Unraveling the characteristics of dissolved organic matter removed by aluminum species based on FT-ICR MS analysis.

Given the complexity of dissolved organic matter (DOM) and its interactions with coagulant chemicals, the mechanisms of DOM removal by aluminum (Al) coagulants remains a significant unknown. In this study, six test waters containing DOM with molecular weight (MW, <1 kDa, 1-10 kDa and >10 kDa) and hydrophobicity (hydrophilic, transphilic and hydrophobic) were prepared and coagulated with Al0, Al13 and Al30. The molecular-level characteristics of DOM molecules that were removed or resistant to removal by Al species were analyzed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed that at the molecular level, saturated and reduced tannins and lignin-like compounds containing abundant carboxyl groups exhibited higher coagulation efficiency. Unsaturated and oxidized lipids, protein-like, and carbohydrates compounds were relatively resistant to Al coagulation due to their higher polarity and lower content of carboxyl groups. Al13 removed molecules across a wider range of molecular weights than Al0 and Al30, thus the DOC removal efficiency of Al13 was the highest. This study furthers the understanding of interactions between Al species and DOM, and provides scientific insights on the operation of water treatment plants to improve control of DOM.

Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma.

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.

Radium-223 therapy for metastatic castration-resistant prostate cancer: survival benefit when used earlier in the treatment pathway.

BACKGROUND: Radium-223 dichloride (Ra-223) therapy improves overall survival in bony metastatic castration-resistant prostate cancer (mCRPC) patients. Recent guidance change recommends Ra-223 following at least two prior therapies for mCRPC. We evaluated how this change affects overall survival and the optimal timing of Ra-223 in the mCRPC treatment pathway. METHODS: Retrospective analysis of all mCRPC patients receiving Ra-223 therapy at a single UK centre over a 70-month period. Overall survival, number of prior lines of therapy commenced before Ra-223 initiation and number of Ra-223 therapy cycles completed were identified. RESULTS: One hundred ninety-one mCRPC patients received Ra-223 therapy during the study period. One hundred twenty-one (63%) received one prior therapy (group 1) and 70 (37%) received two prior therapies (group 2). Median survival in group 1 was significantly improved, compared to group 2 (448 days vs. 341 days (P = 0.03). Subgroup analysis of 111/191 (58%) patients that completed the recommended six Ra-223 therapy cycles showed additional improved survival. Median survival in group 1 was incrementally significantly improved, compared to group 2 within these patients (665 days vs. 552 days; P = 0.05). There was no difference in the number of patients completing the recommenced six cycles of therapy between the groups [72/121 (59%) vs. 39/70 (56%); P = 0.61]. CONCLUSION: We found a significant survival benefit when Ra-223 was used earlier in the mCRPC treatment pathway, with additional survival advantage seen in those patients completing all six Ra-223 cycles. Our results support the use of Ra-223 earlier in the treatment pathway.

Disinfection by-product formation during UV/Chlorine treatment of pesticides in a novel UV-LED reactor at 285 nm and the mitigation impact of GAC treatment.

The UV/Chlorine process has gained attention in recent years due to the high quantum yield and absorbance of the chlorine species. However, there are still many unknowns around its application as a treatment for drinking water. The potential for the formation of disinfection by-products (DBPs) is one of them. There are no studies reporting on the formation of trihalomethanes (THMs) or haloacetic acids (HAAs) in complex matrices, such as real source waters, at UV wavelengths tailored to the UV/Chlorine process, which has been possible thanks to the development of light emitting diodes (LEDs). In addition, consideration of mitigation measures that might be needed after UV/Chlorine treatment for full scale application have not been previously reported. Specifically, the novelty of this work resides in the use of an innovative reactor using UV-LEDs emitting at 285 nm for the removal of three pesticides (metaldehyde, carbetamide and mecoprop), the evaluation of THM, HAA and bromate formation in real water sources by UV/Chlorine treatment and the mitigation effect of subsequent GAC treatment. A new parameter, the applied optical dose (AOD), has been defined for UV reactors, such as the one in the present study, where the irradiated volume is non-uniform. The results showed the feasibility of using the UV/Chlorine process with LEDs, although a compromise is needed between pH and chlorine concentration to remove pesticides while minimising DBP formation. Overall, the UV/Chlorine process did not significantly increase THM or HAA formation at pH 7.9-8.2 at the studied wavelength. At acidic pH, however, THM formation potential increased up to 30% after UV/Chlorine treatment with concentrations up to 60 µg/L. HAA formation potential increased between 100 and 180%, although concentrations never exceeded 35 µg/L. In all cases, GAC treatment mitigated DBP formation, reducing THM formation potential to concentrations between 3 and 16 µg/L, and HAA formation potential between 4 and 30 µg/L.

Estimation of some trace metal pollutants in River Atuwara southwestern Nigeria and spatio-temporal human health risks assessment.

Over twenty thousand persons rely on water from Atuwara River for drinking and other domestic purposes, hence the need to ascertain the human health risk inherent in such practice. Seventy-two water samples were collected from River Atuwara during the dry and wet seasons of 2018, and the concentration of heavy metals (Pb, As, Ni, Cr, Zn, Cu, and Cd) were measured using ICP-OES. A newly developed human health risk assessment method, HHRISK code was used to estimate the health risks associated with consumption of water from Atuwara River. Results obtained revealed that the concentration of heavy metals in the river was as follows: Cd < Ni < Pb < Cr < Cu < As < Zn in the wet season and Cd < Pb < Ni < Cu < Cr < As < Zn during the dry season. Principal component analysis suggested that industrial effluents, agricultural activities and base-rock interaction are responsible for pollution of Atuwara River. The cumulative hazard index (HIcum) obtained was 678.0 ±â€¯36.8 (for adult) and 1392.0 ±â€¯132 (for child) for non-carcinogenic risks. A cumulative carcinogenic risk (CRcum) of 1.01E-1±5.26E-3 and 4.96E-2±5.05E-3 was obtained for adult and children respectively, suggesting that up to 1 in 10 adults and 1 in 20 children may suffer from cancer over their lifetime as a result of consumption and exposure to water from River Atuwara. These results highlight the fact that unavailability of safe drinking water in many parts of the world remains a real and persistent risk which must be tackled.