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This study investigates the connection between the North Pacific Victoria mode (VM) during the boreal spring [February–April (FMA)] and the following boreal winter [January–March (JFM)] rainfall over South China (SC). The VM is defined as the second empirical orthogonal function mode (EOF2) of sea surface temperature (SST) anomalies (SSTAs) in the North Pacific poleward of 20°N. It is found that the boreal spring VM has a significant positive correlation with the following winter rainfall over SC. Analyses indicate that a strong positive VM during spring can induce El Niño during the following winter via an air–sea interaction, resulting in the generation of an anomalous anticyclone over the western North Pacific (WNPAC). The anomalous southwesterlies along the southeast coast of East Asia associated with the WNPAC favor an abundant supply of water vapor and anomalous ascending motion over SC. As a result, winter rainfall over SC increases. A linear regression model based on the VM shows that the VM can act as an effective predictor of winter rainfall over SC about 1 year in advance. It also has a higher prediction skill than ENSO in predicting winter rainfall over SC.

2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and BSA adducts. The observed conjugation/adduction apparently involved the addition of GSH and departure of chloride via the ipso substitution pathway. Two biliary GSH conjugates and one urinary N-acetyl cysteine conjugate were observed in rats given 2,4-DCP. The N-acetyl cysteine conjugate was chemically synthesized and characterized by mass spectrometry and NMR. As expected, 2,4-DCP was found to modify hepatic protein at cysteine residues in vivo by the same chemistry. The observed protein adduction reached its peak at 15 min and revealed dose dependency. The new findings allowed us to better understand the mechanisms of the toxic action of 2,4-DCP.

Background Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in children and adolescents which presents as complex three-dimensional (3D) deformity of the spine and rib cage. This study aimed to estimate the effectiveness and safety of surgical interventions for AIS using Bayesian meta-analysis. Methods The PubMed, EMBASE, and Cochrane Controlled Register of Trials were searched through Oct 1, 2019, without language restrictions. Relevant studies evaluating combined effectiveness and safety of surgical interventions for AIS were included according to eligibility criteria. The primary outcome measures included pulmonary function (change of absolute forced vital capacity and forced expiratory volume in 1 second from pre-operation to post-operation) and incidence of complications. The secondary outcome measure was change of Cobb angle from pre-operation to post-operation. Data was pooled using a random effects model in pairwise meta-analysis. Bayesian meta-analysis combined direct and indirect evidence using a Bayesian framework. Results Twenty-eight case-controlled studies with totally 1970 participants were included. This Bayesian meta-analysis combining direct and indirect evidences indicated that posterior fusion with instrumentation without thoracoplasty (PSF) had the highest probability to achieve better pulmonary function and lower complication rate; video assisted anterior fusion with instrumentation without thoracoplasty (VAT) had the highest probability to obtain better Cobb angle correction based on analysis of rank probability. Conclusion This Bayesian meta-analysis demonstrated that PSF had the highest probability to achieve better post-surgical pulmonary function and lower complication rate, which gives a practical recommendation of PSF as a primary surgical treatment for AIS. The results also support statistics that current surgeries adopted more PSF but less open anterior approach surgery and thoracoplasty. More research work is required to address the effectiveness and safety of VAT for treating AIS more convincingly.

To investigate the value of cardiovascular magnetic resonance tissue-tracking (CMR-TT) imaging in the differentiation of subendocardial and transmural myocardial infarction (MI) and determine whether strain parameters are enable to detect adverse left ventricular (LV) remodeling.Global peak circumferential, longitudinal, and radial strains (GPCS, GPLS, GPRS) and segmental peak circumferential, longitudinal, and radial strains (PCS, PLS, PRS) in accordance with the 16-segment model were all derived. All positive segments were divided into two groups according to transmural degree. All patients were dichotomized in accordance with the existence of LV remodeling, which was defined as infarct size (IS) > 24%.Patients with MI showed significant lower GPRS, GPCS, and GPLS than the control group (16.41% ± 8.92%, -8.77%± 3.51%, -7.54% ± 2.43% versus 32.41% ± 12.99%, -14.92% ± 3.32%, -11.50% ± 2.51%). Lower PRS [3.25% (-5.57, 7.835) versus 19.94% (12.50, 30.75), P < 0.001] and PCS (-3.81 ± 4.60% versus -8.97± 4.43%, P < 0.001) can be found in transmural infarcted segments compared to subendocardial infarcted segments. PLS between transmural and subendocardial infarcted segments (-4.03% ± 4.88% versus -4.34% ± 4.98%), without however statistical significance (P = 0.523). The optimal cutoff value for PRS in the discriminate diagnosis of MI was 8.97% with a sensitivity of 81.8% and specificity of 98.0%. The optimal cutoff value for PCS was -7.56% with a sensitivity of 83.6% and specificity of 72.1%. Receiver operating characteristic (ROC) analysis revealed an optimal cutoff GPRS of 15.45%, and GPCS of -6.72% yielded high diagnostic accuracy in the identification of remodeling, which was higher than left ventricular ejection fraction (LVEF).CMR-TT can differentiate between subendocardial and transmural infarction and detect LV remodeling, and the diagnostic value was superior to conventional functional parameters.

