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Background Diabetes was considered as a risk factor for venous thromboembolism (VTE), but conflicting findings have been reported from observational studies. This study aimed at investigating the causal associations of type 1 and type 2 diabetes with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods We designed a bidirectional two-sample Mendelian randomization (MR) analysis by using summary-level data from large genome-wide association studies performed in European individuals. Inverse variance weighting with multiplicative random effect method was used to obtain the primary causal estimates, and weighted median, weighted mode, and MR egger regression were replenished as sensitivity analyses to test the robustness of the results. Results We found no significant causal effects of type 1 diabetes on VTE (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96–1.00, p = 0.043), DVT (OR: 0.98, 95% CI: 0.95–1.00, p = 0.102), and PE (OR: 0.98, 95% CI: 0.96–1.01, p = 0.160). Similarly, no significant associations of type 2 diabetes with VTE (OR: 0.97, 95% CI: 0.91–1.03, p = 0.291), DVT (OR: 0.96, 95% CI: 0.89–1.03, p = 0.255), and PE (OR: 0.97, 95% CI: 0.90–1.04, p = 0.358) were also observed. Results from multivariable MR analysis were consistent with the findings in univariable analysis. In the other direction, the results showed no significant causal effects of VTE on type 1 and type 2 diabetes. Conclusion This MR analysis demonstrated no significant causal associations of type 1 and type 2 diabetes with VTE in both directions, in conflict with previous observational studies reporting positive association, which provided clues for understanding the underlying pathogenesis of diabetes and VTE.

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Recovery from injury to the peripheral nervous system is different from that of the central nervous system in that it can lead to gene reprogramming that can induce the expression of a series of regeneration-associated genes. This eventually leads to axonal regeneration of injured neurons. Although some regeneration-related genes have been identified, the regulatory network underlying axon regeneration remains largely unknown. To explore the regulator of axon regeneration, we performed RNA sequencing of lumbar L4 and L5 dorsal root ganglion (DRG) neurons at different time points (0, 3, 6, 12 hours, 1, 3 and 7 days) after rat sciatic nerve crush. The isolation of neurons was carried out by laser capture microscopy combined with NeuN immunofluorescence staining. We found 1228 differentially expressed genes in the injured sciatic nerve tissue. The hub genes within these differentially expressed genes include Atf3, Jun, Myc, Ngf, Fgf2, Ezh2, Gfap and Il6. We verified that the expression of the enhancer of zeste homologue 2 gene (Ezh2) was up-regulated in DRG neurons after injury, and this up-regulation differed between large- and small-sized dorsal root ganglion neurons. To investigate whether the up-regulation of Ezh2 impacts axonal regeneration, we silenced Ezh2 with siRNA in cultured DRG neurons and found that the growth of the newborn axons was repressed. In our investigation into the regulatory network of Ezh2 by interpretive phenomenal analysis, we found some regulators of Ezh2 (including Erk, Il6 and Hif1a) and targets (including Atf3, Cdkn1a and Smad1). Our findings suggest that Ezh2, as a nerve regeneration-related gene, participates in the repair of the injured DRG neurons, and knocking down the Ezh2 in vitro inhibits the axonal growth of DRG neurons. All the experimental procedures approved by the Administration Committee of Experimental Animals of Jiangsu Province of China (approval No. S20191201-201) on March 21, 2019.

Aims/hypothesis An association between obesity and deep vein thrombosis (DVT) has been revealed by observational studies, but it is not clear if the observed associations are causal, caused by confounding bias or reverse causation. Methods We performed a two-sample Mendelian Randomization (MR) study by obtaining exposure and outcome data from separate published studies. We utilized data from Genetic Investigation of Anthropometric Traits (GIANT, 339,224 participants) consortium and FinnGen project (FinnGen, 1785 DVT case and 84,462 control participants) to determine the causal effect of BMI on DVT. Results All three MR methods provided a positive association between BMI and DVT. Using IVW, we found evidence of causal relationships between BMI and DVT. BMI is positively associated with DVT (IVW odds ratio [OR] per SD increase in BMI = 1.67 [95% CI, 1.16–2.40]; P = 0.006). MR Egger and weighted median regression also showed directionally similar estimates (MR-Egger OR per SD increase in BMI, 2.50 [95% CI, 1.07–5.84], P = 0.034; weighted median OR per SD increase in BMI, 2.02 [95% CI, 1.10–3.71], P = 0.023). Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed between BMI and DVT. Conclusions/interpretation Our findings provide evidence of significant causal association between BMI and DVT in agreement with observational studies. Taking measures to reduce the proportion of obesity may help reduce the incidence of DVT.

