Combined effects of pH and dissolved organic matter on the availability of pharmaceuticals and personal care products in aqueous environment.

The interaction between pharmaceuticals and personal care products (PPCPs) with dissolved organic matter (DOM) can alter their bioavailability and toxicity. Nevertheless, little is known about how pH and DOM work together to affect the availability of PPCPs. This study investigated the impact of pH and DOM on the availability of seven PPCPs, namely Carbamazepine, Estrone, Bisphenol A, Testosterone Propionate, Triclocarban, 4-tert-Octylphenol and 4-n-Nonylphenol, using negligible depletion solid-phase microextraction (nd-SPME). The uptake kinetics of PPCPs by the nd-SPME fibers increased proportionally with DOM concentrations, likely due to enhanced diffusive conductivity in the unstirred water layer. At neutral pH, the partitioning coefficients of PPCPs for Humic Acid (log KDOC 3.87-5.25) were marginally higher than those for Fulvic Acid (log KDOC 3.64-5.11). Also, the log KDOC values correlated linearly with the log DOW (pH 7.0) values of PPCPs, indicating a predominant role for hydrophobic interactions in the binding of DOM and PPCPs. Additionally, specific interactions like hydrogen bonding, π-π, and electrostatic interactions occur for certain compounds, influenced by the polarity and spatial conformation of the compounds. For these ionizable PPCPs, the log DDOC values exhibit a strong dependence on pH due to the dual influence of pH on both DOM and PPCPs. The log DDOC values rose from pH 1.0 to 3.0, peaked at pH 5.0 to 9.0, and then (sharply) declined from 11.0 to 13.0. The reasons are that in strong acidic circumstances, the coiled and compressed shape of DOM inhibits the hydrophobic interaction, whereas in strong alkaline conditions, significant electrostatic repulsion reduces the sorption. This study reveals that the effects of DOM on the bioavailability of PPCPs are dependent on both pH and the specific compound involved.

Adversarial pair-wise distribution matching for remote sensing image cross-scene classification.

Remarkable achievements have been made in the field of remote sensing cross-scene classification in recent years. However, most methods directly align the entire image features for cross-scene knowledge transfer. They usually ignore the high background complexity and low category consistency of remote sensing images, which can significantly impair the performance of distribution alignment. Besides, shortcomings of the adversarial training paradigm and the inability to guarantee the prediction discriminability and diversity can also hinder cross-scene classification performance. To alleviate the above problems, we propose a novel cross-scene classification framework in a discriminator-free adversarial paradigm, called Adversarial Pair-wise Distribution Matching (APDM), to avoid irrelevant knowledge transfer and enable effective cross-domain modeling. Specifically, we propose the pair-wise cosine discrepancy for both inter-domain and intra-domain prediction measurements to fully leverage the prediction information, which can suppress negative semantic features and implicitly align the cross-scene distributions. Nuclear-norm maximization and minimization are introduced to enhance the target prediction quality and increase the applicability of the source knowledge, respectively. As a general cross-scene framework, APDM can be easily embedded with existing methods to boost the performance. Experimental results and analyses demonstrate that APDM can achieve competitive and effective performance on cross-scene classification tasks.

Downregulation of VEGFA accelerates AGEs-mediated nucleus pulposus degeneration through inhibiting protective mitophagy in high glucose environments.

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.

The Association Between Socioeconomic Factors at Diagnosis and Survival in Medulloblastoma: A Propensity Score-Matched Analysis and Population-Based Study.

BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The associations between socioeconomic statuses (SES) and survival outcomes of medulloblastoma remain unclear. The aim of this study was to develop a nomogram to predict medulloblastoma specific death (MBSD) and overall survival (OS) in patients with medulloblastoma, taking into account socioeconomic factors in patients with medulloblastoma. METHODS: We included patients diagnosed with MB between 1975 and 2016 from the Surveillance, Epidemiology, and End Results database. Propensity Score Matching (PSM) was performed to reduce selection bias. Multivariate cox proportional hazards model was used to assess SES impact and clinically relevant variables of medulloblastoma specific death and overall survival. Independent prognostic factors determined by multivariate analysis were used to construct nomograms. RESULTS: A total of 2660 patients were enrolled after matching. Study showed unemployed rate (MBSD, high level vs. low level, P = 0.020) (OS, high level vs. low level, P = 0.017), and marital status (OS, married vs unmarried/unknown, P = 0.029) were important factors affecting prognosis of medulloblastoma in male. Meanwhile, median household income (MBSD, quartile 1 vs. quartile 3, P = 0.047) (OS, quartile 1 vs. quartile 2, P = 0.017) (OS, quartile 1 vs. quartile 3, P = 0.014), residence (MBSD, urban vs. rural, P = 0.041), and insurance status (MBSD, insured vs. uninsured/unknown, P = 0.002)(OS, insured vs. uninsured/unknown, P = 0.001) were significant factors affecting prognosis of medulloblastoma in female. Through the calibration plot and C-index test, our nomogram was also of predictive significance. CONCLUSIONS: The unique features of MB have provided a scenario for analysis of the impact of racial, ethnic, gender, and socioeconomic factors. The current findings have important public health implications for achieving the goal of a healthy population. Given the known morbidity rates, long-term psychological, financial and medical burdens that these children and their families must bear, it is critical to identify and address these gaps.

Effects of nanoplastics and microplastics on the availability of pharmaceuticals and personal care products in aqueous environment.

Nanoplastics (NPs) and microplastics (MPs) could act as potential carriers for pharmaceuticals and personal care products (PPCPs) and alter the bioavailability in the aquatic environment. The effects of NPs and MPs of polystyrene (PS) and polyethylene (PE) on the availability of five PPCPs including carbamazepine, bisphenol A, estrone, triclocarban and 4-tert-octylphenol were investigated by negligible depletion solid- phase microextraction (nd-SPME). The freely dissolved concentrations of PPCPs decreased with the increasing concentrations of NPs/MPs. The overall order of the sorption coefficients (logKNP / logKMP) of PPCPs was as follows: 100 nm PS > 50 nm PS > 1 µm PS > 100 µm PS > 100 µm PE. Sorption of PPCPs by NPs was generally 1-2 orders of magnitude stronger than to MPs. The log KNP / log KMP values (3.16-5.21) increased with the log KOW (2.45-5.28) of PPCPs, however, linear correlation was only observed between log KMP and log KOW. The particle size, specific surface area, aggregation state as well as hydrophobicity played an important role in the sorption. Coexistence of fulic acid (FA) with NPs inhibited the sorption due to the fouling of FA on NPs. This study suggests that sorption of PPCPs to MPs/NPs could reduce bioavailability of PPCPs in the aquatic environment.

Delta-catenin attenuates medulloblastoma cell invasion by targeting EMT pathway.

Background: Medulloblastoma is the most common pediatric malignant tumor in central nervous system. Although its prognosis has been improved enormously by the combination treatments with surgery, radiotherapy, and chemotherapy, it still could progress via invasion and distant dissemination. We aimed to investigate molecular mechanisms of medulloblastoma invasion in the current work. Methods: The gene expression profile of medulloblastoma were analyzed based on the data deposited in Gene Expression Omnibus (GEO) and filtered according to brain specific proteins in the Uniprot. Delta-catenin was identified and further analyzed about its expression and roles in the prognosis of medulloblastoma patient. The function of delta-catenin on cell invasion and migration were investigated by transwell and wound healing assay. Whether delta-catenin participates in the epithelial-mesenchymal transition (EMT) regulated invasion was also studied. Results: Delta-catenin expression was highly upregulated in tumor tissues compared to normal tissues from medulloblastoma patients in five independent, nonoverlapping cohorts. Furthermore, delta-catenin expression level was upregulated in WNT subgroup, and significantly correlated with better prognosis, and associated with metastasis through GEO database analysis. Functional assays indicated that delta-catenin inhibited medulloblastoma cell invasion and migration through regulating the key factors of EMT pathway, such as E-cadherin and vimentin. Conclusion: Delta-catenin might be a positive predictor for prognosis of medulloblastoma patients, through attenuating medulloblastoma cell invasion by inhibiting EMT pathway.

The application of fluorescein sodium for the resection of medulloblastoma.

INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.

