Recurrence and metastasis of pseudomyxoma peritonei: A rare case report.

Pseudomyxoma peritonei (PMP) is a relatively uncommon condition primarily associated with neoplasms of the appendiceal epithelium. It is characterized by non-specific clinical manifestations, leading to a high rate of misdiagnosis. This report describes the case of a 62-year-old male patient with recurrent and metastatic PMP. The patient first experienced unexplained epigastric pain and paroxysmal abdominal pain accompanied by distension over 8 years ago. He underwent surgical interventions for the condition in other hospitals in 2015 and 2018, respectively.

The efficacy of using a multiparametric magnetic resonance imaging-based radiomics model to distinguish glioma recurrence from pseudoprogression.

OBJECTIVE: The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner. METHODS: A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy. RESULTS: Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93-1). CONCLUSION: The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment.

Abnormal functional connectivity of white-matter networks and gray-white matter functional networks in patients with NMOSD.

Cognitive impairment (CI) has been reported in 29-70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1-4, WM1-8, WM2-6, WM2-7, WM2-8, WM4-8, WM5-8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.

Preserving the left colonic artery in radical sigmoid and rectal cancer surgery is feasible: A meta-analysis.

BACKGROUND: This study aims to investigate the safety and feasibility of preserving left colonic artery (LCA) in radical sigmoid and rectal cancer surgery. METHODS: Relevant articles were systematically searched on the PubMed, Embase, and Cochrane Library. The quality of included studies was evaluated using the Cochrane Handbook. A meta-analysis was conducted to assess the surgical outcomes and oncological outcomes by RevMan 5.4 software. RESULTS: Fifteen studies with a total of 5054 patients, including 2432 patients with LCA preservation and 2622 patients without LCA preservation, were included and analyzed in this study. The meta-analysis revealed that preserving LCA in radical surgery of sigmoid and rectal cancer has lower anastomotic leakage incidence (OR = 1.03, 95% confidence interval = 0.83-1.27, P < .0001). There were no significant differences in the operative time, intraoperative blood loss, number of dissected lymph nodes, postoperative complications as well as the oncological outcomes including systemic recurrence, local recurrence, 5-year overall survival rate, and 5-year disease-free survival rate. CONCLUSION SUBSECTIONS: This pooled analysis showed that preserving the LCA is safe and feasible in radical sigmoid and rectal cancer surgery.

Ion exchange synthesis of copper-based hydroxyapatite for the catalytic degradation of phenol.

Hydroxyapatite (HAP) is a material renowned for its exceptional capabilities in adsorbing and exchanging heavy metal ions, making it a widely employed substance within the environmental domain. This study aims to present a novel material, namely copper-HAP (Cu-HAP), which was synthesized via an ion exchange method. The resulting material underwent comprehensive characterization using scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Brunauer-Emmett-Teller (BET) analysis. Subsequently, based on the principle of the Fenton-like oxidation reaction, the material was used for the degradation of phenol. The outcomes of the investigation revealed that the optimal preparation conditions for the catalyst were achieved at a temperature of 40 °C, a pH value of 5, and a relative dosage of Cu-HAP at 100 mg/g. Under the reaction conditions of a catalyst dosage of 2 g/L, a 30% hydrogen peroxide concentration of 30 mM, a phenol concentration of 20 mg/L, a pH value of 6, a temperature of 40 °C, and the degradation rate of phenol impressively reached 98.12%. Furthermore, the degradation rate remained at 42.31% even after five consecutive cycles, indicating the promising potential of Cu-HAP in the treatment of recalcitrant organic compounds within this field.

MBNL1­AS1 attenuates tumor cell proliferation by regulating the miR­29c­3p/BVES signal in colorectal cancer.

