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The literature on personality trait development has mainly focused on influences of life experiences in one single life domain (e.g., work or family) separate from one another and has primarily examined personality development in early life stages. Thus, less attention has been devoted to influences from interplays across different life domains and personality development in middle and late adulthood. Synthesizing the literature on personality science and organizational research, we built a theoretical model and investigated what, how, and why the interplay between two central life domains—work and family—may be related to personality trait development of people at their middle and late life stages, and more important, change-related reciprocal relationships between personality traits and work–family experiences. Generally, convergent findings with data from two longitudinal studies (National Survey of Midlife in the United States, maximum N = 3,192, three waves; and Health and Retirement Study, maximum N = 1,133, three waves except anxiety) revealed that work-to-family conflict, family-to-work conflict, work-to-family facilitation, and family-to-work facilitation mostly had lagged effects on changes of Conscientiousness, Extraversion, and Neuroticism, and the influences were generally channeled through changes of anxiety. Personality traits also had lagged influences on changes of work–family experiences, with some influences deteriorating over time. Change-related reciprocal relationships were recorded mainly between Neuroticism and Extraversion with work–family experiences. Some selection effects were larger than socialization effects. Our research contributes to the personality and the work–family literature and represents a useful example of cross-fertilization of research in different areas of psychology to advance personality research. [ABSTRACT FROM AUTHOR]

Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms. Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB. Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression. Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats. [ABSTRACT FROM AUTHOR]

The article titled "Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level [Corrigendum]" discusses a correction to the original article. The authors have identified an error in the value for Huangbai solution gavage in the Experimental Design section and Figure 1. The correct value is 3.24 g/kg, not 0.36 g/kg as previously stated. The correction is reflected in the updated text and figure provided in the corrigendum. [Extracted from the article]

The spillover effect serves as the basis of regional collaborative innovation. Existing research on innovation spillover focuses on the overall impact of a region's innovation factors on local and other regions' innovation activities. However, re-spillover may occur since the flow of innovation factors between any two regions may influence the innovation in third-party regions. This study quantifies labor flow, capital flow, and institutional learning between regions in China using a gravity model and a social network analysis model, and then applies a spatial econometric model to investigate innovation spillover and re-spillover. The results show that re-spillover can better explain levels of regional innovation. Capital, government support, labour flow, capital flow, and institutional learning have a positive spillover effect on local innovation, while labour flow also has positive spillover effects to other regions. [ABSTRACT FROM AUTHOR]

Background and Aims: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. Methods: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21‐day all‐cause mortality or requirement for liver transplantation (death/LT). Results: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21‐day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p <.001). There was lower transplant‐free cumulative survival in the hypochloremic group than in the normo‐ or hyper‐chloremic groups (log‐rank, χ2 24.2, p <.001). Serum chloride was inversely associated with the hazard of 21‐day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969–0.985; p <.001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13–0.25) but underestimated the probability of transplant‐free survival in 34% of patients (NRI = −0.34, 95% CI: −0.39 to −0.28). Conclusions: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG‐Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT. [ABSTRACT FROM AUTHOR]

The city is both a carrier and a subject of innovation. Based on the triple helix theory of industry–university research and the theory of spatial correlation, this study constructs a collaborative innovation framework both within the cities and between cities, and uses a network data envelopment analysis (DEA) model and spatial econometric model to measure and analyze the collaborative innovation efficiency in 75 innovative cities in China. The results show that collaborative innovation efficiency within cities is on the rise, and the efficiency of "research to production" is significantly higher than that of "learning to research." Industrial structure and foreign factors have inhibited the efficiency improvements, and infrastructure and living standards have different promoting effects on different stages of efficiency. Between cities, capital flows have obvious spillover effects, which promote the efficiency of innovation networks, while the long‐term characteristics of institutional learning have a near‐term negative impact. [ABSTRACT FROM AUTHOR]

Erjing prescription (EJP) was an ancient formula that was recorded in the General Medical Collection of Royal Benevolence of the Song Dynasty. It has been frequently used to treat type 2 diabetes mellitus (T2DM) in the long history of China. The formula consists of Lycium barbarum L. and Polygonatum sibiricum F. Delaroche with a ratio of 1 : 1. This study aimed to identify the potential effects and mechanisms of EJP treatment T2DM. The target proteins and possible pathways of EJP in T2DM treatment were investigated by the approach of network pharmacology and real-time PCR (RT-PCR). 99 diabetes-related proteins were regulated by 56 bioactive constituents in EJP in 26 signal pathways by Cytoscape determination. According to GO analysis, 606 genes entries have been enriched. The PPI network suggested that AKT1, EGF, EGFR, MAPK1, and GSK3β proteins were core genes. Among the 26 signal pathways, the PI3K-AKT signal pathway was tested by the RT-PCR. The expression level of PI3K p85, AKT1, GSK3β, and Myc mRNA of this pathway was regulated by EJP. The study based on network pharmacology and RT-PCR analysis revealed that the blood sugar level was regulated by EJP via regulating the PI3K-AKT signal pathway. Plenty of new treatment methods for T2DM using EJP were provided by network pharmacology analysis. [ABSTRACT FROM AUTHOR]

