Energy Landscape of the Substrate Translocation Equilibrium of Plasma-Membrane Glutamate Transporters

Glutamate transporters maintain a large glutamate concentration gradient across synaptic membranes and are, thus, critical for functioning of the excitatory synapse. Mammalian glutamate transporters concentrate glutamate inside cells through energetic coupling of glutamate flux to the transmembrane concentration gradient of Na⁺. Structural models based on an archeal homologue, GltPh, suggest an elevator-like carrier mechanism. However, the energetic determinants of this carrier-based movement are not well understood. Although electrostatics play an important role in governing these energetics, their implication on transport dynamics has not been studied. Here, we combine a pre-steady-state kinetic analysis of the translocation equilibrium with electrostatic computations to gain insight into the energetics of the translocation process. Our results show the biphasic nature of translocation, consistent with the existence of an intermediate on the translocation pathway. In the absence of voltage, the equilibrium is shifted to the outward-facing configuration. Electrostatic computations confirm the intermediate state and show that the elevator-like movement is energetically feasible in the presence of bound Na⁺ ions, whereas a substrate-hopping model is energetically prohibitive. Our results highlight the critical contribution of charge compensation to transport and add to results from previous molecular dynamics simulations for improved understanding of the glutamate translocation process

Dilute Au-Containing Ag Nanosponges as a Highly Active and Durable Electrocatalyst for Oxygen Reduction and Alcohol Oxidation Reactions

Zero-dimensional nanoparticles (NPs) have been demonstrated as the promising class of catalysts for various chemical and electrochemical reactions. However, the emerging Au–Ag NP catalysts suffer from single functionality, limited activity enhancement, and unsatisfactory stability problems. Here, we report a facile kinetically controlled solution method to prepare a new class of Au–Ag nanoporous sponges (NSs) composed of three-dimensional networks without using additional stabilizing agents at room temperature. The unexpected shift of the d-band center in our Au–Ag NSs was observed for the first time in Au–Ag bimetallic systems, which effectively activates the Au–Ag NSs for electrochemical reactions. The robust electronic effect coupled with abundant accessible active sites from the hierarchically porous architecture make the bare Au–Ag NSs a superior multifunctional catalyst for oxygen reduction, ethylene glycol (EG) oxidation, and glucose oxidation reactions compared to the commercial Pt/C electrocatalyst in alkaline medium. The optimized AuAg_3.2 NSs deliver a mass activity of 1.26 A mg_Au^–1 toward oxygen reduction reaction, which is ∼8.2 times as high as that of the Pt/C electrocatalyst, simultaneously showing outstanding stability with negligible activity decay after 10 000 cycles. For the anodic reactions, these AuAg_3.2 NSs show extremely high activity and stability toward both EG and glucose catalytic oxidation reactions with a higher mass activity of 7.58 and 1.48 A mg_Au^–1, about 3- and 18.5-fold enhancement than Pt/C, respectively. This work provides important insights into the structural design, performance optimization, and cost reduction to promote the practical applications of liquid fuel cells

<i>O</i>‑(Carboxymethyl)-chitosan Nanofiltration Membrane Surface Functionalized with Graphene Oxide Nanosheets for Enhanced Desalting Properties

A novel <i>O</i>-(carboxymethyl)-chitosan (OCMC) nanofiltration (NF) membrane is developed via surface functionalization with graphene oxide (GO) nanosheets to enhance desalting properties. Using ring-opening polymerization between epoxy groups of GO nanosheets and amino groups of OCMC active layer, GO nanosheets are irreversibly bound to the membrane. The OCMC NF membranes surface-functionalized with GO nanosheets are characterized by Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy, contact angle analyzer, and zeta potential analyzer. The membranes exhibit not only higher permeability but also better salt rejections than the pristine membranes and the commercial NF membranes; besides, the desalting properties are enhanced with the concentration of GO nanosheets increasing. Furthermore, the transport mechanism of GO–OCMC NF membranes reveals that the nanoporous structure of GO–OCMC functional layer and size exclusion and electrostatic repulsion of water nanochannels formed by GO nanosheets lead to the membranes possessing enhanced desalting properties

Data_Sheet_1_The association between the fibrinogen-to-albumin ratio and delirium after deep brain stimulation surgery in Parkinson’s disease.DOCX

IntroductionPostoperative delirium (POD) remains one of the most prevalent neuropsychiatric complications after deep brain stimulation (DBS) surgery. The fibrinogen-to-albumin ratio (FAR) has been shown to significantly correlate with the prognosis of many diseases related to inflammation. However, the association between FAR and POD remains unclear. We aimed to explore the association between POD and FAR in patients with Parkinson’s disease (PD) undergoing DBS surgery.MethodsPatients with PD who underwent DBS surgery in our hospital were included in this retrospective study. FAR was calculated from the blood sample collected on admission. The association between baseline FAR and delirium after surgery was assessed by binary logistic regression analysis, interaction analysis, and stratified analyses.ResultsOf 226 patients, 37 (16.4%) suffered from delirium after surgery. The average age of the participants was 63.3 ± 7.2 years, and 51.3% were male patients. Multivariate logistic regression analysis indicated that patients in the highest FAR tertile had a higher risk of POD compared with patients in the lowest FAR tertile (OR = 3.93, 95% CI: 1.24 ~ 12.67). Subgroup analysis demonstrated that FAR and the preoperative Mini-Mental State Examination score (p = 0.013) had an association with delirium after surgery.ConclusionOur data suggest that a higher preoperative FAR was significantly associated with delirium after DBS surgery. FAR on admission is a useful candidate biomarker to identify patients with PD who are at a high risk of delirium following DBS surgery.</p

High Genetic Diversity and Novelty in Eukaryotic Plankton Assemblages Inhabiting Saline Lakes in the Qaidam Basin

<div><p>Saline lakes are intriguing ecosystems harboring extremely productive microbial communities in spite of their extreme environmental conditions. We performed a comprehensive analysis of the genetic diversity (18S rRNA gene) of the planktonic microbial eukaryotes (nano- and picoeukaryotes) in six different inland saline lakes located in the Qaidam Basin. The novelty level are high, with about 11.23% of the whole dataset showing <90% identity to any previously reported sequence in GenBank. At least 4 operational taxonomic units (OTUs) in mesosaline lakes, while up to eighteen OTUs in hypersaline lakes show very low CCM and CEM scores, indicating that these sequences are highly distantly related to any existing sequence. Most of the 18S rRNA gene sequence reads obtained in investigated mesosaline lakes is closely related to Holozoa group (48.13%), whereas Stramenopiles (26.65%) and Alveolates (10.84%) are the next most common groups. Hypersaline lakes in the Qaidam Basin are also dominated by Holozoa group, accounting for 26.65% of the total number of sequence reads. Notably, Chlorophyta group are only found in high abundance in Lake Gasikule (28.00%), whereas less represented in other hypersaline lakes such as Gahai (0.50%) and Xiaochaidan (1.15%). Further analysis show that the compositions of planktonic eukaryotic assemblages are also most variable between different sampling sites in the same lake. Out of the parameters, four show significant correlation to this CCA: altitude, calcium, sodium and potassium concentrations. Overall, this study shows important gaps in the current knowledge about planktonic microbial eukaryotes inhabiting Qaidam Basin (hyper) saline water bodies. The identified diversity and novelty patterns among eukaryotic plankton assemblages in saline lake are of great importance for understanding and interpreting their ecology and evolution.</p></div

Locations of investigated lakes in Qaidam Basin.

<p>In Figure, K, T, D, M, X and G referred to Lake Keluke, Lake Tuosu, Lake Dasugan, Lake Gahai, Lake Xiaochaidan and Lake Gsikule, respectively.</p

Video_1_Case report: Oral anticoagulant combined with percutaneous coronary intervention for peripheral embolization of left ventricular thrombus caused by myocardial infarction in a patient with diabetes mellitus.AVI

BackgroundLeft ventricular thrombus (LVT) is a well-recognized complication of myocardial infarction (MI) in patients with diabetes. An embolic complication caused by LVT is a key clinical problem and is associated with worsened long-term survival.Case presentationA 45-year-old man with persistent left abdominal pain for 1 week and left leg fatigue was admitted to the emergency department. The cause of abdominal pain was embolism of the renal artery, the splenic artery, and the superior mesenteric artery caused by cardiogenic thrombosis, which further led to splenic infarction and renal infarction. It was unclear when MI occurred because the patient had no typical critical chest pain, which may have been related to diabetic complications, such as diabetic peripheral neuropathy. Diabetes plays a pivotal role in MI and LVT formation. Because coronary angiography suggested triple vessel disease, percutaneous transluminal coronary angioplasty (PTCA) was conducted, and two drug-eluting stents were placed in the left anterior descending coronary artery (LAD). Due to a lack of randomized clinical control trials, the therapy of LVT and associated embolization has been actively debated. According to the present guidelines, this patient was treated with low-molecular-weight heparin and warfarin (oral anticoagulants) for 3 months in addition to aspirin (100 mg/day) and clopidogrel (75 mg/day) for 1 year. No serious bleeding complications were noted, and a follow-up examination showed no thrombus in the left ventricle or further peripheral thrombotic events.ConclusionPeripheral embolization of LVT caused by MI leading to multiple organ embolization remains a rare occurrence. Diabetes plays a pivotal role in MI and LVT formation. Successful revascularization of the infarct-related coronary artery and anticoagulation therapy is important to minimize myocardial damage and prevent LVT. The present case will help clinicians recognize and manage LVT in patients with diabetes and related peripheral arterial thrombotic events with anticoagulation.</p

