A new pepper allergen Zan b 1.01 of 2S albumins: Identification, cloning, characterization, and cross-reactivity.

BACKGROUND: Zanthoxylum bungeanum (Sichuan pepper; in Chinese) is used as a spice worldwide and is a potentially life-threatening allergenic food source, as first reported by our team in 2005. However, its allergen components are unknown. OBJECTIVE: We aim to identify and characterize its major allergen and determine its cross-reactivities with citrus seeds, pistachios, and cashew seeds. METHODS: Ionic exchange and molecular exclusion chromatography were used to isolate the protein components from Sichuan pepper seed. A protein fraction was characterized by SDS-PAGE, analytical ultracentrifugation, mass spectrometry, and circular dichroism spectroscopy. The coding region of it was amplified from the genome. ELISA and competitive ELISA assays were used to investigate the allergenicity and cross-reactivity of allergens. RESULTS: This protein allergen was around 14 kDa. It was a 2S albumin similar to an α-Amylase inhibitor (AAI) domain-containing protein of Citrus sinensis. Circular dichroism spectroscopy showed its thermal stability was high. A 303 bps DNA sequence of the AAI domain was cloned from the genome of the Sichuan pepper. Competitive ELISA assays showed positive cross-reactivities between this allergen and citrus seeds, pistachios, and cashew seeds. CONCLUSION: A major allergen of around 14 kDa from Sichuan pepper seed was confirmed, which belongs to the 2S albumin of plant seed storage proteins. Based on the nomenclature of the IUIS Subcommittee for Allergen Nomenclature, this allergen is designated as Zan b 1.01. The cross-reactivities were demonstrated between Zan b 1.01 and citrus seeds, pistachios, and cashew seeds.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.

Direct bilirubin: A predictor of hematoma expansion after intracerebral hemorrhage.

BACKGROUND: Previous evidence demonstrated that several biomarkers involved in the pathological process of coagulation/hemostasis dysfunction, impairment of brain vascular integrity and inflammation are associated with hematoma expansion (HE) after intracerebral hemorrhage (ICH). We aimed to explore whether there were unreported laboratory biomarkers associated with HE that were readily and commonly available in clinical practice. METHODS: We retrospectively analyzed consecutive acute ICH patients from 2012 to 2020 with admission laboratory tests and baseline and follow-up computed tomography (CT) scans. Univariate and multivariate regression analyses were used to evaluate associations between conventional laboratory indicators and HE. The results were verified in a prospective validation cohort. The relationship of candidate biomarker and 3-month outcomes was also investigated and mediation analysis was undertaken to determine causal associations among candidate biomarker, HE and outcome. RESULTS: Of 734 ICH patients, 163 (22.2%) presented HE. Among the included laboratory indicators, higher direct bilirubin (DBil) was associated with HE (adjusted odds ratio [OR] of per 1.0 µmol/L change 1.082; 95% confidence interval [CI] 1.011-1.158). DBil >5.65 µmol/L was a predictor of HE in validation cohort. Higher DBil was also associated with poor 3-month outcomes. The mediation analysis indicated that the association of higher DBil and poor outcomes was partially mediated by HE. CONCLUSIONS: DBil is a predictor of HE and poor 3-month outcomes after ICH. DBil's metabolic process and involvement in the pathological mechanism of HE are likely to contribute to the association between DBil and HE. Interventions targeting DBil to improve post-ICH prognosis may be meaningful and worthy of further exploration.

SMASH-U aetiological classification: A predictor of long-term functional outcome after intracerebral haemorrhage.

BACKGROUND: SMASH-U is a systematic aetiological classification system for intracerebral haemorrhage (ICH) proven to be a predictor of post-ICH haematoma expansion and mortality. However, its role in predicting functional outcome remains elusive. Therefore, we aimed to investigate whether SMASH-U is associated with long-term functional outcome after ICH and improves the accuracy of prediction when added to max-ICH score. METHODS: Consecutive acute ICH patients from 2012 to 2018 from the neurology department of Tongji Hospital were enrolled. ICH aetiology was classified according to the SMASH-U system. The association of SMASH-U with 12-month functional outcome after ICH and the predictive value were evaluated. RESULTS: Of 1938 ICH patients, the aetiology of 1295 (66.8%) patients were classified as hypertension, followed by amyloid angiopathy (n = 250, 12.9%), undetermined (n = 159, 8.2%), structural lesions (n = 149, 7.7%), systemic disease (n = 74, 3.8%) and medication (n = 11, 0.6%). The baseline characteristics were different among the six aetiologies. In multivariate analysis, SMASH-U was proven to be a predictor of 12-month unfavourable functional outcome. When adding the SMASH-U system, the predictive performance of max-ICH score was improved (area under the receiver operating characteristic curve from 0.802 to 0.812, p = 0.010) and the predictive accuracy was enhanced (integrated discrimination improvement [IDI]: 1.60%, p < 0.001; continuous net reclassification improvement [NRI]: 28.16%, p < 0.001; categorical NRI: 3.34%, p = 0.004). CONCLUSIONS: SMASH-U predicted long-term unfavourable functional outcomes after acute ICH and improved the accuracy of prediction when added to max-ICH score. Integrating the aetiology to a score model to predict the post-ICH outcome may be meaningful and worthy of further exploration.