Cognitive impairment is one of the most common complications associated with chronic pain. Almost 20% of chronic pain patients suffer from cognitive impairment, which may substantially influence their quality of life. Levels of major excitatory neurotransmitters in the central nervous system and alterations in the glutamatergic system may influence cognitive function and the pain sensory pathway. In this study, we adopted the spared nerve injury model to establish the progress of chronic pain and investigated the mechanism underlying the cognitive aspect related to it. At behavioral level, using the novel-object recognition test, mechanical hypersensitivity was observed in peripheral nerve-injured rats because they exhibited recognition deficits. We showed a dramatic decrease in hippocampal glutamate concentration using nuclear magnetic resonance and reduced glutamatergic synaptic transmission using whole-cell recordings. These were associated with deficient hippocampal long-term potentiation induced by high-frequency stimulation of the Schaffer collateral afferent. Ultra-high-performance liquid chromatography revealed lower levels of D-serine in the hippocampus of the spared nerve injury rats and that D-serine treatment could restore synaptic plasticity and cognitive dysfunction. The reduction of excitatory synapses was also increased by administering D-serine. These findings suggest that chronic pain has a critical effect on synaptic plasticity linked to cognitive function and may built up a new target for the development of cognitive impairment under chronic pain conditions.

Austempered ductile iron (ADI) is a type of graphite cast iron produced by an isothermal heat treatment process. It is an alternative to traditional steel castings and forgings and even aluminum due to the exceptional mechanical properties such as high strength, good toughness and excellent machinability. In the matrix, the unique ausferritic structure consists of graphite nodules uniformly surrounded by acicular ferrite and carbon saturated austenite. In the automotive industry, ADI has been commonly applied in the manufacturing of camshafts, crankshafts, gears and engine valves. These components are frequently subjected to surface contact with relative motion and external load. Therefore, it is necessary to understand the wear behavior of ADI in order to solve the tribological issues in existing ADI applications and utilize ADI into future designs appropriately. This paper was aimed at reviewing the fabrication processes of single-step and dual-step ADIs. The corresponding microstructure and mechanical properties were also briefly discussed. The studies on wear performance of ADI and potential mechanisms have been systemically reviewed. Keywords: Austempered ductile iron, Single-step austempering, Dual-step austempering, Stress-induced transformation, Wear resistance

In situ TiC/Al-Cu3.7-Mg1.3 nanocomposites containing 5–20 vol. % nano-TiC with nacre-like structures were prepared via combustion synthesis and hot pressing assisted by hot extrusion. Dry sliding friction and wear tests of the prepared in situ TiC/Al-Cu3.7-Mg1.3 nanocomposites and Al-Cu3.7-Mg1.3 alloy was carried out by a pin-on-disc apparatus under various applied loads and at different sliding velocities at room temperature. The nanocomposites showed much better friction and wear performance than the Al-Cu3.7-Mg1.3 alloy. SEM and EDS analyses were conducted to identify the wear mechanisms. The enhanced wear resistance of the nanocomposites was attributed to the formation of a protective mechanically mixed layer reinforced by nano-TiC particles. Keywords: Nanocomposites, Nano-sized TiC particles, Nacre-like structures, Wear resistance

Manipulating the synergy between magnetic and optical characteristics in a predictable manner by an external stimulus is a highly desirable option to develop smart materials for advanced applications such as information processing and storage in multifunctional devices. Herein we report dinuclear complexes Ln2L2(depma2)Cl2 (1-Ln, Ln = Dy, Gd; H2L = N1,N3-bis(salicylideneimino)diethylenetriamine, depma2 = photodimerized 9-diethylphosphonomethylanthracene) where the lanthanide ions possess pseudo-D5h geometries with five equatorial positions occupied by L2− and the axial positions by depma2 and the Cl− anion. depma2 acts as a bridge between the equivalent LnIII ions and can be opened and closed upon heating and light irradiation. 1-Ln experience consecutive structural transformations, first separation of the depma2 at ca. 170 °C and second elimination of chloroethane at ca. 250 °C, accompanied by a synergetic switch of the photoluminescence and magnetic dynamics for 1-Dy.

Photosensitizers (PSs), a critical drug administered for successful photodynamic therapy (PDT), have been well researched regarding their anticancer or bactericidal capability with high precision and low invasiveness. Although traditional PSs have been explored either in photodynamic anticancer or in antibiosis, they usually require synthesis with multiple steps, harsh synthetic conditions, and a complicated purification process for a single targeted product. Therefore, developing new multifunctional PSs with a simple synthesis and reactant flexibility which combine mitochondrial and bacterial imaging, efficient photodynamic anticancer and antibacterial effects is of the utmost urgency and of great importance for clinical applications. Herein, a large structural investigation of isoquinolinium-based PSs synthesized by a simple Rh-catalysed annulation reaction with high yields is presented. These lipophilic cationic PSs have a tunable photophysical property. LIQ-6 was found to perform not only as an ideal mitochondria targeting probe but also an effective cancer cell killing PS, and moreover, a tracker for bacterial imaging and ablation. LIQ-6 can be used to image a wide range of cancer cells and to monitor the photo-induced cell apoptosis, and simultaneously, it can also image and be a photodynamic germicide for both Gram-positive and Gram-negative bacteria. Furthermore, LIQ-6 shows great effectiveness in the wound healing process, showing its ability to be an ideal PS in vivo as well. This contribution is believed to offer a new platform for the construction of a theragnostic system for future practical applications in biology and biomedicine.

Glutaredoxins (Grx) are redoxin family proteins that reduce disulfides and mixed disulfides between glutathione and proteins.

