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Background: Dementia is associated with a greater burden of cardiovascular risk factors. There is a significant vascular contribution to dementia, and aspirin may play a role in targeting this vascular dysregulation via its anti-inflammatory and antiplatelet effects. We provide an overview of the effects of aspirin therapy on the prevention of dementia and cognitive decline in patients with or without dementia and/or cognitive impairment. Methods: We performed a search for studies enrolling adults with or without dementia or MCI and comparing aspirin with placebo, usual care, or active control with respect to cognitive outcomes. Results: We describe aspirin’s effects on the primary prevention of cognitive impairment and various subtypes of dementia, as well as its role in cognitive decline in certain subsets of patients, including those with cerebral small vessel disease (CVSD), coronary heart disease (CHD), and gender differences. Overall, the benefits of aspirin in preventing dementia and cognitive decline remain inconclusive. The majority of cohort studies investigating aspirin’s role in preventing cognitive decline or dementia looked promising, but this was not supported in most randomised controlled trials. However, aspirin may still be beneficial in certain subgroups of patients (such as CHD, VD, and CSVD) and warrants further investigation.

G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors, are the largest family of cell surface receptors in eukaryotes. There are ∼800 GPCRs in human, regulating diverse physiological processes. The GPCRs are the most intensively studied drug targets. Drugs that target GPCRs account for about a quarter of the global market share of therapeutic drugs. Therefore, to develop physiologically relevant and robust assays to search new GPCR ligands or modulators remain the major focus of drug discovery research worldwide. Early functional GPCR assays mainly depend on the measurement of G-protein-mediated second messenger generation. Recent developments in GPCR biology indicate that the signaling of these receptors is much more complex than the oversimplified classical view. The GPCRs have been found to activate multiple G proteins simultaneously and induce β-arrestin-mediated signaling. They have also been found to interact with other cytosolic scaffolding proteins and form dimer or heteromer with GPCRs or other transmembrane proteins. Here, we mainly discuss technologies focused on detecting protein–protein interactions, such as fluorescence resonance energy transfer/bioluminescence resonance energy transfer (FRET/BRET), NanoLuc binary technology (NanoBiT), Tango, etc., and their applications in measuring GPCRs interacting with various signaling partners. In the final part, we also discuss the species differences in GPCRs when using animal models to study the in vivo functions of GPCR ligands, and possible ways to solve this problem with modern genetic tools.

Precision better than 2.5% can be achieved with the combination of band-selective HSQC and 50% NUS in 0.5 h.

Congenital generalized lipodystrophy (CGL) is an extremely rare genetic disease mainly characterized by absence of whole-body adipose tissue and metabolic dysfunctions such as insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and acanthosis nigricans. In this study, we reported a novel case of a young woman patient with CGL. The patient came to the hospital for early-onset lipodystrophy and diabetes. She was 19-year-old with a height of 160 cm, a weight of 46 kg, BMI of 17.9 kg/m先天性全身性脂肪萎缩(congenital generalized lipodystrophy,CGL)是一种极端罕见的常染色体隐性遗传病,表现为明显的全身脂肪极度缺失,肌肉感明显,并伴有一系列的代谢指标异常,包括严重的胰岛素抵抗,高血糖,高脂血症,脂肪肝以及黑棘皮等。本文针对1例CGL患者及其家系进行研究。先证者为19岁年轻女性,自幼皮下脂肪缺如,血清瘦素水平仅0.14 μg/L。对患者及其亲属(父母、弟弟)进行全基因组检测,显示该患者BSCL2基因5号外显子存在复合杂合突变(c.560AG和c.565GT),c.560AG突变导致对应编码的187位的氨基酸由酪氨酸突变为半胱氨酸(p.Y187C),从而引起BSCL2编码的SEIPIN蛋白发生错义突变;c.565 GT突变引起对应编码的189位氨基酸转为终止密码子(p.E189X),产生蛋白截短突变。经Sanger测序验证,患者父亲携带c.565GT杂合突变,患者母亲携带c.560AG杂合突变,患者弟弟未携带BSCL2基因致病性突变。本研究通过转染突变p.Y187C质粒至HEK293细胞,观察到SEIPIN蛋白量及与甘油-3-磷酸酰基转移酶(glycerol-3-phosphate acyltransferase, GPAT3)互作减少;原代培养的患者皮肤成纤维细胞体外功能实验表明,患者的SEIPIN蛋白量明显低于正常健康人,加入组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors, HDACis)可部分挽救SEIPIN蛋白表达。此外,油酸刺激下患者皮肤成纤维细胞脂滴小于正常健康人。本文同时综述国内外既往文献中报道的BSCL2基因突变位点,丰富了CGL的临床表型谱和致病基因突变谱,有助于提高临床医生对CGL的临床诊治和致病机制的理解。.