Modular Reinforcement Learning decomposes a monolithic task into several tasks with sub-goals and learns each one in parallel to solve the original problem. Such learning patterns can be traced in the brains of animals. Recent evidence in neuroscience shows that animals utilize separate systems for processing rewards and punishments, illuminating a different perspective for modularizing Reinforcement Learning tasks. MaxPain and its deep variant, Deep MaxPain, showed the advances of such dichotomy-based decomposing architecture over conventional Q-learning in terms of safety and learning efficiency. These two methods differ in policy derivation. MaxPain linearly unified the reward and punishment value functions and generated a joint policy based on unified values; Deep MaxPain tackled scaling problems in high-dimensional cases by linearly forming a joint policy from two sub-policies obtained from their value functions. However, the mixing weights in both methods were determined manually, causing inadequate use of the learned modules. In this work, we discuss the signal scaling of reward and punishment related to discounting factor γ , and propose a weak constraint for signaling design. To further exploit the learning models, we propose a state-value dependent weighting scheme that automatically tunes the mixing weights: hard-max and softmax based on a case analysis of Boltzmann distribution. We focus on maze-solving navigation tasks and investigate how two metrics (pain-avoiding and goal-reaching) influence each other's behaviors during learning. We propose a sensor fusion network structure that utilizes lidar and images captured by a monocular camera instead of lidar-only and image-only sensing. Our results, both in the simulation of three types of mazes with different complexities and a real robot experiment of an L-maze on Turtlebot3 Waffle Pi, showed the improvements of our methods. [ABSTRACT FROM AUTHOR]

Temporal collections of news articles (or news archives) contain numerous accurate and time-aligned articles, which offer immense value to our society, helping users to know details of events that occurred at specific time points in the past. Currently, the access to such collections is rather difficult for average users due to their large sizes and complexities. For better use of these valuable resources on our heritage, this study considers the task of machine reading at scale on long-term news article archives. We make use of the observation that questions on news archives are usually related to particular events and show strong temporal aspects. We propose a large scale question answering model designed specifically for long-term news article collections, with an additional module for re-ranking articles by using temporal information from different perspectives. The experimental results show that our model is superior to the existing question answering systems, thanks to dedicated module that allows finding more relevant documents. [ABSTRACT FROM AUTHOR]

Objectives: Cirrhosis is frequently complicated by electrolyte disturbances, with prior studies primarily focused on the importance of hyponatremia. Emerging evidence on patients with chronic heart failure and chronic kidney disease has identified hypochloremia as an independent predictor for mortality. This study aimed to investigate the prognostic value of serum chloride and its association with mortality in cirrhotic patients.Design: Retrospective cohort study.Setting: The medical ICU at Parkland Memorial Hospital, a tertiary care public health system in Dallas, Texas.Patients: Adult patients with confirmed diagnosis of decompensated cirrhosis who were admitted to the ICU between March 2015 and March 2017.Interventions: None.Measurements and Main Results: Kaplan-Meier analysis and multivariable Cox proportional hazard ratio models were performed to determine the impact of hypochloremia on 180-day mortality. Of the 389 enrolled patients, 133 (34.2%) died within 180 days of ICU admission. Patients with hypochloremia had higher 180-day mortality than those with normochloremia (45.2% vs 26.7%; p < 0.0001). Cumulative survival via the Kaplan-Meier method was significantly lower in the hypochloremic group. Serum chloride was independently associated with 180-day mortality with multivariable adjustment (hazard ratio, 0.95; 95% CI, 0.93-0.98; p = 0.001) or after adjusting for Model for End-stage Liver Disease or Sequential Organ Failure Assessment. Contrarily, the inverse association between serum sodium and mortality no longer existed in all multivariable models.Conclusions: Serum chloride is independently and inversely associated with short-term mortality in critically ill cirrhotic patients. Hypochloremia, but not hyponatremia, remained associated with mortality with multivariable analyses, suggesting that hypochloremia may account for the mortality risk previously attributed to hyponatremia. These findings signify the prognostic value of serum chloride and potential inclusion of chloride into future cirrhosis prognostic scores. [ABSTRACT FROM AUTHOR]

This study investigated mass transfer characteristics in a rotor–stator reactor (RSR) in terms of the overall volumetric mass-transfer coefficient ( K x a ) using nitrogen stripping (N 2 –H 2 O–O 2 ) and nitrogen stripping coupled with vacuum degassing (vacuum–N 2 –H 2 O–O 2 ) processes. Principal component regression (PCR) method was used to establish a mass transfer model, and the number of principal components (PCs) was examined by three different techniques including cumulative percent variance (CPV), average eigenvalue (AE), and cross validation (CV). The prediction performance of the PCR model was compared to that of the multiple linear regression (MLR) model. Results reveal that the number of PCs determined by CV based on the predicted residual error sum of squares can be used to determine the optimal number of PCs to express the relationship between various modeling variables and K x a . The values of K x a predicted by the PCR and MLR models in the N 2 –H 2 O–O 2 system were in agreement with the experimental values with deviations within 15% while those in the vacuum–N 2 –H 2 O–O 2 system generally agreed with the experimental values with deviations within 15% and 30%, respectively. These results indicate that the PCR method is best suited for mass transfer modeling in an RSR. [ABSTRACT FROM AUTHOR]

Hydroxyapatite nanoparticles (nHAP) were successfully synthesized using a high-gravity precipitation method. Crystal structure and morphology of the nHAP were confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Chemical nature of the nHAP was analyzed by Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma atomic emission spectrometry (ICP-AES). The characterization results demonstrated formation of nHAP with diameters of 1.9–14.2 nm and lengths of 4.0–36.9 nm and carbonated apatite structures, which were comparable to that of natural bone apatite. Further, biocompatibility of the nHAP was determined by MTT assays on MCF-7 cells. Moreover, potential applications of the nHAP in preparing Calcium Phosphate Cements (CPC) and Gelatin/HAP composite hydrogels were explored. The high-gravity precipitation method provides a new approach in fabrication of nHAP and opens possibilities to realizing great potential of nHAP in various biomedical applications. [ABSTRACT FROM AUTHOR]

Silybin (SLB), akind of antihepatotoxic polyphenolic substance,is currently available for a variety of acute and chronic liver diseases.However, its poor solubility and low bioavailability have stronglylimited its therapeutic applications. In this work, we demonstratea simple solution to address these issues by designing SLB/poly(vinylpyrrolidone)(PVP) nanodrugs via the aerosol solvent extraction system (ASES).In the ASES process, SLB and PVP are prepared via coprecipitationby using the dimethylformamide/dense gas CO2solvent/antisolventstrategy. The size of the as-obtained SLB/PVP nanodrugs (denoted asNanoSLB) can be tuned from 100 to 300 nm. Compared with raw SLB, NanoSLBis of low crystallinity and hence shows drug solubility greatly enhancedby more than 8-fold. This work will broaden the applications of water-insolubledrugs in pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

