Search

Abstract The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

With the advancement of scientific research, an increasing number of studies on metal nanozymes, particularly Au NPs, have been conducted. They possess glucose oxidase (GOD)-like activity and peroxidase (POD)-like activity, with GOD-like activity receiving the most attention. However, there is a lack of research and summary on future trends in Au NPs in biomedical field. Therefore, we conducted a study on the GOD-like activity of Au NPs based on 158 relevant publications downloaded from the Web of Science Core Collection between 2007 and 2023, using citation metrics, authors, nations, institutions, cited references, and keywords. We found that Au NPs were initially utilized for glucose biosensors, glucose detection in human serum, and the detection of other carbohydrates and proteins. Researchers have recently focused on its application in oncotherapy and diabetic wound treatment. In addition to being utilized to treat autoimmune illnesses, inflammation, and other diseases, Au NPs may eventually replace insulin and antibiotics. We anticipate that the use of Au NPs will increase in the future. We hope this study will serve as a guide for future researchers so that Au NPs can be applied more broadly and competently.

Background: A number of patients with Crohn’s disease (CD) suffer from loss of response to infliximab (IFX) therapy. Splenic volume is reported to be enlarged in patients with CD compared to normal individuals. The association between splenic volume and IFX efficacy in CD remains unclear.Methods: We performed a retrospective study of patients with CD who received regular IFX treatment at Zhongshan Hospital, Fudan University, between August 2015 and December 2021. We collected baseline characteristics and clinical features from medical records in the CD database of Zhongshan Hospital. We accurately measured the splenic volume using semi-auto spleen segmentation software, followed by the analysis of splenic volume and IFX efficacy.Results: We included 49 patients with CD receiving IFX treatment, of whom 41 responded to IFX and 8 failed to respond to IFX. Splenic volume, as well as volume adjusted for body mass index (SV/BMI) and body weight (SV/W), was significantly decreased after IFX treatment in responders but increased in non-responders compared to the volume before the treatment. Accordingly, the levels of leukocyte count, platelet count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were decreased after IFX treatment in responders. Contrarily, the levels of hemoglobin, albumin, and tumor necrosis factor (TNF)-α were elevated in responders. Moreover, both CRP and TNF-α levels were significantly positively correlated with SV/BMI in all patients.Conclusion: Splenic volume, especially SV/BMI and SV/W, was reduced after IFX treatment in CD patients responsive to IFX. SV/BMI was positively correlated with disease activity. Splenic volume is a promising indicator to evaluate IFX efficacy in CD.

BackgroundHeart failure is a common cardiovascular disease that imposes a heavy clinical and economic burden worldwide. Previous research and guidelines have supported exercise training as a safe, effective, and cost-efficient treatment to intervene in heart failure. The aim of this study was to analyze the global published literature in the field of exercise training for heart failure from 2002 to 2022, and to identify hot spots and frontiers within this research field.MethodsBibliometric information on literature on the topic of exercise training for heart failure published between 2002 and 2022 was searched and collected in the Web of Science Core Collection. CiteSpace 6.1.R6 (Basic) and VOSviewer (1.6.18) were applied to perform bibliometric and knowledge mapping visualization analyses.ResultsA total of 2017 documents were retrieved, with an upward-stable trend in the field of exercise training for heart failure. The US authors were in the first place with 667 documents (33.07%), followed by Brazilian authors (248, 12.30%) and Italian authors (182, 9.02%). The Universidade de São Paulo in Brazil was the institution with the highest number of publications (130, 6.45%). The top 5 active authors were all from the USA, with Christopher Michael O'Connor and William Erle Kraus publishing the most documents (51, 2.53%). The International Journal of Cardiology (83, 4.12%) and the Journal of Applied Physiology (78, 3.87%) were the two most popular journals, while Cardiac Cardiovascular Systems (983, 48.74%) and Physiology (299, 14.82%) were the two most popular categories. Based on the results of keyword co-occurrence network and co-cited reference network, the hot spots and frontiers of research in the field of exercise training for heart failure were high-intensity interval training, behaviour therapy, heart failure with preserved ejection fraction, and systematic reviews.ConclusionThe field of exercise training for heart failure has experienced two decades of steady and rapid development, and the findings of this bibliometric analysis provide ideas and references for relevant stakeholders such as subsequent researchers for further exploration.