Glucose metabolism plays a central role in energy supply and metabolism regulation in various tissues and organs. Besides, insulin is the sole hormone lowering blood glucose in the body, and islet function and insulin sensitivity are the key steps modulating glucose metabolism. Since the development of glucose clamp technology, it has been recognized as the gold standard for evaluating insulin metabolism. The main categories include hyperinsulinemia-euglycemia clamp, hyperglycemia clamp, and hyperinsulinemia-hypoglycemia clamp. These can be done on either anesthetized mice or conscious and unrestricted mice. This protocol focuses on the establishment and operation of the mouse glucose clamp technique, including preparation of instrument consumables, surgical operations, clamping procedures, and precautions, serving as reference and guidance.葡萄糖代谢是机体能量代谢的核心,在各个组织器官发挥能量供应及代谢调控作用,胰岛素是机体内唯一的降糖激素。胰岛功能及胰岛素敏感性是影响葡萄糖代谢的关键环节。葡萄糖钳夹技术是评估胰岛素敏感性及胰岛功能的金标准,主要类别包括高胰岛素正糖钳夹、高糖钳夹、高胰岛素低糖钳夹等类型。在小鼠葡萄糖钳夹实验中根据是否麻醉分为麻醉和清醒状态钳夹。本文重点阐述了小鼠葡萄糖钳夹技术方法的建立及操作的具体流程,包括器械耗材的准备、手术操作、钳夹过程及注意事项,旨在为实验室搭建各类小鼠葡萄糖钳夹技术平台提供参考。.

Takeda G protein-coupled receptor 5 (TGR5) is a promising target for treating metabolic syndrome and inflammatory diseases. Herein, we identified a new series of betulinic acid derivatives as potent TGR5 agonists, which show remarkable activity on human (h) and canine (c) TGR5 but exhibit unpromising activity on murine (m) TGR5. Species difference was also observed with many other reported TGR5 agonists. Therefore, we screened 29 amino acids which were conserved in hTGR5 and cTGR5 but different in mTGR5 and found a key amino acid, H88 in mTGR5 (Y89 in hTGR5), which contributed to the species difference. With the CRISPR/Cas9 system, the mTGR5H88Y mutation was introduced into mice, and the optimized compound 11d-Na displayed a significant glucose-lowering effect and stimulated GLP-1 and insulin secretion in TGR5H88Y mice but not in wild-type animals. Taken together, our study provides a useful tool to bridge the gap of species difference and discovers a potent TGR5 agonist for further investigation.

Background: To systematically evaluate the effectiveness and safety of traditional Chinese medicine preparation XPYEG combined with SBI and SBI alone in the treatment of REC, and to provide the reference in drugs for the clinical treatment of children with rotavirus enteritis. Methods: Retrieving the English databases: PubMed, Cochrane Library and Embase; Chinese databases: CNKI, CBM and WANFANG Data. Retrieving a randomized controlled trial of XPYEG and SBI in the treatment of REC. The retrieval time is from the above database until September 2020. The retrieval strategy of combining free words and subject words is adopted, and the references included in the literature are searched manually in accordance with the literature studied in this paper and not included in the above database. Two researchers screen the literature according to the literature inclusion and exclusion criteria, extract valid data and evaluate the quality of the literature, and cross-check it. Using the RevMan 5.3 software to conduct the meta-analysis on the main outcome and secondary outcome indicators of the included literature, while assessing the evidence quality of included study. Results: The effectiveness and safety of XPYEG and SBI in the treatment of REC are presented through the main and secondary outcome indicators. OSF Registration number: DOI 10.17605/OSF.IO/3QSZG. Conclusion: This study will conclude whether the combination of XPYEG and SBI is more effective than SBI alone in the treatment of REC, and whether the medication increases the risk of adverse reactions compared with single medication. Ethics and dissemination: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study.

Dengue fever (DF) is a mosquito-borne disease prevalent in the tropics (e.g., sub-Saharan Africa, Asia, and Central and South America) and a common cause of febrile illness in travelers. The high incidence of imported DF in Taiwan has led to a domestic outbreak. This study explored the risk factors associated with individuals given diagnoses of imported DF at international airports in Taiwan. The results may serve as a reference for DF prevention. In this retrospective study, data from the symptom notification system database of the Taiwan Centers for Disease Control (TCDC) were used. These data concerned travelers who returned to Taiwan from DF-endemic areas with suspected DF symptoms. The epidemiological characteristics of the cases were analyzed, and 28 variables related to DF infection were included in the multivariate logistic regression analysis. In 2018–2019, there were 8656 cases (451 positive and 8205 negative cases). The results revealed DF symptoms and a 16–30-day stay in endemic areas to be independent risk factors and the presence of three respiratory symptoms and