• Blood-brain barrier plays a central role in a variety of central nervous system diseases and is a drug target. • Mitochondrial oxidative stress disorder in brain microvascular endothelial cells plays a key role in the occurrence and development of blood–brain barrier damage. • Protection of mitochondrial function in brain microvascular endothelial cells is a potential new strategy for the treatment of central nervous system diseases. Blood-brain barrier disruption plays an important role in central nervous system diseases. This review provides information on the role of mitochondrial oxidative stress in brain microvascular endothelial cells in cellular dysfunction, the disruption of intercellular junctions, transporter dysfunction, abnormal angiogenesis, neurovascular decoupling, and the involvement and aggravation of vascular inflammation and illustrates related molecular mechanisms. In addition, recent drug and nondrug therapies targeting cerebral vascular endothelial cell mitochondria to repair the blood–brain barrier are discussed. This review shows that mitochondrial oxidative stress disorder in brain microvascular endothelial cells plays a key role in the occurrence and development of blood–brain barrier damage and may be critical in various pathological mechanisms of blood–brain barrier damage. These new findings suggest a potential new strategy for the treatment of central nervous system diseases through mitochondrial modulation of cerebral vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we describe, for the first time, a facile and efficient approach for selectively synthesizing reduced graphene oxide (RGO) and RGO/Al(OH)3 nanocomposites using Red Al as both the reducing agent and the precursor of Al(OH)3, which is a very powerful reducing agent frequently used in organic synthetic methodologies to convert several types of oxygen containing carbon moieties. The results revealed that the substantial oxygen functionalities on the graphene oxide (GO) were removed by Red Al, and RGO with a C/O ratio as high as 9.0 was yielded. The electrical conductivity of RGO could get to 90S/cm, which was nearly 9 orders of magnitude higher than that of GO. This work not only provides a new reductant to effectively reduce GO, but also develops a facile route to prepare RGO/Al(OH)3 nanocomposites. [Copyright &y& Elsevier]

Background: Chimeric Antigen Receptors (CARs) consist of the antigen-recognition portion of a monoclonal antibody fused to an intracellular signaling domain capable of activating T-cells. CARs displayed on the surface of transduced cells perform non-MHC-restricted antigen recognition and activating intracellular signaling pathways for induction of target cytolysis, cytokine secretion and proliferation. Clinical trials are in progress assessing the use of mature T-lymphocytes transduced with CARs targeting CD19 antigen to treat B-lineage malignancies. CD19 is an attractive target for immunotherapy because of its consistent and specific expression in most of the stages of maturation and malignancies of B-lymphocyte origin, but not on hematopoietic stem cells. Antibodies against the extracellular domain of the CAR molecule (anti-Fab, Fc or idiotype) have been used for detection of CAR expression in research and clinical samples by flow cytometry, but may need development for each construct and present significant background in samples from xenograft models. Methods: A specific reagent for the detection of anti-CD19 CAR expression was developed, a fusion protein consisting of human CD19 extracellular domains and the Fc region of human IgG1 (CD19sIg). Genes encoding CD19sIg fusion proteins were constructed by fusing either exons 1 to 3 (CD19sIg1-3) or exons 1 to 4 (CD19sIg1-4) of the human CD19 cDNA to a human IgG1Fc fragment. These fusion proteins are intended to work in similar fashion as the MHC Tetramers used for identification of antigen-specific T-cells, and may also have other applications in studies of activation of anti-CD19 CAR bearing cells. The CD19sIg proteins were produced from 293 T cells by stable lentiviral vector transduction and purification from culture medium. Results: ELISA assays using several different monoclonal antibodies to CD19 demonstrated dose-related specific binding by the fusion molecule CD19sIg1-4, but no binding by CD19sIg1-3. Conjugation of the CD19sIg1-4 fusion protein to Alexa Fluor 488 allowed specific and sensitive staining of anti-CD19 CAR-bearing cells for flow cytometry assays, detecting as low as 0.5% of CAR-modified primary cells with minimal background staining. Conclusions: This fusion molecule is a sensitive reagent for detection of anti-CD19 CAR derived from any monoclonal antibody present in CAR-modified T-cells. [ABSTRACT FROM AUTHOR]

Background: Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. Purpose: To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Methods: The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Results: The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. Conclusion: AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid demand response (DR) mechanism considering three types of participants: power grid operator (PGO), retailers and end users. Different from the traditional price-based or incentive-based methods, this hybrid mechanism combines real-time pricing and real-time incentive together to implement demand response programs dispatched by PGO, i.e., the PGO provides incentives to retailers and the retailers set optimal real-time prices to users every 5 min. This hybrid DR mechanism can better motivate retailers to participate by providing them with monetary incentives from PGO for load shifting. We use a three-level Stackelberg game to model the proposed mechanism. The PGO first determines the optimal incentive rate to minimize its cost, then the retailers decide the optimal electricity price to maximize their profits, and the users finally choose the optimal power demand to maximize their welfare. The analytical solutions of the optimal decisions for every participant are given. We also propose a distributed algorithm to implement this mechanism in a practical application by considering information asymmetry. The simulation results verify its advantages over traditional demand response mechanisms. • A novel hybrid demand response (DR) mechanism combining real-time pricing and real-time incentive is proposed. • The hybrid DR mechanism is modeled by a three-level Stackelberg game. • The existence and uniqueness of the solution at game equilibrium is proved and analyzed. • A distributed algorithm is proposed to implement hybrid DR under information asymmetry. • The benefits of the power grid, retailers and users are improved under hybrid DR. [ABSTRACT FROM AUTHOR]

