N-Salicyloyl Tryptamine Derivatives as Potent Neuroinflammation Inhibitors by Constraining Microglia Activation via a STAT3 Pathway.

Neuroinflammation is an important factor that exacerbates neuronal death and abnormal synaptic function in neurodegenerative diseases (NDDs). Due to the complex pathogenesis and the presence of blood-brain barrier (BBB), no effective clinical drugs are currently available. Previous results showed that N-salicyloyl tryptamine derivatives had the potential to constrain the neuroinflammatory process. In this study, 30 new N-salicyloyl tryptamine derivatives were designed and synthesized to investigate a structure-activity relationship (SAR) for the indole ring of tryptamine in order to enhance their antineuroinflammatory effects. Among them, both in vitro and in vivo compound 18 exerted the best antineuroinflammatory effects by suppressing the activation of microglia, which is the culprit of neuroinflammation. The underlying mechanism of its antineuroinflammatory effect may be related to the inhibition of transcription, expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) that subsequently regulated downstream cyclooxygenase-2 (COX-2) expression and activity. With its excellent BBB permeability and pharmacokinetic properties, compound 18 exhibited significant neuroprotective effects in the hippocampal region of lipopolysaccharides (LPS)-induced mice than former N-salicyloyl tryptamine derivative L7. In conclusion, compound 18 has provided a new approach for the development of highly effective antineuroinflammatory therapeutic drugs targeting microglia activation.

Oxygen Vacancy-Laden Confinement Impact on Degradation of Metal Complexes.

Oxygen vacancies (Vo) have been recognized as the superior active site for PS-mediated environmental remediation; however, the formation and activation of Vo associated with the effects of chemical and spatial environments remain ambiguous. Herein, attributing to the low defect-formation energy of Vo in the presence of sulfonate groups, an in situ nucleating Vo-laden CuO nanosheet was deliberately fabricated inside the phase of a sulfonated mesoporous polystyrene substrate (Vo-CuO@SPM). The as-prepared nanocomposite demonstrated an excellent treatment efficiency toward metal complexes [Cu-EDTA as a case] with ignorable Cu(II) leaching, and it can be repeatedly employed for 25 recycles (not limited). Mechanistically, the electron transfer and the mass transport for PDS nonradical activation were proved to be substantially enhanced by the delocalized electrons and with the assistance of the microchannel environment. This work not only establishes insight into the formation of oxygen vacancies but also reveals the PS activation mechanism in the spatially confined sites.

Genome-wide identification and analysis of DEAD-box RNA helicases in Gossypium hirsutum.

DEAD-box RNA helicases, a prominent subfamily within the RNA helicase superfamily 2 (SF2), play crucial roles in the growth, development, and abiotic stress responses of plants. This study identifies 146 DEAD-box RNA helicase genes (GhDEADs) and categorizes them into four Clades (Clade A-D) through phylogenetic analysis. Promoter analysis reveals cis-acting elements linked to plant responses to light, methyl jasmonate (MeJA), abscisic acid (ABA), low temperature, and drought. RNA-seq data demonstrate that Clade C GhDEADs exhibit elevated and ubiquitous expression across different tissues, validating their connection to leaf development through real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Notably, over half of GhDEADs display up-regulation in the leaves of virus-induced gene silencing (VIGS) plants of GhVIR-A/D (members of m6A methyltransferase complex, which regulate leaf morphogenesis). In conclusion, this study offers a comprehensive insight into GhDEADs, emphasizing their potential involvement in leaf development.

Pioneering Piezoelectric-Driven Atomic Hydrogen for Efficient Dehalogenation of Halogenated Organic Pollutants.

The electrocatalytic hydrodehalogenation (EHDH) process mediated by atomic hydrogen (H*) is recognized as an efficient method for degrading halogenated organic pollutants (HOPs). However, a significant challenge is the excessive energy consumption resulting from the recombination of H* to H2 production in the EHDH process. In this study, a promising strategy was proposed to generate piezo-induced atomic H*, without external energy input or chemical consumption, for the degradation and dehalogenation of HOPs. Specifically, sub-5 nm Ni nanoparticles were subtly dotted on an N-doped carbon layer coating on BaTiO3 cube, and the resulted hybrid nanocomposite (Ni-NC@BTO) can effectively break C-X (X = Cl and F) bonds under ultrasonic vibration or mechanical stirring, demonstrating high piezoelectric driven dehalogenation efficiencies toward various HOPs. Mechanistic studies revealed that the dotted Ni nanoparticles can efficiently capture H* to form Ni-H* (Habs) and drive the dehalogenation process to lower the toxicity of intermediates. COMSOL simulations confirmed a "chimney effect" on the interface of Ni nanoparticle, which facilitated the accumulation of H+ and enhanced electron transfer for H* formation by improving the surface charge of the piezocatalyst and strengthening the interfacial electric field. Our work introduces an environmentally friendly dehalogenation method for HOPs using the piezoelectric process independent of the external energy input and chemical consumption.