Abstract Background The aim of this study was to investigate the associations of osteosarcopenic obesity (OSO) and its components with complete blood cell count-derived inflammation indices. Methods In this cross-sectional study, data of 648 participants aged ≥60 years (men/women: 232/416, mean age: 67.21 ± 6.40 years) were collected from January 2018 to December 2020. Areal bone mineral density and body fat percentage were used to define osteopenia/osteoporosis and obesity, respectively. The criteria of the 2019 Asian Working Group for Sarcopenia were used to diagnose sarcopenia. Based on the number of these conditions, participants were divided into four groups: OSO/0, OSO/1, OSO/2, and OSO/3. Logistic regression analysis was conducted to identify associations between blood cell count-derived inflammation indices and the number of disorders with abnormal body composition. Results Systemic inflammation response index (SIRI), white blood cells, neutrophil-to-lymphocyte ratio (NLR), aggregate inflammation systemic index (AISI), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) showed statistically significant differences among the four groups (P

Abstract Background Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. Methods We analyzed 258 patients with acute ischemic stroke who underwent MT from January 2018 to February 2021. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3–6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter’s Z-test to assess the calibration performance of the risk prediction model. Results In our visual nomogram, gender (odds ratio [OR], 3.40; 95%CI, 1.54–7.54), collateral circulation (OR, 0.46; 95%CI, 0.28–0.76), postoperative mTICI (OR, 0.06; 95%CI, 0.01–0.50), stroke-associated pneumonia (OR, 5.76; 95%CI, 2.79–11.87), preoperative Na (OR, 0.82; 95%CI, 0.72–0.92) and creatinine (OR, 1.02; 95%CI, 1.01–1.03) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT. The area under the nomogram curve was 0.8791 with good calibration performance (P = 0.873 for the Spiegelhalter’s Z-test). Conclusions A novel nomogram consisting of gender, collateral circulation, postoperative mTICI, stroke-associated pneumonia, preoperative Na and creatinine can predict the 3-month unfavorable outcomes in stroke patients treated with MT.

Objective: Developing and assessing a risk prediction model of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG), and aims to provide a reference for the prediction and prevention. Design: A retrospective case-control study. Setting: Three major urban teaching and university hospitals and tertiary referral centers. Participants: consecutive patients undergoing CABG. Interventions: The study was retrospective and no interventions were administered to patients. Measurements and main results: In the study, the overall new-onset POAF prevalence was approximately 28%. A prediction model for POAF with nine significant indicators was developed, and identified new predictors of POAF: left ventricular end diastolic diameter (LVEDD), intraoperative defibrillation, and intraoperative temporary pacing lead implantation. The model had good discrimination in both the derivation and validation cohorts, with the area under the receiver operating characteristic curves (AUCs) of 0.621 (95% CI = 0.602–0.640) and 0.616 (95% CI = 0.579–0.651), respectively, and showed good calibration. Compared with CHA2DS2-VASc, HATCH score, and the prediction model of POAF after CABG developed based on a small sample of clinical data from a single center in China, the model in this study had better discrimination. Conclusion: We have developed and validated a new prediction model of POAF after CABG using multicenter data that can be used in the clinic for early identification of high-risk patients of POAF, and to help effectively prevent POAF in postoperative patients.

