We compared the immunogenicity of recombinant S. pneumoniae pneumolysin (rPly) when administered with and without Al(OH)3 adjuvant, and evaluated the protective properties of recombinant protein in the active defense experiment. It was shown that double immunization with rPly+Al(OH)3 increases the levels of IgG antibodies in comparison with the control (p<0.01), while triple immunization results in a more significant increase in IgG antibody levels (p<0.001). Double immunization with rPly without Al(OH)3 does not induce a significant increase in antibody levels in comparison with the control, while triple immunization results in a slight but significant increase in antibody levels (p<0.05). The active defense test proved the protective activity of rPly against S. pneumoniae serotype 3 at intranasal infection.

Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.

Protein-based subunit vaccines like RBD-Fc are promising tools to fight COVID-19. RBD-Fc fuses the receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein with the Fc region of human IgG1, making it more immunogenic than RBD alone. Earlier work showed that combining RBD-Fc with iNKT cell agonists as adjuvants improved neutralizing antibodies but did not sufficiently enhance T cell responses, a limitation RBD-Fc vaccines share with common adjuvants. Here we demonstrate that aluminum hydroxide combined with α-C-GC, a C-glycoside iNKT cell agonist, significantly improved the RBD-Fc vaccine\'s induction of RBD-specific T-cell responses. Additionally, aluminum hydroxide with α-GC-CPOEt, a phosphonate diester derivative, synergistically elicited more robust neutralizing antibodies. Remarkably, modifying αGC with phosphate (OPO3H2) or phosphonate (CPO3H2) to potentially enhance aluminum hydroxide interaction did not improve efficacy over unmodified αGC with aluminum hydroxide. These findings underscore the straightforward yet potent potential of this approach in advancing COVID-19 vaccine development and provide insights for iNKT cell-based immunotherapy.

To recycle aluminum (Al) from waterworks sludge resulting from polyaluminum chloride (PAC) used as coagulants, this study proposed an innovative strong acidic cation (SAC) exchange resin treatment strategy for Al separation from coexisting fulvic acid (FA) and heavy metals (HMs) in the H2SO4 leachate of PAC sludge. Fluorescence titration confirmed the breakdown of the Al-FA complex at pH 2.0, which facilitated Al separation from FA in the acidic leachate. The species distribution of the dissociated Al (i.e. Ala, Alb, and Alc) significantly influenced the adsorption of Al onto the cation exchange resin. The continuous release of H+ during the cation exchange reaction greatly promoted the transformation of dissociated Alc and Alb into Ala, thereby improving the adsorption of total Al. Moreover, the SAC resin column successfully separated the codissolved HMs from the Al in the leachate even at an influent pH of 2.8, which was attributed to the greater selectivity of the sulfonate groups on the cation exchange resin for free Al3+. The Al eluted from the exhausted resin with 1.1 M H2SO4 was collected as the recycled coagulant after proper pH adjustment. The Al adsorption capacity of the SAC resin decreased by approximately 5 % with each operation cycle and was regained by complete regeneration with 1.8 M H2SO4 after 5 cycles. Overall, the integrated efficiency of Al recovery from PAC sludge by H2SO4 acidification and SAC resin separation/purification reached 70.10 %. The recycled Al from sludge has a water treatment performance comparable to that of fresh PAC coagulant.

Clay-algae flocculation is a promising method to remove harmful algal blooms (HABs) in aquatic ecosystems. Many HAB-generating species, such as Microcystis aeruginosa (M. aeruginosa), a common species in lakes, produce toxins and harm the environment, human health, and the economy. Natural clays, such as bentonite and kaolinite, and modification of these clays have been applied to mitigate HABs by forming large aggregates and settling down. In this study, we aim to examine the impact of laponite, a commercially available smectite clay that is synthetic, transparent, compatible with human tissues, and degradable, on removing HABs. We compare the cell removal efficiencies (RE) of laponite, two natural clays, and their polyaluminum chloride (PAC)-modified versions through clay-algae flocculation experiments. Our results show that the optimum concentrations of laponite, bentonite, kaolinite, PAC-modified bentonite, and PAC-modified kaolinite to remove 80 % of the M. aeruginosa cells from the water column are 0.05 g/L, 2 g/L, 4 g/L, 2 g/L and 0.3 g/L respectively. Therefore, to achieve the same cell removal efficiency, the amount of laponite needed is 40 to 80 times less than bentonite and kaolinite, and 6 times less than PAC-modified kaolinite. We demonstrate that the superior performance of laponite clay is because of its smaller particle size, which increases the encounter rate between cells and clay particles. Furthermore, experiments using water samples from Powderhorn Lake confirmed laponite\'s effectiveness in mitigating HABs. Our price analysis also suggests that this commercially-available clay, laponite, can be used in the field at a relatively low cost.