The growth of lithium (Li) dendrites, characterized by construction of internal Li substrate and surface solid electrolyte interphase (SEI), represents a significant hurdle for both liquid‐state and solid‐state Li batteries. To better understand the growth behaviors of these dendrites at atomic to device scale, advanced electron microscopy techniques have emerged as a valuable tool, providing high temporal and spatial resolutions for real‐time observations. In this review, the mechanistic aspects of growth of Li dendrites are delved first from both thermodynamic and kinetic perspectives. Then, a systematic overview of the state‐of‐the‐art in‐situ devices is provided that is developed for integration into electron microscopes, detailing the corresponding static and dynamic structures of Li dendrites. Additionally, the utilization of the non‐destructive cryogenic TEM technique is explored to classify and compare the local fine structure information of as‐formed Li deposits, which are influenced by various factors such as current density, temperature, electrolyte composition, solvents, and additives. Overall, this review article offers a comprehensive understanding of the physical origins associated with Li dendrites, spanning from atomic to device scales and encompassing both liquid and all‐solid‐state battery scenarios, then envisioning fundamental principles and strategies for optimizing batteries and overcoming the critical challenges posed by Li dendrites. [ABSTRACT FROM AUTHOR]

• Synergistic mechanisms due to octahedral distortion of BO 6 and the heterogeneous structure formed in Mo-doped LaFeO 3 composite photocatalyst. • Faster and efficient degradation (>98 %) of 100 ppm level nitrogen-containing heterocyclic compounds in 90 min. • Mo-doped LFO nanoparticles with high adsorption capacity as photocatalysts for degradation of nitrogen-containing heterocyclic compounds. In this study, a series of Mo-doped LaFeO 3 composite photocatalyst nanoparticles (x-LFMO, x = 0.33, 0.5, 0.67) were synthesized by ultrasonic-assisted sol–gel method under controlled Mo doping. X-ray diffraction (XRD) analyses indicate that Mo substitutes one-third of the Fe atoms in the B site of the LaFeO 3 to form orthogonal perovskite structures LaFe 0.67 Mo 0.33 O 3 , which is the only pure phase crystal formed at stoichiometric Fe to Mo ratios of 2:1, 1:1, and 1:2, respectively. SEM and N 2 adsorption/desorption revealed significantly smaller particle sizes (30–50 nm) and the formation of rich channels after Mo doping, thus enriching the specific surface area and pore size dispersion. DRS confirmed that the Mo-doped LFO composites exhibit significantly enhanced absorption in the visible region. This can be further explained by DFT theoretical calculations of energy band structures and density of states, which demonstrate that the effective mass of the electrons in LaFe 0.67 Mo 0.33 O 3 is reduced and the off-domain properties of the electrons are enhanced, facilitating the excitation and transport of the photogenerated electrons. Kinetic studies showed that Mo-doped composite nanoparticles exhibit excellent adsorption capacity for quinoline, indole, and pyridine, and the pure phase LaFe 0.67 Mo 0.33 O 3 and 0.5-LFMO performed well for them with removal efficiencies (>98 %) under visible light irradiation. Based on experimental observations and theoretical insights, it is suggested that the higher quantum yield and photocatalytic reactivity of x-LFMO composites are attributed to the bulk oxygen mobility and surface oxygen reactivity promoted by the octahedral distortion of BO 6 in LaFe 0.67 Mo 0.33 O 3 and the heterogeneous structure formed at the interface of the two phases. [ABSTRACT FROM AUTHOR]

Liposome not only can be used as delivery systems for drugs, but has the ability to act as a solubilizing agent for drugs with low aqueous solubility. However, a key limitation in exploiting liposome technology is the availability of scalable, simple production methods for the preparation of liposome. Here we provide a new method, using high gravity technology, to prepare drug loaded liposome with high throughput. The effects of different variables, such as temperature, high gravity level, flow rate ratio of solvent phase to aqueous phase, the mass ratio of egg phosphatidylcholine (EPC) to cholesterol and the mass ratio of EPC to sorafenib (SFN) on particle size and the drug encapsulation efficiency were investigated using an orthogonal experimental design. Through formulation optimization, liposome with average size of 200 nm was successfully produced and drug encapsulation could reach 89%. The as-prepared SFN loaded liposome exhibited greatly enhanced drug release rate compared with the raw SFN. Moreover, resveratrol, as antioxidant, was added into the drug formulation. The addition of resveratrol in the drug formulation not only increased the anti-oxidizability and stability of the liposome but also produced synergistic anticancer effects by cytotoxicity assay. [ABSTRACT FROM AUTHOR]

Background: Chimeric Antigen Receptors (CARs) consist of the antigen-recognition portion of a monoclonal antibody fused to an intracellular signaling domain capable of activating T-cells. CARs displayed on the surface of transduced cells perform non-MHC-restricted antigen recognition and activating intracellular signaling pathways for induction of target cytolysis, cytokine secretion and proliferation. Clinical trials are in progress assessing the use of mature T-lymphocytes transduced with CARs targeting CD19 antigen to treat B-lineage malignancies. CD19 is an attractive target for immunotherapy because of its consistent and specific expression in most of the stages of maturation and malignancies of B-lymphocyte origin, but not on hematopoietic stem cells. Antibodies against the extracellular domain of the CAR molecule (anti-Fab, Fc or idiotype) have been used for detection of CAR expression in research and clinical samples by flow cytometry, but may need development for each construct and present significant background in samples from xenograft models.Methods: A specific reagent for the detection of anti-CD19 CAR expression was developed, a fusion protein consisting of human CD19 extracellular domains and the Fc region of human IgG1 (CD19sIg). Genes encoding CD19sIg fusion proteins were constructed by fusing either exons 1 to 3 (CD19sIg1-3) or exons 1 to 4 (CD19sIg1-4) of the human CD19 cDNA to a human IgG1Fc fragment. These fusion proteins are intended to work in similar fashion as the MHC Tetramers used for identification of antigen-specific T-cells, and may also have other applications in studies of activation of anti-CD19 CAR bearing cells. The CD19sIg proteins were produced from 293 T cells by stable lentiviral vector transduction and purification from culture medium.Results: ELISA assays using several different monoclonal antibodies to CD19 demonstrated dose-related specific binding by the fusion molecule CD19sIg1-4, but no binding by CD19sIg1-3. Conjugation of the CD19sIg1-4 fusion protein to Alexa Fluor 488 allowed specific and sensitive staining of anti-CD19 CAR-bearing cells for flow cytometry assays, detecting as low as 0.5% of CAR-modified primary cells with minimal background staining.Conclusions: This fusion molecule is a sensitive reagent for detection of anti-CD19 CAR derived from any monoclonal antibody present in CAR-modified T-cells. [ABSTRACT FROM AUTHOR]