Dysregulation of long non­coding RNAs (lncRNAs) is involved in the development of colorectal cancer (CRC). In the present study, the identification of muscle blind like splicing regulator 1 antisense RNA 1 (MBNL1­AS1) lncRNA was reported. Firstly, Cell Counting Kit­8, EdU and colony formation assays were uesed to explore the role of MBNL1­AS1 in regulating the proliferation of CRC cells. According to TCGA database, it was found that MBNL1­AS1 was correlated with microRNA (miR)­29c­3p and blood vessel epicardial substance (BVES) expression in CRC cells. Then, the regulation among MBNL1­AS1, miR­29C­3P and BVES was detected by dual luciferase reporter assay and the function of MBNL1­AS1/miR­29C­3P/BVES axis was explored by rescue assay. The results demonstrated that MBNL1­AS1 expression was decreased in CRC and was associated with the size of tumors derived from patients with CRC. Functionally, the upregulation of MBNL1­AS1 suppressed CRC cell proliferation in vitro and inhibited tumor growth in vivo, while knockdown of MBNL1­AS1 expression caused the opposite effects. MBNL1­AS1 expression correlated with BVES expression in CRC tissues and MBNL1­AS1 enhanced the stability of BVES mRNA by functioning as a competing endogenous RNA to sponge miR­29c­3p; the latter directly targeted MBNL1­AS1 and BVES mRNA 3'UTR. Collectively, the results indicated that MBNL1­AS1 suppressed CRC cell proliferation by regulating miR­29c­3p/BVES signaling, suggesting that the MBNL1­AS1/miR­29c­3p/BVES axis may be a potential therapeutic target for CRC.

Degradation of 2,4-DCP by immobilized laccase on modified biochar carrier.

Rape straw was used as the raw material for the biochar in this study, which was then changed using acid, alkali, and magnetic techniques. The laccase was attached using the adsorptions-crosslinking process, and the three modified biochars served as the carriers. The ideal circumstances for laccase immobilization were explored, and both biochar and immobilized laccase's characteristics were examined. The removal of 2,4-dichlorophenol (2,4-DCP) by immobilized laccase from modified biochar and its degradation products were researched. The main conclusions are as follows: the optimal concentration of glutaraldehyde (GLU) was 4%, and the pH was four, and the enzyme dosage was 1.75 mg/mL for the immobilized laccase of acid-modified biochar (SBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 2 mg/mL for immobilized laccase from alkali-modified biochar (JBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 1.75 mg/mL for immobilized laccase from magnetically modified biochar (CBC@LAC). SEM images could show the changes in the surface morphology of biochar caused by three modification methods. The BET results demonstrated that acid and magnetic modification increased the specific surface area of biochar, and alkali modification mainly expanded the pore size of biochar. FT-IR and XRD showed that modification and laccase loading had little effect on the structure of biochar. The stability of immobilized laccase was better than that of free laccase in acid-base, heat, and storage. Among the three modified biochar immobilized laccases, JBC@LAC showed the best acid-base stability and thermal stability, and the relative enzyme activity changed the least when pH and temperature conditions changed. The storage stability of SBC@LAC is the best. After 30 days of storage, the relative enzyme activity is still 83%. The removal rates of 2,4-DCP were 57, 99, and 63%, respectively, by SBC@LAC, JBC@LAC, and CBC@LAC. After five reuses, the removal rates of 2,4-DCP by SBC@LAC, JBC@LAC and CBC@LAC were 26, 42, and 27%, respectively. The intermediate products of 2,4-DCP degradation by immobilized laccase were p-phenol, p-benzoquinone and maleic acid.

Assessment of Potentially Toxic Elements Pollution and Human Health Risks in Polluted Farmland Soils around Distinct Mining Areas in China-A Case Study of Chengchao and Tonglushan.

This research study investigates the extent of heavy metal pollution and pollution trends in agricultural soil in mining areas during different time periods. A total of 125 soil samples were collected from two mining areas in China, the Chengchao iron mine and Tonglushan ancient copper mine. The samples were analyzed for various potentially toxic elements (PTEs). The index of geoaccumulation (Igeo), pollution index (Pi), potential ecological risk index (Eri), and hazard index (HI) were calculated to evaluate the pollution status of PTEs in the farmland around the two mining areas. The sources of PTEs were inferred by pollution distribution, and the pollution conditions of the two mining areas were compared. The results showed that the pollution of ancient copper mines was relatively severe. The main pollution elements were Cu, Cd, and As, and their average Pi values were 3.76, 4.12, and 1.84, respectively. These PTEs mainly came from mining and transportation. There are no particularly polluted elements in the Chengchao iron mine and the average Pi of all PTEs were classified as light pollution and had a wide range of sources. The findings suggest that the ancient copper mine, due to outdated mining techniques and insufficient mine restoration efforts, resulted in the spread and accumulation of PTEs in the soil over an extended period, making the farmland soil around the ancient copper mine more polluted compared to the Chengchao iron mine. In the two mining areas, there is no risk of cancer for adults and children. However, the RI values of Cr in adults and children are higher than 10-4, which indicates that the carcinogenic risk of Cr in these soils is very high. The non-carcinogenic effects of PTEs on the human body in the soil of ancient copper mine are also higher than that of the Chengchao iron mine.