Conjugation to carrier proteins is necessary for peptides to be able to induce antibody formation when injected into animals together with a suitable adjuvant. This is usually performed by conjugation in solution followed by mixing with the adjuvant. Alternatively, the carrier may be adsorbed onto a solid support followed by activation and conjugation with the peptide by solid-phase chemistry. Different reagents can be used for conjugation through peptide functional groups (-SH, -NH2, -COOH), and various carrier proteins may be used depending on the peptides and the intended use of the antibodies. The solid phase may be an ion exchange matrix, from which the conjugate can subsequently be eluted and mixed with adjuvant. Alternatively, the adjuvant aluminum hydroxide may be used as the solid-phase matrix, whereupon the carrier is immobilized and conjugated with peptide. The resulting adjuvant-carrier-peptide complexes may then be used directly for immunization.

Membrane fouling is a bottleneck issue that hindered the further application of ultrafiltration technology. To alleviate membrane fouling, coagulation-ultrafiltration (C-UF) process using polyaluminum chloride (PACl) and PACl-Al13 with high proportion of Al13O4(OH)247+ as coagulants, respectively, were investigated at various pH conditions. Results indicated that an increase in solution pH contributed to larger floc size and looser floc structure for both PACl and PACl-Al13. It was conducive to the formation of more porous cake, as evidenced by mean pore area and pore area distribution of cake, leading to lower reversible fouling. Furthermore, humic acid (HA) removal presented a trend of first increasing and then decreasing with the increase of pH. The optimal HA removal was achieved at pH 6 regardless of coagulant type, suggesting that the slightest irreversible fouling should be occurred at this point. Interestingly, the irreversible fouling with PACl coagulant achieved a minimum value at pH 9, while the minimal irreversible fouling with PACl-Al13 was observed at pH 6. We speculated that the cake formed by PACl could further intercept HA prior to UF process at alkaline pH. Furthermore, compared with PACl, PACl-Al13 had a stronger charge neutralization ability, thus contributing to more compact floc structure and higher HA removal at various pH conditions. By UF fractionation measurement, higher HA removal for PACl-Al13 was due to higher removal of HA with molecular weight less than 50 kDa.

This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary.

The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, i.e., HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.

This study presents the successful synthesis of Magnesium-aluminum layered double hydroxide composite phosphate-modified hydrothermal biochar for efficient removal of U(VI) from aqueous solutions. A novel synthesis approach involving phosphate thermal polymerization-hydrothermal method was employed, deviating from conventional pyrolysis methods, to produce hydrothermal biochar. The combination of solvent thermal polymerization technique with hydrothermal process facilitated efficient loading of layered double hydroxide (LDH) components onto the biochar surface, ensuring simplicity, low energy consumption and enhanced modifiability. Bamboo waste was utilized as the precursor for biochar, highlighting its superior green and sustainable characteristics. Additionally, this study elucidated the interactions between phosphate-modified hydrothermal biochar and LDH components with U(VI). Physicochemical analysis demonstrated that the composite biochar possessed a high surface area and abundant oxygen-containing functional groups. XPS and FTIR analyses confirmed the efficient adsorption of U(VI), attributed to chelation interactions between phosphate groups, magnesium hydroxyl groups, hydroxyl groups and U(VI), as well as the co-precipitation of U(VI) with multi-hydroxyl aluminum cations captured by LDH. The composite biochar reached adsorption equilibrium with U(VI) within 80 min and exhibited excellent fitting to the pseudo-second-order kinetic model and Langmuir model. Under conditions of pH = 4 and 298 K, it displayed significantly high maximum adsorption capacity of approximately 388.81 mg g⁻1, surpassing untreated biochar by 17-fold. The adsorption process was found to be endothermic and spontaneous and even after five consecutive adsorption-desorption cycles, the removal efficiency of U(VI) remained stable at 75.46%. These findings underscore the promising application prospects of Magnesium-aluminum layered double hydroxide composite phosphate-modified hydrothermal biochar in efficiently separating U(VI) from uranium-containing wastewater, emphasizing its environmental and economic value.