Erythorbic acid assistant synthesis of CdS quantum dots (QDs) was conducted by homogeneous mixing of two continuous liquids in a high-throughput microporous tube-in-tube micro-channel reactor (MTMCR) at room temperature. The effects of the micropore size of the MTMCR, liquid flow rate, mixing time and reactant concentration on the size and size distribution of CdS QDs were investigated. It was found that the size and size distribution of CdS QDs could be tuned in the MTMCR. A combination of erythorbic acid promoted formation technique with the MTMCR may be a promising pathway for controllable mass production of QDs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Erythorbic acid (EA) was employed in aqueous synthesis of CdS quantum dots (QDs). [•] EA acted as an oxygen scavenger and passivating ligand in the synthesis. [•] EA enhanced the optical properties of CdS QDs and the mechanism was discussed. [•] This route offers an easy and green pathway for producing QDs with good dispersion. [Copyright &y& Elsevier]

Mimicking the multi‐scale highly ordered hydroxyapatite (HAp) nanocrystal structure of the natural tooth enamel remains a great challenge. Herein, a bottom‐up step‐by‐step strategy is developed using extrusion‐based 3D printing technology to achieve a high‐precision dental crown with multi‐scale highly ordered HAp structure. In this study, hybrid resin‐based composites (RBCs) with "supergravity +" HAp nanorods can be printed smoothly via direct ink writing (DIW) 3D printing, induced by shear force through a custom‐built nozzle with a gradually shrinking channel. The theoretical simulation results of finite element method are consistent with the experimental results. The HAp nanorods are first highly oriented along a programmable printing direction in a single printed fiber, then arranged in a layer by adjusting the printing path, and finally 3D printed into a highly ordered and complex crown structure. The printed samples with criss‐crossed layers by interrupting crack propagation exhibit a flexural strength of 134.1 ± 3.9 MPa and a compressive strength of 361.6 ± 8.9 MPa, which are superior to the corresponding values of traditional molding counterparts. The HAp‐monodispersed RBCs are successfully used to print strong and bioactive dental crowns with a printing accuracy of 95%. This new approach can help provide customized components for the clinical restoration of teeth. [ABSTRACT FROM AUTHOR]

Mimicking the multi‐scale highly ordered hydroxyapatite (HAp) nanocrystal structure of the natural tooth enamel remains a great challenge. Herein, a bottom‐up step‐by‐step strategy is developed using extrusion‐based 3D printing technology to achieve a high‐precision dental crown with multi‐scale highly ordered HAp structure. In this study, hybrid resin‐based composites (RBCs) with "supergravity +" HAp nanorods can be printed smoothly via direct ink writing (DIW) 3D printing, induced by shear force through a custom‐built nozzle with a gradually shrinking channel. The theoretical simulation results of finite element method are consistent with the experimental results. The HAp nanorods are first highly oriented along a programmable printing direction in a single printed fiber, then arranged in a layer by adjusting the printing path, and finally 3D printed into a highly ordered and complex crown structure. The printed samples with criss‐crossed layers by interrupting crack propagation exhibit a flexural strength of 134.1 ± 3.9 MPa and a compressive strength of 361.6 ± 8.9 MPa, which are superior to the corresponding values of traditional molding counterparts. The HAp‐monodispersed RBCs are successfully used to print strong and bioactive dental crowns with a printing accuracy of 95%. This new approach can help provide customized components for the clinical restoration of teeth. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nano-CaCO3 was synthesized in a microporous tube-in-tube microchannel reactor. [•] The reactor has a high throughput capacity. [•] The reactor exhibits excellent mass transfer and micromixing effect. [•] Nano-CaCO3 particles have an average size of 28nm with narrow size distribution. [Copyright &y& Elsevier]

Abstract: Ag/SiO2 core–shell nanoparticles within the size of 60nm were applied in marine antimicrobial corrosion coatings. TEM and XRD results indicated silver was completely covered by silica and its crystal form was not affected after coated by silica. Effects of Ag/SiO2 nanoparticles in the microbial corrosion of acrylic-coated steel were studied by means of electrochemical noise analysis (ENA). ENA results reveal that 1wt% Ag/SiO2 nanoparticles exhibit better antimicrobial corrosion activity than that of conventional 40wt% Cu2O biocides. Inductively coupled plasmaoptical emission spectrometry (ICP) showed very lower amount of Ag ions leaching from the matrix resin, whereas a higher amount of copper ion leaching from the resin in the same period. It was concluded Ag/SiO2 core–shell nanoparticles could enhance long-term corrosion protection in comparison with the copper biocides. This composite has a strong potential use in environmentally friendly antimicrobial coatings. [Copyright &y& Elsevier]

