Stroke is uncommon among young adults. However, the incidence of stroke among young women increases with pregnancy during peripartum and postpartum periods. The relative risk of suffering from haemorrhagic stroke was three times higher than ischemic stroke during these periods when compared with antenatal period. Neuroimaging should be prioritized in order to establish diagnosis and to facilitate treatment in a patient with suspected acute stroke. Prophylaxic anticoagulants should be used in high risk patients. Treatments of acute stroke in pregnant women include anti-platelet and thrombolytic agents. Further studies should be carried as there is lack of high level of evidences to formulate clear guideline for the management of stroke during pregnancy.
In the crystal structure of the title compound, C(12)H(10)N(4), the pyridine ring makes a dihedral angle of 1.12 (9) degrees with the mean plane of the complete almost planar and crystallographically centrosymmetric molecule. There are stacks of parallel molecules along the a-axis direction, with alternate stacks having a herring-bone arrangement relative to each other and an interplanar spacing of 3.551 A.
Parkinson's disease (PD) is a progressive health issue and influences an increasingly larger number of people, especially at older ages, affecting the central nervous system (CNS). Alpha-synuclein is a biomarker closely correlated with the CNS and PD. The loss of neuronal cells in the substantia nigra leads to the aggregation of alpha-synuclein in the form of Lewy bodies, and Lewy neuritis is a neuropathological hallmark. The therapeutic approach of PD focuses on alpha-synuclein as an important substrate of PD pathology. So far, research has focused on antialpha-synuclein to minimize the burden of extracellular alpha-synuclein in the brain, and as a consequence, it ameliorates inflammation. Interdigitated electrode (IDE) biosensors are efficient tools for detecting various analytes and were chosen in this study to detect alpha-synuclein on amine-modified surfaces by using antiaptamer-alpha-synuclein as the probe. In addition, a gold nanoparticle-conjugated aptamer was used to enhance the detection limit. The limit of detection for the binding between alpha-synuclein and aptamer was found to be 10 pM. Control experiments were performed with two closely related proteins, amyloid-beta and tau, to reveal the specificity; the results show that the aptamer only recognized alpha-synuclein. The proposed strategy helps to identify the binding of aptamer and alpha-synuclein and provides a possible method to lower alpha-synuclein levels and inflammation in PD patients.
As natural agroecology deteriorates, controlled environment agriculture (CEA) systems become the backup support for coping with future resource consumption and potential food crises. Compared with natural agroecology, most of the environmental parameters of the CEA system rely on manual management. Such a system is dependent and fragile and prone to degradation, which includes harmful bacteria proliferation and productivity decline. Proper water management is significant for constructing a stabilized rhizosphere microenvironment. It has been proved that water is an efficient tool for changing the availability of nutrients, plant physiological processes, and microbial communities within. However, for CEA issues, relevant research is lacking at present. The article reviews the interactive mechanism between water management and rhizosphere microenvironments from the perspectives of physicochemical properties, physiological processes, and microbiology in CEA systems. We presented a synthesis of relevant research on water-root-microbes interplay, which aimed to provide detailed references to the conceptualization, research, diagnosis, and troubleshooting for CEA systems, and attempted to give suggestions for the construction of a high-tech artificial agricultural ecology.
OBJECTIVE Traumatic brain injury due to road traffic accidents occurs mainly in the younger age group in which injury-related disability leads to long-term impact on employment and economic and social consequences across the lifespan. This study was designed to assign a monetary cost (in Malaysian ringgits [RM]) to the treatment of patients with surgically treated isolated traumatic head injury as determined up to 1 year after injury. METHODS Relevant resource items used were identified and valued using the direct measurement of costs method, cost accounting methods, standard unit costs method, fees, charges and/or market prices method. These values were then tabulated to generate the total costs for each patient, via a combination of macro-costing and micro-costing methods. Malaysian currency values were converted to US dollars according to the average conversion rate for the period from January to May 2016: RM1 = US$0.2452. RESULTS This costing study analyzed data from 49 patients. The estimated cost for the 1st year of care for all patients was RM1,471,919.80 (US$360,914.735), with a mean (± SD) cost per case of RM30,039.18 ± 22,986.25 or $7365.61 ± $5636.23. The mean cost of care per case was RM11,041.35 ± 10,936.88 or $2707.34 ± $2681.72 for mild head injury, RM32,550.00 ± 20,998.76 or $7981.26 ± $5148.90 for moderate head injury, and RM36,917.86 ± 23,697.34 or $9052.26 ± $5810.59 for severe head injury. Severe head injury (p = 0.001), sustaining 2 or more intracranial pathologies (p = 0.01), having a poor Glasgow Outcome Scale (GOS) score (GOS score 1-3) (p = 0.02), requiring a tracheostomy (p < 0.001), and contracting pneumonia (p < 0.001) were significantly associated with higher cost. Logistic regression analysis revealed that cost of care increased by RM591.60 or $145.06 per year increment of age (β = RM591.60, p = 0.05). CONCLUSIONS The mean cost of treatment for traumatic head injury is high compared to the per capita income of RM37,900 in 2016. The cost values generated in this study provide baseline cost estimates that the authors hope will be used as a guide to determine where adequate funding should be allocated to provide timely and appropriate delivery of care.