Toxicity and endocrine-disrupting potential of PM2.5: Association with particulate polycyclic aromatic hydrocarbons, phthalate esters, and heavy metals.

The adverse effects of fine atmospheric particulate matter with aerodynamic diameters of ≤2.5 µm (PM2.5) are closely associated with particulate chemicals. In this study, PM2.5 samples were collected from highway and industry sites in Hangzhou, China, during the autumn and winter, and their cytotoxicity and pulmonary toxicity and endocrine-disrupting potential (EDP) were evaluated in vitro and in vivo; the particulate polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and heavy metals were then characterized. The toxicological results suggested that the PM2.5 from highway site induced higher cytotoxicity (cell viability inhibition, intracellular oxidative stress, and cell membrane injury) and pulmonary toxicity (inflammatory response (IR) and oxidative stress (OS)) than the samples from industry site, while the PM2.5 from industry site exhibited higher EDP (estrogenic and anti-androgenic activity). The cytotoxicity and pulmonary toxicity of PM2.5 in the winter were higher than those in the autumn, while no seasonal difference in the endocrine-disrupting potential was observed (p > 0.05). The Pearson correlation analysis between the biological effects and particulate chemicals revealed that the PM2.5-induced inflammatory response and oxidative stress were closely associated with the particulate PAHs and heavy metals (Pearson correlation coefficients: rIR, PAHs = 0.822-0.988, rIR, heavy metals = 0.895-0.971, rOS, PAHs = 0.843-0.986, and rOS, heavy metals = 0.887-0.933), while particulate di (2-ethylhexyl)phthalate (DEHP) substantially contributed to the EDP of PM2.5 (rEDP, DEHP = 0.981). This study indicated that the toxicity and EDP of PM2.5 could vary with the surrounding environment and season, which was closely associated with the variations of particulate chemicals. Further studies are needed to clarify the associations between the harmful effects of PM2.5 and other contributing factors.

Increased Levels of Circulating Monocytic- and Early-Stage Myeloid-Derived Suppressor Cells (MDSC) in Acute Myeloid Leukemia.

BACKGROUND: To investigate the levels of circulating myeloid-derived suppressor cells (MDSC) in patients with primary acute myeloid leukemia (AML), and to explore the relationship between the number of MDSC and AML. METHODS: Peripheral blood samples from 29 patients with primary AML and 30 healthy controls were collected. CD33, CD11b, HLA-DR, CD14, and CD15 were used to label cells, and flow cytometry was used to analyze the numbers of total MDSC and subgroups eMDSC (early-stage MDSC), M-MDSC (monocytic MDSCs), PMN-MDSC (polymorphonuclear-MDSCs) or G-MDSC (granulocytic-MDSC) via two gating strategies. Presence of MDSC in AML was determined after assessment of clinical data. RESULTS: Phenotypic analysis of MDSC by the two gating strategies was consistent. Compared with healthy controls, the numbers of total MDSC (CD33+CD11b+ HLA-DR-) and G-MDSC (CD33+CD11b+ HLA-DR-CD14¬-CD15+ or CD14¬-CD15+ CD11b+) in peripheral blood of AML patients were lower (p < 0.05), while numbers of M-MDSC (CD33+CD11b+ HLA-DR-CD14+CD15- or HLA-DR-/LOWCD14+) and eMDSC (CD33+CD11b+ HLA-DR-/LOWCD14-CD15-) were higher (p < 0.05). The levels of G-MDSC in peripheral blood of AML-M2 patients were higher than those in other subtypes, along with total MDSC, while the levels of eMDSC and M-MDSC in AML-M3 patients were higher than those in other subtypes. CONCLUSIONS: The high frequency of HLA-DR-/LOWCD14+M-MDSC and CD33+CD11b+ HLA-DR-/LOWCD14-CD15- eMDSC in peripheral blood of AML patients indicates potential for MDSC as a diagnostic index in AML.

Removal of pharmaceuticals and personal care products (PPCPs) and environmental estrogens (EEs) from water using positively charged hollow fiber nanofiltration membrane.