Although tapping has been widely used for thread fabrication, it is often a time-consuming process causing a delay on an automated production line. This study investigates the fundamental aspects in vibration-assisted tapping. It addresses two major mechanisms that are responsible for torque reduction during vibration-assisted tapping, i.e., friction torque reduction and material property change at an enhanced strain rate. Theoretical analyses are conducted to account for the effect of vibration on tapping torque reduction, and verified by the tapping experiments with and without vibration assistance. Taps of three different sizes and vibrations of two different waveforms are used in the tapping experiments. The theoretical results are applicable to vibration-assisted tapping and other machining processes. [Copyright &y& Elsevier]

Materials-oriented chemical engineering involves the intersection of materials science and chemical engineering. Development of materials-oriented chemical engineering not only contributes to material research and industrialization techniques but also opens new avenues for chemical engineering science. This review details the major achievements of materials-oriented chemical engineering fields in China, including preparation strategies for advanced materials based on the principles of chemical engineering as well as innovative separation and reaction techniques determined by new materials. Representative industrial applications are also illustrated, highlighting recent advances in the field of materials-oriented chemical engineering technologies. In addition, we also look at the ongoing trends in materials-oriented chemical engineering in China. [ABSTRACT FROM AUTHOR]

Ginsenosides are the pharmacologically active constituents of ginseng. So far, more than 30 ginsenosides have been identified and widely used in pharmaceutical formulations. However, the therapeutic applications of ginsenosides are hampered by their poor solubility and low bioavailability. In this study, we selected two of the most important ginsenosides-Re and Rh2 as model drugs to prepare ginsenoside drug nanocomposites (NanoGS) using the simple aerosol solvent extraction system (ASES) technique to address the poor solubility and bioavailability of these compounds. Compared with raw ginsenosides, NanoGS exhibited significantly enhanced dissolution rate owing to their low crystallinity and high surface area. Furthermore, in vitro cellular investigations showed that NanoGS-Rh2 exhibited outstanding anticancer activity against MCF-7 cancer cells. Therefore, this study is expected to provide a promising strategy that could optimize and broaden the applications of ginsenosides, as well as other water-insoluble drugs in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Summary Dopamine controls essential brain functions through volume transmission. Different from fast synaptic transmission, where neurotransmitter release and receptor activation are tightly coupled by an active zone, dopamine transmission is widespread and may not necessitate these organized release sites. Here, we determine whether striatal dopamine secretion employs specialized machinery for release. Using super resolution microscopy, we identified co-clustering of the active zone scaffolding proteins bassoon, RIM and ELKS in ∼30% of dopamine varicosities. Conditional RIM knockout disrupted this scaffold and, unexpectedly, abolished dopamine release, while ELKS knockout had no effect. Optogenetic experiments revealed that dopamine release was fast and had a high release probability, indicating the presence of protein scaffolds for coupling Ca 2+ influx to vesicle fusion. Hence, dopamine secretion is mediated by sparse, mechanistically specialized active zone-like release sites. This architecture supports spatially and temporally precise coding for dopamine and provides molecular machinery for regulation. [ABSTRACT FROM AUTHOR]

Summary Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPβ recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy. [ABSTRACT FROM AUTHOR]

Summary Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPβ recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Computational fluid dynamics (CFD) technique was employed to reveal liquid flow behaviors in a rotor-stator reactor. Highlights • 2D CFD model was developed to reveal liquid flow characteristics of RSR. • The CFD results agreed well with published data of visual experiments. • Effects of operating conditions on liquid flow patterns in RSR were studied. • Effect of rotor/stator-ring layers of RSR on liquid flow was investigated. Abstract Rotor-stator reactor (RSR) is a novel device for the intensification of multiphase processes and can greatly boost mass transfer and mixing efficiency. However, due to the unique structure, the flow characteristics in the RSR is unknown and difficult to acquire by experiments. Therefore, this work employed computational fluid dynamics (CFD) technique to reveal liquid flow behaviors in an RSR for the first time. The volume of fluid (VOF) multiphase model, sliding model (SM) and standard k–ε model were used to simulate liquid flow field in a typical two-dimensional computational framework of the RSR. It was found that the droplet size and velocity in the cavity zone of the RSR were in agreement with the published data of the visual experiments. The results show that the liquid was quickly split and synchronized with the motion of the rotor layers when injected into the RSR. Two droplet formation schemes were observed in the RSR: “ligament to droplets disintegration” and “droplets disintegration”. The droplets size distribution could be well described by Rosin–Rammler model. The droplets diameter decreased but the droplet velocity increased with increasing rotational speed, while the droplets diameter increased and the droplet velocity changed little with increasing liquid inlet velocity. With the increase of the number of rotor/stator layers, droplet size decreased and velocity increased. The agreement of the experiment and simulation results indicate that the CFD technique is an effective tool to analyze the hydrodynamic characteristics of RSR. [ABSTRACT FROM AUTHOR]

The objectives of this article were (i) to find the association between extreme temperatures and respiratory emergency department (ED) visits and (ii) to explore the added effects of heat waves and cold spells on respiratory ED visits in Beijing from 2009 to 2012. A quasi-Poisson generalised linear model combined with a distributed lag non-linear model was performed to quantify this association. The results indicated that (i) ambient temperature related to respiratory ED visits exhibited a U-shaped association. The minimum-morbidity temperature was 21.5 °C. (ii) the peak relative risk (RR) of cold spells on respiratory ED visits was observed in relatively mild cold spells with a threshold below the 3rd percentile for 4 days (RR = 1.885, 95% CI: 1.300–2.734), and there was a reduction in risk during extremely chilly cold spells (RR = 1.811, 95% CI: 1.229–2.667). However, the risk of heat waves increased with the thresholds, and the greatest risk was found for extremely hot heat waves (RR = 1.932, 95% CI: 1.461–2.554). (iii) the added effect of heat waves was small, and we observed that the added heat wave effect only introduced additional risk in females (RR = 1.166, 95% CI: 1.007–1.349). No added effect of cold spells was identified. In conclusion, the main effects of heat waves and cold spells on respiratory ED visits showed different change trends. In addition, the added effects of extreme temperatures on respiratory ED visits were small and negligible. [ABSTRACT FROM AUTHOR]