Objective To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. Data Sources PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. Study Selection Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. Data Extraction Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. Data Synthesis Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. Conclusions BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.

Three new triterpenoid glycosides, 2

The design and assembly of polyoxometalate-resorcin[4]arene-based metal-organic molecular materials are particularly attractive for their elegant structures and potential functions. By applying a newly designed resorcin[4]arene ligand (TPC4R-II), a copper(I)-coordinated polyoxometalate-based metal-organic molecular material, namely, [CuI6(Br)3(TPC4R-II)3(PMo12O40)]·8H2O (1), was rationally assembled. Three copper(I)-coordinated resorcin[4]arenes are held together by a central [PMo12O40]3- to yield a supramolecular propeller. 1 features efficient catalytic performances for oxidation desulfurization (ODS) and azide-alkyne cycloaddition (AAC) reactions. This work affords a feasible method for the nanosized polyoxometalate-based metal-resorcin[4]arene assemblies by well combinating two types of large composites as well as low coordination metal cations.

BACKGROUND Little is known about the clinical significance of upper esophageal sphincter (UES) motility disorders and their association with the treatment response of type II achalasia. None of the three versions of the Chicago Classification of Esophageal Motility Disorders has defined UES abnormality metrics or their function. UES abnormalities exist in some patients and indicate a clinically significant problem in patients with achalasia. AIM To demonstrate the manometric differentiation on high-resolution esophageal manometry between subjects with abnormal UES and normal UES, and the association between UES type and the treatment response of type II achalasia. METHODS In total, 498 consecutive patients referred for high-resolution esophageal manometry were analyzed retrospectively. The patients were divided into two groups, those with normal and abnormal UES function. UES parameters were analyzed after determining lower esophageal sphincter (LES) function. Patients with type II achalasia underwent pneumatic dilation for treatment. Using mixed model analyses, correlations between abnormal UES and treatment response were calculated among subjects with type II achalasia. RESULTS Of the 498 consecutive patients, 246 (49.40%) were found to have UES abnormalities. Impaired relaxation alone was the most common UES abnormality (52.85%, n = 130). The incidence rate of type II achalasia was significantly higher in subjects with abnormal UES than those with normal UES (9.77% vs 2.58%, P = 0.01). After pneumatic dilation, LES resting pressure, LES integrated relaxation pressure, and UES residual pressure were significantly decreased (41.91 ± 9.20 vs 26.18 ± 13.08, 38.94 ± 10.28 vs 16.71 ± 5.65, and 11.18 ± 7.93 vs 5.35 ± 4.77, respectively, P < 0.05). According to the Eckardt score, subjects with type II achalasia and abnormal UES presented a significantly poorer treatment response than those with normal UES (83.33% vs 0.00%, P < 0.05). CONCLUSION Impaired relaxation alone is the most common UES abnormality. The incidence of type II achalasia is associated with abnormal UES. Type II achalasia with abnormal UES has a poorer treatment response, which is a potentially prognostic indicator of treatment for this disease.