The surgical masks have been essential consumables for public in the COVID-19 pandemic. However, long-time wearing masks will make wearers feel uncomfortable and massive discarded non-biodegradable masks lead to a heavy burden on our environment. In this paper, we adopt degradable chitosan@silver (CS@Ag) core-shell fibers and plant fibers to prepare an eco-friendly mask with excellent thermal comfort, self-sterilization, and antiviral effects. The thermal network of CS@Ag core-shell fibers highly improves the in-plane thermal conductivity of masks, which is 4.45 times higher than that of commercial masks. Because of the electrical conductivity of Ag, the fabricated mask can be electrically heated to warm the wearer in a cold environment and disinfect COVID-19 facilely at room temperature. Meanwhile, the in-situ reduced silver nanoparticles (AgNPs) endow the mask with superior antibacterial properties. Therefore, this mask shows a great potential to address the urgent need for a thermally comfortable, antibacterial, antiviral, and eco-friendly mask.

Dietary salt causes synaptic deficits and tau hyperphosphorylation, which are detrimental to cognitive function. However, the specific effects of a high-salt diet on synapse and tau protein remain poorly understood. In this study, aged (15-month-old) C57BL/6 mice received a normal (0.5% NaCl) or high-salt (8% NaCl) diet for 3 months, and N2a cells were treated with normal culture medium or a NaCl medium (40 mM). Spatial learning and memory abilities were tested using the Morris water maze. The levels of metabolites and related enzymes in the tricarboxylic acid (TCA) cycle were confirmed using liquid chromatography-tandem mass spectrometry, western blotting, and immunofluorescence. We also investigated synapse morphology and the phosphorylation of tau protein. Under the high-salt diet, mice displayed impaired learning and memory compared to mice fed the normal diet. Furthermore, excessive salt intake disturbed the TCA cycle in both animals and cells compared to the respective normal controls. High dietary salt reduced postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) expression, impaired neurons, and caused synaptic loss in the mice. We also detected tau hyperphosphorylation at different sites (Thr205, Thr231, and Thr181) without increasing total tau levels in response to high salt treatment, both in vivo and in vitro. We concluded that elevated salt intake impairs the TCA cycle and induces tau hyperphosphorylation and synapse dysfunction during aging, which ultimately results in cognitive impairment.

Circular RNAs (circRNAs) have been identified as critical regulators in human cancers, including cervical cancer (CC). However, the precise action of circ_0084904 in cervical carcinogenesis remains to be elucidated. The levels of circ_0084904, microRNA (miR)-802, and Mal, T cell differentiation protein 2 (MAL2) were checked by quantitative real-time PCR (qRT-PCR) or western blot. Ribonuclease R (RNase R) and subcellular localization assays were used to detect the stability and localization of circ_0084904, respectively. Cell colony formation ability was assessed by colony formation assay. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion abilities were gauged by transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to determine the direct relationship between miR-802 and circ_0084904 or MAL2. The xenograft experiments were performed to evaluate the role of circ_0084904 in tumor growth in vivo. Circ_0084904 was markedly up-regulated in CC tissues and cell lines. Silencing endogenous circ_0084904 impeded cell colony formation, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0084904 targeted miR-802, and the effects of circ_0084904 silencing were mediated by miR-802. MAL2 was directly targeted and inhibited by miR-802, and MAL2 was a functional target of miR-802. Moreover, circ_0084904 modulated MAL2 expression via miR-802. Our study identified circ_0084904 as a novel oncogenic driver in CC depending on the modulation of the miR-802/MAL2 axis, establishing the notion that silencing of circ_0084904 might represent a promising targeted therapy for CC.

Background Bacterial abortive infection (Abi) systems are type IV toxin–antitoxin (TA) system, which could elicit programmed cell death and constitute a native survival strategy of pathogenic bacteria under various stress conditions. However, no rhizobial AbiE family TA system has been reported so far. Here, a M. huakuii AbiE TA system was identified and characterized. Results A mutation in M. huakuii abiEi gene, encoding an adjacent GntR-type transcriptional regulator, was generated by homologous recombination. The abiEi mutant strain grew less well in rich TY medium, and displayed increased antioxidative capacity and enhanced gentamicin resistance, indicating the abiEi operon was negatively regulated by the antitoxin AbiEi in response to the oxidative stress and a particular antibiotic. The mRNA expression of abiEi gene was significantly up-regulated during Astragalus sinicus nodule development. The abiEi mutant was severely impaired in its competitive ability in rhizosphere colonization, and was defective in nodulation with 97% reduction in nitrogen-fixing capacity. The mutant infected nodule cells contained vacuolation and a small number of abnormal bacteroids with senescence character. RNA-seq experiment revealed it had 5 up-regulated and 111 down-regulated genes relative to wild type. Of these down-regulated genes, 21 are related to symbiosis nitrogen fixation and nitrogen mechanism, 16 are involved in the electron transport chain and antioxidant responses, and 12 belong to type VI secretion system (T6SS). Conclusions M. huakuii AbiEi behaves as a key transcriptional regulator mediating root nodule symbiosis.