Decatungstate Catalyzed Synthesis of Trifluoromethylthioesters from Aldehydes via a Radical Process.

Here we report a mild and general method for the trifluoromethylthiolation of aldehydes using N-trifluoromethylthiosaccharin as the CF3S radical source and sodium decatungstate (NaDT) as the photocatalyst. This reaction proceeds via hydrogen atom abstraction by photoactivated DT and features good functional groups and substrate tolerance. Generally, electron-rich aldehydes demonstrate better reactivity than electron-deficient ones and good selectivity is observed for the trifluoromethylthiolation of aldehydic C-H bonds over tertiary and benzylic C-H bonds. Preliminary mechanistic studies have shown that a free radical process is involved.

Apolipoprotein E genotype predicts subarachnoid extension in spontaneous intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE. METHODS: A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data. RESULTS: A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p = 0.020), but not APOE ε4 copies (p > 0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p < 0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p < 0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p = 0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p = 0.026) but not in deep ICH (p > 0.2). No significant association was found between APOE ε4 copies and either lobar (p > 0.2) or deep ICH (p > 0.2). CONCLUSIONS: The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.

Nickel/NHC-Catalyzed Asymmetric C-H Alkylation of Fluoroarenes with Alkenes: Synthesis of Enantioenriched Fluorotetralins.

Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C-H alkylation of polyfluoroarenes with alkenes is described. The reaction employs bulky chiral N-heterocyclic carbene (NHC) ligands for nickel catalysts to enable exclusive activation of C-H bonds over C-F bonds and complete endo-selective C-H annulation and excellent enantioselectivity. A wide variety of chiral fluorotetralins, compounds otherwise difficultly accessed but serve as important bioisosteric analogs of both tetralin and heterocycle units for drug design, are expediently synthesized from easily available substrates. To our knowledge, this is the first example of catalytic enantioselective C-H functionalization of polyfluoroarenes.

Biased Lewis Pairs: A General Catalytic Approach to Ether-Ester Block Copolymers with Unlimited Ordering of Sequences.

Polymerizing epoxides after cyclic esters remains a major challenge, though their block copolymers have been extensively studied and used for decades. Reported here is a simple catalytic approach based on a metal-free Lewis pair that addresses the challenge. When the Lewis acid is used in excess of a base, selective (transesterification-free) polymerization of epoxides occurs in the presence of esters, while selectivity toward cyclic esters is achieved by an oppositely biased catalyst. Hence, one-pot block copolymerization can be performed in both ester-first and ether-first orders with selectivity being switchable at any stage, yielding ether-ester-type block copolymers with unlimited ordering of sequences as well as widely variable compositions and architectures. The selectivity can also be switched back and forth several times to generate a multiblock copolymer. Experimental and calculational results indicate that the selectivity originates mainly from the state of catalyst-activated hydroxy species.

Heart-type fatty acid binding protein (H-FABP) as a biomarker for acute myocardial injury and long-term post-ischemic prognosis.

Acute myocardial infarction (AMI) is a life-threatening event. Even with timely treatment, acute ischemic myocardial injury and ensuing ischemia reperfusion injury (IRI) can still be difficult issues to tackle. Apart from radiological and other auxiliary examinations, laboratory tests of applicable cardiac biomarkers are also necessary for early diagnosis and close monitoring of this disorder. Heart-type fatty acid binding protein (H-FABP), which mainly exists inside cardiomyocytes, has recently emerged as a potentially promising biomarker for myocardial injury. In this review we discuss the sensitivity and specificity of H-FABP in the assessment of myocardial injury and IRI, especially in the early stage, and its long-term prognostic value in comparison with other commonly used cardiac biomarkers, including myoglobin (Mb), cardiac troponin I (cTnI), creatine kinase MB (CK-MB), C-reactive protein (CRP), glycogen phosphorylase isoenzyme BB (GPBB), and high-sensitivity cardiac troponin T (hs-cTnT). The potential and value of combined application of H-FABP with other biomarkers are also discussed. Finally, the prospect of H-FABP is summarized; several technical issues are discussed to facilitate wider application of H-FABP in clinical practice.

Altered Cisatracurium Pharmacokinetics and Pharmacodynamics in Patients with Congenital Heart Defects.

The neuromuscular blocking agent cisatracurium is frequently used adjunctively in anesthesia to facilitate endotracheal intubation and to provide muscle relaxation during surgery. We aimed to determine the pharmacokinetics (PK)/pharmacodynamics (PD) of cisatracurium in patients with congenital heart defects (CHDs), such as ventricular septal defects and atrial septal defects, and to assess the effects of CHDs on the PK/PD profiles of cisatracurium. A modified two-compartment model with drug clearance from both compartments was best fitted to the PK data to determine the PK parameters. The model suggested that septal defects significantly lowered the rate of cisatracurium distribution from the central to peripheral compartment. The intercompartment rate constants k12 and k21 were significantly reduced (35%-60%, P < 0.05) in patients with ventricular septal defects and in patients with atrial septal defects compared with control patients. Consistently, septal defects caused a marked increase (160%-175%, P < 0.001) in the distribution half-life. Furthermore, significantly delayed pharmacodynamic responses to cisatracurium were observed in patients with septal defects. The onset time (i.e., the time to maximal neuromuscular block) was prolonged from 2.2 minutes to 5.0 minutes. PK/PD modeling suggested that reduced concentrations of cisatracurium in the effect compartment due to poorer distribution were the main cause of lagged pharmacodynamic responses. In conclusion, cisatracurium PK/PD were significantly altered in patients with septal defects. Our study should be of use in clinical practice for the administration of cisatracurium to patients with CHDs.

The effects of monovalent metal ions on the conformation of human telomere DNA using analytical ultracentrifugation.

A human telomere DNA segment (HT-DNA) can fold into a G-quadruplex in the presence of some monovalent cations. These cations can interact with the phosphate groups of the DNA segment and/or with the O6 oxygen atom of guanines, which are called non-specific interactions and specific interactions, respectively. However, until now how these two interactions affect the structure of HT-DNA has not been well understood. In this study, a combination of analytical ultracentrifugation (AUC) and circular dichroism (CD) was used to explore the effects of these two interactions on the structure of a 22-mer single-stranded DNA with a sequence of 5'-AGGG(TTAGGG)3-3'. The results showed that the standard sedimentation coefficient (s20,w) of HT-DNA starts to increase when the concentration of potassium ions (CK(+)) is higher than 10.0 µM due to the formation of a G-quadruplex through specific interactions. Whereas, for a control DNA, a higher CK(+) value of 1.0 mM was needed for increasing s20,w due to non-specific interactions. Moreover, potassium ions could promote the formation of the G-quadruplex much more easily than lithium, sodium and cesium ions, presumably due to its appropriate size in the dehydrated state and easier dehydration. The molar mass of DNA at different cation concentrations was nearly a constant and close to the theoretical value of the molar mass of monomeric HT-DNA, indicating that what we observed is the structural change of individual DNA chains.

Investigation of pH-induced conformational change and hydration of poly(methacrylic acid) by analytical ultracentrifugation.

Analytical ultracentrifugation was performed on poly(methacrylic acid) (PMAA) with a series of weight average molar masses (Mw) in aqueous solutions as a function of pH. The scales of the sedimentation coefficient (s) and the diffusion coefficient (D) to Mw at infinite dilutions were obtained at different pH values, indicating that PMAA chains adopt a collapsed structure at low pH values, and stretch at pH higher than 5.2. Our results show that the sedimentation coefficient exhibits a minimum at pH ∼ 6.0, presumably due to the effect of the conformational change and the hydration state of PMAA chains. When pH increases from 6.0 to 8.5, PMAA chains with high molar mass shrink a little bit, presumably because the sodium ions act as a bridging agent between nonadjacent carboxylate groups. Furthermore, the weight average molar mass of PMAA at pH 8.5 increases by one fold than that at pH 4.0, indicating the condensation of sodium ions and the increase in the number of hydration water molecules around carboxylate groups at high pH values.

Detection of spotted fever group Rickettsiae in ticks from Zhejiang Province, China.