Geographic features play an important role in shaping the phylogeographic structures of species. Salvia miltiorrhiza Bunge is a widely studied medicinal crop. In this study, we used three cpDNA sequences (trnL–trnF, atpB–rbcL, and rpl16) to investigate the phylogeographic structure and evolutionary history of 190 S. miltiorrhiza endemic plants taken from 11 locations in the Qinling, Dabie, and Mengshan Mountains of Central China. Fifty-three total haplotypes were identified, and 50 of these were population-specific. In addition, moderate-to-high genetic differentiation was observed among the populations (mean Fst = 0.325), while phylogeographic structure was also observed based on STRUCTURE and spatial analysis of molecular variance (SAMOVA) analyses. In addition, BEAST and DIYABC analyses suggested that divergence times of the haplotypes in the AHS and ALQ2 populations of the Dabie Mountains were earlier than those in the Qinling and Mengshan Mountains. Consequently, an evolutionary scenario of S. miltiorrhiza populations in the Qinling and Mengshan Mountains diverging from populations in the Dabie Mountains was highly supported. The results reported here provide a useful framework for understanding the role of geographic features in shaping the spatial genetic variation and evolutionary history of S. miltiorrhiza plants.

This work aimed to assess the role of TLR8 in cerebral I/R injury and its in-depth pathogenesis. Bioinformatics analysis indicated that TLR8 was up-regulated in patients with ischemic stroke than that in healthy control, and miR-18a-5p was the upstream regulatory of TLR8. Then, the rat pheochromocytoma PC12 cells were exposed in oxygen-glucose-deprivation/reoxygenation (OGD/R) conditions to construct a model in vitro. The functional experiments indicated that OGD/R can decline the viability and elevate the apoptosis of PC12 cells, while up-regulation of miR-18a-5p can alleviate OGD/R-induced cell injury. Notably, overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury. Finally, we found that up-regulation of miR-18a-5p obviously declined the protein levels of TLR4 and TLR7 as well as the phosphorylation of NF-κB, while overexpression of TLR8 canceled the decrease caused by miR-18a-5p up-regulation. In summing, our results illustrated that miR-18a-5p/TLR8 axis can mitigate OGD/R-induced cells injury through TLRs and NF-κB pathway. Overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury.

Mesoporous silica nanoparticles (MSNs) have received increasing interest due to their tunable particle size, large surface area, stable framework, and easy surface modification. They are increasingly being used in varying applications as delivery vehicles including bio-imaging, drug delivery, biosensors and tissue engineering etc. Precise structure control and the ability to modify surface properties of MSNs are important for their applications. This review summarises the different synthetic methods for the preparation of well-ordered MSNs with tunable pore volume as well as the approaches of drugs loading, especially highlighting the facile surface functionalization for various purposes and versatile biomedical applications in oncology. Finally, the challenges of clinical transformation of MSNs-based nanomedicines are further discussed.\ud \ud Keywords: Mesoporous silica nanoparticles; synthesis method; surface functionalization; drug delivery; biomedical application.

Many medical schools that have implemented team-based learning (TBL) have also incorporated an electronic learning architecture, commonly referred to as a learning management system (LMS), to support the instructional process. However, one LMS feature that is often overlooked is the LMS's ability to record data that can be used for further analysis. In this article, the authors present a case study illustrating how one medical school used data that are routinely collected via the school's LMS to make informed decisions. The case study started with one instructor's observation that some teams in one of the undergraduate medical education learning modules appeared to be struggling during one of the team activities; that is, some teams seemed unable to explain or justify their responses to items on the team readiness assurance test (tRAT). Following this observation, the authors conducted 4 analyses. Their analyses demonstrate how LMS-generated and recorded data can be used in a systematic manner to investigate issues in the real educational environment. The first analysis identified a team that performed significantly poorer on the tRAT. A subsequent analysis investigated whether the weaker team's poorer performance was consistent over a whole module. Findings revealed that the weaker team performed poorer on the majority of the TBL sessions. Further investigation using LMS data showed that the weaker performance was due to the lack of preparation of one individual team member (rather than a collective poor tRAT performance). Using the findings obtained from this case study, the authors hope to convey how LMS data are powerful and may form the basis of evidence-based educational decision making. Published version

Single’s Daywas first promoted by Alibaba's shopping website on November 11, 2009. Ten years later, Taobao successfully developed this day into a global carnival shopping festival. This research focuses on undergraduate business school students through online questionnaires across the Taiwan Strait. This study is based on five impact factors, including impulse buying tendencies, herd behavior, website features, promotional techniques and impulse buying behavior. No evidence showed that gender, age and monthly disposable income affect students’ buying behavior. This study also found that herd behavior, website features and promotional techniques are moderator effects between impulse buying tendency and impulse buying behavior. We also proved that website design and the opinions of their peers affect consumers' decision aking. According to the analysis, in the current online shopping environment, operators should pay more attention to herd behavior, website features and promotional techniques. This study suggests that the industry should provide sufficient information to reduce emotional conflict, and use these important factors to attract consumers' future purchases.

This article explores the economic and family experiences of first- and second-generation Hong Kong Chinese in the Republic of Ireland. Although they are the earliest Chinese group in Ireland, thei...

Lysophosphatidylcholine (LPC) is an essential mediator in human lipid metabolism and is associated with a variety of diseases, but the exact identity of LPC receptors remains controversial. Through extensive biochemical and structural analyses, we have identified the orphan receptor GPR119 as the receptor for LPC. The structure of the GPR119-G-protein complex without any added ligands reveals a density map that fits well with LPC, which is further confirmed by mass spectrometry and functional studies. As LPCs are abundant on the cell membrane, their preoccupancy in the receptor may lead to 'constitutive activity' of GPR119. The structure of GPR119 bound to APD668, a clinical drug candidate for type 2 diabetes, reveals an exceedingly similar binding mode to LPC. Together, these data highlight structural evidence for LPC function in regulating glucose-dependent insulin secretion through direct binding and activation of GPR119, and provide structural templates for drug design targeting GPR119.

Two dimensional (2D)

Takeda G protein-coupled receptor 5 (TGR5) is a promising target for treating metabolic syndrome and inflammatory diseases. Herein, we identified a new series of betulinic acid derivatives as potent TGR5 agonists, which show remarkable activity on human (h) and canine (c) TGR5 but exhibit unpromising activity on murine (m) TGR5. Species difference was also observed with many other reported TGR5 agonists. Therefore, we screened 29 amino acids which were conserved in hTGR5 and cTGR5 but different in mTGR5 and found a key amino acid, H88 in mTGR5 (Y89 in hTGR5), which contributed to the species difference. With the CRISPR/Cas9 system, the mTGR5

A series of poly(ethylene-styrene-hexene) samples with relatively low glass-transition temperatures (Tg = −38 ‒28 °C) were synthesized using Me2Si(Me4Cp)(N-t-Bu)TiCl2/MMAO system. For the first time, nonuniform sampling with 2D-1H/13C HSQC and HMBC experimentsis employed to determine the microstructure of these complicated terpolymers. The signals hiddenin the specta overlaps are clearly discriminated, and the assignments of new peaksfrom novel sequences are successfully achieved with about 50% of conventional experiment time. The distributionsof 11 triads are quantatively presented. The results demonstrate that 2D NMR with nonuniform sampling is superior to the traditional uniform sampling approaches in terms of resolution, experiment time, signal-to-noise ratio and structural information gathered, and this approach represents a fast way for microstructure determination of complicated synthetic polymers.

The transmembrane protein, CD47, is recognized as an important innate immune checkpoint, and CD47-targeted drugs have been in development with the aim of inhibiting the interaction between CD47 and the regulatory glycoprotein SIRPα, for antitumor immunotherapy. Further, CD47 mediates other essential functions such as cell proliferation, caspase-independent cell death (CICD), angiogenesis and other integrin-activation-dependent cell phenotypic responses when bound to thrombospondin-1 (TSP-1) or other ligands. Mounting strategies that target CD47 have been developed in pre-clinical and clinical trials, including antibodies, small molecules, siRNAs, and peptides, and some of them have shown great promise in cancer treatment. Herein, the authors endeavor to provide a retrospective of ligand-mediated CD47 regulatory mechanisms, their roles in controlling antitumor intercellular and intracellular signal transduction, and an overview of CD47-targetd drug design.

The neurotoxicity caused by cadmium (Cd) is well known in humans and experimental animals. However, there is no effective treatment for its toxicity. In this study, we established Cd toxicity models in cultured cells or mice to investigate the detoxification effect of edaravone (Eda). We found that Eda protected GL261 cells from Cd toxicity and prevented the loss of cell viability. In Cd-exposed mice, liver, kidney and testicular damage, as well as cognitive dysfunction were observed. Oxidative stress and inflammatory responses, such as decreased SOD and CAT, increased LDH and MDA, and abnormal changes in the inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 were detected in serum and brain tissue. Eda protected mice from Cd-induced toxicity and abrogated oxidative stress and inflammatory responses. Also, Eda prevented inflammatory activation of microglia and astrocytes and was accompanied by restoration of the neuronal marker protein MAP2, indicating restoration of neuronal function. In addition, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the response of Eda to the elimination of Cd toxicity. In conclusion, Eda does contribute to the clearance of Cd-induced toxicity.

Resibufogenin (RBF), an active compound from Bufo bufonis, has been used for the treatment of multiple malignant cancers, including pancreatic cancer, colorectal cancer, and breast cancer. However, whether RBF could exert its antitumor effect by inhibiting angiogenesis remains unknown. Here, we aimed to explore the antiangiogenic activity of RBF and its underlying mechanism on human umbilical vein endothelial cell (HUVEC), and the therapeutic efficacy with regard to antiangiogenesis in vivo using two triple-negative breast cancer (TNBC) models. Our results demonstrated that RBF can inhibit the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Spheroid sprouts were thinner and shorter after RBF treatment in vitro 3D spheroid sprouting assay. RBF also significantly suppressed VEGF-mediated vascular network formation in vivo Matrigel plug assay. In addition, Western blot analysis was used to reveal that RBF inhibited the phosphorylation of VEGFR2 and its downstream protein kinases FAK and Src in endothelial cells (ECs). Molecular docking simulations showed that RBF affected the phosphorylation of VEGFR2 by competitively binding to the ATP-bound VEGFR2 kinase domain, thus preventing ATP from providing phosphate groups. Finally, we found that RBF exhibited promising antitumor effect through antiangiogenesis in vivo without obvious toxicity. The present study first revealed the high antiangiogenic activity and the underlying molecular basis of RBF, suggesting that RBF could be a potential antiangiogenic agent for angiogenesis-related diseases.

BackgroundNon-missile penetrating spinal injuries (NMPSI) can cause delayed neural injury, including cerebrospinal fluid (CSF) leakage and spinal cord herniation, related to dural defects. To repair ventral dural defect (VDD) is particularly challenging in trauma patients and, in a meanwhile, there has been a well-established method: sling technique, used for patients with idiopathic spinal cord herniation (ISCH) in whom VDD being the primary pathology to deal with.Case presentationThis 51-year-old man fell down from an altitude of six meters and landed on a plier. The neurological examination revealed decreased muscle strength (grade 3/3) in bilateral lower extremities. Computed tomography showed a pair of pliers penetrating L4 lamina, spinal canal through vertebral body, psoas muscle into retroperitoneal cavity with inferior vena cava (IVC) indentation. Emergent laparotomy revealed intact IVC with no major organ damage, and the plier was removed from back under direct visualization of IVC. Immediate posterior approach showed a through-and-through VDD. Sling technique with COOK® dura substitute was applied to cover the VDD and fixed with 7-0 prolene after neurolysis. There was no CSF leakage or nerve tissue herniation afterward. He regained working ability with full muscle strength except for a minor sequal of paresthesia of right toe.ConclusionsIn patients with NMPSI with VDD, indirect duraplasty using sling technique originally developed for treating patients with ISCH is suitable and effective in preventing CSF leakage and delayed neural injury. We further propose an algorithm emphasizing key decision makings for repairing dural defect while preventing delayed neural injury.

To analyze 8-year cone-beam CT (CBCT) data of early, delayed and late implantation around maxillary area of patients with single dental implant after tooth extraction, and to investigate the effect of implantation at different times on implants, in order to provide valuable information for correct selection of appropriate implant timing after tooth extraction.Clinical data of 68 patients who received single-tooth implant after tooth extraction in our hospital from January 2010 to December 2010 were retrospectively analyzed. According to different implantation times, the patients were divided into three groups: group A (n=25), group B (n=24) and group C (n=19). All patients were followed up for 8 years, and the buccal bone defects were recorded. The adjacent bone level and bone defects were analyzed based on CBCT images and posteroanterior(PA) radiographs. The data were processed with SPSS 18.0 software package.The success rate of mini-implants was 92.59%(150/162). Univariate analysis of variance showed that there was significant difference in the success rate of implantation among three groups(P0.05). Paired comparison showed that the success rate of implantation among three groups was the highest in group C, followed by group B and group A (P0.05). 8-year CBCT image data of 51 patients included 16 in group A, 20 in group B and 15 in group C. The adjacent bone levels showed no significant difference between CBCT and PA images(P0.05). Insertion torque and pullout torque showed no significant difference among three groups(P0.05). Implant timing, insertion torque and pullout torque were the high-risk factors affecting implant success rate(P0.05). After 8 years of implant placement, there was no significant difference in bone level among three groups (P0.05). In the second stage of operation, bone defect rate of group C was significantly less than that of group A and B (P0.05). The average maxillary bone level of implants with no bone defects was lower than that of implants with dehiscence-type defects (P0.05).Implant placement time after extraction has no impact on adjacent bone level, but different implant times can affect the success rate of implant; moreover, the indication of immediate implant should be strictly controlled.

To explore the association between pulmonary artery systolic pressure (PASP) and success to wean from mechanical ventilation in COVID-19 patients.Thirty-four critically ill COVID-19 patients who had been placed on ventilator support were enrolled in this retrospective study and were divided into two groups: the weaning success group (group I) and the weaning failure group (group II). Physical examination, echocardiography, and routine laboratory test data were collected. The levels of troponin I, myoglobin, interleukin 6, and D-dimer were significantly lower in group I than in group II. The interventricular septum end-diastolic thickness (IVSd) was thicker (14.00 [13.50‒15.00] mm) and the PASP was higher (61.63 ± 13.53 mmHg) in group II. Logistic regression analysis showed that D-dimer and IVSd were factors associated with ventilator weaning. The odds ratio (OR) of D-dimer was 0.81 (95% CI 0.69‒0.95) and the OR of IVSd was 0.16 (95% CI 0.045‒0.59). Cox analysis revealed that the adjusted hazard ratio (HR) for a 1-mmHg increase in PASP was 0.94 (95% CI 0.90‒0.97) for weaning events (P < 0.001). PASP was negatively correlated with the PaO2:FiO2 (r = -0.48, P < 0.01). A receiver operating characteristic curve showed that the best cutoff value of PASP for ventilator weaning was 39.50 mmHg, with a sensitivity of 100% and a specificity of 96.15% PASP was an independent risk factor for the difficulty of weaning severely ill COVID-19 patients off mechanical ventilation. PASP can be used as one of the indicators for evaluating the condition of COVID-19 patients.

One of the most commonly utilized techniques for microstructure determination of polyolefins is quantitative 13C NMR, but it generally requires long experiment times and large amounts of samples to achieve reliable quantification for its low sensitivity. In this context, we report the use of two-dimensional (2D) 1H–13C heteronuclear single-quantum correlation (HSQC) spectroscopy to rapidly determine the microstructure of a typical linear low density polyethylene (LLDPE), poly(ethylene-co-1-hexene) at triads. Moreover, the 2D HSQC with non-uniform sampling (NUS) enable the reduction of experiment time from more than 23 h to several minutes with composition accuracy higher than 99.5%. The methodology is robust, and it can find wide-spread applications in areas where a quantitative analysis of polymers is necessary.

Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells. ALA also restrained angiogenesis in chick embryo chorioallantoic membrane and delayed the growth of human MDA-MB-231 breast cancer xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed the phosphorylation of vascular endothelial growth factor receptor 2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt in endothelial cells. Taken together, the antiangiogenic activity of ALA and its molecular mechanism are identified for the first time, indicating that ALA may be a potential drug candidate or lead compound for antiangiogenic cancer therapy.

To further extend temperature range of application and low temperature performance of the ethylene-styrene copolymers, a series of poly(ethylene-styrene-propylene) samples with varying monomer compositions and relatively low glass-transition temperatures (Tg = −28 – 22 °C) were synthesized by Me2Si(Me4Cp)(N-t-Bu)TiCl2/MMAO system. Since the 13C NMR spectra of the terpolymers were complex and some new resonances were present, 2D-1H/13C heteronuclear single quantum coherence and heteronuclear multiple bond correlation experiments were conducted. A complete 13C NMR characterization of these terpolymers was performed qualitatively and quantitatively, including chemical shifts, triad sequence distributions, and monomer average sequence lengths. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 340–350

A series of heteroligated (salicylaldiminato)(β-enaminoketonato)titanium complexes [3-But-2-OC6H3CH = N(C6F5)] [PhN = C(R1)CHC(R2)O]TiCl2 [3a: R1 = CF3, R2 = tBu; 3b: R1 = Me, R2 = CF3; 3c: R1 = CF3, R2 = Ph; 3d: R1 = CF3, R2 = C6H4Ph(p); 3e: R1 = CF3, R2 = C6H4Ph(o); 3f: R = CF3, R2 = C6H4Cl(p); 3g: R1 = CF3; R2 = C6H3Cl2(2,5); 3h: R1 = CF3, R2 = C6H4Me(p)] were investigated as catalysts for ethylene (co)polymerization. In the presence of modified methylaluminoxane as a cocatalyst, these complexes showed activities about 50%–1000% and 10%–100% higher than their corresponding bis(β-enaminoketonato) titanium complexes for ethylene homo- and ethylene/1-hexene copolymerization, respectively. They produced high or moderate molecular weight copolymers with 1-hexene incorporations about 10%–200% higher than their homoligated counterpart pentafluorinated FI-Ti complex. Among them, complex 3b displayed the highest activity [2.06 × 106 g/molTi•h], affording copolymers with the highest 1-hexene incorporations of 34.8 mol% under mild conditions. Moreover, catalyst 3h with electron-donating group not only exhibited much higher 1-hexene incorporations (9.0 mol% vs. 3.2 mol%) than pentafluorinated FI-Ti complex but also generated copolymers with similar narrow molecular weight distributions (Mw/Mn = 1.20–1.26). When the 1-hexene concentration in the feed was about 2.0 mol/L and the hexene incorporation of resultant polymer was about 9.0 mol%, a quasi-living copolymerization behavior could be achieved. 1H and 13C NMR spectroscopic analysis of their resulting copolymers demonstrated the possible copolymerization mechanism, which was related with the chain initiation, monomer insertion style, chain transfer and termination during the polymerization process. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2787–2797