Existing research on leader humility primarily demonstrates its positive effects. This study challenges this view by proposing the potential negative effects of leader humility on followers’ behaviors. Furthermore, this paper employs the person-situation interactionist perspective to extend the research on integrating followers’ personality traits and leader humility. Specifically, this study proposed that leader humility triggers their followers’ sense of power; moreover, this study wagers that whether followers’ sense of power encourages self-interested or prosocial behavior in followers depends on their particular Machiavellian traits. The theoretical model was tested using the time-lagged supervisor–subordinate matched data obtained. Our findings revealed that follower Machiavellianism fosters the relationship between a sense of power and self-interested behavior but it weakens the relationship between a sense of power and prosocial behavior. Thus, this study provides a better understanding regarding the effect of follower personality and leader humility on follower behavioral reactions.

Fruit of Citrus wilsonii Tanaka called as “Xiang yuan” in Chinese, which means fragrant and round. It was widely used in the pharmaceutical and food industries. This fruit has well-known health benefits such as antioxidant, radical scavenging, and anti-inflammatory. Naringin, deacetylnomilin, citric acid, limonin, and nomilin were the characteristic components of Citrus wilsonii Tanaka. Although the fruit of Citrus wilsonii Tanaka possessed many applications, there was a lack of research on the growth period and drying process. In this study, plant metabolomics was used to analyze the biomarkers of the growth period, and appearance indicators and metabolites abundance were combined for the analysis of change regularities of the growth period. The representative differential metabolites of naringin, citric acid, and limonin were screened out, and the abundance of these components was relatively highest in the middle of the growth period. Therefore, the fruit of Citrus wilsonii Tanaka should be harvested before it turned yellow completely, which could effectively ensure the content of potential active ingredients. In the comparison of different drying methods, citric acid and naringin were considered to be representative differential components, but limonoids were relatively stable and not easily affected by drying methods. Naringin was an index component that could not only be reflected the maturity but also related to different drying methods. Considering its physical and chemical properties and its position, naringin had the potential to be a biomarker of Citrus wilsonii Tanaka.

Background Central sensitization is considered a critical pathogenic mechanism of chronic migraine (CM). Activation of microglia in the trigeminal nucleus caudalis (TNC) contributes to this progression. Microglial glucagon-like peptide-1 receptor (GLP-1R) activation can alleviate pain; however, whether it is involved in the mechanism of CM has not been determined. Thus, this study aims to investigate the precise role of GLP-1R in the central sensitization of CM. Methods Repeated nitroglycerin injection-treated mice were used as a CM animal model in the experiment. To identify the distribution and cell localization of GLP-1R in the TNC, we performed immunofluorescence staining. Changes in the expression of GLP-1R, Iba-1, PI3K and p-Akt in the TNC were examined by western blotting. To confirm the effect of GLP-1R and PI3K/Akt in CM, a GLP-1R selective agonist (liraglutide) and antagonist (exendin(9–39)) and a PI3K selective antagonist (LY294002) were administered. Mechanical hypersensitivity was measured through von Frey filaments. To investigate the role of GLP-1R in central sensitization, calcitonin gene-related peptide (CGRP) and c-fos were determined using western blotting and immunofluorescence. To determine the changes in microglial activation, IL-1β and TNF-α were examined by western blotting, and the number and morphology of microglia were measured by immunofluorescence. We also confirmed the effect of GLP-1R on microglial activation in lipopolysaccharide-treated BV-2 microglia. Results The protein expression of GLP-1R was increased in the TNC after nitroglycerin injection. GLP-1R was colocalized with microglia and astrocytes in the TNC and was fully expressed in BV-2 microglia. The GLP-1R agonist liraglutide alleviated basal allodynia and suppressed the upregulation of CGRP, c-fos and PI3K/p-Akt in the TNC. Similarly, the PI3K inhibitor LY294002 prevented nitroglycerin-induced hyperalgesia. In addition, activating GLP-1R reduced Iba-1, IL-1β and TNF-α release and inhibited TNC microglial number and morphological changes (process retraction) following nitroglycerin administration. In vitro, the protein levels of IL-1β and TNF-α in lipopolysaccharide-stimulated BV-2 microglia were also decreased by liraglutide. Conclusions These findings suggest that microglial GLP-1R activation in the TNC may suppress the central sensitization of CM by regulating TNC microglial activation via the PI3K/Akt pathway.

Plenty of factors affect the oncogenesis and progression of colorectal cancer in the tumor microenvironment, including various immune cells, stromal cells, cytokines, and other factors. Chemokine is a member of the cytokine superfamily. It is an indispensable component in the tumor microenvironment. Chemokines play an antitumor or pro-tumor role by recruitment or polarization of recruiting immune cells. Meanwhile, chemokines, as signal molecules, participate in the formation of a cross talk among signaling pathways and non-coding RNAs, which may be involved in promoting tumor progression. In addition, they also function in immune escape. Chemokines are related to drug resistance of tumor cells and may even provide reference for the diagnosis, therapy, and prognosis of patients with colorectal cancer.

Background RNA binding protein (RBP) is an active factor involved in the occurrence and development of colorectal cancer (CRC). Therefore, the potential mechanism of RBP in CRC needs to be clarified by dry-lab analyses or wet-lab experiments. Methods The differential RBP gene obtained from the GEPIA 2 (Gene Expression Profiling Interactive Analysis 2) were performed functional enrichment analysis. Then, the alternative splicing (AS) events related to survival were acquired by univariate regression analysis, and the correlation between RBP and AS was analyzed by R software. The online databases were conducted to analyze the mutation and methylation of RBPs in CRC. Moreover, 5 key RBP signatures were obtained through univariate and multivariate Cox regression analysis and established as RBP prognosis model. Subsequently, the above model was verified through another randomized group of TCGA CRC cohorts. Finally, multiple online databases and qRT-PCR analysis were carried to further confirm the expression of the above 5 RBP signatures in CRC. Results Through a comprehensive bioinformatics analysis, it was revealed that RBPs had genetic and epigenetic changes in CRC. We obtained 300 differentially expressed RBPs in CRC samples. The functional analysis suggested that they mainly participated in spliceosome. Then, a regulatory network for RBP was established to participate in AS and DDX39B was detected to act as a potentially essential factor in the regulation of AS in CRC. Our analysis discovered that 11 differentially expressed RBPs with a mutation frequency higher than 5%. Furthermore, we found that 10 differentially expressed RBPs had methylation sites related to the prognosis of CRC, and a prognostic model was constructed by the 5 RBP signatures. In another randomized group of TCGA CRC cohorts, the prognostic performance of the 5 RBP signatures was verified. Conclusion The potential mechanisms that regulate the aberrant expression of RBPs in the development of CRC was explored, a network that regulated AS was established, and the RBP-related prognosis model was constructed and verified, which could improve the individualized prognosis prediction of CRC.

This study investigated the safety and effect of oxymatrine (OMT) and/or diammonium glycyrrhizinate (DG) on allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB) in ICR mice. Mice were topically smeared with vehicle (control) or DNFB on their ear and skin to induce ACD. The mice were randomized and injected with saline as the model, treated intraperitoneally with dexamethasone (DEX), 45 or 90 mg·kg−1 OMT and/or DG daily beginning one day post the first smearing for two weeks. The body weights, the severity of ear and skin inflammation, the levels of serum IgE, IL-4, and IFNγ, creatinine and urea as well as plasma sodium and potassium in individual mice were measured. In comparison with the control group, the model group did not change the body weights, but developed severe skin and ear inflammation with increased ear thickness, accompanied by many inflammatory infiltrates in the lesions and high levels of serum IgE, IL-4, and IFNγ. Combination of OMT and DG prevented the OMT- or DG-altered body weights in mice. While treatment with either OMT or DG moderately reduced the skin and ear inflammation, their thickness and inflammatory infiltrates, combination of OMT and DG further significantly increased their anti-inflammatory effects in mice. A similar pattern of inhibitory effect on the levels of serum IgE, IL-4, and IFNγ was observed in the different groups of mice. Combination of OMT and DG also prevented the OMT-, DG-, or DEX-altered plasma sodium or potassium levels in mice. Therefore, combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in mice and attenuated DG- or OMT-related adverse effects. Impact statement Diammonium glycyrrhizinate (DG) and oxymatrine (OMT) have similar anti-inflammatory, anti-allergic, anti-tumor, immunomodulatory, and other pharmacological properties. Our previous study has shown that when DG and OMT are combined, DG can attenuate both high-dose (347.44 mg·kg−1) and regular-dose (90 mg·kg−1) OMT-induced mortality and adverse effects (such as body weight loss and hyponatremia). Furthermore, OMT can similarly attenuate the adverse effects (such as body weight gain, hypernatremia, and hypokalemia) induced by regular dose (90 mg·kg−1) of DG. Accordingly, we tested whether combination of OMT and DG would increase anti-inflammatory activities and reduce their adverse effect in a mouse model of allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Our findings indicated that combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in ICR mice and attenuated adverse effects of DG or OMT alone.

Multifunctional alginate microspheres encapsulated with in situ-formed bismuth sulfide nanoparticles (denoted as Bi2S3@BCA) were developed in this work. In comparison with conventional hybrid polymer microspheres usually involved in complicate preparation process, Bi2S3@BCA microspheres can be easily one-step prepared using a droplet-based microfluidic technique with alginate as a soft template and microspheric matrix. As-prepared Bi2S3@BCA microspheres has unique nano-in-micro structure. The obtained wet microspheres show good uniform size with approximately 170 μm in diameter. Scanning electron microscopy images show that Bi2S3 nanoparticles with a size of 300 nm were homogeneously distributed in the microspheres. In addition, Bi2S3@BCA microspheres exhibit strong absorption of near-infrared (NIR) light and excellent photothermal effect in vitro. Furthermore, anti-cancer drug (doxorubicin)-loaded Bi2S3@BCA microspheres show sustained drug release behavior and enhanced release rate under NIR laser irradiation. The in vitro cytotoxicity experiments confirm that chemotherapy combined with NIR-induced hyperthermia can act synergistic effect to kill more tumor cells. Therefore, the as-prepared drug-loaded Bi2S3@BCA microspheres may potentially be used as a novel embolic material for tumor therapy due to their multifunction including embolization, hyperthermia and controlled local chemotherapy.

Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intratracheally instilled to induce ALI in lung-specific GGPPS1-knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells was examined. The severity of lung injury and inflammation was determined in lung-specific GGPPS1 knockout and wild-type mice by measuring alveolar exudate, neutrophil infiltration, lung injury, and cell death. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro. We found that GGPPS1 levels increased significantly in lung tissues and alveolar epithelial cells in LPS-induced ALI mice. Compared with wild-type and simvastatin treated mice, the specific deletion of pulmonary GGPPS1 attenuated the severity of lung injury by inhibiting apoptosis of AECs. Furthermore, deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1β release and pyroptosis, by downregulating NLRP3 expression. Finally, downregulation of GGPPS1 reduced the membrane expression of Ras-related protein Rab10 and Toll-like receptor 4 (TLR4) and inhibited the phosphonation of IκB. This effect might be attributed to the downregulation of GGPP levels. Our results suggested that inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI predominantly by suppressing the NLRP3 inflammasome through Rab10-mediated TLR4 replenishment.

This work is to develop a kind of multifunctional embolic material, which will possess a synergized tumor ablation effect combining transcatheter arterial chemoembolization and hyperthermia therapy. Herein, monodispersed calcium alginate (CA) microspheres containing gold nanostars (Au NSs) have been prepared in one step by using a droplet-based microfluidic technique. The droplets containing sodium alginate (SA) and HAuCl4 formed in the microfluidic device are solidified by Ca2+ to obtain CA microspheres while HAuCl4 is successively reduced to Au(0) by SA and vitamin C in the collecting solution to produce Au NSs in situ-encapsulated in CA microspheres. Herein, alginate acts as a co-reducing agent and stabilizer for in situ-formed Au NSs, and also as a drug carrier and embolic agent. Studies of scanning electronic microscopy combined with energy-dispersive X-ray spectroscopy, transmission electronic microscopy and X-ray diffraction verified the existence and morphology of the in situ-formed Au NSs. The as-prepared microspheres can absorb near-infrared (NIR) light and the temperature increment of the microsphere suspension can be more than 60 °C under NIR irradiation due to the presence of Au NSs. The drug release rate can be accelerated by NIR irradiation. The study of in vitro cytotoxicity indicates that tumor cells can be efficiently killed by the combination of chemotherapy and NIR-induced hyperthermia. As potential embolic materials, the hybrid microspheres provide new insights into synergistic therapy of cancer.

In this study, degradation of hydroxyoxime extractants by nitration was studied in nitrate media. The effect of nitrate concentration in the range of 10–40 g/L, pH value range of 1.5–2.3, temperature in the range of 25–35 °C and different modifiers including 2,2,4-trimethylpentanediol diisobutyrate, tridecyl alcohol and nonyl phenol on the nitration of hydroxyoxime extractants was investigated. A new type of inhibitor reagent consisted of tertiary butylhydroquinone (TBHQ) and styrolfenol blend (1:2, w/w) was investigated in a nitrate media under 180 g/L H2SO4 at 30 °∁ for required time. It is shown that the new inhibitor reagent (3%, w/w) can reduce the nitration to half for hydroxyoxime extractants. In addition, other measures such as increasing the pH to above 2.3, using more stable reagents like ketoximes, to reduce nitration were suggested.

An aggregation-enhanced emission mitochondrial probe, LIQ-3, was developed for ultrafast labeling within one minute and for distinguishing cancer cells from normal cells. Furthermore, the probe revealed high-fidelity tracking of mitochondria in a three-dimensional localization with advantages that include a specific targeting capacity and a high signal-to-noise ratio.

Background: The production and accumulation of amyloid-β (Aβ) is the most important pathological feature of Alzheimer’s Disease (AD), and the deficiency of Aβ clearance contributes to the progression of AD. TREM2-dependent microglial activation may be the key to Aβ clearance. BBR plays the neuroprotective role in the progression of AD by inhibiting Aβ production and promoting Aβ degradation. However, the specific relationship between BBR and microglial activation remains unclear. Thus, we aimed to investigate whether BBR can inhibit the pathological progression of Aβ in AD by changing the phenotype of microglia.Methods: Western blot and Immunofluorescence staining were applied to detect the effects of BBR on the transformation of resting microglia to different phenotypes. ELISA, Immunohistochemistry and Immunofluorescence were used to detect the effect of BBR on microglial phagocytosis of Aβ. Morris water maze (MWM) test was applied to test the effect of BBR on the spatial learning and memory of experimental animals.Results: Firstly, BBR promoted the phagocytosis of Aβ1-42 by BV2 cells. Secondly, BBR promoted the changes of microglia to phenotypes M2 and DAM in vivo and in vitro, which were in close proximity to Aβ and reduced Aβ aggregation. Finally, BBR ameliorated spatial learning and memory impairment in APP/PS1 mice.Conclusion: BBR could enhance the phagocytosis of microglia, which decreased Aβ level and improved the spatial learning and memory of APP/PS1 mice.

Fruit of Citrus wilsonii Tanaka called as “Xiang yuan” in Chinese, which means fragrant and round. It was widely used in the pharmaceutical and food industries. This fruit has well-known health benefits such as antioxidant, radical scavenging, and anti-inflammatory. Naringin, deacetylnomilin, citric acid, limonin, and nomilin were the characteristic components of Citrus wilsonii Tanaka. Although the fruit of Citrus wilsonii Tanaka possessed many applications, there was a lack of research on the growth period and drying process. In this study, plant metabolomics was used to analyze the biomarkers of the growth period, and appearance indicators and metabolites abundance were combined for the analysis of change regularities of the growth period. The representative differential metabolites of naringin, citric acid, and limonin were screened out, and the abundance of these components was relatively highest in the middle of the growth period. Therefore, the fruit of Citrus wilsonii Tanaka should be harvested before it turned yellow completely, which could effectively ensure the content of potential active ingredients. In the comparison of different drying methods, citric acid and naringin were considered to be representative differential components, but limonoids were relatively stable and not easily affected by drying methods. Naringin was an index component that could not only be reflected the maturity but also related to different drying methods. Considering its physical and chemical properties and its position, naringin had the potential to be a biomarker of Citrus wilsonii Tanaka.