Abstract Background MADS-box transcription factors (TFs) are the key regulators of multiple developmental processes in plants; among them, a chrysanthemum MADS-box TF CmANR1 has been isolated and described as functioning in root development in response to high nitrate concentration signals. However, how CmANR1 affects root and shoot development remains unclear. Results We report that CmANR1 plays a positive role in root system development in chrysanthemum throughout the developmental stages of in vitro tissue cultures. Metabolomics combined with transcriptomics assays show that CmANR1 promotes robust root system development by facilitating nitrate assimilation, and influencing the metabolic pathways of amino acid, glycolysis, and the tricarboxylic acid cycle (TCA) cycle. Also, we found that the expression levels of TFs associated with the nitrate signaling pathways, such as AGL8, AGL21, and LBD29, are significantly up-regulated in CmANR1-transgenic plants relative to the wild-type (WT) control; by contrast, the expression levels of RHD3-LIKE, LBD37, and GATA23 were significantly down-regulated. These results suggest that these nitrate signaling associated TFs are involved in CmANR1-modulated control of root development. In addition, CmANR1 also acts as a positive regulator to control shoot growth and development. Conclusions These findings provide potential mechanisms of MADS-box TF CmANR1 modulation of root and shoot development, which occurs by regulating a series of nitrate signaling associated TFs, and influencing the metabolic pathways of amino acid and glycolysis, as well as TCA cycle and nitrate assimilation.

Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor (P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079 (100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079 (100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126 (2 µg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23 (3.5 µg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039 (100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China (approval No. TJ-A20160805) on August 26, 2016.

Depression can be a non-motor symptom, a risk factor, and even a co-morbidity of Parkinson’s disease (PD). In either case, depression seriously affects the quality of life of PD patients. Unfortunately, at present, a large number of clinical and basic studies focused on the pathophysiological mechanism of PD and the prevention and treatment of motor symptoms. Although there has been increasing attention to PD-related depression, it is difficult to achieve early detection and early intervention, because the clinical guidelines mostly refer to depression developed after or accompanied by motor impairments. Why is there such a dilemma? This is because there has been no suitable preclinical animal model for studying the relationship between depression and PD, and the assessment of depressive behavior in PD preclinical models is as well a very challenging task since it is not free from the confounding from the motor impairment. As a common method to simulate PD symptoms, neurotoxin-induced PD models have been widely used. Studies have found that neurotoxin-induced PD model animals could exhibit depression-like behaviors, which sometimes manifested earlier than motor impairments. Therefore, there have been attempts to establish the PD-related depression model by neurotoxin induction. However, due to a lack of unified protocol, the reported results were diverse. For the purpose of further promoting the improvement and optimization of the animal models and the study of PD-related depression, we reviewed the establishment and evaluation strategies of the current animal models of PD-related depression based on both the existing literature and our own research experience, and discussed the possible mechanism and interventions, in order to provide a reference for future research in this area.

Glucose can serve as both the source of energy and regulatory signaling molecule in plant. Due to the environmental and metabolic change, sugar levels could affect various developmental processes. High glucose environment is hardly conductive to the plant growth but cause development arrest. Increasing evidence indicate that alternative splicing (AS) plays a pivotal role in sugar signaling. However, the regulatory mechanism upon glucose stress remains unclear. The full-length transcriptomes were obtained from the samples of Arabidopsis seedlings with 3% glucose and mock treatment, using Oxford Nanopore sequencing technologies. Further analysis indicated that many genes involved in photosynthesis were significantly repressed and many genes involved in glycolysis, mitochondrial function, and the response to oxidative stress were activated. In total, 1,220 significantly differential alternative splicing (DAS) events related to 619 genes were identified, among which 75.74% belong to intron retention (IR). Notably, more than 20% of DAS events come from a large set of glycine-rich protein (GRP) family genes, such as GRP7, whose AS types mostly belong to IR. Besides the known productive GRP transcript isoforms, we identified a lot of splicing variants with diverse introns spliced in messenger RNA (mRNA) region coding the glycine-rich (GR) domain. The AS pattern of GRPs changed and particularly, the productive GRPs increased upon glucose stress. These ASs of GRP pre-mRNAs triggered by glucose stress could be abolished by AZD-8055, which is an ATP competitive inhibitor for the target of rapamycin (TOR) kinase but could be mimicked by H2O2. Additionally, AS pattern change of arginine/serine-rich splicing factor 31(RS31) via TOR pathway, which was previously described in response to light and sucrose signaling, was also induced in a similar manner by both glucose stress and reactive oxygen species (ROS). Here we conclude that (i) glucose stress suppresses photosynthesis and activates the glycolysis-mitochondria energy relay and ROS scavenging system; (ii) glucose stress triggers transcriptome-wide AS pattern changes including a large set of splicing factors, such as GRPs and RS31; (iii) high sugars regulate AS pattern change of both GRPs and RS31 via TOR-ROS pathway. The results from this study will deepen our understanding of the AS regulation mechanism in sugar signaling.