Bimetallic Mn–Co Oxide Nanoparticles Anchored on Carbon Nanofibers Wrapped in Nitrogen-Doped Carbon for Application in Zn–Air Batteries and Supercapacitors

The exploration and rational design of cost-effective, highly active, and durable catalysts for oxygen electrochemical reaction is crucial to actualize the prospective technologies such as metal–air batteries and fuel cells. Herein manganese cobalt oxide nanoparticles anchored on carbon nanofibers and wrapped in a nitrogen-doped carbon shell (MCO/CNFs@NC) is successfully prepared. Benefiting from the synergistic effect between the core nanoparticles and nitrogen-doped carbon shell, MCO/CNFs@NC catalyst exhibits oxygen reduction reaction (ORR) activity with comparable onset potential (1.00 V vs RHE) and half-wave potential (0.76 V vs RHE) which is only about 40 mV lower than that of the state of art Pt/C catalyst. Furthermore, the MCO/CNFs@NC catalyst exceeds the Pt/C catalyst by a great margin in terms of stability in alkaline media. Additionally, MCO/CNFs@NC catalyst is strongly tolerant to methanol crossover, promising its applicability as cathode catalyst in alcohol fuel cells. Moreover, MCO/CNFs@NC catalyst exhibits the oxygen evolution reaction (OER) activity with low overpotential of 0.41 V at the current density of 10 mA cm^–2 and ORR/OER potential gap (Δ<i>E</i>) as low as 0.88 V, suggesting its strong bifunctionality. The Zn–air battery based on MCO/CNFs@NC catalyst is found to deliver a specific capacity of 695 mA h g^–1_Zn and an energy density of 778 W h kg^–1_Zn at a current density of 20 mA cm^–2. The mechanically rechargeable Zn–air battery based on MCO/CNFs@NC catalyst is also found to function continually by only reloading the consumed Zn anode and electrolyte. Furthermore, the electrically rechargeable battery based on MCO/CNFs@NC catalyst is found to function for more than 220 cycles with negligible loss of voltaic efficiency. Moreover, MCO/CNFs@NC is found to display a supercapacitive nature with a good discharge capacity of 478 F g^–1 at a discharge current density of 1 A g^–1

Data_Sheet_1_Case report: Oral anticoagulant combined with percutaneous coronary intervention for peripheral embolization of left ventricular thrombus caused by myocardial infarction in a patient with diabetes mellitus.docx

BackgroundLeft ventricular thrombus (LVT) is a well-recognized complication of myocardial infarction (MI) in patients with diabetes. An embolic complication caused by LVT is a key clinical problem and is associated with worsened long-term survival.Case presentationA 45-year-old man with persistent left abdominal pain for 1 week and left leg fatigue was admitted to the emergency department. The cause of abdominal pain was embolism of the renal artery, the splenic artery, and the superior mesenteric artery caused by cardiogenic thrombosis, which further led to splenic infarction and renal infarction. It was unclear when MI occurred because the patient had no typical critical chest pain, which may have been related to diabetic complications, such as diabetic peripheral neuropathy. Diabetes plays a pivotal role in MI and LVT formation. Because coronary angiography suggested triple vessel disease, percutaneous transluminal coronary angioplasty (PTCA) was conducted, and two drug-eluting stents were placed in the left anterior descending coronary artery (LAD). Due to a lack of randomized clinical control trials, the therapy of LVT and associated embolization has been actively debated. According to the present guidelines, this patient was treated with low-molecular-weight heparin and warfarin (oral anticoagulants) for 3 months in addition to aspirin (100 mg/day) and clopidogrel (75 mg/day) for 1 year. No serious bleeding complications were noted, and a follow-up examination showed no thrombus in the left ventricle or further peripheral thrombotic events.ConclusionPeripheral embolization of LVT caused by MI leading to multiple organ embolization remains a rare occurrence. Diabetes plays a pivotal role in MI and LVT formation. Successful revascularization of the infarct-related coronary artery and anticoagulation therapy is important to minimize myocardial damage and prevent LVT. The present case will help clinicians recognize and manage LVT in patients with diabetes and related peripheral arterial thrombotic events with anticoagulation.</p

The geographical, physical, and chemical characteristics of the investigated lakes. <i>ND</i> not determined, <i>n.d</i>. not detectable.

<p>The geographical, physical, and chemical characteristics of the investigated lakes. <i>ND</i> not determined, <i>n.d</i>. not detectable.</p