BackgroundThe CD47-SIRPα pathway acts as an important myeloid cell immune checkpoint and targeting the CD47/SIRPα axis represents a promising strategy to promote antitumor immunity. Several CD47-targeting agents show encouraging early activity in clinical trials. However, due to ubiquitous expression of CD47, the antigen sink and hematologic toxicity, such as anemia and thrombocytopenia, are main problems for developing CD47-targeting therapies. Considering the limited expression of SIRPα, targeting SIRPα is an alternative approach to block the CD47-SIRPα pathway, which may result in differential efficacy and safety profiles.MethodsSIRPα-targeting antibody BR105 was generated by hybridoma fusion and following humanization. BR105 was characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. The functional activity was determined in in vitro phagocytosis assays by using human macrophages. The effect of BR105 on human T cell activation was studied using an OKT3-induced T-cell proliferation assay and an allogeneic mixed lymphocyte reaction. Human SIRPα-humanized immunodeficient mice were used in cancer models for evaluating the in vivo antitumor efficacy of BR105. Safety was addressed in a repeat-dose toxicity study in cynomolgus monkeys, and toxicokinetic analysis was further evaluated.ResultsBR105 shows broad binding activity across various SIRPα variants, and potently blocks the interaction of SIRPα and CD47. In vitro functional assays demonstrated that BR105 synergizes with therapeutic antibodies to promote phagocytosis of tumor cells. Moreover, the combination of BR105 and therapeutic antibody significantly inhibits tumor growth in a xenograft tumor model. Although BR105 may slightly bind to SIRPγ, it does not inhibit T cell activation, unlike other non-selective SIRPα-targeting antibody and CD47-targeting agents. Toxicity studies in non-human primates show that BR105 is well tolerated with no treatment-related adverse effects noted.ConclusionsThe novel and differentiated SIRPα-targeting antibody, BR105, was discovered and displays promising antitumor efficacy in vitro and in vivo. BR105 has a favorable safety profile and shows no adverse effects on T cell functionality. These data support further clinical development of BR105, especially as a therapeutic agent to enhance efficacy when used in combination with tumor-targeting antibodies or antibodies that target other immune checkpoints.

The Acinetobacter indicus strain ZJB20129 isolated from an urban sewage treatment plant demonstrated the heterotrophic nitrification-aerobic denitrification (HN-AD) ability. Stain ZJB20129 could remove 98.73% of ammonium-N, 97.26% of nitrite-N and 96.55% of nitrate-N, and the maximum removal rate was 3.66, 4.62 and 5.21 mg/L/h, respectively. Ammonium was preferentially used during simultaneous nitrification and denitrification. Strain ZJB20129 exhibited highest ammonium removal capability when carbon source was sodium succinate, C/N ratio was 15, pH was 8.0, and temperature was 35 ℃. Key enzymes involved in HN-AD including hydroxylamine oxidase, periplasmic nitrate reductase and nitrite reductase as well as their encoding genes were detected, and the metabolic pathway of HN-AD was subsequently predicted. Our results suggested that Acinetobacter indicus ZJB20129 displayed superior nitrogen removal performance on actual wastewater and thus made it have a good application prospect in wastewater biological treatment.

BACKGROUND False tendon is a common intraventricular anatomical variation. It refers to a fibroid or fibromuscular structure that exists in the ventricle besides the normal connection of papillary muscle and mitral or tricuspid valve. A large number of clinical studies have suggested that there is a significant correlation between false tendons and premature ventricular complexes. However, few studies have verified this correlation during radiofrequency catheter ablation of premature ventricular complexes. CASE SUMMARY A 45-year-old male was admitted to receive radiofrequency ablation for symptomatic premature ventricular complexes. A three-dimensional model of the left ventricle was established by intracardiac echocardiography using the CartoSoundTM mapping system. In addition to the left anterior papillary muscle, the posterior papillary muscle was mapped. False tendons were found at the base of the interventricular septum, and the other end was connected to the left ventricular free wall near the apex. An irrigated touch force catheter was advanced into the left ventricle via the retrograde approach. The earliest activation site was marked at the interventricular septum attachment of the false tendons and was successfully ablated. CONCLUSION This case verified that false tendons can cause premature ventricular complexes and may be cured by radiofrequency ablation guided by intracardiac echocardiography with the CartoSoundTM system.

