Degradation of ambroxol by UV/chloramine process: Kinetics, degradation pathway, and control of the risk of highly toxic disinfection by-products.

Ambroxol (AMB) is a commonly used bromine-containing organic compound in medical applications and has been frequently found in water environments, which might pose risks of forming brominated disinfection by-products (Br-DBPs) in water treatment systems. The degradation kinetics as well as the degradation mechanism of AMB in the UV/chloramine process were investigated in this study. It was determined that reactive chlorine species (RCS) and the reactive nitrogen species (RNS) were the dominant free radicals for AMB degradation. Debromination occurred mainly in the initial stage of the degradation process, with a debromination rate of 34.5% at 10 min. Four possible degradation pathways of AMB were proposed based on liquid chromatography mass spectrometry (LC-MS) analysis as well as density functional theory (DFT) calculations, meanwhile the ECOSAR model was used to predict the toxicity risk of AMB and its degradation intermediates. Furthermore, after assessing the formation of DBPs during the UV/chloramine pre-oxidation process and conducting a toxicity risk analysis based on the results, it has been verified that this method can effectively remove AMB while reducing the formation potential of DBPs in the water environment. This suggests that the UV/chloramine process shows promise for treating bromine-containing organic compounds in real-world water treatment applications.

Toxicity of Dibutyl phthalate (DBP) toward isolated human blood lymphocytes: Apoptosis initiated from intracellular calcium enhancement and mitochondrial/lysosomal cross talk.

Dibutyl phthalate (DBP) is a phthalate ester with wide application in industrial products, so human exposure can happen in workplaces and environment. Conflicting results have been acquired in researches which measured the influences of phthalates contact on immune responses in laboratory animals. Nevertheless, the straight influence of DBP on human lymphocytes and entire mechanisms of its effect against these cells continue to be unexplored. The major purpose of present research was to evaluate the mechanisms which lead to the DBP toxicity on human lymphocytes using accelerated cytotoxicity mechanisms screening (ACMS) technique. Cell viability was determined following12h incubation of lymphocytes with 0.05-1 mM DBP, and mechanistic parameters were assessed after 2, 4 and 6 h of lymphocyte treatment with ½ the IC5012h (0.3 mM), the IC5012h (0.6 mM) and twice the IC5012h (1.2 mM) of DBP. The IC5012 h of a chemical/toxicant is defined as concentration that kills 50 % of cells after 12 h of exposure. The results indicate that DBP exerts toxic effects on isolated human lymphocytes, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress. In this study, suppression of cytokines (IL2, INF-gamma and TNF-alpha) production and increase in intracellular calcium were also related to DBP induced lymphocyte toxicity.

Cell-free analysis reveals the role of RG/RGG motifs in DDX3X phase separation and their potential link to cancer pathogenesis.

The DEAD-box RNA helicase DDX3X is a multifunctional protein involved in RNA metabolism and stress responses. In this study, we investigated the role of RG/RGG motifs in the dynamic process of liquid-liquid phase separation (LLPS) of DDX3X using cell-free assays and explored their potential link to cancer development through bioinformatic analysis. Our results demonstrate that the number, location, and composition of RG/RGG motifs significantly influence the ability of DDX3X to undergo phase separation and form self-aggregates. Mutational analysis revealed that the spacing between RG/RGG motifs and the number of glycine residues within each motif are critical factors in determining the extent of phase separation. Furthermore, we found that DDX3X is co-expressed with the stress granule protein G3BP1 in several cancer types and can undergo co-phase separation with G3BP1 in a cell-free system, suggesting a potential functional interaction between these proteins in phase-separated structures. DDX3X and G3BP1 may interact through their RG/RGG domains and subsequently exert important cellular functions under stress situation. Collectively, our findings provide novel insights into the role of RG/RGG motifs in modulating DDX3X phase separation and their potential contribution to cancer pathogenesis.

Water Quality Trade-offs for Risk Management Interventions in a Green Building.

Premise plumbing water quality degradation has led to negative health impacts from pathogen outbreaks (e.g., Legionella pneumophila and non-tuberculous mycobacteria), as well as chronic effects from exposure to heavy metals or disinfection by-products (DBP). Common water quality management interventions include flushing, heat shock (thermal disinfection), supplemental disinfection (shock or super chlorination), and water heater temperature setpoint change. In this study, a Legionella pneumophila- colonized Leadership in Energy and Environmental Design (LEED) certified building was monitored to study health-relevant water quality changes before and after three controlled management interventions: (1) flushing at several points throughout the building; (2) changing the water heater set point; and (3) a combination of interventions (1) and (2) by flushing during a period of elevated water heater set point (incompletely performed due to operational issues). Microbial (culturable L. pneumophila, the L. pneumophila mip gene, and cATP) and physico-chemical (pH, temperature, conductivity, disinfectant residual, disinfection by-products (DBPs; total trihalomethanes, TTHM), and heavy metals) water quality were monitored alongside building occupancy as approximated using Wi-Fi logins. Flushing alone resulted in a significant decrease in cATP and L. pneumophila concentrations (p = 0.018 and 0.019, respectively) and a significant increase in chlorine concentrations (p = 0.002) as well as iron and DBP levels (p = 0.002). Copper concentrations increased during the water heater temperature setpoint increase alone to 140°F during December 2022 (p = 0.01). During the flushing and elevated temperature in parts of the building in February 2023, there was a significant increase in chlorine concentrations (p = 0.002) and iron (p = 0.002) but no significant decrease in L. pneumophila concentrations in the drinking water samples (p = 0.27). This study demonstrated the potential impacts of short term or incompletely implemented interventions which in this case were not sufficient to holistically improve water quality. As implementing interventions is logistically- and time-intensive, more effective and holistic approaches are needed for informing preventative and corrective actions that are beneficial for multiple water quality and sustainability goals.

Prenatal exposure to dibutyl phthalate contributes to erectile dysfunction in offspring male rats by activating the RhoA/ROCK signalling pathway.

Prenatal exposure to dibutyl phthalate (DBP) has been reported to cause erectile dysfunction (ED) in adult offspring rats. However, its underlying mechanisms are not fully understood. Previously, we found that DBP activates the RhoA/ROCK pathway in the male reproductive system. This study investigated how prenatal exposure to DBP activates the RhoA/ROCK signalling pathway, leading to ED in male rat offspring. Pregnant rats were stratified into DBP-exposed and NC groups, with the exposed group receiving 750 milligrams per kilogram per day (mg/kg/day) of DBP through gavage from days 14-18 of gestation. DBP exposure activated the RhoA/ROCK pathway in the penile corpus cavernosum (CC) of descendants, causing smooth muscle cell contraction, fibrosis, and apoptosis, all of which contribute to ED. In vitro experiments confirmed that DBP induces apoptosis and RhoA/ROCK pathway activation in CC smooth muscle cells. Treatment of DBP-exposed offspring with the ROCK inhibitor Y-27632 for 8 weeks significantly improved smooth muscle cell condition, erectile function, and reduced fibrosis. Thus, prenatal DBP exposure induces ED in offspring through RhoA/ROCK pathway activation, and the ROCK inhibitor Y-27632 shows potential as an effective treatment for DBP-induced ED.

Copy Number Variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Duffy-positive and Duffy-negative Ethiopians.