Nanofiltration (NF) membranes show great potential for advanced water treatment, especially for trace organic pollutant removal. The removal efficiency of pharmaceuticals and personal care products (PPCPs) and environmental estrogenic hormones (EEHs) by positively charged hollow fiber NF membranes (PEI-NF) were evaluated. The separation properties were evaluated by changing the operating pressure, temperature, ionic strength, and cation species. A relationship between the physicochemical characteristics of the pharmaceuticals and the NF membrane retention behavior was established. The results showed that the rejection rates of the PEI-NF membrane for the selected PPCPs and EEHs ranged from 81 to ~ 91.26%. For positively (negatively) charged pharmaceutical molecules, the electrostatic repulsion (attraction) effect and steric hindrance were the dominant rejection mechanisms of the PEI-NF membrane. For neutral pharmaceutical molecules, in addition to the size sieving effect, the hydration-induced size increase of hydrophilic substances improved the rejection rates. Both the molecular structure and diffusion coefficient of pharmaceutical molecules influenced their rejection by the PEI-NF membrane to a certain extent. Moreover, the PEI-NF membrane showed a high removal effect for PPCPs and EEHs in water samples from actual tap water plants.

Application of Peripheral Blood Lymphocyte Count in Prediction of the Presence of Atypical Lymphocytes.

BACKGROUND: Atypical lymphocytes (AL), or reactive lymphocyte, exist in peripheral blood when stimulated by viral infection, drugs, inflammatory signals or allergens. Studies have shown that specific changes in peripheral blood (PB) analysis can predict morphological changes in blood cells. The objective of this study was to explore the value of the peripheral blood lymphocyte count in predicting the presence of AL. METHODS: One hundred ninety-nine outpatients were selected from Beijing Chao-Yang Hospital, Capital Medical University from January to April 2015 and underwent manual cell classification with evaluation of complete clinical data. The results of manual classification of peripheral blood leukocytes and peripheral blood routine analysis were assessed, and the correlation between peripheral blood lymphocyte counts and presence of atypical lympho-cytes evaluated using receiver operating characteristic (ROC) curves for each subject. RESULTS: Peripheral blood lymphocytes ≥ 2.375 x 109/L was found to be the optimal cutoff point for predicting atypical lymphocytes. The area under the curve (AUC), 95% confidence interval (CI), sensitivity and specificity were 0.7984, 0.7121 - 0.8846, 68.42%, and 82.8%, respectively, while the accuracy was moderate. When the proportion of peripheral blood lymphocytes was greater than 35.90%, the AUC, 95% CI, sensitivity, and specificity were 0.8729, 0.8092 - 0.9366, 89.47%, and 76.34%, respectively, while the accuracy was moderate. CONCLUSIONS: The peripheral blood lymphocyte count of a patient has good predictive value for the existence of atypical lymphocytes, which is helpful for clinical diagnosis.

Negatively-charged nanofiltration membrane and its hexavalent chromium removal performance.

To enhance hexavalent chromium (Cr(VI)) removal performance under acidic conditions, the nanofiltration (NF) membrane with enhanced negative charge was fabricated via introducing 2, 5-diaminobenzenesulfonic acid (DABSA) into polyamide layer. The control membrane (NF-P) was directly prepared from piperazine and 1, 3, 5-benzenetricarbonyltrichloride. Surface chemical compositions, morphology, surface charge, pore size, permeability and pH-dependent separation performance of the fabricated membranes were characterized. The membranes showed the similar water permeance (∼11.5 L m-2 h-1 bar-1) and Na2SO4 rejections (∼98%) under neutral environments. The DABSA introduced NF membrane (NF-PD) was negatively charged in the pH range of 2.5-11, while the isoelectric point for NF-P was ∼pH 4.0. Cr(VI) removal ability was then evaluated under various concentrations and pH environments. The results indicated that NF-PD showed the better Cr(VI) rejection performance in all tested conditions than NF-P, especially under acidic environments (e.g., pH 4 and pH 5). Moreover, there was a fluctuation of the rejection with the increase of Cr(VI) concentration under acidic environments, which was mainly caused by the formation of Cr2O72- species. The harmful Cr(VI) was efficiently removed by the NF membrane with enhanced negative charge under acidic environments, which indicated the wider application range of the NF membrane.

A novel air-assisted liquid-liquid microextraction based on in-situ phase separation for the HPLC determination of bisphenols migration from disposable lunch boxes to contacting water.

In this study, a novel air-assisted liquid-liquid microextraction (AALLME) method was developed for the HPLC determination of bisphenols migration from disposable plastic lunch box to contacting water. The AALLME was carried out in commercially-available medical plastic syringes with low-density extraction solvent (n-octanol), and the reaction of NaHCO3 and HCl was introduced to simultaneously induce the in-situ phase separation and salt effect. After the AALLME processes, the upper organic phase was pushed into the end of syringes (narrow tube) by moving the piston so that it could be readily collected for the HPLC analysis. The factors including the type and volume of extraction solvent, NaHCO3 addition and extraction cycles were optimized. Under the optimal conditions, the limits of detection (LODs) for target bisphenols were evaluated to be 0.2-0.7 µg L-1, and good linearities with correlation coefficients higher than 0.9955 were obtained. The recoveries for target bisphenols ranged from 80% to 106%, with the relative standard deviations (RSDs) of 4.4-14.1%. The proposed method was successfully applied to investigate the migration of bisphenols from the disposable plastic lunch boxes to the contacting water, revealing that compared to the conventional water-bath heating, the microwave heating could induce the significant migration of bisphenols in a much shorter time.

Typical pharmaceutical molecule removal behavior from water by positively and negatively charged composite hollow fiber nanofiltration membranes.

The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin, were characterized in this study. The saturation adsorption behaviors of the different pharmaceutical molecules on each membrane surface were studied and found to be related to the molecular weight, charge and hydrophilicity of the pharmaceutical molecules. After the pharmaceutical molecules reached adsorption equilibrium, the rejection rates of different NF membranes were characterized. The rejection rates of primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin by the PEI-NF membrane were 85.6%, 91.8%, 79.9%, 98.1%, 93.3%, and 97.1%, respectively. Meanwhile, the rejection rates of the pharmaceutical molecules by the PIP-NF membrane were 82.2%, 85.4%, 91.5%, 79.1%, 87% and 93.3%, respectively. The influence of feed concentration, operation pressure, temperature, pH and ionic strength on the rejection behaviors of the different charged NF membranes were also studied.

Characterization of PAHs in size-fractionated submicron atmospheric particles and their association with the intracellular oxidative stress.

The submicron atmospheric particulate matters (PMs), consisting of 7 size-resolved fractions, were collected by two Dekati low pressure impactors from December 2015 to January 2016 in Hangzhou, China. The chemical analysis revealed the higher accumulation efficiency of polycyclic aromatic hydrocarbons (PAHs) in the finer submicron PMs, and 77.0% of particulate PAHs in PM1 were associated with PM0.4. Moreover, the BaP equivalent concentrations (BaPeq) were evaluated for size-fractionated submicron PMs, indicating that 77.2% of carcinogenicity of particulate PAHs in PM1 were associated with PM0.4. In the cytotoxic tests, a significant size-dependent decrease of glutathione (GSH) level was observed in the PMs-exposed human pulmonary epithelial cells (A549), demonstrating the greater intracellular oxidative stress induced by the finer submicron PMs. The results also suggested that 82.4% of PM1-induced oxidative stress were associated with PM0.4, and the intracellular oxidative stress was significantly correlated with the particulate PAHs. Therefore, besides PM10, PM2.5 and PM1, special attentions should be given to PM0.4 as well.

Transmission and Accumulation of Nano-TiO2 in a 2-Step Food Chain (Scenedesmus obliquus to Daphnia magna).

The recent increase in nanomaterial usage has led to concerns surrounding its health risks and environmental impact. The food chain is an important pathway for high-trophic-level organisms absorbing and enriching nanomaterials. Our study therefore simulated nanometer titanium dioxide (nano-TiO2) transfer along a 2-step food chain, from the unicellular alga Scenedesmus obliquus to the water flea Daphnia magna. We also explored the effect of sodium dodecyl benzene sulfonate (SDBS) on nano-TiO2 bioavailability. A suspension of 10 mg/L nano-TiO2 was optimally dispersed in aqueous solutions by 5 mg/L SDBS. After 72 h, S. obliquus growth was not significantly affected by 10 mg/L nano-TiO2, 5 mg/L SDBS and their mixed suspension. SDBS not only improved nano-TiO2 stability in water, but also increased its uptake in S. obliquus and enhanced its accumulation in D. magna. Our study suggests that nano-TiO2 is mildly toxic to S. obliquus, and can be transferred along the aquatic food chain with a biomagnification effect.