New Porous Carbon Material Derived from Carbon Microspheres Assembled in Hollow Carbon Spheres and Its Application to Toluene Adsorption.

In this paper, a new porous carbon material adsorbent was prepared using carbon microspheres assembled in hollow carbon spheres (HCS) with a hydrothermal method. Transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy were used to characterize the adsorbents. It was found that the diameter of carbon microspheres derived from 0.1 mol/L glucose was about 130 nm, which could be inserted inside HCS (pore size was 370-450 nm). The increase in glucose concentration would promote the diameter of carbon microspheres (CSs), and coarse CSs could not be loaded in the mesopores or macropores of HCS. Thus, the C0.1@HCS adsorbent had the highest Brunauer-Emmett-Teller surface area (1945 m2/g) and total pore volume (1.627 cm3/g). At the same time, C0.1@HCS posed a suitable ratio of micropores and mesopores, which could provide adsorption sites and volatile organic compound diffusion channels. Moreover, oxygen-containing functional groups -OH and C═O in CSs were also introduced into HCS, and the adsorption capacity and regenerability performance of the adsorbents were improved. The dynamic adsorption capacity of C0.1@HCS for toluene reached 813 mg/g, and the Bangham model was more suitable for describing the toluene adsorption process. The adsorption capacity was stably kept above 770 mg/g after eight adsorption-desorption cycles.

Identification of prognostic immune-related lncRNA signature predicting the overall survival for colorectal cancer.

Long non-coding RNA (lncRNA) is an important regulator of gene expression and serves a fundamental role in immune regulation. The present study aimed to develop a novel immune-related lncRNA signature to assess the prognosis of patients with colorectal cancer (CRC). Transcriptome data and clinical information of patients with CRC were downloaded from The Cancer Genome Atlas (TCGA) and UCSC Xena platforms. Immune-related mRNAs were extracted from the Molecular Signatures Database (MSigDB), and the immune-related lncRNAs were identified based on correlation analysis. Then, univariate, Lasso and multivariate Cox regression were applied to construct an immune-related lncRNA signature, and CRC patients were divided into high- and low-risk groups according to the median risk score. Finally, we evaluated the signature from the perspectives of clinical outcome, clinicopathological parameters, tumor-infiltrating immune cells (TIICs), immune status, tumor mutation burden (TMB) and immunotherapy responsiveness. In total, 272 immune-related lncRNAs were identified, five of which were applied to construct an immune-related lncRNA signature. The signature divided patients with CRC into low- and high-risk groups, the prognosis of patients in the high-risk group were significantly poorer than those in low-risk group, and the results were further confirmed in external validation cohort. Furthermore, the high-risk group showed aggressive clinicopathological characteristics, specific TIIC and immune function status, and low sensitivity to immunotherapy. The immune-related lncRNA signature could be exploited as a promising biomarker for predicting the prognosis and immune status of patients with CRC.

Assessment soil cadmium and copper toxicity on barley growth and the influencing soil properties in subtropical agricultural soils.

Evaluation joint cadmium (Cd) and copper (Cu) phytotoxicity in wide range of subtropical agricultural soils is highly vital for phytoremediation of soils contaminated with Cd and Cu. In this study, barley root elongation assays were performed in 30 representative soils in response to single and combined Cd and Cu inhibition. The single Cd caused nearly 50% inhibition of barley root elongation, and Cu induced more than 50% inhibition in most soils. Mixed Cd + Cu caused significant inhibition on barley growth with average relative root elongation values of 20.0% and 30.4% in soil with a pH < 7 and pH > 7, respectively. An antagonistic interaction was evaluated in combined Cd + Cu toxicity, which was strong in soils containing low soluble Cu and Cd contents. Soil pH was the controlling factor in predicting single and mixed Cd and Cu phytotoxicity, which could explain 44% and 46% variation of single Cd and Cu toxicity, respectively. Soil organic carbon and effective cation exchange capacity were another important factor positively influencing metal toxicity, which further improved empirical prediction models accuracy, with determined coefficient (r2) values of 0.44-0.84. These results provide a theoretical basis for soils Cd and Cu pollution control.