Recent evidence challenges the belief that Duffy-negative individuals are resistant to Plasmodium vivax due to lacking Duffy Antigen Receptor for Chemokines (DARC). Erythrocyte Binding Protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytes in vitro. Reticulocyte Binding Protein 2b (RBP2b) interactions with Transferrin Receptor 1 (TfR1) suggest involvement in Duffy-negative infections. Gene copy number variations (CNVs) in PvDBP1, PvEBP/DBP2, and PvRBP2b were investigated in Duffy-positive and Duffy-negative P. vivax-infected individuals from Ethiopia. Among Duffy-positive samples, 34% displayed PvDBP1 duplications (Cambodian-type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian-type. For PvEBP/DBP2 and PvRBP2b, Duffy-positive samples exhibited higher duplication rates (1-8 copies for PvEBP/DBP2, 1-5 copies for PvRBP2b 46% and 43% respectively) compared to Duffy-negatives (20.8% and 26% respectively). The range of CNVs was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding of P. vivax evolution in Duffy-negative Africans.

Indian ASD probands with 25(OH)D and vitamin D binding protein deficiency exhibited higher severity.

The severity of autism spectrum disorder (ASD) shows wide variations, though the reason remains unclear. Vitamin D (VitD) deficiency is considered a risk factor for ASD and its supplementation was reported to reduce symptom severity. Since VitD, either synthesized in the skin or absorbed from the food, is transported to the liver by the vitamin D binding protein (DBP), we have analyzed DBP genetic polymorphisms [rs7041 (A/C), rs4588 (G/T), and rs3755967 (C/T)] affecting DBP function [Case = 411; Control = 397], levels of plasma 25(OH)D and DBP [Case = 25; Control = 26], and DBP mRNA expression [Case = 74; Control = 44] in a group of Indo-Caucasoid ASD probands and neurotypical subjects. ASD probands with rs7041'CC', rs4588 'TT', and rs3755967 'TT' genotypes exhibited higher scores for a few traits. Scores for Imitation and Listening response were also higher in the presence of the "A-T" haplotype (rs7041-rs4588). Plasma 25(OH)D and DBP levels as well as DBP mRNA expressions were significantly lower in the ASD probands as compared to the neurotypical subjects. We infer that DBP deficiency, in the presence of risk genetic variants, could be one of the reasons for the reported 25(OH)D deficiency of the ASD probands.

The impact of PAC-loaded polymer membrane thickness on chloroform removal and comparison of solvent and thermal membrane regeneration methods.

Powdered activated carbon (PAC) has better adsorption performance than granular activated carbon (GAC) and is widely used in water purification. In most cases, PAC is dosed into water directly, then precipitated as sludge, and landfilled. In this study, PAC was mixed with a polymer and dissolved in dimethylformamide (DMF) solvent to form a PAC-loaded membrane, which was then tested for chloroform removal. The chloroform adsorption capacity of the PAC membrane increased with increasing membrane thickness because of higher carbon loading. However, regardless of membrane thickness, the flux of the PAC membranes was similar since flux resistance predominantly occurred at the top dense polymer surface. This dense surface can be removed by sandpaper polishing, where the adsorption capacity of the polished PAC membranes was 20% higher than the unpolished membranes because of more even distribution of feed water on the polished surface. Removal of the dense surface via polishing increased the flux by 97% to 130%, exceeding the flux of typical household carbon block filters. Using DMF to regenerate the membrane recovered 48% to 66% of the initial adsorption capacity. Thermal regeneration of the exhausted PAC membrane at 250°C was more effective than DMF regeneration (both in terms of cost and performance), with 83% to 94% PAC membrane regeneration efficiency over four regeneration recycles. After four thermal regeneration cycles, flux increased by 300% and the membrane became brittle because of thermal aging of the polymer, indicating that a total of 6 h of regeneration time (equivalent to three cycles in this study) was the limit for effective PAC membrane performance. PRACTITIONER POINTS: Powdered activated carbon was immobilized on a membrane to remove chloroform from water. Thicker membranes increased adsorption capacity but did not impact flux. Flux and capacity increased using polishing to remove the dense polymer surface and more evenly distribute flow across the membrane. Thermal regeneration of the membrane at 250°C was effective for up to three cycles and outperformed solvent-based regeneration. PAC-loaded filters are relevant for applications such as household carbon block filtration.

Indicator displacement-based colorimetric assay for dibutyl phthalate in pharmaceutical products with titanium(IV)-pyridylazo resorcinol (PAR).

Taking advantage of the competitive binding affinity towards Ti(IV) between 4-(2-pyridylazo) resorcinol (PAR) and phthalate, a simple indicator displacement (ID)-based colorimetric assay was designed for indirect determination of a well-known phthalic acid ester, dibutyl phthalate (DBP). The indicator PAR and Ti(IV) formed a purplish-red-colored Ti(IV)-PAR complex (λmax = 540 nm) at a 1:1 ratio. In the presence of pre-hydrolyzed DBP, colorless complex formation of phthalate ion (emerging from alkaline hydrolysis of DBP) with Ti(IV) resulted in a hypsochromic shift in absorbance maximum, accompanying a color change from purplish-red to yellowish-orange (λmax = 390 nm) by the release of PAR from Ti(IV)-PAR system. Based on this mechanism, the linear response range of the system for DBP was found to lie between 0.16 and 0.37 mmol L-1 with an experimental detection limit of 11.6 µmol L-1. The recommended Ti(IV)-PAR system was successfully applied to DBP-containing pharmaceutical products (as real sample) after a simple clean-up process for removing possible water-soluble interferents. The analytical results obtained from the recommended method (by applying the standard addition approach) and the reference liquid chromatography-tandem mass spectrometric (LC-MS/MS) method were statistically compared using DBP-extract of the drug samples. Consequently, a simple and selective colorimetric ID strategy was proposed for the analysis of DBP in pharmaceuticals for the first time.

The Characteristics of Adsorption of Di-n-Butyl Phthalate by Surface Sediment from the Three Gorges Reservoir.

Phthalic acid esters (PAEs), recognized as endocrine disruptors, are identified as predominant organic pollutants in the Three Gorges Reservoir (TGR). Di-n-butyl phthalate (DBP), a representative PAE, has been extensively studied for its sources, distribution and ecological risks. However, there are few studies on the adsorption of DBP by sediment from the TGR, and the adsorption characteristics of surface sediment on DBP are not clear. Therefore, based on the actual sediment contents and particle sizes in the TGR, the kinetics and isothermal adsorption characteristics of surface sediment on DBP were investigated in this study. The results showed that the equilibrium time was 120 min, the adsorption kinetics were more in line with the pseudo-second-order kinetic model, and the sediment in water from the Yangtze River exhibited a higher adsorption rate and maximum adsorption amount on DBP than that observed in deionized water. Additionally, a decrease in DBP adsorption was observed with increasing sediment content, while sediment particle size and specific surface area had a slight influence. Analysis using SEM, TGA and FTIR revealed that organic matter on the sediment surface significantly contributed to DBP adsorption. This study contributes valuable insights into the adsorption characteristics of DBP by the surface sediment from the TGR, providing a scientific foundation for understanding the migration and transformation of DBP in this critical reservoir in China.

An Improved Helper Plasmid Containing Deletions Within the E4 and E2a Genes Results in Increased Adeno-Associated Virus Productivity.

The use of a helper plasmid to replace adenovirus infection for adeno-associated virus (AAV) manufacturing has been common practice for decades. Adenovirus E4, E2a, and VA RNA genes are sufficient to support efficient AAV replication. In an effort to ensure that all transfected DNA has a functional role in AAV production, deletions were introduced to the E4 and E2a genes to determine if any portions were dispensable. Although a 900 bp deletion in the E2a intron did not have an impact, the removal of open reading frames (orf) 1-4 from the E4 gene resulted in a doubling of AAV productivity. The E4Δorf1-4 deletion was associated with a reduction in E4orf6 transcripts, along with an increase in Rep and Cap transcripts and protein levels, which corresponded to increased AAV productivity in crude lysate. The final product of these studies was a helper plasmid, termed OXB-Helper_3, that is >3.4 kb smaller than the original control plasmid and resulted in ∼2× improvement in vector genome productivity across multiple capsid serotypes, genome designs, and transfection platforms.

Evaluation of electrokinetic-assisted phytoremediation efficiency of dibutyl phthalate contaminated soil by maize (Zea mays L.) under different electric field intensities.

The excessive accumulation of dibutyl phthalate (DBP) in soil poses a serious threat to soil ecosystems and crop safety production. Electrokinetic-assisted phytoremediation (EKPR) has been considered as a potential technology for remediating organic contaminated soils. In order to investigate the effect of different electric fields on removal efficiency of DBP, three kinds of electric fields were set up in this study (1 V·cm-1, 2 V·cm-1 and 3 V·cm-1). The results showed that 59 % of DBP in soil was removed by maize (Zea mays L.) within 20 d in low-intensity electric field (1 V·cm-1), and the accumulation of DBP in maize tissues decreased significantly compared to the non-electrified treatment group. Interestingly, it could be observed that the low-intensity electric field could maintain ion homeostasis and improve the photosynthetic efficiency of the plant, thereby relieving the inhibition of DBP on plant growth and increasing the chlorophyll content (94.1 %) of maize. However, the removal efficiency of DBP by maize decreased significantly under the medium-intensity (2 V·cm-1) and high-intensity electric field (3 V·cm-1). Moreover, the important roles of soil enzyme and rhizosphere bacterial community in low-electric field were also investigated and discussed. This study provided a new perspective for exploring the mechanism of removing DBP through EKPR.

Polyamide 6 microplastics as carriers led to changes in the fate of bisphenol A and dibutyl phthalate in drinking water distribution systems: The role of adsorption and interfacial partitioning.

Microplastics (MPs) co-exist with plastic additives and other emerging pollutants in the drinking water distribution systems (DWDSs). Due to their strong adsorption capacity, MPs may influence the occurrence of additives in DWDSs. The article investigated the occurrence of typical additives bisphenol A (BPA) and dibutyl phthalate (DBP) in DWDSs under the influence of polyamide 6 (PA6) MPs and further discussed the partitioning of BPA/DBP on PA6s, filling a research gap regarding the impact of adsorption between contaminants on their occurrence within DWDSs. In this study, adsorption experiments of BPA/DBP with PA6s and pipe scales were conducted and their interaction mechanisms were investigated. Competitive adsorption experiments of BPA/DBP were also carried out with site energy distribution theory (SEDT) calculations. The results demonstrated that PA6s might contribute to the accumulation of BPA/DBP on pipe scales. The adsorption efficiencies of BPA/DBP with both PA6s and pipe scales were 26.47 and 2.61 times higher than those with only pipe scales. It was noteworthy that BPA had a synergistic effect on the adsorption of DBP on PA6s, resulting in a 26.47 % increase in DBP adsorption. The article provides valuable insights for the compounding effect of different types of additives in water quality monitoring and evaluation.

Disinfection by-product formation potential in response to variability in dissolved organic matter and nutrient inputs: Insights from a mesocosm study.

Changes in rainfall patterns driven by climate change affect the transport of dissolved organic matter (DOM) and nutrients through runoff to freshwater systems. This presents challenges for drinking water providers. DOM, which is a heterogeneous mix of organic molecules, serves as a critical precursor for disinfection by-products (DBPs) which are associated with adverse health effects. Predicting DBP formation is complex due to changes in DOM concentration and composition in source waters, intensified by altered rainfall frequency and intensity. We employed a novel mesocosm approach to investigate the response of DBP precursors to variability in DOM composition and inorganic nutrients, such as nitrogen and phosphorus, export to lakes. Three distinct pulse event scenarios, mimicking extreme, intermittent, and continuous runoff were studied. Simultaneous experiments were conducted at two boreal lakes with distinct DOM composition, as reflected in their color (brown and clear lakes), and bromide content, using standardized methods. Results showed primarily site-specific changes in DBP precursors, some heavily influenced by runoff variability. Intermittent and daily pulse events in the clear-water mesocosms exhibited higher haloacetonitriles (HANs) formation potential linked to freshly produced protein-like DOM enhanced by light availability. In contrast, trihalomethanes (THMs), associated with humic-like DOM, showed no significant differences between pulse events in the brown-water mesocosms. Elevated bromide concentration in the clear mesocosms critically influenced THMs speciation and concentrations. These findings contribute to understanding how changing precipitation patterns impact the dynamics of DBP formation, thereby offering insights for monitoring the mobilization and alterations of DBP precursors within catchment areas and lake ecosystems.