A highly orchestrated gene expression program establishes the properties that define mature adipocytes, but the contribution of posttranscriptional factors to the adipocyte phenotype is poorly understood. Here we have shown that the RNA-binding protein PSPC1, a component of the paraspeckle complex, promotes adipogenesis in vitro and is important for mature adipocyte function in vivo. Cross-linking and immunoprecipitation followed by RNA sequencing revealed that PSPC1 binds to intronic and 3'-untranslated regions of a number of adipocyte RNAs, including the RNA encoding the transcriptional regulator EBF1. Purification of the paraspeckle complex from adipocytes further showed that PSPC1 associates with the RNA export factor DDX3X in a differentiation-dependent manner. Remarkably, PSPC1 relocates from the nucleus to the cytoplasm during differentiation, coinciding with enhanced export of adipogenic RNAs. Mice lacking PSPC1 in fat displayed reduced lipid storage and adipose tissue mass and were resistant to diet-induced obesity and insulin resistance due to a compensatory increase in energy expenditure. These findings highlight a role for PSPC1-dependent RNA maturation in the posttranscriptional control of adipose development and function. [ABSTRACT FROM AUTHOR]

pH-sensitive polymer poly (polylactide-co-methacrylic acid)–b-poly (acrylic acid) was synthesized using atom transfer radical polymerization and ring-opening polymerization and characterized by gel permeation chromatography and1H NMR. The polymers can self-assemble to form micelles in aqueous medium, which respond rapidly to pH change within the gastrointestinal relevant pH range. Critical micelle concentrations and pH response behavior of the polymeric micelle were investigated. Water-insoluble drug nifedipine was loaded and the drug-loading content can be controlled by tuning the composition of the polymers. Thein vitrorelease studies indicate pH sensitivity enabled rapid drug release at the environment of simulated intestinal fluid (pH 7.36), the cumulative released amount of NFD reached more than 80% within 24 h, while only 35% in the simulated gastric fluid (pH 1.35). All the results showed that the pH-sensitive P(PLAMA-co-MAA)–b-PAA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior. [ABSTRACT FROM PUBLISHER]

Molecular targeted cancer therapy is a promising strategy to overcome the lack of specificity of anticancer drug. While the binding of c(RGDfK) (cyclic Arginine-Glycine-Aspartic acid-Phenylalanine-Lysine) to α v β 3 over-expressed on tumor cell has been validated, the underlying interaction remains poorly understood. In this work, docking calculation was applied to investigate the interactions between c(RGDfK)/c(RGDfK)-PEG and α v β 3 . The calculated results indicated that c(RGDfK) interacted with α v β 3 mainly by electrostatic interaction, stabilization interaction, and hydrophobic interaction. Conjugation of PEG chain to the c(RGDfK) weakened the binding affinity of c(RGDfK) to α v β 3 . Accordingly, docetaxel(DTX)-loaded target micelles (c(RGDfK)-PEG-PLA/PEG-PLA/DTX) were designed, characterized and evaluated using HeLa cells. In vitro release studies demonstrated both target and non-target micelles displayed almost the same profiles, which best fit in Ritger-Peppas model. Cellular uptake and MTT studies revealed that the target micelles with the presence of c(RGDfK) were more efficiently taken up by HeLa cells and significantly improved the cytotoxicity compared to that of non-target micelles. Cell inhibition rate of target micelles was improved by 20% after 24 h. Our findings suggest that target micelles may be a potential anticancer drug delivery system in the treatment of integrin α v β 3 over-expressed on tumor cell. [ABSTRACT FROM AUTHOR]

Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. [ABSTRACT FROM AUTHOR]

The current investigation showed that oxidation of graphite with low concentration KMnO 4 led to formation of edge-oxidized graphite (EOG) which preserved high crystalline graphitic structure on the basal planes while the edges were functionalized by oxygen-containing groups. Medium and short-time sonication of EOG in water using sodium cholate (SC) as a stabilizer could yield edge-oxidized graphene nanosheets (EOGNs) dispersion at a concentration of up to 0.59 mg/ml. This dispersion was stable at room temperature for more than 6 months. Later, the prepared EOGNs dispersion was used to produce transparent conducting EOGN films by vacuum filtration method. The resulting thin films are uniform and exhibit a transparency of ∼85% at 550 nm and a sheet resistance of ∼26.44 kΩ/□. Moreover, the prepared EOG was found to be dispersible in a wider variety of solvents than GO (graphite oxide), which verifies wider application fields for EOG compared to GO. These results open up new possibilities for preparation of graphene dispersions with insignificant defects. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5 h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers. [ABSTRACT FROM AUTHOR]

This study was conducted to investigatethe effect of inorganicsalts on the mass-transfer coefficient of O3and decolorizationof azo dye (Acid Red 14, AR14) solution through ozonation in a microporoustube-in-tube microchannel reactor (MTMCR). The overall volumetricmass-transfer coefficient (KGa) of O3in the MTMCR was deduced by material balance.The effects of different salts on the KGaof O3and decolorization efficiencyof the AR14 solution were studied, and results show that both weresignificantly affected by the inorganic salts. Although the KGaof O3and thedecolorization efficiency of AR14 increased with increasing salt concentrationand pH, the effect of NaNO3was much weaker than that ofNaCl, Na2SO4, Na2CO3,and NaHCO3. The enhanced KGaof O3and decolorization could be dueto the generation of species with high oxidizing ability in the presenceof the salts. [ABSTRACT FROM AUTHOR]