Magnesium/aluminum-pillared montmorillonite loaded with lanthanum hydroxide (Mg/Al-MMT-La(OH)

In this paper, two improved microstrip-slot transition structures are proposed. The top layer are microstrip lines with two fan-shaped open-circuit terminals, and the bottom layer is the cross-finger slotline which is perpendicular to the microstrip lines, and the short-circuit terminals of the slotline are circular or petal-shaped. These two structures work in the 1–13GHz frequency band. HFSS is used to simulate these two structures, S-parameters and VSWR are compared among the ring slot, petal shaped slot and the original fan-shaped slot. The results show that petal shaped slot transition structure has the best performance. The S11 is less than −19.5 dB and the VSRW is less than 1.23 within 2.5–11.2GHz and 12.4–13GHz.

Cough and expectoration are the most common clinical symptoms. Based on the illness course, cough can be classified into acute cough ( 8 weeks). The etiology of cough is complex and widely involved. And the diseases that induce chronic cough include nasal cavity and sinus abnormalities, asthma, gastroesophageal reflux disease, non-asthmatic eosinophilic bronchitis, and allergic cough. And along with the development of medical technologies, the clinicians have known that pulmonary aspergillosis with presenting symptoms of cough and expectoration is not rare.

The lesion of invasive pulmonary aspergillosis rapidly spreads. With no timely appropriate treatment, progressive and finally fatal respiratory failure develops. Extrapulmonary diffuse aspergillosis may involve the liver, kidneys, brain, or other tissues, which commonly causes occurrence of death. Pulmonary allergic aspergillosis may induce inflammatory infiltration that is not related to fungal invasion of tissue.

A novel multiple extraction (ME) process integrated heat reflux extraction (HRE) with cyclohexanone (CYC) followed by ultrasonic assisted extraction (UAE) with N -methyl-2-pyrrolidone/CS 2 (NMP/CS 2 ) mixed solvent was developed for extraction of four different rank demineralized coals. Raw coals and their demineralized coals were evaluated by X-ray diffraction, X-ray fluorescence, and Fourier transform infrared (FTIR) spectroscopy analytical techniques to determine HCl/HF leaching on the properties and FTIR spectra of coals first. And then the demineralized coals as well as their extraction residues were studied using FTIR spectrometry and curve–fitting technique to clarify the performance of ME process and investigate the structural changes in coals during extraction. The results showed that acids treatment could remove most of the mineral matters in coals and did not seem to produce significant changes in IR spectra of the coals except for disappearance of those peaks caused by mineral matters. The removal of solvents soluble portions led to decrease in the amount of organic species containing C C vibration mode and carbon content in all coal samples. The alkyl side chains on aromatics of all coal samples except for NM lignite became longer and less branched after extraction according to the curve–fitting study in the region 3000–2700 cm − 1 . In addition, it was found that the contents of carbon and organic portions containing C C vibration mode, C O bonds, and aliphatic hydrogen for SD, HLJ, and NX coals all decreased following the order of raw coal > extraction residue with CYC > extraction residue with NMP/CS 2 > extraction residue from ME process during extraction processes. This result inferred that the NMP/CS 2 mixed solvent could only show good solubility to coals after they were initially extracted using CYC. Furthermore, the detectable concentration of hydroxy groups in coals increased after extraction, especially for the HRE process of NM coal with CYC.

In this work, thermal behavior of five different coal particle fractions were investigated using thermogravimetric analyzer (TGA) under various heating rates with the maximum of 1000 K/min. An on–line Fourier Transform Infrared Spectrometry (FTIR) was employed to evaluate the evolution characteristics of the gaseous products. The results showed that the coal particle size remarkably affected the mass loss and the ash amount. The larger the particle size was, the higher mass loss and the more ash could be, which revealed its high pyrolysis reactivity. In addition, with increasing the particle size, the initial devolatilization temperature (T in ) and devolatilization index (D i ) increased, whereas, the final devolatilization temperature (T f ) decreased. This phenomenon was explained by a proposed mechanism of the obstacle escaping of volatiles from the interparticles corresponding to forming large block unit of metaplast. The heating rate has significant effect on the performance of devolatilization profiles and gaseous products releasing. T in , T max and T f displayed the logistic distribution along with heating rate up to 1000 K/min, whereas, R max and the heating rate were highly linear correlated with different particle fractions. The enhanced yield at maximum releasing rate for all the gas species were observed with increasing the heating rate. Moreover, the peak of maximum releasing rate on the evolving profiles of gaseous products became narrower and sharper, and releasing time of the gaseous products reduced extremely with increasing the heating rate. These findings can provide fundamental data for practical applications, plant designing, handling, and modeling of integrated coal fluidized bed gasification system as well as other coal fluidized bed pyrolysis/gasification process.

Normalization of the tumor microenvironment is a promising approach to render conventional chemotherapy more effective. Although passively targeted drug nanocarriers have been investigated to this end, actively targeted tumor priming remains to be explored. In this work, we demonstrate an effective tumor priming strategy using metronomic application of nanoparticles actively targeted to tumor neovasculature. F56 peptide-conjugated paclitaxel-loaded nanoparticles (F56-PTX-NP) were formulated from PEGylated polylactide using an oil in water emulsion approach. Metronomic F56-PTX-NP specifically targeted tumor vascular endothelial cells (ECs), pruned vessels with strong antiangiogenic activity and induced thrombospondin-1 (TSP-1) secretion from ECs. The treatment induced tumor vasculature normalization as evidenced by significantly increased coverage of basement membrane and pericytes. The tumor microenvironment was altered with enhanced pO2, lower interstitial fluid pressure, and enhanced vascular perfusion and doxorubicin delivery. A "normalization window" of at least 9 days was induced, which was longer than other approaches using antiangiogenic agents. Together, these results show that metronomic, actively-targeted nanomedicine can induce tumor vascular normalization and modulate the tumor microenvironment, opening a window of opportunity for effective combination chemotherapies.

The application of LCD has been very common. One important inspection item for LCD manufacturers is screen flicker, and its optimization has become a crucial task. An automated inspection system that aims to achieve such a goal is presented. It uses photodetector to detect the degree of LCD screen flicker and converts the detected result to digital signal by sampling circuit, acquires the degree of flickering by signal analysis, and applies signal control method to adjust LCD's VCOM voltage which optimize LCD flickering automatically to improve measurement efficiency and meet the product requirements. This translates into an improvement in efficiency by 90%, and the accuracy is also improved .

We report here a series of novel spontaneously healable thermoplastic elastomers (TPEs) with a combination of improved mechanical and good autonomic self-healing performances. Hard-soft diblock and hard-soft-hard triblock copolymers with poly[exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-benzeno-l,4-methanoanthracene] (PHBM) as the hard block and secondary amide group containing norbornene derivative polymer as the soft block were synthesized via living ring-opening metathesis copolymerization by use of Grubbs third-generation catalyst through sequential monomer addition. The microstructure, mechanical, self-healing, and surface morphologies of the block copolymers were thoroughly studied. Both excellent mechanical performance and self-healing capability were achieved for the block copolymers because of the interplayed physical cross-link of hard block and dynamic interaction formed by soft block in the self-assembled network. Under an optimized hard block (PHBM) weight ratio of 5%, a significant recovery of tensile strength (up to 100%) and strain at break (ca. 85%) was achieved at ambient temperature without any treatment even after complete rupture. Moreover, the simple reaction operations and well-designed monomers offer versatility in tuning the architectures and properties of the resulting block copolymers.

Isorhamnetin is one of the most important active ingredients in the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L., which possesses extensive pharmacological activities. At present, there have been numerous investigations on isorhamnetin, which has the effects of cardiovascular and cerebrovascular protection, anti-tumor, anti-inflammatory, anti-oxidation, organ protection, prevention of obesity, etc. The related mechanisms involve the regulation of PI3K/AKT/PKB, NF-κB, MAPK and other signaling pathways as well as the expression of related cytokines and kinases. Isorhamnetin has a high value of development and application. However, the investigations on its mechanism of action are limited and lack of detailed scientific validation. The manuscript reviewed the pharmacological effects of isorhamnetin and related mechanisms of action for the development of its medicinal properties further.

Muscle vibration measurement has long been an unique scientific study, in general, and the direct reaction of animals to feel pain (algesia), either from vascular or muscle contraction, is a complex perceptual experience. Thus this paper proposes a way to measure animal algesia quantitatively, by measuring the changes in muscle vibration due to a pinprick on the surface of the skin of a Spodoptera litura larva. Using the laser optical triangulation measurement principle, along with a CMOS image sensor, linear laser, software analysis, and other tools, we quantify the subtle object point displacement, with a precision of up to $10{\mu}m$ , for our chosen Spodoptera litura larva animal model, in which it is not easy to identify the tiny changes in muscle contraction dynamics with the naked eye. We inject different concentrations of formalin reagent (empty needle, 12% formalin, and 37% formalin) to obtain a variety of different muscle vibration frequencies as the experimental results. Because of the high concentrations of reagent applied, we see a high frequency shift of muscle vibration, which can be presented as pain indices, so that the algesia can be quantified.