Tick species distribution and prevalence of spotted fever group Rickettsiae (SFGR) in ticks were investigated in Zhejiang Province, China in 2010 and 2011. PCR was used to detect SFGR and positive amplicons were sequenced, compared to published sequences and phylogenic analysis was performed using MEGA 4.0. A total of 292 adult ticks of ten species were captured and 7.5 % (22/292) of the ticks were PCR-positive for SFG Rickettsia. The PCR-positive rates were 5.5 % (6/110) for Haemaphysalis longicornis, 3.6 % (1/28) for Amblyomma testudinarium and 16 % (15/94) for Ixodes sinensis, respectively. Phylogenetic analyses of gltA genes detected in ticks indicated that there are two dominating groups of SFGR. Sequences of group one were closely related to Rickettsia monacensis, whereas sequences of group two were closest related to Rickettsia heilongjiangensis and Rickettsia japonica, which are human pathogens. Our findings underline the importance of these ticks in public health surveillance in Zhejiang Province, China.

Transcriptomic analyses reveal the adaptive features and biological differences of guts from two invasive whitefly species.

BACKGROUND: The gut of phloem feeding insects is critical for nutrition uptake and xenobiotics degradation. However, partly due to its tiny size, genomic information for the gut of phloem feeding insects is limited. RESULTS: In this study, the gut transcriptomes of two species of invasive whiteflies in the Bemisia tabaci complex, Middle East Asia Minor 1 (MEAM1) and Mediterranean (MED), were analyzed using the Illumina sequencing. A total of 12,879 MEAM1 transcripts and 11,246 MED transcripts were annotated with a significant Blastx hit. In addition, 7,000 and 5,771 gut specific genes were respectively identified for MEAM1 and MED. Functional analyses on these gut specific genes demonstrated the important roles of gut in metabolism of insecticides and secondary plant chemicals. To reveal the molecular difference between guts of MEAM1 and MED, a comparison between gut transcriptomes of the two species was conducted and 3,910 pairs of orthologous genes were identified. Based on the ratio of nonsynonymous and synonymous substitutions, 15 genes were found evolving under positive selection. Many of those genes are predicted to be involved in metabolism and insecticide resistance. Furthermore, many genes related to detoxification were expressed at an elevated level in the gut of MED compared to MEAM1, which might be responsible for the MED's higher resistance to insecticides and environmental stresses. CONCLUSION: The sequencing of MED and MEAM1 gut transcriptomes and extensive comparisons of MEAM1 and MED gut transcripts provide substantial sequence information for revealing the role of gut in whiteflies.

Thermal properties of glycinin in crowded environments.

Crowded environments, commonly found in the food system, are utilized to enhance the properties of soybean proteins. Despite their widespread application, little information exists regarding the impact of crowded environments on the denaturation behaviors of soybean proteins. In this study, we investigated how crowding agents with varying molecular weights, functional groups, and topology affect the denaturation behavior of glycinin under crowded conditions. The results reveal that thermal stability in PEG crowded environments is mainly influenced by both preferential hydration and binding. The stabilization is primarily enthalpy-driven, with aggregation contributing additional entropic stabilization. Specifically, ethylene glycol and diethylene glycol exhibit temperature-dependent, bilateral effects on glycinin stability. At the denaturation temperature, hydrophobic interactions play a predominant role, decreasing glycinin's thermal stability. However, at a molecular weight of 200 g/mol, there is a delicate balance between destabilizing and stabilizing effects, leading to no significant change in thermal stability. With the addition of PEG 400, 1000, and 2000, besides preferential hydration, additional hard-core repulsions between glycinin molecules enhance thermal stability. Methylation modification experiments demonstrated that 2-methoxyethyl ether exerted a more pronounced denaturing effect. Additionally, the cyclization of PEG 1000 decreased its stabilizing effect.

Surface facet of palladium nanocrystals: a key parameter to the activation of molecular oxygen for organic catalysis and cancer treatment.

In many organic reactions, the O(2) activation process involves a key step where inert ground triplet O(2) is excited to produce highly reactive singlet O(2). It remains elusive what factor induces the change in the electron spin state of O(2) molecules, although it has been discovered that the presence of noble metal nanoparticles can promote the generation of singlet O(2). In this work, we first demonstrate that surface facet is a key parameter to modulate the O(2) activation process on metal nanocrystals, by employing single-facet Pd nanocrystals as a model system. The experimental measurements clearly show that singlet O(2) is preferentially formed on {100} facets. The simulations further elucidate that the chemisorption of O(2) to the {100} facets can induce a spin-flip process in the O(2) molecules, which is achieved via electron transfer from Pd surface to O(2). With the capability of tuning O(2) activation, we have been able to further implement the {100}-faceted nanocubes in glucose oxidation. It is anticipated that this study will open a door to designing noble metal nanocatalysts for O(2) activation and organic oxidation. Another perspective of this work would be the controllability in tailoring the cancer treatment materials for high (1)O(2) production efficiency, based on the facet control of metal nanocrystals. In the cases of both organic oxidation and cancer treatment, it has been exclusively proven that the efficiency of producing singlet O(2) holds the key to the performance of Pd nanocrystals in the applications.

Coagulation kinetics of humic aggregates in mono- and di-valent electrolyte solutions.

Coagulation behaviors of humic acids (HAs) aggregates in electrolyte solutions at different pHs, valences and concentrations of electrolyte cations were investigated using dynamic light scattering technique in combination of other analytical tools. For monovalent electrolyte sodium chloride (NaCl) solution, at its low concentrations the average hydrodynamic radius () of aggregates kept nearly constant. However, at high NaCl concentrations, could be scaled to the time t as ∝ t(a), suggesting a diffusion-limited colloid aggregation (DLCA). The coagulation value of NaCl in a buffer at pH 7.1 was calculated to be in a range of 61.3-84.4 mM. Divalent cation Mg(2+) was far more effective in enhancing the HA coagulation, as evidenced by a lower coagulation value (between 1.0 and 1.7 mM) and a more rapid coagulation rate. Such an enhancement could be explained by the combined effects of electrostatic repulsion, complexation and bridging. The highest coagulation rate (d/dt) and coagulation value at different pHs followed the order of: acidic > neutral > alkaline, and alkaline > neutral > acidic, respectively. Such a difference was associated with the extent of hydrogen bond and electrostatic repulsion at different protonation/deprotonation states of carboxyl and phenolic -OH groups. Transmission electron microscopic imaging reveals that HA was predominantly globular aggregates with a rough periphery at pH 5.26, and was changed to smooth spherical particles at pH 10.00. These results are useful for better understanding the coagulation behaviors of HAs in both natural and engineered aqueous systems.

An engineered bispecific nanobody in tetrameric secretory IgA format confers broad neutralization against SARS-CoV-1&2 and most variants.

SARS-CoV-2, a type of respiratory virus, has exerted a great impact on global health and economy over the past three years. Antibody-based therapy was initially successful but later failed due to the accumulation of mutations in the spike protein of the virus. Strategies that enable antibodies to resist virus escape are therefore of great significance. Here, we engineer a bispecific SARS-CoV-2 neutralizing nanobody in secretory Immunoglobulin A (SIgA) format, named S2-3-IgA2m2, which shows broad and potent neutralization against SARS-CoV-1, SARS-CoV-2 and its variants of concern (VOCs) including XBB and BQ.1.1. S2-3-IgA2m2 is ∼1800-fold more potent than its parental IgG counterpart in neutralizing XBB. S2-3-IgA2m2 is stable in mouse lungs at least for three days when administrated by nasal delivery. In hamsters infected with BA.5, three intranasal doses of S2-3-IgA2m2 at 1 mg/kg significantly reduce viral RNA loads and completely eliminate infectious particles in the trachea and lungs. Notably, even at single dose of 1 mg/kg, S2-3-IgA2m2 prophylactically administered through the intranasal route drastically reduces airway viral RNA loads and infectious particles. This study provides an effective weapon combating SARS-CoV-2, proposes a new strategy overcoming the virus escape, and lays strategic reserves for rapid response to potential future outbreaks of "SARS-CoV-3".

pH dependence of structure and surface properties of microbial EPS.

The flocculation of microorganisms plays a crucial role in bioreactors, and is substantially affected by pH. However, the mechanism for such an effect remains unclear. In this work, with an integrated approach, the pH dependence of structure and surface property of microbial extracellular polymeric substances (EPS), excreted from Bacillus megaterium TF10, and accordingly its flocculation is elucidated. From the Fourier transform infrared spectra and acid-base titration test results, the main functional groups and buffering zones in the EPS responsible for the microbial flocculation are indentified. The laser light scattering analysis reveals that the deprotonated or protonated states of these functional groups in EPS result in more dense and compact structure at a lower pH because of hydrophobicity and intermolecular hydrogen bonds. The zeta potential measurements identify the isoelectric point and indicate that the electrostatic repulsion action of EPS is controlled by pH. The highest flocculation efficiency is achieved near the isoelectric point (pH 4.8). These results clearly demonstrate that the EPS structure, surface properties, and accordingly the microbial flocculation are dependent heavily on pH in solution.

Caspase-1: A Promising Target for Preserving Blood-Brain Barrier Integrity in Acute Stroke.

The blood-brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.