H19 may regulate the immune cell infiltration in carcinogenesis of gastric cancer through miR-378a-5p/SERPINH1 signaling.

BACKGROUND: Increasing studies have indicated that noncoding RNA (ncRNA)-mediated competing endogenous RNA (ceRNA) network serves as a significant role in cancer progression, but the underlying regulatory mechanisms of which in gastric cancer (GC) remain largely unclear. METHODS: Based on Gene Expression Omnibus and The Cancer Genome Atlas datasets, potential biomarkers for GC were screened and validated by machine learning. Then, upstream regulatory ncRNA of potential biomarkers was identified to construct a novel ceRNA network in GC through means of stepwise reverse prediction and validation. Ultimately, tumor immune cell infiltration analysis was performed based on the EPIC algorithm. RESULTS: A total of 188 differentially expressed genes (DEGs) were screened, and three candidate diagnostic biomarkers (FAP, PSAPL1, and SERPINH1) for GC were identified and validated. Subsequently, H19 and miR-378a-5p were identified as upstream regulatory ncRNAs that could potentially bind SERPINH1 in GC. Moreover, Immune infiltration analysis revealed that each component in the ceRNA network (H19/miR-378a-5p/SERPINH1) was significantly correlated with the infiltration abundances of diverse tumor-infiltrating immune cells. CONCLUSIONS: H19 may regulate the immune cell infiltration in carcinogenesis of GC through miR-378a-5p/SERPINH1 signaling.

Degradation of 2,4-DCP by the immobilized laccase on the carrier of sodium alginate-sodium carboxymethyl cellulose.

In this paper, sodium alginate-sodium carboxymethyl cellulose (SA-CMC) composite material was used as a carrier, and sodium alginate-embedded laccase (Lac@SC) was prepared by traditional embedding method. After that, ethylene glycol diglycidyl ether (EGDE) and glutaraldehyde (GLU) were used as cross-linking agents, two different cross-linking-embedded co-immobilized laccases (Lac@SCG and Lac@SCE) were innovatively prepared, respectively, and then these immobilized laccases were characterized by SEM, FT-IR and XRD, and the stability of the three immobilized laccases was explored. In addition, the effects of different factors on the removal of 2,4-DCP by immobilized laccase were studied, and the degradation kinetic models of three immobilized laccases on 2,4-DCP were summarized, the possible degradation pathways of pollutants were also given. Experimental results showed that compared to free laccase, the pH stability, thermal stability and storage stability of immobilized laccase were greatly improved. These immobilized laccases could maintain high activity at pH3~6, 45~55 °C. Lac@SCG had the best storage stability. After 30 days of storage, the relative enzyme activity was still more than 40%. Lac@SC had good reusability, the relative enzyme activity was still more than 50% after 5 uses. In the degradation of 2,4-DCP, all three immobilized laccases showed good performance, when Lac@SCE was at pH5, 35 °C, 25 h, the removal rate of 2,4-DCP could reach 95.2%; When at 45 °C, Lac@SC had the highest degradation rate which reach to 94%; At 45 °C, the degradation rate of Lac@SCG reached 83.2%.

Adsorption and removal of direct red 31 by Cu-MOF: optimization by response surface.

Cu(PABA) is a Cu-based MOF material assembled from Cu2+ and the organic ligand p-aminobenzoic acid (PABA). Cu (PABA) was synthesized by a solvothermal method, characterized and applied to the adsorption of direct red 31 dye (DR-31). The effects of pH, DR-31 concentration and temperature on the adsorption performance of Cu(PABA) were investigated. The adsorption kinetics were analyzed by pseudo-first-order, pseudo-second-order and intra-particle diffusion models, and the adsorption equilibrium data was fitted by Langmuir and Freundlich isotherm models. The pseudo-first-order kinetics and Langmuir model satisfactorily described the adsorption kinetics and adsorption equilibrium, respectively. The maximum adsorption capacity of Cu(PABA) for DR-31 dye at room temperature was 1,244.8 mg/g, as calculated using the Langmuir adsorption isotherm model. By response surface methodology (RSM), the optimal adsorption was found at pH value of 10.9, DR-31 dye concentration of 216.6 mg/L, and temperature of 27 °C, and the removal rate was as high as 99.4%. Therefore, Cu(PABA) can be used as an efficient adsorbent for removing DR-31 dye from aqueous solution.

