The development of highly efficient coagulants with broad pH adaptability remains a critical challenge in water treatment. In this study, a new type of polyaluminum chloride-manganese chloride composite coagulant (PAMCs) was synthesized, and the effect of manganese on changing the types of hydrolysis products and enhancing coagulation performance was systematically studied. A series of PAMCs with varying Al/Mn molar ratios and basicity (B = [OH[-]]/[M[3+]]) were prepared, and their interactions with humic acid (HA) were evaluated. Results demonstrated that PAMC2 (Al/Mn = 2:1, B = 2) exhibited superior HA removal efficiency under weakly alkaline conditions (pH 8-9), while maintaining stability over a broader pH range (pH 4-11). Mechanistic studies revealed that manganese incorporation primarily modified the speciation of hydrolysis products and the coordination structure of traditional flocs, favoring colloidal Al/Mn species rich in reactive hydroxyl groups (-OH) with stronger adsorption-complexation capabilities. Spectroscopic analyses confirmed that PAMC2 preferentially interacted with the -COOH and -OH functional groups of HA to form stable HA-metal complexes. Hydrolysis product characterization further indicated that Mn addition promoted the formation of colloidal aggregates, enhancing sweep flocculation and ligand exchange under alkaline conditions. Furthermore, the promising application potential of PAMCs was evaluated in treating industrial dye wastewater. However, it must be acknowledged that the residual manganese concentration in treated water exceeded the WHO drinking water standard (0.1 mg/L), which currently limited its applicability in potable water treatment. Nevertheless, this study provided a new cost-effective strategy for another important issue (efficient treatment of neutral/alkaline industrial wastewater) and underscores the role of Mn in tailoring hydrolysis reactivity and broadening pH adaptability.

The development of genetically engineered multivalent subunit vaccines is needed to provide protection against infections caused by Clostridium septicum and multiple types of Clostridium perfringens. In this study, a pET-32a(+) plasmid encoding the C. septicum α-toxin gene and the C. perfringens β-toxin gene was constructed; a positive clone was designated pET-32a-α-β1. This plasmid, along with pET-32a-α-β2-ε-previously engineered to express a C. perfringens α-β2-ε trivalent recombinant chimeric fusion protein-was transformed into Escherichia coli DE3 for recombinant protein expression after isopropyl-β-D-thiogalactopyranoside induction. Recombinant proteins α-β1 and α-β2-ε were purified, mixed at a protein concentration ratio of 1:1, and subsequently freeze-dried. The freeze-dried proteins were reconstituted with an aluminum hydroxide adjuvant and administered to sheep at various doses. Based on antibody titers and serum neutralization titers in immunized sheep, 0.2 mg of mixed protein was identified as the minimum immunization dose for the subunit vaccine. Toxin neutralization tests performed 21 days post-vaccination showed that sera from immunized sheep neutralized 10, 10, 27, and nine times the mouse lethal doses of C. perfringens types B, C, and D, and C. septicum toxins, respectively. All immunized sheep were protected against C. perfringens types B, C, and D, and C. septicum toxins, with a survival rate of 100%; the negative control group showed a survival rate of 0%. These encouraging findings provide a foundation for the development of novel subunit vaccines.

Background/Objectives: Gonorrhea remains one of the most prevalent sexually transmitted infections globally, with an estimated 82-87 million new infections annually and no licensed vaccine available. Antigenic variability and the lack of durable protective immunity following natural infection have been major obstacles to vaccine development. We previously developed an adjuvanted, formalin-inactivated whole-cell gonococcal microparticle (GC-MP) vaccine delivered by dissolving microneedles and demonstrated that it induced functional antibodies and enhanced bacterial clearance in murine models. Here, we evaluated this GC-MP microneedle platform in Rhesus macaques to provide proof-of-concept data in a relevant large-animal model and to compare different adjuvants. Methods:Rhesus macaques were allocated into five groups and vaccinated, and serum antigen-specific IgG and IgA responses were quantified by ELISA, with functional activity assessed by serum bactericidal assay. In parallel, the potency of delta-inulin-, aluminum-phosphate-, or aluminum-hydroxide-adjuvanted N. gonorrhoeae-loaded microparticles to activate dendritic cells was assessed in vitro via changes in surface expression of MHC I, MHC II, CD40, and CD80. Results: The serum from vaccinated primates demonstrated elevated gonococcal-specific IgG and IgA responses compared with naïve controls and measurable bactericidal activity against live, homologous N. gonorrhoeae strains. All adjuvanted formulations increased dendritic cell expression of MHC I, MHC II, CD40, and CD80. Conclusions: These findings indicate that an adjuvanted whole-cell inactivated gonorrhea vaccine delivered transdermally via microneedles elicits clearly elevated, relative to controls, functional antibody responses, supporting its advancement toward clinical evaluation.

Fluoride contamination in water sources poses significant risks to human health and ecosystems, necessitating effective treatment strategies. This study investigates the influence of calcium chloride (CaCl2) and the basicity of polyaluminum chloride (PAC) on fluoride removal using PAC-PDMDAAC coagulation. Through systematic jar tests, the effects of varying PAC basicity (0.5, 1.0, and 2.0) and CaCl2 addition sequences were examined under different fluoride concentrations (1.0, 3.0, and 10.0 mg/L). Results indicate that PAC with lower basicity (B = 0.5) exhibits superior fluoride removal efficiency, showing an increase of 20%-40% compared to PAC (B = 2.0), primarily due to the electro-neutralization mechanism of monomeric aluminum species (Ala). The introduction of PDMDAAC reduced the coagulation performance of PAC, especially at an initial fluoride concentration of 1 mg/L. The fluoride removal rate decreased from 80% to 57% at B = 0.5, from 91% to 62% at B = 1.0, and from 72% to 25% at B = 2.0. The order of adding CaCl2 affects the removal rate of fluoride, with the CaCl2 + PAC sequence outperforming the reverse sequence. The study highlights the importance of optimizing coagulant basicity and CaCl2 dosing order to enhance fluoride removal efficiency, providing valuable insights for water treatment processes. These findings contribute to the development of more efficient and cost-effective coagulation strategies for fluoride removal in water treatment plants.

The limited availability of safe and effective vaccine adjuvants remains a major bottleneck in modern vaccinology, particularly for inducing balanced and robust cellular and humoral immune responses. This study investigated the adjuvant potential of polysaccharides isolated from Paris mairei (PMM, 740 kDa) and Paris yunnanensis (PPM, 92 kDa). Structural analysis confirmed that both polysaccharides are primarily composed of a (1 → 4)-linked β-D-Man backbone with mannose residues partially acetylated at the O-2 or O-3 positions. However, only PMM effectively activated antigen-presenting cells (APCs). In combination with aluminum hydroxide (AH), PMM enhanced both IgG1 and IgG2a humoral responses and promoted Th1-associated cellular immune responses in Varicella-zoster virus glycoprotein E (VZV gE) models. Mechanistic studies revealed that AH functions as a local antigen depot, while soluble PMM accumulates in draining lymph nodes to activate APCs. PMM-induced macrophage activation involves TLR4 signaling, accompanied by NF-κB/MAPK activation and M1 polarization. This study identifies Paris-derived polysaccharides as promising innate immune modulators and provides a feasible polysaccharide-AH combination strategy for improving vaccine adjuvant design.

Divergent pulpal responses following dental trauma may manifest as inflammatory resorption in one tooth and pulp canal obliteration (PCO) in other affected teeth. When such changes occur in an immature tooth with an open apex, diagnosis and treatment planning become particularly challenging. This case report describes a traumatised maxillary right central incisor in a young male patient with non-perforating internal root resorption (RR), external inflammatory RR and pulp necrosis, while the maxillary right lateral and left central incisors exhibited PCO. Cone-beam CT allowed precise definition of lesion extent and supported a conservative treatment strategy comprising chemomechanical disinfection with calcium hydroxide, placement of a mineral trioxide aggregate apical barrier and thermoplastic obturation. At the 48-month follow-up, the tooth was asymptomatic and functional, with imaging evidence of periapical healing and arrest of resorption. The biologically based conservative approach resulted in sustained function, satisfactory aesthetics and overall patient satisfaction.

Abnormal tumor vasculature impedes T-cell migration and compromises immunotherapy. Conventional anti-angiogenic strategies fail to restore the endothelial barrier and adhesion molecules. This limitation hinders long-term therapeutic benefits. Therefore, simultaneously restoring vascular function and activating immunity is essential. Herein, a pH-responsive, salvianic acid A-loaded manganese-aluminum layered double hydroxide nanosystem (S-LDH) was developed for synergistic regulation. In the acidic tumor microenvironment, S-LDH degrades in situ to release salvianic acid A and manganese ions. Released salvianic acid A directly repairs endothelial junctions via the β-catenin/claudin-5 pathway, restoring vascular integrity to promote immune cell infiltration. Concurrently, released manganese ions induce oxidative stress and trigger ICD via Fenton-like reactions while amplifying the cGAS-STING pathway to promote dendritic cell maturation and cytotoxic T-cell responses. Furthermore, STING activation upregulates endothelial adhesion molecules, further facilitating T-cell infiltration. In a 4T1 murine breast cancer model, S-LDH increased CD8+ T-cell infiltration by 10.9-fold and CD4+ T-cell infiltration by 4.3-fold compared with free salvianic acid A, confirming that simultaneous vascular repair and immune activation overcome the endothelial barrier. This work establishes a strategy that repairs tumor endothelial integrity and upregulates adhesion molecules to overcome this limitation by enabling T-cell infiltration.

By 2050, surging global population will intensify food insecurity, making it imperative to develop innovative strategies that boost plant productivity. Plants are our core food supply. Engineered nanoparticles have emerged as promising growth stimulants; however, carbon nanotubes (CNTs), despite their efficacy, are inedible and pose eco-toxicity concerns that restrict their agrobiological deployment. Furthermore, conventional whole-tissue studies obscure individual cell responses, preventing precise characterization of nanoparticle-cell interactions. Here, we introduce magnesium-aluminium layered double hydroxide (MgAl-LDH) nanoparticles, which is a food-grade material derived from commercial antacid formulations, that outperformed CNTs in accelerating plant cell development. This enhancement is suggested to be associated with the presence of magnesium ions and the positively charged LDH surface architecture, although the detailed molecular mechanisms remain to be fully elucidated.

This study investigated 1235D aluminum alloys with varying Zr additions to elucidate how Zr content affects the alloy microstructure and corrosion resistance. The results showed that Al3Zr precipitates refined the grains by pinning grain boundaries. The 0.06% Zr alloy exhibited the finest grain structure, the lowest fraction of low-angle grain boundaries, the lowest geometrically necessary dislocation density, and the fewest microstructural defects susceptible to corrosion. Electrochemical and immersion corrosion tests indicated that the corrosion resistance followed the order 0.06% Zr > 0.12% Zr > 0.02% Zr. The 0.06% Zr alloy exhibited the highest polarization resistance and formed a dense, stable passive film that effectively hindered Cl[-] penetration, thereby minimizing matrix dissolution and the formation of loose hydroxide corrosion products. An insufficient Zr content provided limited grain refinement, whereas excessive Zr promoted precipitate agglomeration; both conditions intensified localized corrosion. Considering both microstructural evolution and corrosion behavior, 0.06% was identified as the optimal Zr addition for this alloy system. These findings provide a theoretical basis for optimizing the Zr content and improving the corrosion resistance of 1235D aluminum alloys in industrial production.

Normophosphatemic familial tumoral calcinosis (NFTC) is characterized by cutaneous calcifications with no metabolic disorders; it manifests in the first years of life; associated with mutations in SAMD9 gene. Chronic trauma and transient hyperphosphatemia play a leading role in calcification formation.Surgical treatment can remove calcifications, but it does not prevent recurrence and can cause complications. Various conservative therapy is used. Lowering of blood phosphate levels is considered a promising pathogenetic treatment method.We present a clinical case of a patient with NFTC associated with the homozygous variant p.E1200K in SAMD9. A characteristic feature of our patient is the presence of multiple calcifications not only in the areas of injury (limbs), but also in areas of acne (face), as well as particularly active progression of the disease during puberty. A reduction in calcification size was observed after one year of continuous hypophosphatemic therapy (aluminum hydroxide and sevelamer 800 mg). The effectiveness of this therapy is debatable and limited by both poor patient tolerability of sevelamer and poor adherence.This is the first description of a patient with molecularly confirmed NFTC in Russia. A precise diagnosis allowed us to clarify the pathogenetic mechanism of calcification formation and propose treatment options.

In previously completed Phase 1 and 2 clinical trials, a recombinant gE-Fc fusion protein subunit vaccine adjuvanted with aluminum hydroxide (called LZ901) demonstrated favorable safety profiles and elicited robust immune responses. This randomized, placebo-controlled, double-blind, phase 3 trial (ChiCTR2300076253) evaluated the efficacy and safety of LZ901 in adults ≥40 years. 26,018 participants received either two intramuscular doses of LZ901 (30-day interval; n = 13,010) or a placebo (30-day interval; n = 13,008). The primary objective was to assess herpes zoster risk within 12-months after LZ901 vaccination. During the follow-up period, 15 LZ901 recipients and 178 placebo recipients were confirmed positive for herpes zoster. Overall vaccine efficacy against herpes zoster was 91.6% (95% confidence interval, 86.3 to 95.3; p < 0.001); efficacy was higher in participants aged 40-69 years [93.9% (95% confidence interval, 89.1 to 97.0; p < 0.001)] than in participants aged ≥70 years [66.9% (95% confidence interval, 14.6 to 89.2; p = 0.016)]. Post-herpetic neuralgia occurred in 1 of 15 herpes zoster cases in the LZ901 group and in 24 of 187 herpes zoster cases in the placebo group, corresponding to a vaccine efficacy of 95.9% (95% confidence interval, 63.9 to 99.93; p < 0.001) against post-herpetic neuralgia. LZ901 recipients had more injection-site and systemic reactions within 7 days of vaccination compared to the placebo group; grade 3 reactions were comparably low in both the LZ901 and placebo groups (0.3% versus 0.4%, respectively). No serious adverse events or safety concerns associated with LZ901 were noted. LZ901 reduces the risk of herpes zoster in adults who were 40 years of age or older in 12 months, with a favorable safety profile.

An eco-friendly hybrid biohydrogel adsorbent, namely GK-SA/AlO(OH)-NiO (Gum Karaya-Sodium Alginate/ Aluminum oxide hydroxide-Nickel Oxide nanocomposite), was successfully synthesized via a green ionic gelation technique followed by Ca[2+] crosslinking-bead formation and subsequent thermal stabilization of the embedded nanoparticles. Characterization through FTIR, XRD, SEM, EDX, and BET surface analysis confirmed the successful integration of the biopolymer matrix and metal oxides. SEM micrographs revealed a highly porous, three-dimensional, and rough surface morphology ideal for mass transfer. Furthermore, BET analysis demonstrated a significant textural enhancement, where the specific surface area increased from ~42 m[2]/g for the pristine hydrogel to ~118 m[2]/g for the GK-SA/AlO(OH)-NiO composite. The batch adsorption performance was evaluated using aqueous solutions of anionic Congo red (CR) dye. Under optimized operational conditions (pH 5.0, dosage 0.2 g, and 25 °C), the composite exhibited an exceptional maximum monolayer adsorption capacity (qmax) of 298.6 mg/g within a rapid equilibrium time of 90 min. Equilibrium data were accurately represented by the Langmuir isotherm model, while the capture kinetics followed tightly to the pseudo-second-order model. The apparent activation energy was determined to be +42.9 k J.mol[-1], confirming that the interfacial uptake process is highly temperature-dependent and chemically accelerated. Mechanistic evaluations revealed that the efficient remediation process is governed by a synergistic combination of electrostatic attraction between the anionic dye and the protonated hybrid matrix, hydrogen bonding, n-π stacking, and robust surface complexation reactions. Overall, the successful synthesis of GK-SA/AlO(OH)-NiO nanocomposite offers a promising environmentally sustainable framework for highly efficient remediation of toxic CR dyes from industrial wastewater.

Adequate protection of adjuvanted vaccines against accidental freezing is of utmost importance to prevent loss of potency of the Drug Product, and in turn ensure adequate efficacy and safety when injected into patients. In this lessons learned we present two cases, at large- and small-scale manufacturing level, where a loss of potency was observed for an adjuvanted vaccine. By successful application of a shake-test protocol this loss of potency was traced back to atypical transport conditions, leading to accidental freezing of multiple drug product syringes. Controlled experiments show a consistent trend indicating faster settling with an increasing numbers of freeze-thaw cycles. Additionally, we observe an apparent inversely proportional relationship between the freezing speed and the settling rate. The observations further suggest that severe freeze-thaw damage, by for example slow freezing and/or multiple freeze-thaw cycles, can lead to reduced turbidity of the drug product right after resuspension, providing a clear signature of severe freeze-thaw damage. Finally, we show that inspection of the sedimentation layer thickness may provide semi-quantitative information on the severity of freeze-thaw damage. The cases presented in this lessons learned support the effectiveness of a shake test in a manufacturing setting as an additional tool to understand and investigate potential freezing impact during root cause investigations.