Metal-organic frameworks containing responsive organic linkers are attractive for potential applications in sensors and molecular devices. Herein we report three cobalt(II) phosphonates incorporating responsive dianthracene linkers, namely, Co2 (amp2 H2 )2 (H2 O)4 ⋅ 6H2 O (MDAF-1), Co2 (amp2 )(H2 O)4 ⋅ 2H2 O (MDAF-2) and Co(amp2 H2 ) ⋅ 2H2 O ⋅ 0.5DMF (MDAF-3), where amp2 H4 is pre-photodimerized 9-anthrylmethylphosphonic acid. MDAF-1 shows a layer structure in which dinuclear Co2 (PO3 H)2 units are inter-connected by dianthracene ligands. In MDAF-2 and MDAF-3, inorganic chains of corner-sharing {CoO4 } (or {CoO6 }) and {PO3 C} are cross-linked by dianthracene ligands into 3D frameworks. All compounds underwent thermo-induced phase transitions, first the de-solvation and then the de-dimerization of dianthracene (as well as the release of the remaining solvent molecules for MDAF-2 and -3), associated with magnetic changes. MDAF-1 can be exfoliated into single-layer nanosheets in water which show light-triggered luminescent changes.

Rho-associated coiled-coil kinase (ROCK), a serine/threonine kinase regulated by the small GTPase RhoA, is involved in regulating cell migration, proliferation, and survival. Numerous studies have shown that the RhoA/ROCK signaling pathway can promote Alzheimer's disease (AD) occurrence. ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. This is suggestive of a possible positive feedback role for Aβ and ROCK. Moreover, ROCK activation promotes the formation of neurofibrillary tangles and abnormal synaptic contraction. Additionally, ROCK activation can promote the neuroinflammatory response by activating microglia and astrocytes to release inflammatory cytokines. Therefore, ROCK is a promising drug target in AD; further, there is a need to elucidate the specific mechanism of action.

This study investigated the effects of 9t18:1 (representing I-TFAs), 9t16:1, and 11t18:1 (representing R-TFAs) and their mixtures on the normal human hepatocyte LO2 cell function, the possible mechanism of lipid metabolism by lipidomics, and the relationship between phospholipase A2 (PLA2) and the arachidonic acid (AA) metabolic pathway. Here, we found that the damaging effect of 9t18:1 on the LO2 cell function was significantly greater than those of 11t18:1 and 9t16:1 (

The incidence and mortality of colorectal cancer (CRC) have always been among the highest in the world, although the diagnosis and treatment are becoming more and more advanced. At present, the main reason is that patients have acquired drug resistance after long-term conventional drug treatment. An increasing number of evidences confirm the existence of cancer stem cells (CSCs), which are a group of special cells in cancer, only a small part of cancer cells. These special cell populations are not eliminated by chemotherapeutic drugs and result in tumor recurrence and metastasis after drug treatment. CSCs have the ability of self-renewal and multidirectional differentiation, which is associated with the occurrence and development of cancer. CSCs can be screened and identified by related surface markers. In this paper, the characteristic surface markers of CSCs in CRC and the related mechanism of drug resistance will be discussed in detail. A better understanding of the mechanism of CSCs resistance to chemotherapy may lead to better targeted therapy.

An emerging concept termed the “neuro-glia-vascular unit” (NGVU) has been established in recent years to understand the complicated mechanism of multicellular interactions among vascular cells, glial cells, and neurons. It has been proverbially reported that the NGVU is significantly associated with neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Physiological aging is an inevitable progression associated with oxidative damage, bioenergetic alterations, mitochondrial dysfunction, and neuroinflammation, which is partially similar to the pathology of AD. Thus, senescence is regarded as the background for the development of neurodegenerative diseases. With the exacerbation of global aging, senescence is an increasingly serious problem in the medical field. In this review, the coupling of each component, including neurons, glial cells, and vascular cells, in the NGVU is described in detail. Then, various mechanisms of age-dependent impairment in each part of the NGVU are discussed. Moreover, the potential bioenergetic alterations between different cell types in the NGVU are highlighted, which seems to be an emerging physiopathology associated with the aged brain. Bioenergetic intervention in the NGVU may be a new direction for studies on delaying or diminishing aging in the future.

Glutathione (GSH) plays a key role in regulating the cellular Redox Homeostasis, and appears to be essential for initiation and development of root nodules. Glutathione peroxidase (Gpx) catalyzes the reduction of H2O2 and organic hydroperoxides by oxidation of GSH to oxidized GSH (GSSG), which in turn is reduced by glutathione reductase (GR). However, it has not been determined whether the Rhizobium leguminosarum Gpx or GR is required during symbiotic interactions with pea. To characterize the role of glutathione-dependent enzymes in the symbiotic process, single and double mutants were made in gpxA (encoding glutathione peroxidase) and gshR (encoding glutathione reductase) genes. All the mutations did not affect the rhizobial growth, but they increased the sensitivity of R. leguminosarum strains to H2O2. Mutant in GpxA had no effect on intracellular GSH levels, but can increase the expression of the catalase genes. The gshR mutant can induce the formation of normal nodules, while the gpxA single and double mutants exhibited a nodulation phenotype coupled to more than 50% reduction in the nitrogen fixation capacity, these defects in nodulation were characterized by the formation of ineffective nodules. In addition, the gpxA and gshR double mutant was severely impaired in rhizosphere colonization and competition. Quantitative proteomics using the TMT labeling method was applied to study the differential expression of proteins in bacteroids isolated from pea root nodules. A total of 27 differentially expressed proteins were identified in these root bacteroids including twenty down-regulated and seven up-regulated proteins. By sorting the down-regulated proteins, eight are transporter proteins, seven are dehydrogenase, deoxygenase, oxidase, and hydrolase. Moreover, three down-regulating proteins are directly involved in nodule process.