Transforming growth factor-β (TGF-β) is a member of a superfamily of pleiotropic proteins that regulate multiple cellular processes such as growth, development and differentiation. Following binding to type I and II TGF-β serine/threonine kinase receptors, TGF-β activates downstream signaling cascades involving both SMAD-dependent and -independent pathways. Aberrant TGF-β signaling is associated with a variety of diseases, such as fibrosis, cardiovascular disease and cancer. Hence, the TGF-β signaling pathway is recognized as a potential drug target. Various organic molecules have been designed and developed as TGF-β signaling pathway inhibitors and they function by either down-regulating the expression of TGF-β or by inhibiting the kinase activities of the TGF-β receptors. In this review, we discuss the current status of research regarding organic molecules as TGF-β inhibitors, focusing on the biological functions and the binding poses of compounds that are in the market or in the clinical or pre-clinical phases of development.
Transport of environmental pollutants in groundwater systems can be greatly influenced by colloids. In this study, the cotransport of Pb2+ and silica (SiO2) colloids at different Pb2+ concentrations was systematically investigated by batch adsorption and saturated sand column experiments. Results showed that SiO2 colloids had low adsorption capacity for Pb2+ (less than 1% of the input) compared with sands. In saturated porous media, SiO2 colloids showed a high mobility; however, with the increase of Pb2+ concentration in the sand column, the mobility of SiO2 colloids gradually decreased. Notably, SiO2 colloids could facilitate Pb2+ transport, although they did not serve as effective carriers of Pb2+. Under the condition of low Pb2+ concentration, SiO2 colloids promoted the Pb2+ transport mainly through the way of "transport channel," while changing the porosity of the medium and masking medium adsorption sites were the main mechanisms of SiO2 colloid-facilitated Pb2+ transport under the condition of high Pb2+ concentration. The discovery of this non-adsorption effect of colloids would improve our understanding of colloid-facilitated Pb2+ transport in saturated porous media, which provided new insights into the role of colloids, especially colloids with weak Pb2+ adsorption capacity, in Pb2+ occurrence and transport in soil-groundwater systems.
Ethylenediaminetetraacetic acid (EDTA) can serve as a washing agent in the remediation of low-permeability layers contaminated by heavy metals (HMs). Therefore, batch adsorption experiments, where pure quartz (SM1) and mineral mixtures (SM2) were used as typical soil minerals (SMs) in low-permeability layers, were implemented to explore the effects of different EDTA concentrations, pH, and exogenous chemicals on the HM-SM-EDTA adsorption system. As the EDTA concentration increased, it gradually cut down the maximum Cd adsorption capacities of SM1 and SM2 from approximately 135 to 55 mg/kg and 2660 to 1453 mg/kg; and the maximum Pb adsorption capacities of SM1 and SM2 were reduced from 660 to 306 mg/kg and 19,677 to 19,262 mg/kg, respectively. When the initial mole ratio (MR = moles of HM ions/sum of moles of HM ions and EDTA) was closer to 0.5, the effect of EDTA was more effective. Additionally, EDTA worked well at pH below 7.0 and 4.0 for Cd and Pb, respectively. Low-molecular-weight organic acids (LMWOAs) affected the system mainly by bridging, complexation, adsorption site competition, and reductive dissolution. Cu2+, Fe2+ ions could significantly increase the Cd and Pb adsorption onto SM2. Notably, there were characteristic changes in mineral particles, including attachment of EDTA and microparticles, agglomeration, connection, and smoother surfaces, making the specific surface area (SSA) decrease from 16.73 to 12.59 m2/g. All findings indicated that EDTA could effectively and economically reduce the HM adsorption capacity of SMs at the reasonable MR value, contact time, and pH; EDTA reduced the HM adsorption capacity of SMs not only by complexation with HM ions but also by decreasing SSA and blocking active sites. Hence, the acquired insight from the presented study can help to promote the remediation of contaminated low-permeability layers in groundwater.