Structure-dependent degradation of phthalate esters with persulfate oxidation activated by thermal in soil.

Phthalate esters (PAEs) have become one of the most concerned emerging organic pollutants in the world, due to the toxicity to human health, and hard to remove it efficiently. In this study, the degradation performance of DBP and DEHP in the soil by water bath heating activated sodium persulfate (PS) method under different factors were studied, in which the degradation rate of DBP and DEHP were improved with the increasing of temperature, PS concentration and water/soil ratio, and higher diffusion efficiency treatments methods, due to the improved mass transfer from organic phase to aqueous media. However, the degradation rate of DEHP was much lower than that of DBP, because DEHP in the soil was more difficult to contact with SO4•- for reaction on soil surface, and the degradation rate of PAEs in soil was significantly lower than that in water. Redundancy analysis of degradation rate of DBP and DEHP in water demonstrated that the key factors that determine the degradation rate is time for DBP, and cosolvent dosage for DEHP, indicating that the solubility and diffusion rate of PAEs from soil to aqueous are predominance function. This study provides comprehensive scenes in PAEs degradation with persulfate oxidation activated by thermal in soil, reveal the difference of degradation between DBP and DEHP is structure-dependent. So that we provide fundamental understanding and theoretical operation for subsequent filed treatment of various structural emerging pollutants PAEs contaminated soil with thermal activated persulfate.

Identification of sensitive endpoints for the assessment of phthalates-induced reproductive and developmental toxicity: A literature mining study.

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 µg/kg/day and 36 µg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.

Exploring the genetic diversity pattern of PvEBP/DBP2: A promising candidate for an effective Plasmodium vivax vaccine.

Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which the design of a multivalent vaccine stands out. However, the effectiveness of this strategy has been hindered, among other reasons, by the genetic diversity observed in parasite antigens. In Plasmodium vivax, the Erythrocyte Binding Protein (PvEBP, also known as DBP2) is an alternate ligand to Duffy Binding Protein (DBP); given its structural resemblance to DBP, EBP/DBP2 is proposed as a promising antigen for inclusion in vaccine design. However, the extent of genetic diversity within the locus encoding this protein has not been comprehensively assessed. Thus, this study aimed to characterize the genetic diversity of the locus encoding the P. vivax EBP/DBP2 protein and to determine the evolutionary mechanisms modulating this diversity. Several intrapopulation genetic variation parameters were estimated using 36 gene sequences of PvEBP/DBP2 from Colombian P. vivax clinical isolates and 186 sequences available in databases. The study then evaluated the worldwide genetic structure and the evolutionary forces that may influence the observed patterns of genetic variation. It was found that the PvEBP/DBP2 gene exhibits one of the lowest levels of genetic diversity compared to other vaccine-candidate antigens. Four major haplotypes were shared worldwide. Analysis of the protein's 3D structure and epitope prediction identified five regions with potential antigenic properties. The results suggest that the PvEBP/DBP2 protein possesses ideal characteristics to be considered when designing a multivalent effective antimalarial vaccine against P. vivax.

Neurotoxicity of dibutyl phthalate in zebrafish larvae: Decreased energy acquisition by neurons.

This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 µg/L and 10 µg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 h of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy. Further comprehensive biochemical analyses and RNA-Seq, validated by RT-qPCR, glutamate metabolism and PPAR signaling pathway were significantly enriched in the DBP stress group, this may be the main reason for the disruption of glycolysis/gluconeogenesis processes and the reduction of energy substrates for the astrocyte-neuron lactate shuttle (ANLS). In addition, the DBP-exposed group showed aberrant activation of endoplasmic reticulum (ER) stress signaling pathway, which may be related to ROS as well as neuronal apoptosis and autophagy. In conclusion, DBP-induced neurotoxicity may be the combined result of insufficient neuronal energy acquisition, damage to mitochondrial structure, apoptosis and autophagy. These results provide a theoretical basis for understanding the neurotoxic effects of DBP.

Vaccines and monoclonal antibodies: new tools for malaria control.

SUMMARYMalaria remains one of the biggest health problems in the world. While significant reductions in malaria morbidity and mortality had been achieved from 2000 to 2015, the favorable trend has stalled, rather significant increases in malaria cases are seen in multiple areas. In 2022, there were 249 million estimated cases, and 608,000 malaria-related deaths, mostly in infants and children aged under 5 years, globally. Therefore, in addition to the expansion of existing anti-malarial control measures, it is critical to develop new tools, such as vaccines and monoclonal antibodies (mAbs), to fight malaria. In the last 2 years, the first and second malaria vaccines, both targeting Plasmodium falciparum circumsporozoite proteins (PfCSP), have been recommended by the World Health Organization to prevent P. falciparum malaria in children living in moderate to high transmission areas. While the approval of the two malaria vaccines is a considerable milestone in vaccine development, they have much room for improvement in efficacy and durability. In addition to the two approved vaccines, recent clinical trials with mAbs against PfCSP, blood-stage vaccines against P. falciparum or P. vivax, and transmission-blocking vaccine or mAb against P. falciparum have shown promising results. This review summarizes the development of the anti-PfCSP vaccines and mAbs, and recent topics in the blood- and transmission-blocking-stage vaccine candidates and mAbs. We further discuss issues of the current vaccines and the directions for the development of next-generation vaccines.

Association of Pre-PCI Blood Pressure and No-Reflow in Patients with Acute ST-Elevation Coronary Infarction.

Background: Previous studies have established blood pressure (BP) as a pivotal factor influencing no-reflow following primary percutaneous coronary intervention (PCI) in patients with ST-elevation acute coronary infarction (STEMI). However, no relevant study has been conducted to investigate the optimal range of BP associated with the lowest risk of no-reflow among STEMI patients so far. Therefore, our objective was to evaluate the association between pre-PCI BP and the occurrence of no-reflow in patients with STEMI. Method: We included 1025 STEMI patients undergoing primary PCI. The BP pre-PCI was categorized into 20-mmHg increments. Logistic models were employed to assess the association of no-reflow with systolic blood pressure (SBP) or diastolic blood pressure (DBP). Three sensitivity analyses were conducted to further confirm the robustness of the association between blood pressure and no-reflow. Results: SBP or DBP exhibited a U-shaped curve association with no-reflow. No-reflow was higher in patients with lower SBP (<100 mmHg) (adjusted hazard ratio (OR) 3.64, 95% confidence interval (CI) 1.84,7.21; p < 0.001) and lower DBP (<60 mmHg) (OR 3.28, 95% CI 1.63,6.49; p < 0.001) [reference: 120 ≤SBP <140; 80 ≤DBP <100 mmHg], respectively. Furthermore, no-reflow was higher in patients with higher SBP (≥160 mmHg) (OR 2.07, 95% CI 1.27,3.36; p = 0.003) and DBP (≥100 mmHg) (OR 3.36, 95% CI 2.07,5.46; p < 0.001), respectively. The results of sensitivity analyses were consistent with the above findings. Conclusion: Maintaining a pre-PCI SBP within the range of 120 to 140 mmHg and a DBP within the range of 80 to 100 mmHg may be confer benefits to patients with STEMI in no-reflow.