Objectives: Postoperative neurological deficits remain a challenge in cardiac surgery employing deep hypothermic circulatory arrest (DHCA). This study aimed to investigate the effect of WIN55, 212-2, a cannabinoid agonist, on brain injury in a rat model of DHCA. Methods: Twenty-four male Sprague Dawley rats were randomly divided into three groups: a control group (which underwent cardiopulmonary bypass (CPB) only), a DHCA group (CPB with DHCA), and a WIN group (WIN55, 212-2 pretreatment before CPB with DHCA). Histopathological changes in the brain were evaluated by hematoxylin–eosin staining. Plasma levels of superoxide dismutase (SOD) and proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-a) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression of SOD in the hippocampus was detected by Western blot and immunofluorescence staining. Levels of apoptotic-related protein caspase-3 and type 1 cannabinoid receptor (CB1R) in the hippocampus were evaluated by Western blot. Results: WIN55, 212-2 administration attenuated histopathological injury of the hippocampus in rats undergoing DHCA, associated with lowered levels of IL-1β, IL-6, and TNF-α (p < 0.05, p < 0.001, and p < 0.01, vs. DHCA, respectively) and an increased level of SOD (p < 0.05 vs. DHCA). WIN55, 212-2 treatment also increased the content of SOD in the hippocampus. The protein expression of caspase-3 was downregulated and the expression of CB1R was upregulated in the hippocampus by WIN55, 212-2. Conclusions: the administration of WIN55, 212-2 alleviates hippocampal injury induced by DHCA in rats by regulating intrinsic inflammatory and oxidative stress responses through a CB1R-dependent mechanism.

In the North China Plain, the excessive application of nitrogen (N) fertilizer for ensuring high yield and a single application at sowing for simplifying management in farmer practice lead to low N use efficiency and environmental risk in maize (Zea mays L.) production. However, it is unclear whether and how late split application with a lower level of N fertilizer influences maize yield. To address this question, a two-year field experiment was conducted with two commercial maize cultivars (Zhengdan 958 and Denghai 605) using a lower level of N input (180 kg ha−1) by setting up single application at sowing and split application at sowing and later stages (V12, R1, and R2) with four different ratios, respectively. The maize yield with split-applied 180 kg ha−1 N did not decrease compared to the average yield with 240 kg ha−1 N input in farmer practice, while it increased by 6.7% to 11.5% in the four N split-application treatments compared with that of the single-application control. Morphological and physiological analyses demonstrated that late split application of N (i) increased the net photosynthetic rate and chlorophyll content and thus promoted the photosynthetic efficiency during the reproductive stages; (ii) promoted the sink capacity via improved kernel number, endosperm cells division, and grain-filling rate; and (iii) increased the final N content and N efficiency in the plant. Therefore, we propose that late split application of N could reduce N fertilizer input and coordinately improve N efficiency and grain yield in summer maize production, which are likely achieved by optimizing the source–sink relations during the grain-filling stage.

Stem cell transplantation has brought new hope for the treatment of neurological diseases. The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells. Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors, the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located. Accordingly, the optimal microenvironment for inducing stem cell differentiation is a hot topic. EGb761 is extracted from the leaves of the Ginkgo biloba tree. It is used worldwide and is becoming one of the focuses of stem cell research. Studies have shown that EGb761 can antagonize oxygen free radicals, stabilize cell membranes, promote neurogenesis and synaptogenesis, increase the level of brain-derived neurotrophic factors, and replicate the environment required during the differentiation of stem cells into nerve cells. This offers the possibility of using EGb761 to induce the differentiation of stem cells, facilitating stem cell transplantation. To provide a comprehensive reference for the future application of EGb761 in stem cell therapy, we reviewed studies investigating the influence of EGb761 on stem cells. These started with the composition and neuropharmacology of EGb761, and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

Highlight MADS-box TF CmANR1 modulates both AR and LR development by directly regulating auxin transport gene CmPIN2 in chrysanthemum.