Immobilization of laccase on chitosan functionalized halloysite nanotubes for degradation of Bisphenol A in aqueous solution: degradation mechanism and mineralization pathway.

As a hazardous organic chemical raw material, Bisphenol A (BPA) has attracted a great deal of scientific and public attention. In this study, the chitosan functionalized halloysite nanotubes immobilized laccase (lac@CS-HNTs) was prepared by simultaneous adsorption-covalent binding method to remove BPA for the first time. We optimized the preparation of lac@CS-NHTs by controlling one-factor variable method and response surface methodology (RSM). The cubic polynomial regression model via Design-Expert 12 was developed to describe the optimal preparation conditions of immobilized laccase. Under the optimal conditions, lac@CS-NHTs obtained the maximum enzyme activity, and the enzyme loading was as high as 60.10 mg/g. The results of batch removal experiment of BPA showed that under the optimum treatment condition, the BPA removal rate of lac@CS-NHTs, FL and heat-inactivated lac@CS-NHTs was 87.31 %, 60.89 % and 24.54 %, respectively, which indicated that the contribution of biodegradation was greater than adsorption. In addition, the relative activity of lac@CS-NHTs dropped to about 44.24 % after 8 cycles of BPA removal, which demonstrated that lac@CS-NHTs have the potential to reduce costs in practical applications. Finally, the possible degradation mechanism and mineralization pathway of BPA were given via High-performance liquid chromatography (HPLC) analysis and gas chromatography-mass spectrometry (GC-MS) analysis.

Up-regulation of LINC00665 contributes to the progression of glioma and correlates with its MRI characteristics.

BACKGROUND: LncRNA LINC00665 partakes in controlling the malignant phenotype of cancer cells, but its role in glioma and the related regulatory mechanism remain uncertain. METHODS: RT-PCR was exploited to examine LINC00665 expression. The relationships among the LINC00665 expression, the clinicopathologic values and magnetic resonance imaging (MRI) characteristics of glioma were analyzed. The multiplication, movement, and aggressiveness of glioma cell lines were evaluated by CCK-8, EdU, and Transwell experiments after constructing LINC00665 overexpression and LINC00665 knockdown cell models. A dual-luciferase reporter gene experiment and RIP experiment were executed to validate the interactions between LINC00665 and miR-129-5p, and between miR-129-5p and HMGB1. Western blot and RT-PCR were conducted to find the impact of LINC00665 and miR-129-5p on HMGB1 expression. Nude mouse model was also constructed to examine the impact of LINC00665 on multiplication and aggressiveness of glioma cells in vivo. RESULTS: LINC00665 expression was markedly increased in glioma. High LINC00665 expression in glioma was closely linked to larger tumor diameter, higher pathologic grade, heterogeneous MRI signal of the tumor, increased peritumoral edema, and stronger MRI enhancement characteristics. LINC00665 overexpression facilitated the malignant behavior of glioma cells, while LINC00665 knockdown played the reverse role. Mechanistically, LINC00665 could decoy miR-129-5p, and indirectly increased HMGB1 expression. CONCLUSION: LINC00665 functions as an oncogenic lncRNA in glioma, to accelerate glioma progression by modulating miR-129-5p and increasing HMGB1 expression.

Evaluating risk of SARS-CoV-2 infection of the elderly in the public bus under personalized air supply.