The proportion of patients with hypochloremia (< 99 mmol/L), normal chloride (99-112 mmol/L), and hyperchloremia (> 112 mmol/L) was 19.2%, 68.9%, and 11.8%, respectively, and the inhospital mortality in these three groups was 40.6%, 24.4% and 32.2%, respectively. Online Letters to the Editor e340 www.ccmjournal.org March 2021 • Volume 49 • Number 3 to see that hypochloremia is again associated with higher inhospital mortality in a different patient cohort, with 40.6% mortality rate in hypochloremic patients compared with 24.4% in normochloremic patients. Downloaded from http://journals.lww.com/ccmjournal by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60Etgtdnn9T1vLQWJq3kbRMjK/ocE on 03/31/2021 Downloaded from http://journals.lww.com/ccmjournal by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60Etgtdnn9T1vLQWJq3kbRMjK/ocE on 03/31/2021 Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. [Extracted from the article]

Despite the importance of dopamine for striatal circuit function, mechanistic understanding of dopamine transmission remains incomplete. We recently showed that dopamine secretion relies on the presynaptic scaffolding protein RIM, indicating that it occurs at active zone-like sites similar to classical synaptic vesicle exocytosis. Here, we establish using a systematic gene knockout approach that Munc13 and Liprin-α, active zone proteins for vesicle priming and release site organization, are important for dopamine secretion. Furthermore, RIM zinc finger and C 2 B domains, which bind to Munc13 and Liprin-α, respectively, are needed to restore dopamine release after RIM ablation. In contrast, and different from typical synapses, the active zone scaffolds RIM-BP and ELKS, and RIM domains that bind to them, are expendable. Hence, dopamine release necessitates priming and release site scaffolding by RIM, Munc13, and Liprin-α, but other active zone proteins are dispensable. Our work establishes that efficient release site architecture mediates fast dopamine exocytosis. [Display omitted] • Evoked striatal dopamine release necessitates the active zone proteins Munc13 and RIM • Ablating Munc13 from dopamine neurons leads to defects in their axon structure • Dopamine release depends on Liprin-α2 and Liprin-α3, but not on RIM-BP1 and RIM-BP2 • RIM domains that bind to Munc13 and Liprin-α restore some release after RIM ablation Dopamine is a key neuromodulator for the control of striatal circuit function. Banerjee et al. show that evoked dopamine secretion occurs at release hotspots that contain active zone proteins. Munc13, Liprin-α, and RIM cooperate to mediate vesicle priming and release, while other known active zone proteins are dispensable. [ABSTRACT FROM AUTHOR]

In this work, dasatinib (DAS) nanoemulsion and nanocrystal are produced by high-gravity technology that approaches to practical mass production. The drug nanoformulations were systematically characterized and evaluated. At a low high-gravity level (β) = 47, nanoemulsion droplets were 16.15 ± 0.42 nm with a PDI of 0.122 ± 0.021. The nanoemulsion's size and active pharmaceutical ingredient (API) content remained stable at long-term (4 months) freeze–thaw and dilution experiments. At a high β = 188, the as-prepared nanocrystal was lamellar with a short diameter of about 200 nm and a long diameter of about 750 nm. In vitro performances demonstrated the nanoemulsion displayed higher cytotoxicity on MDA-MB-231 tumor cells, Caco-2 cell permeability and drug release than that of the nanocrystal, indicating that nanoemulsion should be an ideal alternative for dasatinib oral administration. [ABSTRACT FROM AUTHOR]

Highlights: [•] We predict the crystal habits of five different dirithromycin solvates. [•] Main crystal habit faces were analyzed by calculating the energy values. [•] The solvent effect was studied by molecular dynamics simulation. [•] Solvents with different properties were investigated in a systematic study. [•] Polarity and hydrogen bond donor/acceptor ability were further analyzed. [ABSTRACT FROM AUTHOR]

Dirithromycin (DIR) was crystallized from acetone solvent in the form of an acetone solvate. Its crystal structure belongs to monoclinic, space group P21, with the unit cell parameters a=14.688(3)Å, b=11.6120(12)Å, c=14.9129(12)Å, β=94.794(10)°, and Z=2. Results of X-ray diffraction (XRD) and thermogravimetry–differential scanning calorimetry (TG–DSC) indicated that the solvent molecules could enter the crystal lattice and thus the solvate is formed. The molecular dynamics (MD) simulation method was applied to study the solvent effect. It revealed that the relative growth rates of the main crystal habit faces changed a lot, which made the most morphologically important habit face shift from (001) face to (100) face due to polar groups or atoms exposure and hence a large solvent interaction. The prism habit predicted by a modified attachment energy (AE) model agreed well with the observed experimental morphology grown from the acetone solution. This prediction method may help for a solvent selection to improve the morphology in the drug crystallization process. [ABSTRACT FROM AUTHOR]

A bi-solvent system (ethanol and water) with the presence of l -glutamic acid (L-glu) was developed to achieve the controlled synthesis of whisker-like or urchin-like Sr-substituted HA (SrHA) through hydrothermal treatment. The effects of initial temperature of aqueous solution (ASIT), the presence of Sr, and ethanol proportion on HA morphology were investigated and the underlying mechanisms were illustrated. The results indicate that Sr and ethanol have antagonistic effects on the size of HA whisker, the introduction of Sr tends to reduce the whisker size, while the addition of ethanol tends to increase the nucleation efficiency. Finally, the whisker size and uniformity of SrHA can be regulated via ethanol proportion in the bi-solvent system. ASIT mainly affects the uniformity of solution by affecting Brownian motion in solution, which couples with the different solubility of l -glu and reactant ions in water and ethanol, ultimately determines whether the morphology of HA is whisker-like or urchin-like. Our bi-solvent system simplifies the complex process of template agent screening compared with the ways that introducing several templates agents to achieve the morphology regulation, and enriches the methods of controlled synthesis of different morphological Sr-HA. This feasible method may provide new strategy for simplifying the synthesis of other ions-doping HA with a certain morphology. [ABSTRACT FROM AUTHOR]