Predictive Significance of Peripheral Blood Smears in Patients with Fever of Unknown Origin: A Retrospective Study of 2871 Cases.

BACKGROUND: Fever of unknown origin (FUO) is a common manifestation and diagnostic problem especially in primary care. Pointing out a diagnosis of FUO often requires numerous noninvasive and invasive procedures. Peripheral blood (PB) smear examination frequently provides many timely and valuable diagnostic clues in various disorders. Few assessments of PB smear morphologic examinations used in the diagnostic evaluation of FUO have been reported. METHODS: To determine whether PB smears have important roles in exploring the causes of FUO, we collected PB smears of 2871 FUO patients from Beijing Chao-yang Hospital affiliated to Capital Medical University from September 2012 to August 2014. Combined with relevant clinical data, we analyzed the PB morphologic features in all the FUO patients. RESULTS: We found the presence of atypical lymphocytes (64.33%), nuclear left shift (46.33%), toxic granulation, vacuolization, and 4 cases of malaria in FUO patients, markedly more than the health control group (p < 0.05), and morphologically consistent with the diagnosis of infectious diseases. Notably, the presence of blasts or immature cells in 26 cases (9%o) and the abnormal changes of leukocytes, erythrocytes or platelets in 4 cases provided predictive information for exploring the causes of FUO, followed by bone marrow smears and other procedures to further confirm the diagnosis as hematological diseases, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), Evans syndrome, agranulocytosis, immune thrombocytopenic purpura (ITP). CONCLUSIONS: Our findings demonstrate that a timely and careful observing of PB smears is helpful for clarifying the diagnosis and contributes to appropriate treatment in patients with FUO.

[Clinical significance of serum vascular endothelial growth factor in patients with multiple myeloma].

This study was purposed to investigate the relation of serum vascular endothelial growth factor (VEGF) levels with clinical types and therapeutic efficacy of multiple myeloma (MM), and to analyze the significance of VEGF in MM. The levels of serum VEGF were detected by enzyme-linked immunosorbent assay (ELISA) technique in 76 patients with MM. The relationship between the serum VEGF levels with MM patients' age, stages, types, and efficacy were analyzed. The results showed that the patients who were less than 65 years old had higher serum VEGF levels than elder patients, however, the difference between them had no statistical significance (P > 0.05). The VEGF level was the highest in IgG type patients, and then in light chain type, lowest in IgA type, however there were no statistical differences between them (P > 0.05). Patients of DS stage III had higher VEGF level than that of stage II, and there was also no statistical difference (P > 0.25). Patients of ISS stage I had lower VEGF level than that of stage II and III, and it also showed no statistical difference (P > 0.05). After treatment, patients obtained complete remission (CR) or very good partial remission (VGPR) had decrease of serum VEGF level, however, patients obtained less than partial remission (PR) had increase of serum VEGF level. Patients were divided into two groups according serum VEGF level ( ≤ 150 ng/L), patients with high VEGF levels had short overall survival time, there was statistical difference (P = 0.03). It is concluded that the serum VEGF level of MM patients dose not relate with age, clinical stages and M protein types; however, there was a certain association between overall survival and serum VEGF level, and the later may be one of poor prognostic factors.

[Studies on the dispersion and deposition behavior of nano-TiO2 in aquatic system].

The existing form and environmental behavior of nTiO2 in aquatic system are mainly affected by environmental factors. The dispension and deposition behavior of nTiO2 was investigated by changing pH values of the suspension liquid and adding electrolytes and surfactants using P25 nano-TiO2 as the research object. The results indicated that the pH value obviously affected the stability of nTiO2 by changing the charge distribution on the nTiO2 particles. TiO2 nanoparticles were highly aggregated to deposit when the pH value was close to the isoelectric point. The characteristic adsorption ion of AlCl3, CaCl2, NaCl and Na2SO, after ionization on the surface of nTiO, particles varied from each other. The adsorption of cations neutralized the negative charge on the surface of nTiO2 particles which led to the quick aggregation and deposition of nTiO2 particles. The adsorption of anions improved the stability of nTiO2 particles in water by increasing electrostatic repulsion between TiO2 particles. Surfactants would adsorb onto the surface of nTiO2 particles and enhance the stability of nTiO, by changing the surface properties of the nanoparticles. The potential energy of nTiO2 particles were simulated by the DLVO theory. The simulative potential energy curve confirmed that the change of relevant water environment conditions led to the change of potential energy of nTiO, particles, which determined the dispension and deposition behavior of nTiO2 particles.