Glutaredoxins (Grx) are redoxin family proteins that reduce disulfides and mixed disulfides between glutathione and proteins. Rhizobium leguminosarum bv. Viciae 3841 contains three genes coding for glutaredoxins: RL4289 (grxA) codes for a dithiolic glutaredoxin, RL2615 (grxB) codes for a monothiol glutaredoxin, while RL4261 (grxC) codes for a glutaredoxin-like NrdH protein. We generated mutants interrupted in one, two, or three glutaredoxin genes. These mutants had no obvious differences in growth phenotypes from the wild type RL3841. However, while a mutant of grxC did not affect the antioxidant or symbiotic capacities of R. leguminosarum, grxA-derived or grxB mutants decreased antioxidant and nitrogen fixation capacities. Furthermore, grxA mutants were severely impaired in rhizosphere colonization, and formed smaller nodules with defects of bacteroid differentiation, whereas nodules induced by grxB mutants contained abnormally thick cortices and prematurely senescent bacteroids. The grx triple mutant had the greatest defect in antioxidant and symbiotic capacities of R. leguminosarum and quantitative proteomics revealed it had 56 up-regulated and 81 down-regulated proteins relative to wildtype. Of these proteins, twenty-eight are involved in transporter activity, twenty are related to stress response and virulence, and sixteen are involved in amino acid metabolism. Overall, R. leguminosarum glutaredoxins behave as antioxidant proteins mediating root nodule symbiosis.IMPORTANCE Glutaredoxin catalyzes glutathionylation/deglutathionylation reactions, protects SH-groups from oxidation and restores functionally active thiols. Three glutaredoxins exist in R. leguminosarum and their properties were investigated in free-living bacteria and during nitrogen-fixing symbiosis. All the glutaredoxins were necessary for oxidative stress defense. Dithiol GrxA affects nodulation and nitrogen fixation of bacteroids by altering deglutathionylation reactions, monothiol GrxB is involved in symbiotic nitrogen fixation by regulating Fe-S cluster biogenesis, and GrxC may participate in symbiosis by an unknown mechanism. Proteome analysis provides clues to explain the differences between the grx triple mutant and wild-type nodules.

Objectives Dried ginger and ginger are the same type of medicine and food. The differential components of ginger and dried ginger, dried ginger and ginger charcoal were investigated. Materials and Methods The experimental materials were divided into three sample groups: the ginger group, dried ginger group, and ginger charcoal group. The ginger group, dried ginger group, and ginger charcoal group were qualitatively analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The data were processed by Marker View Software. Principal component analysis and orthogonal partial least-square discriminant analysis were performed with SIMCA 13.0 Software. The differential components of the ginger and dried ginger groups as well as the dried ginger and ginger charcoal groups with a variable importance in the projection > 2 (P < 0.05) were identified with PeakView 1.2 Software. Results Ten differential components, including 6-gingerol, 8-gingerol, and 10-gingerol, were identified between the ginger group and dried ginger group; 13 differential components, including 6-shogaol, 10-gingerol, and zingiberone, were identified between the dried ginger group and ginger charcoal group. Conclusions The main differential components between the ginger and dried ginger groups and the dried ginger and ginger charcoal groups were gingerols and diphenylheptanes. Based on metabolomics analysis of the chemical composition of ginger’s medicinal materials, effects, and other related factors, it is recommended that 6-gingerol, 6-shogaol, and zingiberone should be used as indicative components for the respective quality evaluation of ginger, dried ginger and ginger charcoal. The results of this study may provide a basis for the reasonable quality evaluation of ginger medicinal materials.

More than 110,000,000 tons of mismanaged plastics were to be produced in 2020. Polymers are favored in the preparation of thermally conductive materials due to their excellent comprehensive properties. However, most polymers fabricated for thermally conductive materials are difficult to degrade in the natural environment. To alleviate the increasingly severe environmental problems, we reported a novel eco-friendly material with high thermal conductivity, which was composited of chitosan microspheres (CSM) and hydroxyl-functionalized hexagonal boron nitride (OH-h-BN) nanoplatelets. Utilizing their significant difference in scales, the OH-h-BN nanoplatelets were arranged between each CSM. Their overall structure was similar to the honeycomb: CSM were honeycomb cores, and OH-h-BN nanoplatelets were honeycomb network. The routine-structure OH-h-BN/CS nanocomposites were only 0.94 ± 0.02 W·m−1·K−1 at 50 wt% in thermal conductivity. However, the OH-h-BN/CSM nanocomposites with honeycomb structure can reach 5.66 ± 0.32 W·m−1·K−1 in the same loading, for enhancement of 502% and 1914% than OH-h-BN/CS nanocomposites and pure CS, respectively.