Flocculation of Chlorella vulgaris-induced algal blooms: critical conditions and mechanisms.

Algal blooms have posed great threats to livestocks and human health. Although flocculation is effective, its efficiency may hinder the direct application for algal blooms. In this study, critical (optimal) conditions and mechanisms for AlCl3, FeCl3, poly-aluminum chloride (PAC), chitosan, and polydimethyldiallylammonium chloride (PDADMAC)-induced flocculation of Chlorella vulgaris (C. vulgaris) were studied. Results identified the critical conditions which can cause flocculation efficiencies over 90% in 45 min for the five flocculants. Specifically, 4~10-mg/L doses of PDADMAC were proved to be appropriate for the treatment of C. vulgaris-induced algal blooms at pH 6.0~12.0. To probe the underlying mechanisms, functional groups involved in flocculation, zeta potential, and species distribution were analyzed during flocculation. FT-IR results indicated that N-H stretching in amine and C-H deformation in aliphatics were involved in algal flocculation with FeCl3, and C-H deformation played an important role with PDADMAC, PAC, and chitosan. For AlCl3, zeta potential and species distribution results suggested that charge neutralization and adsorption bridging were responsible for algal flocculation at pH 6~8. However, adsorption bridging and sweeping effects were the main mechanisms at pH >3 for FeCl3. The flocculation mechanisms for the rest of the three polymers were charge neutralization, adsorption bridging, and sweeping. Meanwhile, all the flocculation processes followed second-order kinetics. Strong linkages were found between the rate constant, fractal dimension, and flocculation efficiency (P < 0.05). The results of critical flocculation conditions and mechanisms indicated that PDADMAC was an excellent flocculant for C. vulgaris removing and recycling, especially in water bloom treatment.

Correlation of Tim-3 expression with chemokine levels for predicting the prognosis of patients with glioblastoma.

Glioblastoma (GBM) immunotherapy, which blocks the checkpoint inhibitor molecule T cell immunoglobulin domain and mucin domain-3 (Tim-3), has potential therapeutic applications. However, not all patients do benefit from the targeted therapy. This study aimed to explore Tim-3 expression correlated chemokine profiles and immune cell infiltration and investigate their potential as prognostic markers of glioblastoma (GBM) immunotherapy. We analyzed transcriptional data of GBM from TCGA database, to measure Tim-3 expression by R package DESeq2 analysis and observed differentially expressed genes in GBM samples with high Tim-3 expression levels. We also probed the relative gene enrichment pathways. Tim-3 expression was evident in biological processes including the recruitment of immune cells. We also identified some chemokines related to Tim-3 expression. The expression levels of CCL18, CXCL13 and CCL7 were significantly higher in GBM tissues with high Tim-3 expression than in GBM tissues with low Tim-3 expression. In addition, exploring the relationship between immune cell infiltration and Tim-3 expression suggested that Tim-3 expression was positively related to significant immune cell infiltration.

Complications following titanium cranioplasty compared with nontitanium implants cranioplasty: A systematic review and meta-analysis.

Decompressive craniectomy is widely used to treat medically refractory intracranial hypertension. There were still few studies focusing on the complications between titanium cranioplasty with non-titanium materials cranioplasty. Our systematic review and meta-analysis aimed to assess the complications following titanium cranioplasty and to make a comparison with nontitanium materials. A systematic review was used to review titanium cranioplasty characters in recent articles. A systematic literature review and meta-analysis were performed by using PubMed/MEDLINE, Scopus, the Cochrane databases and Embase for studies reporting on cranioplasty procedures that compared complication outcomes between titanium with non-titanium materials. The final 15 studies met inclusion criteria and represented 2258 cranioplasty procedures (896 titanium, 1362 nontitanium materials). Overall complications included surgical site infection, hematoma, implant exposure, seizure, cerebrospinal fluid leak, imprecise fitting. Titanium cranioplasty was associated with a significant decrease in overall complications rate (OR, 0.72; P = 0.007), hematoma rate (OR, 0.31; P = 0.0003) and imprecise fitting rate (OR, 0.35; P = 0.04). However, it also suggested that titanium cranioplasty can be greatly increased implant exposure rate (OR, 4.11; P < 0.00001). Our results confirmed the advantages of titanium cranioplasty in reducing complications including hematoma, imprecise fitting, and also suggested that clinicians should pay more attention to postoperative implant exposure. With new synthetic materials emerging, it would also be interesting to study the cost-effect and functional outcomes associated with cranioplasty materials.

