Search

Toxicological studies show that exposure to disinfection byproducts, including trihalomethanes (THMs), negatively affects thyroid function; however, few epidemiological studies have explored this link. This study included 2233 adults (ages ≥20 years) from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) who were measured for blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), or bromoform (TBM)] and serum thyroid function biomarkers [thyroid-stimulating hormone, free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb)]. Multivariable linear regression models showed positive associations between blood TCM, BDCM, and total THMs (the sum of all four THMs) concentrations and serum FT4, whereas inverse associations were found between blood DBCM and total brominated THM (Br-THM; the sum of BDCM, DBCM, and TBM) concentrations and serum TT3 (all p < 0.05). Besides, positive associations were observed between blood TCM concentrations and FT4/FT3 ratio, between BDCM, DBCM, and Br-THM concentrations and TT4/TT3 ratio, and between DBCM and Br-THM concentrations and FT3/TT3 ratio (all p < 0.05). Blood THM concentrations were unrelated to the serum levels of thyroid autoantibodies TgAb or TPOAb. In summary, exposure to THMs was associated with altered serum biomarkers of thyroid function but not with thyroid autoimmunity among U.S. adults.

Nutrient metabolism is crucial for the survival of insects through the diapause. However, little is known about the metabolic mechanism of prolonged diapause. The sawfly, Cephalcia chuxiongica (Hymenoptera: Pamphiliidae), is a notorious defoliator of pine trees in southwest China. One of the distinguishing biological characteristics of this pest is the prolonged diapause of about 1.5 years. In this study, the body lipid, carbohydrate (total body sugar, glycogen, trehalose, and glucose), protein, and glycerol contents were measured in diapausing larvae of C. chuxiongica. The results showed that the changes of biochemical composition in C. chuxiongica are associated with the diapause initiation, maintenance, and termination phases. During the initiation phase, trehalose, glucose, and glycerol increased significantly, but glycogen decreased sharply. In general, the lipid, carbohydrate, and glycerol levels decreased gradually across the maintenance phase. At termination phase, the contents of glycogen and lipid persistently decreased, while an increase of trehalose, glucose, and glycerol contents were detected. The protein level was significantly higher at maintenance phase than at initiation and termination phases. It was also found that elevation of trehalose, glucose, and glycerol contents occurred in winter. These implies that the metabolites with altered levels in diapausing larvae of C. chuxiongica are responsible for maintaining a prolonged development and overwintering.

Self-microemulsifying drug delivery systems (SMEDDSs) have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules. However, information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare. Aggregation-caused quenching (ACQ) fluorescent probes are utilized to visualize the in vivo behaviors of SMEDDSs, because the released probes during lipolysis are quenched upon contacting water. Two SMEDDSs composed of medium chain triglyceride and different ratios of Tween-80 and PEG-400 are set as models, meanwhile Neoral® was used as a control. The SMEDDS droplets reside in the digestive tract for as long as 24 h and obey first order kinetic law of lipolysis. The increased chain length of the triglyceride decreases the lipolysis of the SMEDDSs. Ex vivo imaging of main tissues and histological examination confirm the trans-epithelial transportation of the SMEDDS droplets. Approximately 2%–4% of the given SMEDDSs are transported via the lymph route following epithelial uptake, while liver is the main termination. Caco-2 cell lines confirm the cellular uptake and trans-epithelial transport. In conclusion, a fraction of SMEDDSs can survive the lipolysis in the gastrointestinal tract, permeate across the epithelia, translocate via the lymph, and accumulate mainly in the liver.

Accurate and reliable evaluations of potential groundwater areas are of significance in the hydrogeological assessments of coalfields because water inrush disasters may be caused by unclear groundwater potential. A three-dimensional geological model of porosity based on deterministic modeling and a facies-controlled method are used to determine the groundwater potential of the coal measure aquifer. The modeling processes are as follows: based on the interlayer and discontinuity (faults) data extracted from boreholes and geological maps, an integrated sequence framework model is developed. Using the results of sedimentary microfacies identification and the method of deterministic modeling, a sedimentary microfacies model is successfully established. Finally, based on facies-controlled and sequential Gaussian methods, an effective porosity model is established that can predict the groundwater potential. The predicted results show that sandstones sedimented in channel, point bar, and batture environments possess high effective porosity and strong groundwater potential; however, the sandstones sedimented in interdistributary bays, flood plains, and sand sheets possess low effective porosity. Model validation was performed based on the hydrological pumping test data collected from observation boreholes, drainage water inflow data from dewatered boreholes in the tunnel around workface, and the mine water inflow in tunnels and the workfaces. The validation analysis results show that the effective porosity and sedimentary facies were correlated with the actual flux. The predicted results are consistent with the actual flux data, validating the predicted model.