Nanomaterials are threatening the environment and human health, but there has been little discussion about the stability and mobility of nanoparticles (NPs) in saturated porous media at environmentally relevant concentrations of surfactants, which is a knowledge gap in exploring the fate of engineered NPs in groundwater. Therefore, the influences of the anionic surfactant (sodium dodecylbenzene sulfonate, SDBS), the cationic surfactant (cetyltrimethylammonium bromide, CTAB), and the nonionic surfactant (Tween-80) with environmentally relevant concentrations of 0, 5, 10, and 20 mg/L on nano-TiO2 (nTiO2, negatively charged) and nano-CeO2 (nCeO2, positively charged) transport through saturated porous media were examined by column experiments. On the whole, with increasing SDBS concentration from 0 to 20 mg/L, the concentration peak of nTiO2 and nCeO2 in effluents increased by approximately 0.2 and 0.3 (dimensionless concentration, C/C0), respectively, because of enhanced stability and reduced aggregate size resulting from enhanced electrostatic and steric repulsions. By contrast, the transportability of NPs significantly decreased with increasing CTAB concentration due to the attachment of positive charges, which was opposite to the charge on the medium surface and facilitated the NP deposition. On the other hand, the addition of Tween-80 had no significant influence on the stability and mobility of nTiO2 and nCeO2. The results were also demonstrated by the colloid filtration theory (CFT) modeling and the Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction calculations; it might promote the assessment and remediation of NP pollution in subsurface environments.
Herein, biochar was prepared using rice straw, and it served as the peroxymonosulfate (PMS) activator to degrade naphthalene (NAP). The results showed that pyrolysis temperature has played an important role in regulating biochar structure and properties. The biochar prepared at 900°C (BC900) had the best activation capacity and could remove NAP in a wide range of initial pH (5-11). In the system of BC900/PMS, multi-reactive species were produced, in which 1O2 and electron transfer mainly contributed to NAP degradation. In addition, the interference of complex groundwater components on the NAP removal rate must get attention. Cl- had a significant promotional effect but risked the formation of chlorinated disinfection by-products. HCO3-, CO32-, and humic acid (HA) had an inhibitory effect; surfactants had compatibility problems with the BC900/PMS system, which could lead to unproductive consumption of PMS. Significantly, the BC900/PMS system showed satisfactory remediation performance in spiked natural groundwater and soil, and it could solve the problem of persistent groundwater contamination caused by NAP desorption from the soil. Besides, the degradation pathway of NAP was proposed, and the BC900/PMS system could degrade NAP into low or nontoxic products. These suggest that the BC900/PMS system has promising applications in in-situ groundwater remediation.
Transforming growth factor-β (TGF-β) plays an important role in regulating epithelial to mesenchymal transition (EMT) and the TGF-β signaling pathway is a potential target for therapeutic intervention in the development of many diseases, such as fibrosis and cancer. Most currently available inhibitors of TGF-β signaling function as TGF-β receptor I (TβR-I) kinase inhibitors, however, such kinase inhibitors often lack specificity. In the present study, we targeted the extracellular protein binding domain of the TGF-β receptor II (TβR-II) to interfere with the protein-protein interactions (PPIs) between TGF-β and its receptors. One compound, CJJ300, inhibited TGF-β signaling by disrupting the formation of the TGF-β-TβR-I-TβR-II signaling complex. Treatment of A549 cells with CJJ300 resulted in the inhibition of downstream signaling events such as the phosphorylation of key factors along the TGF-β pathway and the induction of EMT markers. Concomitant with these effects, CJJ300 significantly inhibited cell migration. The present study describes for the first time a designed molecule that can regulate TGF-β-induced signaling and EMT by interfering with the PPIs required for the formation of the TGF-β signaling complex. Therefore, CJJ300 can be an important lead compound with which to study TGF-β signaling and to design more potent TGF-β signaling antagonists.
Nanobubbles (NBs), given their unique properties, could theoretically be paired with rhamnolipids (RL) to tackle polycyclic aromatic hydrocarbon contamination in groundwater. This approach may overcome the limitations of traditional surfactants, such as high toxicity and low efficiency. In this study, the remediation efficiency of RL, with or without NBs, was assessed through soil column experiments (soil contaminated with phenanthrene). Through the analysis of the two-site non-equilibrium diffusion model, there was a synergistic effect between NBs and RL. The introduction of NBs led to a reduction of up to 24.3 % in the total removal time of phenanthrene. The direct reason for this was that with NBs, the retardation factor of RL was reduced by 1.9 % to 15.4 %, which accelerated the solute replacement of RL. The reasons for this synergy were multifaceted. Detailed analysis reveals that NBs improve RL's colloidal stability, increase its absolute zeta potential, and reduce its soil adsorption capacity by 13.3 %-19.9 %. Furthermore, NBs and their interaction with RL substantially diminish the surface tension, contact angle, and dynamic viscosity of the leaching solution. These changes in surface thermodynamic and rheological properties significantly enhance the migration efficiency of the eluent. The research outcomes facilitate a thorough comprehension of NBs' attributes and their relevant applications, and propose an eco-friendly method to improve the efficiency of surfactant remediation.
The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.