Prognostic Value of the Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Patients With Medulloblastoma Undergoing Surgical Resection.

Background: The progression and metastasis of cancers are associated with systematic immune inflammation and nutritional dysfunction. The systemic immune-inflammation index and prognostic nutritional index (PNI) have shown a prognostic impact in several malignancies. Therefore, our study aimed to evaluate immune inflammation and nutritional index prognostic significance in patients with medulloblastoma (MB). Methods: We retrospectively analyzed 111 patients with MB between 2001 and 2021 at our institution. The optimal cutoff values for systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte counts ration (MLR), and PNI were evaluated with receiver operating characteristic (ROC) curve analysis. Clinical characteristics and SII, NLR, MLR, and PNI were tested with the Pearson's chi-squared test. The Kaplan-Meier survival curves and the Cox proportional hazards model were used to evaluate the effects of immune inflammation and nutritional index on overall survival (OS). Results: Receiver operating characteristic curve analysis determined the optimal SII, NLR, MLR, and PNI cutoff values of 2,278, 14.83, 0.219, and 56.5 that significantly interacts with OS and divided the patients into two groups. Comparative survival analysis exhibited that the high-SII cohort had significantly shorter OS (p = 0.0048) than the low-SII cohort. For the univariate analysis, the results revealed that preoperative hydrocephalus (p = 0.01), SII (p = 0.006), albumin-bilirubin score (ALBI) (p = 0.04), and coSII-PNI were predictors of OS. In the multivariate analysis, preoperative hydrocephalus (p < 0.001), ALBI (p = 0.010), SII (p < 0.001), and coSII-PNI as independent prognostic factors were significantly correlated with OS. Conclusion: The preoperative SII, ALBI, and coSII-PNI serve as robust prognostic biomarkers for patients with MB undergoing surgical resection.

Identification of a Twelve-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival for Medulloblastoma.

BACKGROUND: Medulloblastoma is the common pediatric malignant tumor with poor prognosis in cerebellum. However, MB is always with clinical heterogeneity. To provide patients with more clinically beneficial treatment strategies, there is a pressing need to develop a new prognostic prediction model as a supplement to the prediction outcomes of clinical judgment. MATERIALS AND METHODS: Four datasets of mRNA expression and clinical data were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and functionally enriched among GSE50161, GSE74195, GSE86574. Then we used STRING and Cytoscape to constructed and analyze protein-protein interaction network (PPI) and hub genes. Univariate cox regression analysis was performed to identify overall survival-related hub genes in an unique dataset from GSE85217 as train cohort. Lasso Cox regression model was used to construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve, univariate and multivariate Cox regression analysis were used to assess the prognostic capacity of the twelve-gene signature. A unique dataset from GSE85217 was downloaded to further validate the results. Finally, we established the nomogram by using the gene signature and validated it with ROC curve. Gene set enrichment analysis (GSEA) was carried out to further investigate its potential molecular mechanism. Besides, the twelve genes expression at the mRNA and protein levels was validated using external database such as Oncomine, cBioportal and HPA, respectively. RESULTS: A twelve-gene signature comprising FOXM1, NEK2, CCT2, ACTL6A, EIF4A3, CCND2, ABL1, SYNCRIP, ITGB1, NRXN2, ENAH, and UMPS was established to predict overall survival of medulloblastoma. The ROC curve showed good performance in survival prediction in both the train cohort and the validation cohort. The twelve-gene signature could stratify patients into a high risk and low risk group which had significantly different survival. Univariate and multivariate Cox regression revealed that the twelve-gene signature was an independent prognostic factor in medulloblastoma. Nomogram, which included twelve-gene signatures, was established and showed some clinical benefit. CONCLUSION: Our study identified a twelve-gene signature and established a prognostic nomogram that reliably predicts overall survival in medulloblastoma. The above results will help us to better analyze the pathogenesis and treatment of medulloblastoma in the future.