pooled prevalence of VTE was 10.0% (95% CI: 7.0-14.0%). Subgroup and metaregression analyses found that thromboprophylaxis strategy, simplified acute physiology score (SAPS II), age, study quality, sample size, malignancy, sex, spinal cord injury and injury severity score (ISS) moderated the prevalence of VTE in intensive care patients. CONCLUSIONS: The present meta-analysis revealed a high prevalence of VTE in critically ill patients. The risk factors of VTE included thromboprophylaxis strategy, SAPS II, age, malignancy, sex, spinal cord injury and ISS. Therefore, we need to pay more attention to high-risk populations of VTE in intensive care patients.

19.
Cells ; 11(19)2022 09 27.
Article in English | MEDLINE | ID: mdl-36230972

ABSTRACT

Cisplatin is commonly used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer, but its immune-related mechanism is still unclear. Exploration of the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and explored the important function of these immune effects in the bladder cancer microenvironment in a mice tumor model. We found cisplatin induced immune response in bladder cancer by RNA sequencing and validated that cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8+ T cells and dendritic cells in a transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Our findings indicated a cisplatin-related immune effect in bladder cancer, and cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.


Subject(s)
Cisplatin , Membrane Proteins/metabolism , Urinary Bladder Neoplasms , Animals , Cell Proliferation , Chromatin , Cisplatin/pharmacology , Cisplatin/therapeutic use , Mice , Nucleotidyltransferases/metabolism , Tumor Microenvironment , Urinary Bladder Neoplasms/drug therapy
20.
Article in English | MEDLINE | ID: mdl-36231927

ABSTRACT

The recycling of construction waste is key to reducing waste generation and CO2 emissions. This study aimed to develop a quantitative model for analyzing the carbon reduction potential of recycling construction, demolition, and renovation waste (CDRW) in Jiangsu province. The waste generation rate calculation method and nonlinear autoregressive artificial neural network model were used to estimate and predict CDRW generation. The life cycle assessment was performed to calculate the carbon reduction potential of recycling CDRW. In quantifying the carbon reduction potential, not only construction and demolition waste, but also renovation waste was considered for the first time. The results showed that the total carbon reduction potential of recycling CDRW increased from 3.94 Mt CO2e in 2000 to 58.65 Mt CO2e in 2020. Steel and concrete were the main contributors. By scenario analysis, the carbon reduction potential of fully recycling CDRW in 2020 increased by 37.79 Mt CO2e, a growth rate of 64%. The study further predicts future CDRW generation and the corresponding carbon reduction potential. Our conclusions indicate that 245.45 Mt of CDRW will be generated in 2030, and carbon reduction potential may reach 82.36 Mt CO2e. These results will help the government manage construction waste better and reach early achievement of the carbon peak target.


Subject(s)
Construction Industry , Waste Management , Carbon , Carbon Dioxide , Construction Industry/methods , Construction Materials , Industrial Waste , Life Cycle Stages , Recycling/methods , Steel , Waste Management/methods
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