The design and synthesis of polynuclear metal cluster-based coordination cages is of considerable interest due to their appealing structural characteristics and potential applications. Herein, we report a calix[4]resorcinarene-based [Co12] coordination cage, [Co12(TPC4R-I)2(1,3-BDC)10(μ3-OH)4(H2O)10(DMF)2]·7DMF·23H2O (1), assembled with 2 bowl-shaped calix[4]resorcinarenes (TPC4R-I), 10 angular 1,3-benzenedicarboxylates (1,3-BDC), and 12 Co(II) cations. Remarkably, it is shown to be a highly efficient recyclable heterogeneous catalyst for CO2 conversion due to its exposed Co(II) Lewis acid sites.

Our previous study found that the anthelmintic drug niclosamide relaxed the constricted arteries and inhibited proliferation and migration of vascular smooth muscle cells. Here, we investigated the effect of niclosamide ethanolamine (NEN) on trachea function and the proliferation and migration of trachea smooth muscle cells. Isometric tension of trachea was recorded by multi-channel myograph system. The cell proliferation was detected by using BrdU cell proliferation assay. The cell migration ability was evaluated by using scratch assay. The protein level was measured by using western blot technique. Acute treatment with NEN dose-dependently relaxed acetylcholine chloride (Ach)- and High K+ physiological salt solution (KPSS)-induced constriction of mice trachea. Pre-treatment with NEN inhibited Ach- and KPSS-induced constriction of mice trachea. NEN treatment inhibited proliferation of human bronchial smooth muscle cells (HBSMCs), inhibited migration of HBSMCs and rat primary trachea smooth muscle cells. NEN treatment activated adenosine monophosphate activated protein kinase (AMPK) activity and inhibited signal transducer and activator of transcription 3 (STAT3) activity in HBSMCs. In conclusion, niclosamide ethanolamine induces trachea relaxation and inhibits proliferation and migration of trachea smooth muscle cells, indicating that niclosamide might be a potential drug for chronic asthma treatment.

Aims The aim of this study was to apply the Mendelian randomization (MR) design to explore the potential causal association between COVID-19 and the risk of hypertension disorders in pregnancy. Methods Our primary genetic instrument comprised 8 single-nucleotide polymorphisms (SNPs) associated with COVID-19 at genome-wide significance. Data on the associations between the SNPs and the risk of hypertension disorders in pregnancy were obtained from study based on a very large cohort of European population. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches. Results Using IVW, we found that genetically predicted COVID-19 was significantly positively associated with hypertension disorders in pregnancy, with an odds ratio (OR) of 1.111 [95% confidence interval (CI) 1.042–1.184; P = 0.001]. Weighted median regression also showed directionally similar estimates [OR 1.098 (95% CI, 1.013–1.190), P = 0.023]. Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed. Conclusions Our findings provide direct evidence that there is a shared genetic predisposition so that patients infected with COVID-19 may be causally associated with increased risk of hypertension disorders in pregnancy.

In this paper, a microwave triple-frequency multiplier based on multilayer MoS2 is designed. The multilayer MoS2 stripped from the MoS2 crystal has a strong nonlinearity. It has the physical characteristics of developing a microwave multiplier, such as a tripler. A multilayer MoS2 film is used to cover the microstrip line gap, and a triple-frequency multiplier (MFT) fabricated by multilayer MoS2 is designed. If the input power of the signal source is 15 dBm and the bandwidth of the input frequency is 0.8–1.2 GHz, the minimum conversion loss through the MFT is −41.5 dBm, and the even harmonic nonlinearity is far weaker than the odd harmonic nonlinearity. Therefore, multilayer MoS2 is a promising MFT material. Finally, by adding a recycling branch behind the tripler, the third-frequency output power is increased by recovering the low-order signal harmonics.

Hepatotoxicity with low-molecular-weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Liver dysfunction was identified in 79 patients (17.1%), of whom 97.5% had grade 1 drug-induced liver injury (DILI) and 2.5% had grade 2 DILI. The results showed that liver dysfunction usually occurred in the first week after anticoagulant administration, and the liver tests of all patients with liver dysfunction gradually recovered or alleviated at discharge. The multivariable logistic regression analysis indicated that a longer treatment course and hepatitis B surface antigen-positive (HBsAg+) were risk factors for liver dysfunction (P < .05). Moreover, nadroparin calcium had the highest risk of liver dysfunction, approximately 2.2 times (95% confidence interval [CI], 1.1740-4.224; P = .015) that of enoxaparin sodium. In conclusion, nearly one-fifth and 10% of patients prescribed with LMWH or fondaparinux, respectively, for pulmonary embolism had liver dysfunction, mainly with mild liver injury and characterized by self-limited elevated serum transaminase levels. Hence, during the 3 anticoagulant applications, we should pay more attention to the monitoring of liver function in the first week and transit to oral anticoagulants if possible, especially for patients who are HBsAg+ or suffering from other liver diseases.

We herein propose a design assembly of calix[4]resorcinarene-based proton-conductive [Co16] coordination cages (1-SO3H and 1-OH) by carefully mediating the acidic sites of isomorphous auxiliary ligands. Markedly, 1-SO3H exhibits a proton conductivity that increased about 1 order of magnitude relative to its counterpart 1-OH, reaching 1.35 × 10−2 S cm−1 at 90 °C and under 98% relative humidity.

The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology departments can most effectively respond to this public health emergency.

Nine undescribed (1–4, 6–10) sesquiterpene coumarins, together with a new natural one (5) and ten known ones (11–20), were isolated from the low polarity fraction of the 95% ethanol extract of the resin of Ferula sinkiangensis. Their structures were elucidated based on the comprehensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. All the identified SCs were evaluated for their anti-neuroinflammatory activities in LPS-induced BV-2 cells. Ferusingensine G (8) displayed a significant inhibitory effect on nitric oxide (NO) production with an IC50 value of 1.2 μM. The results suggested that natural SCs might be served as potential neuroinflammatory inhibitors.

Ethnopharmacological relevance Ferula sinkiangensis K. M. Shen is a traditional Chinese medicine that has a variety of pharmacological properties relevant to neurological disorders and inflammations. Kellerin, a novel compound extracted from Ferula sinkiangensis, exerts a strong anti-neuroinflammatory effect by inhibiting microglial activation. Microglial activation plays a vital role in ischemia-induced brain injury. However, the potential therapeutic effect of kellerin on focal cerebral ischemia is still unknown. Aim of the study To explore the effect of kellerin on cerebral ischemia and clarify its possible mechanisms, we applied the middle cerebral artery occlusion (MCAO) model and the LPS-activated microglia model in our study. Materials and methods Neurological outcome was examined according to a 4-tiered grading system. Brain infarct size was measured using TTC staining. Brain edema was calculated using the wet weight minus dry weight method. Neuron damage and microglial activation were observed by immunofluorescence in MCAO model in rats. In in vitro studies, microglial activation was examined by flow cytometry and the viability of neuronal cells cultured in microglia-conditioned medium was measured using MTT assay. The levels of pro-inflammatory cytokines were measured by qRT-PCR and ELISA. The proteins involved in NF-κB signaling pathway were determined by western blot. Intracellular ROS was examined using DCFH-DA method and NADPH oxidase activity was measured using the NBT assay. Results We found that kellerin improved neurological outcome, reduced brain infarct size and decreased brain edema in MCAO model in rats. Under the pathologic conditions of focal cerebral ischemia, kellerin alleviated neuron damage and inhibited microglial activation. Moreover, in in vitro studies of LPS-stimulated BV2 cells kellerin protected neuronal cells from being damaged by inhibiting microglial activation. Kellerin also reduced the levels of pro-inflammatory cytokines, suppressed the NF-κB signaling pathway, and decreased ROS generation and NADPH oxidase activity. Conclusions Our discoveries reveal that the neuroprotective effects of kellerin may largely depend on its inhibitory effect on microglial activation. This suggests that kellerin could serve as a novel anti-inflammatory agent which may have therapeutic effects in ischemic stroke.

Two new inorganic–organic hybrid complexes, namely, {[Co4(L)2(HCOO)2(OH)2][SiO4(W3O9)4]}·6DMF·5H2O (1) and {[Zn4(L)2(HCOO)2(OH)2][SiO4(W3O9)4]}·6DMF·5H2O (2), have been solvothermally prepared by using a new methyl imidazole functionalized resorcin[4]arene (L), polyoxometalate (POM), and metal cation. Isostructural 1 and 2 feature porous supramolecular architectures and represent an unusual example of a successful combination of resorcin[4]arenes with polyoxometalates. Remarkably, selective adsorptions for organic dyes were studied by using 1 and 2 as adsorbents. Moreover, their electrocatalytic activities for the oxidation of ascorbic acid and reduction of NaBrO3 were also studied.

Buoyancy-driven underwater gliders are highly efficient winged underwater vehicles driven by modifying the net buoyancy and internal shape. Many advantages, such as wide cruise range, less power consumption, low noise, and no pollution, make the underwater glider an important platform for marine environment observation and ocean resource exploration. For the wide cruise range, attitude control of underwater glider becomes the core technology. In this paper, the underwater glider named OUC-III has been developed for marine observation. To control the attitude of glider, the kinematic and dynamic models of it have been calculated by mathematical analysis. Furthermore, a novel control algorithm is proposed to control the attitude of glider. The algorithm is combined reinforcement learning with Active Disturbance Rejection Control (ADRC) and compared with classical ADRC by simulation based on the dynamic model of OUC-III. The simulation experimental results indicate that the proposed algorithm compensates well for the ocean current disturbances on OUC-III attitude control mission and it obtains high-precision and high-adaptive control ability.

Jatrophane diterpenoids (JDs) have frequently been found existing in plants of Euphorbiaceae family, mainly distributing in Euphorbia genus, such as the famous Traditional Chinese Medicine Gan Sui (E. kansui) and Ze Qi (E. helioscopia). The skeleton of JDs is biosynthesized from four isoprene s by oxidation and cyclization. More than 200 JDs from herbals have been reported so far. This special type of diterpene is characterized by a flexible 5/12-membered carbon ring system substituted with multiple acyl and benzoyl groups. Their significant pharmacological effects have attracted more attention, including the multidrug resistance (MDR) reversal activity, anticancer, antiviral, antimalarial, anti-inflammatory, and lipid-lowering activities. As a good resource of leading compounds, many JD derivatives have been synthesized and modified by organic chemists. MDR remains a major threat for the successful chemotherapy, accounting for approximately 90% of treatment failure. JDs represent a novel scaffold for the discovery and development of effective MDR modulators to be used for cancer treatment in combination with chemotherapy. Among the reported JDs, 138 were examined for their MDR reversal activities and 70% of those were more effective than clinical medicines verapamil and doxorubicin. Based on the characterization of the special natural molecules, some structure-activity relationships (SARs) of related JDs have been concluded. Therefore, we summarized the research progress of JDs and threw light on finding more leading compounds as potential MDR modulators for cancer therapy.

The design and synthesis of polynuclear metal cluster-based coordination cages is of considerable interest due to their appealing structural characteristics and potential applications. Herein, we report a calix[4]resorcinarene-based [Co

Two remarkable polyoxometalate-bridged Cu(I)- and Ag(I)-thiacalix[4]arene dimers, namely, [Cu4(SiW12O40)(L)2(DMF)2]·2EtOH·DMF (1-Cu) and [Ag4(PMo12O40)(L)2]·OH (1-Ag), were prepared by using a new ...

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia-mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti-neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)-activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.

We herein propose a design assembly of calix[4]resorcinarene-based proton-conductive [Co16] coordination cages (1-SO3H and 1-OH) by carefully mediating the acidic sites of isomorphous auxiliary ligands. Markedly, 1-SO3H exhibits a proton conductivity that increased about 1 order of magnitude relative to its counterpart 1-OH, reaching 1.35 × 10-2 S cm-1 at 90 °C and under 98% relative humidity.