To improve efficiency in the use of water resources in water-limited environments such as the North China Plain (NCP), where winter wheat is a major and groundwater-consuming crop, the application of water-saving irrigation strategies must be considered as a method for the sustainable development of water resources. The initial objective of this study was to evaluate and validate the ability of the CERES-Wheat model simulation to predict the winter wheat grain yield, biomass yield and water use efficiency (WUE) responses to different irrigation management methods in the NCP. The results from evaluation and validation analyses were compared to observed data from 8 field experiments, and the results indicated that the model can accurately predict these parameters. The modified CERES-Wheat model was then used to simulate the development and growth of winter wheat under different irrigation treatments ranging from rainfed to four irrigation applications (full irrigation) using historical weather data from crop seasons over 33 years (1981–2014). The data were classified into three types according to seasonal precipitation: 140 mm. Our results showed that the grain and biomass yield, harvest index (HI) and WUE responses to irrigation management were influenced by precipitation among years, whereby yield increased with higher precipitation. Scenario simulation analysis also showed that two irrigation applications of 75 mm each at the jointing stage and anthesis stage (T3) resulted in the highest grain yield and WUE among the irrigation treatments. Meanwhile, productivity in this treatment remained stable through different precipitation levels among years. One irrigation at the jointing stage (T1) improved grain yield compared to the rainfed treatment and resulted in yield values near those of T3, especially when precipitation was higher. These results indicate that T3 is the most suitable irrigation strategy under variable precipitation regimes for stable yield of winter wheat with maximum water savings in the NCP. The application of one irrigation at the jointing stage may also serve as an alternative irrigation strategy for further reducing irrigation for sustainable water resources management in this area.

Abstract Background The roles in photosystem I (PSI) assembly of the nucleus-encoded thylakoid protein Y3IP1 who interacts with the plastid-encoded Ycf3 protein that has been well-characterized in plants. However, its function and potential mechanisms in other aspects remain poorly understood. Results We identified the apple MdY3IP1 gene, which encodes a protein highly homologous to the Arabidopsis Y3IP1 (AtY3IP1). Ectopic expression of MdY3IP1 triggered early-flowering and enhanced salt tolerance in Arabidopsis plants. MdY3IP1 controlled floral transition by accelerating sugar metabolism process in plant cells, thereby influencing the expression of flowering-associated genes. The increase in salt stress tolerance in MdY3IP1-expressing plants correlated with reduced reactive oxygen species (ROS) accumulation, and an increase in lateral root development by regulating both auxin biosynthesis and transport, as followed by enhancement of salt tolerance in Arabidopsis. Overall, these findings provide new evidences for additional functions of Y3IP1-like proteins and their underlying mechanisms of which Y3IP1 confers early-flowering and salt tolerance phenotypes in plants. Conclusions These observations suggest that plant growth and stress resistance can be affected by the regulation of the MdY3IP1 gene. Further molecular and genetic approaches will accelerate our knowledge of MdY3IP1 functions in PSI complex formation and plants stress resistance, and inform strategies for creating transgenic crop varieties with early maturity and high-resistant to adverse environmental conditions.

Abstract: Recent studies have shown that the R2R3-MYB transcription factor MdMYB73 is involved in salt stress response in apple. However, no research was done whether MdMYB73 mediated cold tolerance in apple or not. In this study, we found that the expression of MdMYB73 was obviously induced by cold stress. Functional analysis showed that MdMYB73 significantly increased cold tolerance in transgenic apple calli and Arabidopsis. Quantitative real-time PCR (qRT-PCR) assay indicated that the expression levels of cold-responsive genes including MdCBF2, MdCBF3, MdCBF4, and MdCBF5 were obviously enhanced in MdMYB73 transgenic calli, suggesting that MdMYB73 increased cold tolerance via C-repeat binding factor (CBF) cold response pathway. Finally, we found that soluble sugar, which provides an osmoticum for cells, was increased in MdMYB73 transgenic calli compared to that in the wild type control. These findings provide a new insights into how MdMYB73 is involved in cold stress response.