Perovskite synthesis out in the open Although methods have been developed that create the photoactive black perovskite phase of formamidinium lead iodide (α-FAPbI 3 ), these routes are temperature and humidity sensitive and less compatible with large-scale solar cell production. Hui et al. report an alternative route in which vertically aligned lead iodide thin films are grown from the ionic liquid methylamine formate. Nanoscale channels in the films lower the barrier to permeation of formamidinium iodide and enable transformation to α-FAPbI 3 , even at high humidity and room temperature. Solar cells made with these films have power conversion efficiencies as high as 24.1% that display high stability. Science , this issue p. 1359

As the beginning of rare earth industry, several days are normally required for characterization of rare earth elements (REEs) fractionation in ore samples. Herein, rapid fractionation analysis of 15 REEs and accompanied metal (Fe, Mn, etc.) in ore samples has been achieved within 1 h using ICP-MS with a homemade device for online sequential solvent extraction. As a result, five fractionations for REEs occurrences, i.e., water soluble, exchangeable, reducible, oxidizable and crystalline, have been identified, offering chemical insights which not only reveal the formation mechanism of REEs ores but also show great implications for guiding the exploitation and separation of REEs. In comparison with conventional methods, the present approach significantly shortened the analysis time (1 h vs. ∼80 h) and reduced the sample consumption (1.0 mg vs. 5.0 g) with high recovery (>95%), providing a useful platform for the rapid quantitative fractionation analysis of REEs in complexed samples such as ore and fossils.

The development of an efficient and low-cost strategy for the production of monoethylene glycol (MEG) through hydration of ethylene oxide (EO) at low H2O/EO molar ratios is an important industrial challenge. We have established that by using CO2 as the reaction atmosphere, hydration of EO can be achieved at a low H2O/EO ratio of 1.5 : 1 along with high yields (88–94%) and selectivities (91–97%) of MEG catalyzed by binary catalysts of ionic liquids and organic bases. The results are significantly better than those of experiments conducted under an atmosphere of N2. Isotope labeling experiments revealed that CO2 had altered the reaction pathway and participated in the reaction, in which cycloaddition of EO with CO2 occurred first followed by the hydrolysis of ethylene carbonate (EC) to generate MEG and recover CO2. The ionic liquids and organic bases synergistically catalyzed the one-pot two-step reaction. DFT calculations confirmed that this route is more kinetically favorable compared to the pathway of direct epoxide hydration.

In order to reduce the immunoreactivity of sarcoplasmic calcium-binding protein (SCP), site-directed mutations were used to replace key amino acids in the conformational epitopes and calcium-binding sites. The mutant SCPs (mSCPs) were expressed in Escherichia coli, and their immunoreactivities were analyzed using iELISA and basophil activation assays. Furthermore, the structural changes of mSCPs were determined from the circular dichroism spectra. The iELISA results showed that mSCPs could effectively inhibit the binding of wild-type SCP (wtSCP) to sensitive serum, with inhibition rates that reached 90%. Moreover, mSCPs could downregulate the expression levels of CD63 and CD203c on the basophil surface. Compared with wtSCP, the peak values were significantly changed, and the calcium binding ability was impaired, which explained the decline in immunoreactivities of the mSCPs. All of the data confirmed that this approach was effective in reducing the immunoreactivity of SCP and could be applied to other shellfish allergens.

Activation of astrocytes and abnormal synaptic glutamate metabolism are closely associated with the induction and maintenance of neuropathic pain (NP), but the exact mechanism underlying this association remains unclear. N-myc downstream-regulated gene 2 (NDRG2), a novel tumor-suppressor protein and stress-response gene, is involved in the pathogenesis of several neurodegenerative diseases. However, its role in nociceptive transduction has rarely been investigated. Here, we found that NDRG2, which was mainly expressed in the astrocytes in the central nervous system (CNS), was increased in the spinal cord of a spinal nerve ligation (SNL) rat model for NP. Suppression of NDRG2 by intrathecal injection of an NDRG2-RNAi-adenovirus significantly alleviated SNL-induced mechanical and thermal hypersensitivity, as well as elevated astrocytic glutamate transporter 1 (GLT-1) expression and downregulated pro-inflammatory cytokine levels, in the spinal dorsal horn of rats on Day 10 after SNL. Furthermore, in lipopolysaccharide (LPS)-stimulated primary astrocytic cultures derived from neonatal rats, inhibition of NDRG2 significantly reversed both the LPS-induced activation of astrocytes and decreased expression of GLT-1. By contrast, overexpression of NDRG2 by an adenoviral vector carrying NDRG2 resulted in astrocytic activation, aberrant glutamatergic neurotransmission, and spontaneous nociceptive responses in rats. Intrathecal injection of AG490, which is an inhibitor of the Janus tyrosine kinase and signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway, significantly attenuated both mechanical and thermal hyperalgesia, as well as inhibited reactive astrocytes and restored normal expression levels of astrocytic GLT-1, in the spinal dorsal horn of NDRG2-overexpression rats. In conclusion, spinal astrocytic NDRG2 is critical in the maintenance of NP. Moreover, NDRG2 modulates astrocytic activation and inflammatory responses via regulating GLT-1 expression through the JAK/STAT3 signaling pathway. Our findings suggested that NDRG2 could be a novel therapeutic target for the treatment of NP.

Bioactive compound 3-aryl-2-oxazolidinone could be synthesized by a green method mixing carbon dioxide, aniline, and ethylene oxide. Our group previously proposed a parallel mechanism for this conv...

Purpose This study aimed to investigate the role of miR-21 expression in the reduction of placental function in GDM patients. Materials and methods qRT-PCR was used to detect the differential expression of miR-21 in the serum of gestational diabetes mellitus (GDM) and normal pregnant women, and to verify the functional target gene PPAR-α of miR-21 by double fluorescence experiments. Cellular experiments were performed to verify the effect of PPAR-α on cell function. Results miR-21 is down-regulated in the serum and placenta of GDM patients compared to normal pregnant women. In the case of insulin resistance, miR-21-5p knockdown promoted glucose uptake, but no significant effect was found under physiological condition. Functional studies have shown that reduced PPAR-α expression can restore miR-21 knockdown-mediated cell growth and metastasis inhibition. Additionally, decreased expression of miR-21 but increased expression of -PPAR-α was observed in patients with GDM and GDM rats. Conclusion The expression of the placental miR-21-5p, which inhibits cell growth and infiltration by up-regulating PPAR-α, is downregulated in pregnant GDM patients, which in turn may affect the placental function.

Acetogenic bacteria are rising in popularity as chassis microbes for biotechnology due to their capability of converting inorganic one-carbon (C1) gases to organic chemicals. To fully uncover the potential of acetogenic bacteria, synthetic biology tools are imperative to either engineer designed functions or to interrogate the physiology. Here, we report a genome-editing tool at a one-nucleotide resolution, namely base editing, for acetogenic bacteria based on CRISPR-targeted deamination. This tool combines nuclease deactivated Cas9 with activation-induced cytidine deaminase to enable cytosine-to-thymine substitution without DNA cleavage, homology-directed repair, and donor DNA, which are generally the bottlenecks for applying conventional CRISPR-Cas systems in bacteria. We designed and validated a modularized base-editing tool in the model acetogenic bacterium Clostridium ljungdahlii. The editing principles were investigated, and an in-silico analysis revealed the capability of base editing across the genome and the potential for off-target events. Moreover, genes related to acetate and ethanol production were disrupted individually by installing premature STOP codons to reprogram carbon flux toward improved acetate production. This resulted in engineered C. ljungdahlii strains with the desired phenotypes and stable genotypes. Our base-editing tool promotes the application and research in acetogenic bacteria and provides a blueprint to upgrade CRISPR-Cas-based genome editing in bacteria in general.

The one-pot tandem hydroformylation-reduction to synthesize alcohols from olefins is in great demand but suffering from low yields, poor selectivity and harsh condition. Herein, 1,10-phenanthroline (L1) modified Ir-catalyst proved to exhibit multiple catalysis in terms of FA dehydrogenation, hydroformylation of olefins, and transfer hydrogenation of aldehydes to accomplish the tandem hydroformylation-transfer hydrogenation of olefins with formic acid (FA) as hydrogen source, as the result of 52–70% yields for the target alcohols and the corresponding formate esters (obtained upon esterification of the alcohol with FA). In this sequence, only the use of FA with trans- and cis-conformers could fulfill the reduction of aldehydes to the alcohols through transfer hydrogenation as well as greatly depress hydrogenation of the olefin, which universally occurred in the high pressured gaseous H2. Both the in situ FT-IR spectroscopic analysis and the DFT-calculations verified that, over L1-[Ir(COD)Cl]2 catalyst, cis-FA serving as the hydride-ligand was responsible for the efficient dehydrogenation of FA to release H2 along with CO2, and trans-FA serving as the carbonyl O-containing ligand corresponded to the transfer hydrogenation of the aldehydes to the alcohols under the same catalytic conditions.

Oysters are an important shellfish group known to cause food allergy; however, knowledge of their sensitization components and cross-reactivity is limited. This study aimed to identify a novel allergen in Crassostrea angulata and investigate its cross-reactivity. To this end, a 20 kDa protein was purified from oyster and confirmed to be a sarcoplasmic-calcium-binding protein (SCP) by LC-MS/MS. A 537 bp open reading frame was obtained from oyster SCP total RNA, which encoded 179 amino acids, and was expressed in Escherichia coli. According to the circular dichroism results, digestion assay, and inhibition ELISA, the recombinant SCP (rSCP) exhibited similar physicochemical properties and IgG-binding activity to native SCP. rSCP displayed stronger IgE-binding activity by immunological method. Moreover, a different intensity of cross-reactivity and sequence homology were demonstrated between shellfish species. Collectively, these findings provide novel insight into shellfish allergens, which can be used to aid in the in vitro diagnosis of oyster-sensitized patients.

The transition-metal Cu catalysts CuCl and CuCl2 have been widely employed to catalyze a series of chemical reactions with diazo compounds because of their high efficiency and selectivity. However,...

The conversion of CO2 to high value-added chemicals in water using environment-friendly and cost-effective catalysts is a very significant topic. In this work, a green method for the conversion of CO2 catalyzed by alcohol amines has been developed. Alcohol amines showed considerable activating ability to CO2 in the cyclization with 2-aminobenzonitrile to quinazoline-2,4(1H,3H)-dione in water. Notably, when diethanolamine (DEA) was used as the catalyst, 94% yield of quinazoline-2,4-(1H,3H)-dione could be achieved. A plausible mechanism has been proposed based on the 1H NMR, FT-IR analysis and DFT calculation. The excellent catalytic performance is attributed to the combined effect of both the secondary amine and hydroxyl groups on alcohol amines with the assistance of water in the formation of carbamate. Water plays a bi-functional role of solvent and co-catalyst in this catalytic process. Catalysts can be easily recovered and reused five times without significant loss of activity.

The H7N9 influenza virus has been circulating in China for more than six years. The neuraminidase (NA) has gained great concern for the development of antiviral drugs, therapeutic antibodies, and new vaccines. In this study, we screened seven mouse monoclonal antibodies (mAbs) and compared their protective effects against H7N9 influenza virus. The epitope mapping from escape mutants showed that all the seven mAbs could bind to the head region of the N9 NA close to the enzyme activity sites, and four key sites of N9 NA were reported for the first time. The mAbs D3 and 7H2 could simultaneously inhibit the cleavage of the sialic acid of fetuin protein with large molecular weight and NA-XTD with small molecule weight in the NA inhibition experiment, prevent the formation of virus plaque at a low concentration, and effectively protect the mice from the challenge of the lethal dose of H7N9 virus.

Lipid rafts are generally considered as nanodomains on cell membranes and play important roles in signaling, viral infection, and membrane trafficking. However, the raft hypothesis is still debated with many inconsistencies because the nanoscale and transient heterogeneous raft structure creates difficulties in its location and functional analysis. In the present study, we report a DNA nanotweezer composed of a cholesterol-functionalized DNA duplex that stabilizes transient lipid rafts, which facilitate the further analysis of the raft component and its functions via other spectroscopy tools. The proposed DNA nanotweezer can induce clustering of raft-associated components (saturated lipids, membrane protein and possibly endogenous cholesterol), leading to the T cell proliferation through clustering of a T-cell antigen receptor (TCR). The flexibility of random sequence noncoding DNA provides versatile possibilities of manipulating lipid rafts and activating T cells, and thus opens new ways in a future T cell therapy., We report a DNA nanotweezer that recruits raft-associated lipids, proteins and possibly endogenous cholesterol on living cell membrane. The DNA nanotweezers could activate T cell proliferation in a nonspecific activation manner.

Three M(II)(tBu)4phthalocyanines (M = Co(II), Ni(II), Cu(II)) were revisited and constructed as nanosheets through solvent and ultrasonication dual-controlled aggregations. These M(II)Pc molecules have exhibited higher electrochemical catalytic efficiency compared with amorphous metallophthalocyanine molecules, which provides new insights into phthalocyanine based material catalysis.

Background Population studies show that the use of swimming pools is associated with the risk of asthma and allergic diseases among children. Our objective was to explore the associations between blood trihalomethane (THM) concentrations and asthma among US adolescents, and assess to what extent the association is modified by active tobacco smoke exposure. Methods We included 2359 adolescents aged 12–19 years with measured blood concentrations of chloroform (trichloromethane (TCM)), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (tribromomethane (TBM)) from the National Health and Nutrition Examination Survey 2005–2012. Logistic regression models were fitted to assess the odds ratios for the association of blood THM concentrations (three or four categories) with the risk of self-reported current and ever (lifetime) asthma. Results Blood DBCM concentrations were associated with a higher risk of ever asthma among all adolescents (OR 1.54 (95% CI 1.07–2.21), comparing the extreme exposure categories). The relationship was stronger among adolescents exposed to tobacco smoke (OR 3.96 (95% CI 1.89–8.30), comparing the extreme exposure categories). We also found positive relationships between blood brominated THM concentrations (sum of BDCM, DBCM and TBM) and risk of ever asthma and between blood DBCM and brominated THM concentrations and risk of current asthma among adolescents with tobacco smoke exposure. The relative excess risk of ever asthma due to the interaction between high blood DBCM and brominated THM concentrations and tobacco smoke exposure was 1.87 (95% CI 0.30–3.43) and 0.78 (95% CI 0.07–1.49), respectively. Conclusions Exposure to THMs is associated with a higher risk of asthma in adolescents, particularly among those exposed to tobacco smoke., National Natural Science Foundation of China (NSFC) 81903281, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Environmental Health Sciences (NIEHS) R01ES031657

EF24, a curcumin analog, exerts a potent anti-tumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long non-coding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression re-enhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.

Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.

Background Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. Methods We used the approach of photo-affinity labeling (PAL) in the design of a chloroquine probe and developed a combined deconvolution strategy – activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CESTA) – that identified the protein targets of chloroquine in an unbiased manner in this study. Results We developed a novel photo-affinity chloroquine analog probe (CQP), which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP, which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. Together, we identified 8 proteins as the most potential hits which were commonly identified by both methods. Conclusions We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its known inhibitory effect of hemozoin formation. This is the first report of identifying chloroquine antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.

Microplastics (MPs) are ubiquitous in drinking water and pose potential threats to human health. Despite increasingly attentions on the toxicity of MPs, the deleterious effects of MPs after chlorine disinfection, which might be a more accessible form of MPs, has rarely been considered. Here, we first treated pristine polystyrene microplastics (PS-MPs) with chlorine to simulate the reactions that occur during drinking water treatment, and investigated and compared the cytotoxicity of chlorinated PS-MPs to those of pristine PS-MPs. Chlorine disinfection did not change the size of pristine PS-MPs, but increased the surface roughness. In addition, abundant carbon-chlorine bonds and persistent free radicals were generated on the surface of chlorinated PS-MPs. Compared with pristine PS-MPs, chlorinated PS-MPs markedly inhibited the cell proliferation, changed cellular morphology, destroyed cell membrane integrity, induced cell inflammatory response and apoptosis. Proteomics confirmed the difference in interactions with intracellular proteins between these particles. Furthermore, we found that the regulation of PI3K/AKT and Bcl-2/Bax pathways, oxidative stress-triggered mitochondrial depolarization, and the activation of caspase cascade were identified as the underlying mechanisms for the enhanced apoptosis ratio in GES-1 cells when exposed to chlorinated PS-MPs. This exacerbated cytotoxicity could be explained by the enhanced surface roughness and changed surface chemistry of these PS-MPs after chlorine disinfection. This work discloses the impacts of chlorine disinfection on the cytotoxicity of PS-MPs, which provides new insights for a more systematic risk assessment of MPs.

Objective: A model of alveolar cleft phenotype was established in rabbits to evaluate the effect of active bone particles containing modified rhecombinant human BMP-2 on the repair of the alveolar cleft. Methods: 2-month-old Japanese white rabbits were selected and randomly divided into four groups: normal, control, material and BMP groups. Blood biochemical analysis, skull tomography (microfocus computerized tomography), and histological and immunohistochemical staining analysis of paraffin sections were performed 3 and 6 months after operation. Results: Both types of collagen particles showed good biocompatibility and promoted bone regeneration. The effect of active bone particles on bone repair and regeneration was better than that of bone collagen particles. Conclusions: Active bone particles containing modified rhecombinant human BMP-2 can be used for incisors regeneration.

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy’s potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine’s ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.

The Ras protein is one of the most important drug targets for battling cancers. To effectively design novel drugs of Ras, we characterize here its conformational ensembles for the hydrolysis intermediate state RasGDP·Pi and the product state RasGDP by extensive replica-exchange molecular dynamics simulations. Several substates for RasGDP·Pi have been identified, while structural analyses have revealed an unrecognized hydrogen-bonding network that stabilizes the hydrolysis intermediate state. More interestingly, Gln61, which is involved in numerous oncogenic mutations, was found to be engaged in this hydrogen-bonding network, adopting a specific conformation that always points to Pi in contrast to that in the RasGTP state. The simulations also reveal that RasGDP has more than one substate, suggesting a conformational selection mechanism for the interaction between Ras and the guanine nucleotide exchange factors (GEFs). These findings offer new opportunities for the drug design of Ras by stabilizing the hydrolysis intermediate or disrupting its interaction with the GEFs.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

In response to the awareness of limited fossil resources and environmental concerns, catalytic conversion of renewable lignocellulose biomass to value-added chemicals and fuels is of great significance and attractive for sustainable chemistry. Division of Biomass Conversion and Bio-Energy attached to Dalian National Laboratory for Clean Energy has devoted themselves to valorization of lignocellulose biomass since launched in 2011. Our research interests focus on breeding of biomass resources (inulin and microalgae), exploration of catalytic and biological technologies, and production of energy chemicals and fuels. Although lignocellulose biomass is renewable and abundant, the way of utilization should be reasonable according to its structural characteristics in view of efficiency and economy. In this review, to celebrate the DICP's 70th anniversary, we will highlight the major fundamental advances in DICP about the conversion of lignocellulose to value-added chemicals and liquid fuels. Particular attention will be paid to the transformation of cellulose and its derivatives to glycols, acids and nitrogen-containing chemicals, hemicellulose-derived platform molecule furfural to jet fuels and lignin to aromatics using catalytic technologies.

Producing polyester monomer 2,5-furandicarboxylic acid (FDCA) from biomass as an alternative to fossil-derived terephthalic acid has drawn much attention from both academy and industry. In this work, an efficient FDCA synthesis was proposed from 10.6 wt % 2,5-diformylfuran (DFF) in acetic acid using a combined catalytic system of Co/Mn acetate and N-hydroxyimides. The intermediate product of 5-formyl-2-furandicarboxylic acid (FFCA) possesses the least reactive formyl group. N-hydroxysuccinimide was found to be superior to N-hydroxyphthalimide in catalyzing the oxidation of the formyl group in FFCA intermediate, affording a near 95 % yield of FDCA under mild conditions of 100 °C. Trace maleic anhydride was detected as by-product, which mainly came from the oxidative cleavage of DFF via furfural, furoic acid and 5-acetoxyl-2(5H)-furanone as intermediates.

Aims To investigate the distribution of complete ammonia oxidizers (comammox) and canonical ammonia-oxidizing bacteria (AOB) in tidal flat sediments of the Yangtze River estuary at different depths over four seasons. Methods and results A two-step PCR with highly degenerate primers (THDP-PCR), coupled with Illumina Miseq-based sequencing, was used to analyse the distribution of comammox and AOB in tidal flat sediments. The proportion of comammox compared with that of AOB was relatively high in spring. The intermediate sediments (1-5 cm) had higher proportions of comammox than those on the surface (0-1 cm) and lower sediments (5-10 cm). Diversity indices confirmed a higher diversity of comammox in the lower sediments (5-10 cm). The proportion of comammox clade A.1 was much higher than that of comammox clade A.2 in all seasons. Redundancy analysis demonstrated that comammox clade A.1 was negatively correlated with total carbon and ammonium concentrations, whereas the opposite was observed in AOB. Conclusions Results revealed the specific distribution of comammox and AOB in tidal flat sediments of the Yangtze River estuary. Significance and impact of the study This study will contribute to the understanding of nitrification by comammox and AOB in tidal flat sediments.

As lanthanum oxide (La2O3) has a large bandgap, it exhibits excellent optical properties. In this work, La2O3 thin films are prepared by the sol-gel method from a lanthanum chloride (LaCl3) precursor, on quartz and sapphire (0001) substrates. The effect of the annealing temperature (400–800 °C) on the optical properties of the La2O3 films is investigated. The structure and optical properties are analyzed by X-ray diffraction, atomic force microscopy, scanning electronic microscopy, X-ray photoemission spectroscopy, Raman spectroscopy, ultraviolet (UV)–visible spectroscopy, Fourier transform infrared spectroscopy, and infrared variable angle spectroscopic ellipsometry. Results indicate that with an annealing temperature of ~600 °C, the roughness and optical properties of La2O3 films can be significantly improved.

The design of metal oxide catalysts predominantly focuses on the composition or geometry engineering to enable optimized reactivity on the surface. Despite the numerous reports investigating the surface chemisorption of organic molecules on metal oxides, insights into how adsorption of organic modifiers can be exploited to optimize the catalytic properties of metal oxides are lacking. Herein, we describe the use of enolic acetylacetones to modify the surface Lewis acid properties of manganese oxide catalysts. The acetylacetone modification is stable under the reaction conditions and strongly influences the redox-acid cooperative catalysis of manganese oxides. This enables a rational control of the oxidation selectivity of structurally diverse arylmethyl amines to become switchable from nitriles to imines., Exploiting the organic adsorbate-metal oxide interaction to optimize the catalytic properties of metal oxides has been rarely explored. Here, the authors use enolic acetylacetones to modify the surface Lewis acid properties of manganese oxide, enabling a rational control of the oxidation selectivity of structurally diverse arylmethyl amines.

Recently, there has been increasing global concerns about the ecological impact of micro- and nano-sized polystyrene particles in marine environments. However, the potential threats of polystyrene nanoparticles to primary producers in freshwater systems remain unclear. Here, we explore the metabolite profiles and signaling pathways of freshwater cyanobacterium Synechococcus elongatus in response to short-term (48 h) amino-modified polystyrene nanoparticle (PS-NH2; 50 nm) exposure. We demonstrate that the positively charged PS-NH2 were acutely toxic to S. elongatus with an EC50 of 3.81 μg mL−1. Non-targeted metabolomics analyses suggested oxidative stress and membrane destruction as the main causes of PS-NH2 toxicity. Furthermore, disruption of glutathione metabolism and damage to membrane integrity were confirmed using two engineered strains of S. elongatus. These results provide new insights into polystyrene nanoparticles' impact on primary producers, improving the understanding of the toxic mechanisms of polystyrene nanoparticles in the freshwater primary producers.

Objective To isolate high-purity gentiopicroside from the Chinese herbal Gentiana officinalis and investigate its anti-inflammatory activity against iNOS and COX-2 targets. Methods The purity and structures of gentiopicroside were determined by HPLC, IR, NMR, and MS. The anti-inflammatory effects of gentiopicroside were investigated by in vivo, in vitro, and molecular experiments. Results In vitro experiment results showed that gentiopicroside inhibited nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) production in mouse macrophages RAW 264.7 stimulated by lipopolysaccharide. In vivo experiment found that xylene-induced mouse ear swelling was inhibited by gentiopicroside with an inhibition rate of 34.17%. Molecular docking of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) with gentiopicroside showed that hydrogen bonds (H-bonds) were formed between the sugar fragments in gentiopicroside structure with Tyr355, Ser353, Leu352, Ser530, Arg120, and His90 of COX-2, and Glu377, Asp382, Tyr373, Tyr347, Gln263, Asn370, and Gly371 of iNOS. Thus, gentiopicroside had a lower docking score and displayed satisfactory anti-inflammatory activities. Conclusion These results suggested that the mechanism of anti-inflammatory activity of gentiopicroside was associated with the downregulation of inflammatory cytokines, such as NO, PGE2, and IL-6, and the suppression of iNOS and COX-2. Therefore, gentiopicroside is a potential and selective iNOS and COX-2 inhibitor.

We herein report the synthesis and pH-sensing properties of novel gallium corrole derivatives based on 8-hydroxyquinoline. The free base corrole and its gallium corrole derivatives were fully characterized using NMR spectroscopy and mass spectrometry. Their photophysical and electrochemical properties were also investigated using UV/Vis spectroscopy, fluorescence spectroscopy, MCD spectroscopy and cyclic voltammetry. A Ga-corrole derivative showed a good fluorescence response to change in pH in a wide pH range, from pH 1 to 12. Specifically, its fluorescence gradually diminished, from a high intensity at neutral pH, as the pH was either decreased or increased, i.e., into acidic and basic conditions, respectively. These results indicated that the Ga-corrole derivative would be able to serve as an efficient “off–on–off” fluorescent sensor of pH in the solution state.

Many types of shellfish, including shrimp, are sometimes cooked before ingestion. Hence, it is necessary to investigate how cooking (boiling, pressure treatment or none (raw)) affects the structure, digestibility and immunoreactivity of multi-component shrimp muscle. Protein extraction, simulated gastrointestinal digestion, immunoreactivity, immunoglobulin E (IgE)-mediated human mast cell degranulation, morphology, particle size and UV absorbance scanning were used to investigate changes in the shrimp muscle upon treatment. The extractability of proteins and allergens was highest with 0.5 mol L-1 NaCl. Pressure treatment increased the digestibility and reduced the immunoreactivity of shrimp edible portions. Thermal processing induced the production of regular fiber bundles, blue shifts of absorbance peaks and reduction of particle size in the complex food matrix. These changes in macro- and micro-structure can further affect gastrointestinal digestibility and immunoreactivity due to the interactions between multiple components in the whole food. In conclusion, the digestibility, immunoreactivity and structure were altered by thermal processing of the complex food matrix.

A Pd-catalyzed multicomponent reaction was developed by trapping oxomium ylide with nitrosobenzene via Pd-promoted umpolung chemistry. The Pd catalyst plays two important roles: diazo compound decomposed catalyst and Lewis acid for the activation of nitrosobenzene. This strategy provides some insight into a new way for discovery of multicomponent methodology to construct complex molecules. The developed method also provides rapid access to a series of O-(2-oxy) hydroxylamine derivatives, which exhibit good anticancer activity in osteosarcoma cells.

Estuary and coastal environments have essential ecosystem functions in greenhouse gas sinks and removal of nitrogen pollution. Methane-oxidizing bacteria (MOB) and ammonia-oxidizing bacteria (AOB) communities play critical functions in the estuary's tidal flat sediments. Therefore, the effects of ammonium on MOB communities and methane on AOB communities need to be further explained. In this study, microcosm incubations with different contents of ammonium or methane were conducted for a relatively short (24 h) or long (28 days) period with tidal flat sediments from the Yangtze River estuary. Subsequently, the tagged highly degenerate primer PCR and DNA-based stable isotope probing method were employed to demonstrate the effects on MOB and AOB populations. The results indicated that the methane consumption was enhanced with ammonium supplements within 24 h of incubation. Supplement of 2 μmol/g d.w.s (μmol per gram dry weight soil) NH4+ increased the amount of MOB and its proportion to the total bacteria (p < 0.05) for 28 days incubation. The ammonium supplement increased the proportion of Methylomonas and Methylobacter based on the 16S rRNA gene. According to the functional gene analysis, the MOB primarily engaged in methane oxidation include Methylomonas, Methylobacter, Methylomicrobium, and Methylosarcina, which were associated with Type Ia MOB. It suggested that ammonium supplement may promote methane oxidation by stimulating the Type Ia MOB in tidal flat sediments of the Yangtze River estuary. The current research helps understand the effect of ammonium on methane consumption in the estuary and coastal environments.

Scylla paramamosain frequently elicits IgE-mediated type-I hypersensitivity reactions. Molecular candidates for crab allergen-specific immunotherapy have not been studied previously. In this study, reduced and alkylated (red/alk) derivatives with destroyed conformational epitopes and mutant derivatives (mtALLERGEN) with deleted heat/digestion-stable linear epitopes were produced of tropomyosin and myosin light chain. Structural changes and the allergenicity of derivatives was analyzed. Compared with wild-type allergens, red/alk derivatives had dramatically altered protein structures, whereas mtALLERGEN showed slightly structural effects. Enzyme linked immunosorbent assay revealed the heterogeneous epitope-recognition patterns with derivatives among 29 crab-sensitised patients, of whom 13% and 62% recognised conformational and linear epitopes, respectively, whereas 25% recognised both epitope types to the same extent. Furthermore, mtALLERGEN could not bind to IgE or induce basophil activation in some patients. These results imply that hypo-allergenic derivatives of crab myofibril allergens that specifically lacked linear epitopes may serve as viable candidates for immunotherapy.

Food processing can change the structure and immunoreactivity of purified allergens, but the effect of food processing on the immunoreactivity of the processed and purified allergen is still poorly understood. In this study, tropomyosin (TM) was obtained from Scylla paramamosain and purified after different treatments. A basophil activation test was employed to detect the allergenicity of allergens. The protein structure was detected by mass spectrometry, circular dichroism spectroscopy and surface hydrophobicity. Critical amino acids were identified by Dot blot. Heating obviously affects the biochemical characteristics of TM. The allergenicity of TM was decreased in high temperature-pressure-processed crabs, due to alteration in the protein structure (e.g. denaturation). Seven critical amino acids, namely, R21, E103, E104, E115, A116, E122 and E156, related to the maintenance of the IgE-binding activity of TM were identified. This research of thermal processing helps to accurately reduce or eliminate the immunoreactivity of crabs by food processing.