In developing countries, public transportation is the first choice for the elderly because of its convenience and cheapness. The high density population of public transportation increases the risk of passengers contracting infectious diseases, so it is extremely critical to determine healthy transportation systems to safeguard the health of passengers. The propagation characteristics of droplets in the ZK-type public bus were studied by computational fluid simulation employing the Realizable k-ε turbulence model and discrete phase model. The modified Wells-Riley model was used to quantitatively assess the infection risk of SARS-CoV-2 spread by droplets on the elderly. The risk assessment shows that when the personalized air supply angle is 30°, the number of infected passengers is the least, reaching 14, which shows that the infection risk of passengers can be reduced through the design of personalized air supply angle. Regardless of the angle of the personalized air supply, the rear seats are in a low-risk area. Therefore, it's recommended that elderly passengers choose the rear seats of the public bus during the epidemic to prevent being infected. This study can provide a reference for healthy transportation systems to construct a healthy environment inside the public bus.

Circular RNA circTLK1 regulates dopaminergic neuron injury during Parkinson's disease by targeting miR-26a-5p/DAPK1.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is featured by the elevated loss of substantia nigra pars compacta dopaminergic neurons and the disruption of motor functions. Aberrant expression of circular RNAs (circRNAs) is correlated with neurodegenerative diseases. This study aimed to explore the role of circTLK1 in PD pathology. METHODS: MPTP-stimulated in vivo PD mouse model and MPP + and rotenone-induced in vitro PD model were established to investigate the function of circTLK1/miR-26a-5p/DAPK1 axis during dopaminergic neuron injury. The motor function of mice was evaluated by using the Rotarod test. Brain tissue damage was checked by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labeling. Cell viability, apoptosis, and cytotoxicity were evaluated by cell counting kit 8 (CCK-8), flow cytometry, and LDH activity. The interaction between circTLK1 and miR-26a-5p as well as miR-26a-5p and DAPK1 was detected by luciferase reporter assay. RESULTS: The expression of circTLK1 was notably elevated in in vitro and in vivo PD models. Knockdown of circTLK1 significantly improved cell viability, suppressed apoptosis and cytotoxicity, whereas inhibition of miR-16a-5p and overexpression of DAPK1 abolished these effects. MiR-26a-5p acts as a sponge of DAPK1 to mediate circTLK1 functions. Luciferase reporter gene assay confirmed the interaction between circTLK1 and miR-26a-5p as well as miR-26a-5p and DAPK1. CONCLUSION: Depletion of circTLK1 mitigates dopaminergic neuron injury in vitro and in vivo, via releasing miR-26a-5p to target DAPK1 expression. Targeting circTLK1 may contribute to improving PD therapy.

Construction of a Novel Immune-Related mRNA Signature to Predict the Prognosis and Immune Characteristics of Human Colorectal Cancer.

Background: Anti-cancer immunotherapeutic approaches have gained significant efficacy in multiple cancer types. However, not all patients with colorectal cancer (CRC) could benefit from immunotherapy due to tumor heterogeneity. The purpose of this study was to construct an immune-related signature for predicting the immune characteristics and prognosis of CRC. Methods: RNA-sequencing data and corresponding clinical information of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal (ImmPort). Then, we utilized univariate, lasso regression, and multivariate cox regression to identify prognostic IRGs and develop the immune-related signature. Subsequently, a nomogram was established based on the signature and other prognostic factors, and its predictive capacity was assessed by receiver operating characteristic (ROC) and decision curve analysis (DCA). Finally, associations between the signature and the immune characteristics of CRC were assessed. Results: In total, 472 samples downloaded from TCGA were divided into the training cohort (236 samples) and internal validation cohort (236 samples), and the GEO cohort was downloaded as an external validation cohort (122 samples). A total of 476 differently expressed IRGs were identified, 17 of which were significantly correlated to the prognosis of CRC patients. Finally, 10 IRGs were filtered out to construct the risk score signature, and patients were divided into low- and high-risk groups according to the median of risk scores in the training cohort. The high-risk score was significantly correlated with unfavorable survival outcomes and aggressive clinicopathological characteristics in CRC patients, and the results were further confirmed in the internal validation cohort, entire TCGA cohort, and external validation cohort. Immune infiltration analysis revealed that patients in the low-risk group infiltrated with high tumor-infiltrating immune cell (TIIC) abundances compared to the high-risk group. Moreover, we also found that the immune checkpoint biomarkers were significantly overexpressed in the low-risk group. Conclusion: The prognostic signature established by IRGs showed a promising clinical value for predicting the prognosis and immune characteristics of human CRC, which contribute to individualized treatment decisions.