Abstract Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely RXFP1–4. Among these receptors, RXFP3 lacks a specific natural or synthetic agonist at present. A previously designed chimeric R3/I5 peptide, consisting of the B-chain of relaxin-3 and the A-chain of INSL5, displays equal activity towards the homologous RXFP3 and RXFP4. To increase its selectivity towards RXFP3, in the present study we conducted extensive mutagenesis around the B-chain C-terminal region of R3/I5. Decreasing or increasing the peptide length around the B23–B25 position dramatically lowered the activation potency of R3/I5 towards both RXFP3 and RXFP4. Substitution of B23Gly with Ala or Ser converted R3/I5 from an efficient agonist to a strong antagonist for RXFP3, but the mutants retained considerable activation potency towards RXFP4. Substitution of B24Gly increased the selectivity of R3/I5 towards RXFP3 over the homologous RXFP4. The best mutant, [G(B24)S]R3/I5, displayed 20-fold higher activation potency towards RXFP3 than towards RXFP4, meanwhile retained full activation potency at RXFP3. Thus, [G(B24)S]R3/I5 is the best RXFP3-selective agonist known to date. It is a valuable tool for investigating the physiological functions of RXFP3, and also a suitable template for developing RXFP3-specific agonists in future.

With the rapid development of the Internet of things (IoT) technology and cloud computing technology, the search engine for Internet of things become a hot research topic. However, because of the openness of the search of IoT, the privacy in traditional Internet search area becomes more prominent and faces more challenges. Firstly, the research background and challenges of data privacy preservation for search of IoT were described. Secondly, the scheme of data privacy preservation for the search of Internet of things based on fine-grained authorization was pro-posed, which combined the encrypted search algorithm with the attribute based access control algorithm. Thirdly, the security analysis and performance analysis of the scheme were also carried out. Finally, the future research work was summarized and pointed out.

With the rapid development of the internet of things(IoT) technology and big data technology,the search engine for internet of things become a hot research topic.However,because of the openness of the search of IoT,the privacy in traditional internet search area become more prominent and face more challenges.Firstly,the research background and challenges of privacy preservation for search of IoT were described.Secondly,the framework of data privacy preservation for search of IoT were presented and several main research domain in this framework were described.Thirdly,several privacy preservation technology appropriated for search of IoT were described in detail,including the background,recent research work,main research directions.Finally,the current problems and important research field for future were presented.

Neural stem cells (NSCs) have been shown as a potential source for replacing degenerated neurons in neurodegenerative diseases. However, the therapeutic potential of these cells is limited by the lack of effective methodologies for controlling their differentiation. Inducing endogenous pools of NSCs by small molecule can be considered as a potential approach of generating the desired cell types in large numbers. Here, we reported the characterization of a small molecule (Methyl 3,4-dihydroxybenzoate; MDHB) that selectively induces hippocampal NSCs to differentiate into cholinergic motor neurons which expressed synapsin 1 (SYN1) and postsynaptic density protein 95 (PSD-95). Studies on the mechanisms revealed that MDHB induced the hippocampal NSCs differentiation into cholinergic motor neurons by inhibiting AKT phosphorylation and activating autophosphorylation of GSK3β at tyrosine 216. Furthermore, we found that MDHB enhanced β-catenin degradation and abolished its entering into the nucleus. Collectively, this report provides the strong evidence that MDHB promotes NSCs differentiation into cholinergic motor neurons by enhancing gene Isl1 expression and inhibiting cell cycle progression. It may provide a basis for pharmacological effects of MDHB directed on NSCs.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2′,7′-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells.