Hemin/G-quadruplex and AuNPs-MoS2 based novel dual signal amplification strategy for ultrasensitively sandwich-type electrochemical thrombin aptasensor.

In this work, a novel sandwich-type electrochemical aptasensor based on the dual signal amplification strategy of hemin/G-quadruplex and AuNPs-MoS2 was designed and constructed, which realized the highly sensitive and specific detection of thrombin (TB). In this aptasensor, the 15-mer TB-binding aptamer (TBA-1) modified with thiol group was immobilized on the surface of AuNPs modified glassy carbon electrode (AuNPs/GCE) as capturing elements. Another thiol-modified 29-mer TB-binding aptamer (TBA-2) sequence containing G-quadruplex structure for hemin immobilization was designed. The formed hemin/G-quadruplex/TBA-2 sequence was further combined to the AuNPs decorated flower-like molybdenum disulfide (AuNPs-MoS2) composite surface via Au-S bonds, acting the role of reporter probe. In presence of the target TB, the sandwich-type electrochemical aptamer detection system could be formed properly. With the assistance of the dual signal amplification of AuNPs-MoS2 and hemin/G-quadruplex toward H2O2 reduction, the sandwich-type electrochemical aptasensor was successfully constructed for sensitive detection of TB. The results demonstrate that the fabricated aptasensor displays a wide linear range of 1.0 × 10-6 âˆ¼ 10.0 nM with a low detection limit of 0.34 fM. This proposed aptasensor shows potential application in the detection of TB content in real biological samples with high sensitivity, selectivity, and reliability.

Host-Guest Photosensitizer of a Cationic BODIPY Derivative and Cucurbit[7]uril for High-Efficiency Visible Light-Induced Photooxidation Reactions.

In recent years, there has been a notable surge of interest in the fields of organic and pharmaceutical research about photocatalysts (PCs) and photosensitizers (PSs). In this study, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) molecule adorned with quaternary ammonium (TMB) functionality was meticulously designed and synthesized. This compound has remarkable characteristics such as exceptional water solubility, great optical qualities, and commendable photostability. It can form a 1:1 complex (TMB-CB[7]) with cucurbit[7]uril (CB[7]) through host-guest interactions in the aqueous solution and shows obvious fluorescence enhancement. The reactive oxygen species (ROS) including superoxide anion radical (O2·-) and singlet oxygen (1O2) generation ability of TMB-CB[7] were promoted compared with that of TMB in the aqueous solution. More interestingly, the ROS generated from TMB-CB[7] can be used as PCs for aerobic cross dehydrogenation coupling reactions and photooxidation reactions in water with high yields of 89 and 95%, respectively. Therefore, the utilization of a host-guest PS presents a novel and environmentally friendly approach for conducting photocatalyzed organic processes under ambient conditions using visible light.

Construction of an efficient artificial light-harvesting system based on hyperbranched polyethyleneimine and improvement of photocatalytic performance.

An artificial light-harvesting system (ALHS) was developed in aqueous solution by employing the electrostatic co-assembly of a tetraphenylethylene derivative modified with two sulfonate groups (TPE-BSBO) and hyperbranched polyethyleneimine (PEI) as the energy donors, and 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (DBT) as the energy acceptors. The ALHS exhibits not only high efficiency in energy transfer and conversion but also a significant enhancement in the generation of reactive oxygen species (ROS), especially superoxide anion radicals (O2˙-), facilitating its utilization in photocatalytic oxidation reactions.

Unraveling the complexities of Cd-aniline composite pollution: Insights from standalone and joint toxicity assessments in a bacterial community.

Cadmium (Cd) and aniline frequently co-occur in industrial settings but have rarely been addressed as composite toxicants in terms of the overall toxicity despite extensive knowledge of the environmental impact of each individual pollutant. In this study, we attempt to assess the relation of individual and combined toxic effects of Cd and aniline using a bacterial consortium cultured from soils as a model system. Results showed that the consortial bacteria exhibited drastically stronger tolerance to stand-alone Cd and aniline in comparison to literature data acquired from single species studies. When occurring simultaneously, the joint toxicity displayed a concentration-dependent behavior that wasn't anticipated based on individual chemical tests. Specifically, additive effects manifested with Cd and aniline at their IC10s, but changed to synergistic when the concentrations increased to IC20, and finally transitioned into antagonistic at IC30s and beyond. In addition, co-occurring aniline appeared to have retarded the cellular accumulation of Cd while increasing the enzymatic activities of superoxide dismutase and catalase relative to that in Cd-alone treatments. Finally, the bacterial community experienced distinct compositional changes under solo and combined toxicities with several genera exhibiting inconsistent behavior between treatments of single and composite toxicants. Findings from this study highlight the complexity of bacterial response to composite pollutions and point to the need for more comprehensive references in risk and toxicology assessment at multi-chemical contamination sites.

Construction of aggregation-induced emission photosensitizers through host-guest interactions for photooxidation reaction and light-harvesting.

In the present work, we have designed and synthesized a triphenylamine modified cyanophenylenevinylene derivative (TPCI), which can self-assembly with cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) through host-guest interactions to form supramolecular complexes (TPCI-CB[6]) and supramolecular polymers (TPCI-CB[8]) in the aqueous solution. The supramolecular assemblies of TPCI-CB[6] and TPCI-CB[8] not only exhibited high singlet oxygen (1O2) production efficiency as photosensitizers, but also realized the application in the construction of artificial light-harvesting systems due to the excellent fluorescence properties in the aqueous solution. The production efficiency of 1O2 has been effectively improved after the addition of CB[6] and CB[8] for TPCI, which were applied as efficient photosensitizers in the photooxidation reactions of thioanisole and its derivatives with the highest yield of 98% in the aqueous solution. The excellent fluorescence properties of TPCI-CB[6] and TPCI-CB[8] can be used as energy donors in artificial light-harvesting systems with energy acceptors sulforhodamine 101 (SR101) and cyanine dye 5 (Cy5), in which one-step energy transfer processes of TPCI-CB[6]+SR101 and TPCI-CB[8]+Cy5, and a two-step sequential energy transfer process of TPCI-CB[6]+SR101+Cy5 were constructed to simulate the natural photosynthesis system.

Aberrant expression of GOLM1 protects ALK+ anaplastic large cell lymphoma from apoptosis by enhancing BCL-XL stability.

Golgi membrane protein 1 (GOLM1) is aberrantly expressed in many types of solid tumors and contributes to cancer development; however, its role in hematopoietic and lymphoid neoplasms remains unknown. Here, we report that GOLM1 was significantly upregulated in anaplastic large cell lymphoma (ALCL), particularly in anaplastic lymphoma kinase-positive (ALK+) ALCL. Mechanistically, the expression of GOLM1 was induced by nucleophosmin-ALK in both ALK-transformed T cells and ALCL cell lines through AKT/mTOR pathway. Knockdown of GOLM1 expression led to a reduction in the growth and viability of ALCL cells with increased spontaneous apoptosis, whereas ectopic expression of GOLM1 protected ALCL cells from apoptosis induced by staurosporine treatment. Moreover, GOLM1 directly interacted with B-cell lymphoma-extra large protein (a crucial anti-apoptosis regulator) and significantly prolonged its stability. Introduction of GOLM1 promoted ALK+ ALCL cells colony formation in vitro and tumor growth in a murine xenograft model. Taken together, our findings demonstrate, to our knowledge, for the first time that GOLM1 plays a critical role in suppressing apoptosis and promoting the progression of ALK+ ALCL and provide evidence that GOLM1 is a potential biomarker and therapeutic target in ALK-induced hematological malignancies.

Construction of artificial light-harvesting systems based on a variety of polyelectrolyte materials and application in photocatalysis.

In the present work, we designed and synthesized a cationic cyano-substituted p-phenylenevinylene derivative (PPTA), which can form supramolecular assemblies through electrostatic interaction with a type of polyelectrolyte material anionic guar gum (GP5A). A polyelectrolyte-based artificial light-harvesting system (LHS) was constructed by selecting a fluorescent dye sulforhodamine 101 (SR101) that matched its energy level as an energy acceptor. The energy harvested by the acceptors was used in the aqueous phase cross dehydrogenation coupling (CDC) reaction with a yield of up to 87%. In addition, the general applicability of polyelectrolyte materials to build artificial LHS was demonstrated by three other polyelectrolyte materials sodium polyphenylene sulfonate (RSS), sodium carboxymethyl cellulose (CMC), and sodium polyacrylate (PAAS), in which the CDC reaction was also carried out by these three LHSs and obtained high yields. This work not only provides a new method to construct LHSs by using polyelectrolyte materials, but also provides a beneficial exploration for further applying the energy harvested in LHSs to the field of photocatalysis in an aqueous solution.

Transmissible Endoplasmic Reticulum Stress Mediated by Extracellular Vesicles from Adipocyte Promoting the Senescence of Adipose-Derived Mesenchymal Stem Cells in Hypertrophic Obesity.

Hypertrophic obesity, characterized by an excessive expansion of subcutaneous adipocytes, causes chronic inflammation and insulin resistance. It is the primary feature of obesity in middle-aged and elderly individuals. In the adipose microenvironment, a high level of endoplasmic reticulum (ER) stress and changes in the extracellular vesicle (EV) composition of adipocytes may cause the senescence and restrained differentiation of progenitor cells of adipose, including adipose-derived mesenchymal stem cells (ASCs). In this study, a hypertrophic obesity mouse model was established, and the effects of adipocytes on the ER stress and senescence of ASCs were observed in a coculture of control ASCs and hypertrophic obesity mouse adipocytes or their derived EVs. The adipocytes of hypertrophic obesity mice were treated with GW4869 or an iron chelation agent to observe the effects of EVs secreted by adipocytes and their iron contents on the ER stress and senescence of ASCs. Results showed higher ER stress level and senescence phenotypes in the ASCs from the hypertrophic obesity mice than in those from the control mice. The ER stress, senescence phenotypes, and ferritin level of ASCs can be aggravated by the coculture of ASCs with adipocytes or EVs released by them from the hypertrophic obesity mice. GW4869 or iron chelator treatment improved the ER stress and senescence of the ASCs cocultured with EVs released by the adipocytes of the hypertrophic obesity mice. Our findings suggest that EV-mediated transmissible ER stress is responsible for the senescence of ASCs in hypertrophic obesity mice.

Association of heart rate with cardiovascular events and mortality in hypertensive and normotensive population: a nationwide prospective cohort study.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. We assessed the association of baseline heart rate with cardiovascular events and mortality in hypertensive and normotensive populations using a prospective urban and rural epidemiology cohort study in China. METHODS: A total of 29,554 individuals were involved in our analysis, distributed equally between groups of normotensive and hypertensive. The primary outcomes were myocardial infarction, stroke, major cardiovascular diseases, and cardiovascular mortality. Cox frailty models were utilized to estimate hazard ratios for cardiovascular outcomes, and restricted cubic splines were used to explore the shape of the association between baseline heart rate and cardiovascular mortality. RESULTS: During a total observational time of 230,813 person-years, 402 myocardial infarction events, 1,096 stroke events, 1,540 major cardiovascular events, and 356 cardiovascular deaths were documented. In adjusted analyses, normotensive subjects with baseline heart rate >82.5 beats per minute had a 3.30-fold greater risk of cardiovascular death and an increased 72% risk of myocardial infarction, compared with individuals whose baseline heart rate was 65.5-71 beats per minute. A similar trend was observed for cardiovascular mortality in the hypertensive population, but the association was attenuated. Multivariable-adjusted restricted cubic splines showed linear associations between baseline heart rate and cardiovascular mortality in two groups of people (all P<0.05 for linearity). CONCLUSIONS: Elevated baseline heart rate is associated with an increased risk of cardiovascular mortality and myocardial infarction in the normotensive population. The association is attenuated for cardiovascular death in hypertensive patients.

[Exploration and practice of the "trinity" rescue system of aviation, ground and Internet emergency treatment].

With the development of society and economy, the disease spectrum of Chinese residents has undergone a major change, and the public health emergencies have occasionally occurred. The new situation has put forward higher requirements on the emergency capacity, professional technical level and treatment quality of critical care treatment system. Combining with the advantages of hospital aviation, ground and Internet emergency, Henan Provincial People's Hospital established a new construction path of emergency and critical care treatment system, namely "trinity" rescue system of aviation, ground and Internet emergency treatment and the "five-ring" model of critical care treatment system in hospital. The purpose of this paper is to summarize the practical experience of the construction of emergency and critical care system in Henan Provincial People's Hospital, so as to provide reference for the management of emergency and critical care in China.

A case of giant main pulmonary artery aneurysm associated with complicated congenital heart disease and simultaneous chronic pulmonary artery dissection.

BACKGROUND: Pulmonary artery aneurysm (PAA), usually associated with congenital heart disease (CHD), is a very rare clinical condition. Pulmonary artery dissection (PAD) is considered the most life-threatening complication of PAA, and patients can progress from being asymptomatic to sudden death. We report the following case of PAA associated with complicated congenital heart disease and simultaneous chronic PAD. To our knowledge, few such complicated cases have ever been reported. CASE PRESENTATION: A 36-year-old male presented to our hospital with a 10-year history of heart fatigue after activities and aggravated for 2 years. Computed tomography angiography (CTA) and echocardiogram showed a giant main pulmonary artery aneurysm (14 cm) with complicated congenital heart disease (a small patent ductus arteriosus, ventricular septal defects, aortic coarctation). Chronic PAD, which was mistaken for a pulmonary valve before operation, was detected during surgery. CONCLUSIONS: PAA associated with complicated CHD and simultaneous PAD is very rare, and its clinical symptoms are varied. Radiologists and surgeons should pay attention to determining whether this patient simultaneously had PAD when PAA was detected on preoperative CTA imaging.

Palladium-Catalyzed C-2 and C-3 Dual C-H Functionalization of Indoles: Synthesis of Fluorinated Isocryptolepine Analogues.

Here we report a protocol to synthesize diversiform fluorinated isocryptolepine analogues with potential biological activities in one step via directed C-2 and C-3 dual C-H functionalization of indoles. We also attempted to take into account fluorinated imidoyl chlorides as a novel kind of synthons in the directed C-H functionalization reactions. As a result, a variety of fluorinated isocryptolepine analogues were obtained in up to 96% yield. Moreover, we conducted control experiments to disclose the reaction mechanism.

The association of calcium intake with osteoporotic vertebral fractures in a large Chinese cohort.

The effect of calcium on prevention of osteoporosis and related fracture which are aging issues is unclear. The aim of this study is to explore the association of calcium intake with vertebral fracture. This study enrolled 3,457 participants from China Action on Spine and Hip Status (CASH) study from 2013 and 2017. Dietary calcium intake was collected using validated food frequency questionnaires (FFQ). Vertebral fracture of CT images was defined as the primary outcome. The mean calcium intake of men and women were 522.75mg/day and 507.21mg/day, respectively. 6% reduction in the odds of fracture risk was observed per 100 unit increase of calcium intake from food among females (OR, 0.94; 95% CI, 0.89-0.99), but results among males were not significant. We divided calcium intake into quintiles when modelling its associations with fracture risk, negative associations of fracture risk with calcium intake were found among females. In a population with low usual calcium intake, higher dietary calcium intake was associated with fewer vertebral fracture in women and that no such association was seen in men.

Spatial distribution of phthalate esters and the associated response of enzyme activities and microbial community composition in typical plastic-shed vegetable soils in China.

The widespread use of phthalate esters (PAEs) in plastic products has made them ubiquitous in environment. In this study, 93 soil samples were collected in 31 plastic-sheds from one of China's largest vegetable production bases, Shouguang City, Shandong Province, to investigate the pollution characteristics and composition of PAEs in soils. Eleven PAEs were detected in the soil samples with the total concentration of 756-1590 µg kg-1 dry soil. Di (2-ethylhexyl) phthalate (DEHP), bis (2-n-butoxyethyl) phthalate (DBEP), di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DBP) were the main pollutants with the highest concentrations. Moreover, soil properties, including pH, total organic carbon (TOC), soil enzyme activities, and soil microbial community characteristics, were monitored to explore the associated formation mechanisms. The concentration of PAEs in the plastic-shed vegetable soils was regionalized and the contamination degree in different regions was related to soil microbial characteristics and soil enzyme activities. Phthalate ester is positively correlated with catalase and sucrase, and negatively correlated with dehydrogenase and urease. Furthermore, some tolerant and sensitive bacteria were selected, which possibly could be used as potential indicators of PAE contamination in soil. Dimethyl phthalate (DMP) and DBP also had greater effects on the soil microbial community than other PAEs. The results will provide essential data and support the control of PAEs in plastic-shed vegetable soils in China.

Fluorescence resonance energy transfer (FRET)-based nanoarchitecture for monitoring deubiquitinating enzyme activity.

A novel nanoarchitecture (MSN-Tb-UbR) was prepared by modifying rhodamine B-labelled Ubs (Ub-Rs) on the surface of mesoporous silica nanoparticles (MSNs) loaded with Tb3+-complexes. The MSN-Tb-UbR exhibits ratiometric sensing ability for DUB (UCH-L1) with good sensitivity and selectivity.

[Study on present status of ICU in county-level general hospitals of Henan Province].

OBJECTIVE: To investigate the present status of intensive care unit (ICU) in the county-level general hospitals of Henan Province and provide basis for improving the construction level and rational allocation of medical resources of ICU. METHODS: According to The guidelines for the construction and management of critical care medicine (trial implementation) issued by National Health Commission (NHC) (hereinafter referred as the guidelines), a cross-sectional survey was conducted on the present status of ICU in 93 county-level general hospitals in Henan Province in 2018 by using a self-designed questionnaire concerning this topic. The survey included the basic information of ICU (establishment time, organization and management mode, development of special departments in ICU, construction of key disciplines), scale and staffing allocation and training, and the equipment and technology development situation in ICU. RESULTS: The basic aspects of ICU situation were as follows: firstly, the establishment time: the ICU of county-level general hospitals in Henan Province started relatively late. The survey showed that all the 93 hospitals had set up ICU, of which the earliest was the ICU of Xunxian People's Hospital in 1989, only 4 county-level general hospitals established their ICUs before 2000, and 34 before 2009. Secondly, the management mode: the proportion of ICU closely managed was accounting for 68.82% (64/93), while semi-open management was 18.28% (17/93), and 12.90% (12/93) hospitals still adopted the open management mode. Thirdly, development of specialized ICU and construction of key disciplines: comprehensive ICUs were founded in 86 hospitals, and the proportions of specialized ICUs such as neonatal ICU, emergency ICU and coronary heart disease care unit (CCU) were higher than other kinds of special department; the ICUs of 8 hospitals were the key discipline of Henan Provincial Health Commission, and the ICUs of 9 hospitals were the discipline of Municipal Health Commission. Scale and staffing of ICU: a total of 2 189 ICU beds were opened in 93 county-level general hospitals. The utilization rate reaching the targets of ICU beds and the compliance rate of ICU bed area per bed were relatively high, 76.34% and 80.64%, while the compliance rates of ICU doctors/ICU beds, ICU nurses/ICU beds were low, which were 8.60% and 7.52% respectively, indicating that the clinicians and nursing facilities were insufficient. There were 1 tertiary hospital, 76 secondary-A hospitals and 16 secondary-B hospitals in this survey. Compared with secondary-B hospitals in the total number of beds (sheets: 922.22±285.99 vs. 636.75±258.84) and ICU beds (sheets: 25.28±21.15 vs. 14.63±6.89), the secondary-A hospitals were significantly higher (all P < 0.01), and the rate of bed use compliance of secondary-A hospitals was significantly higher than that in secondary-B hospitals [81.6% (62/76) vs. 50.0% (8/16), P < 0.01]. In terms of staffing, the proportion of clinicians and nurses with elementary titles was the highest, the proportion of full-time senior professional titles was relatively low, the proportion of doctors with bachelor's degree was the highest, and that of nurses with junior college degree was the highest. In personnel training, the hospitals surveyed had sent the doctors and nurses mostly to participate in the continuing education and training of critical care medicine at or above the provincial level for 745 person-times and 1 156 person-times, and there were in the mean for 8 and 12 person-times in each hospital, respectively. In terms of equipment configuration and technology development of ICU, mostly the equipment in ICU of county-level general hospitals consisted of microinjection pump, monitor, infusion pump, invasive ventilator, expectorant machine, etc. but the overall equipment was insufficient. Although an extracorporeal membrane oxygenation (ECMO) equipment was introduced in one hospital, it had not been carried out clinically. All county-level general hospitals in Henan Province had set up ICUs, but there were gaps between the compliance rates of many indicators and the requirements of the guidelines, and the medical personnel and equipment were relatively insufficient. CONCLUSIONS: The ICUs of county-level general hospitals in Henan Province have developed rapidly in recent years, but there is still much room for improvement.

Gold core-satellite nanostructure linked by oligonucleotides for detection of glutathione with LSPR scattering spectrum.

We demonstrated a sensitive method for detection of glutathione (GSH) based on LSPR scattering spectrum using gold core-satellite nanostructure linked by T-Hg2+-T base pair. The core-satellite assembly caused coupling between plasmonic nanoparticles, which inducing distinct change of LSPR peak wavelength. As the interaction between Hg2+ and GSH, the core-satellite nanostructure would be disassembled, which accompanied with spectral blue-shift of the scattering spectrum. By using this method, GSH could be quantitatively detected, and the detection limits can reach to 0.1 µM.

Does utilizing WHO's interim targets further reduce the risk - meta-analysis on ambient particulate matter pollution and mortality of cardiovascular diseases?

Long-term exposed to ambient particulate matter (PM) has been recognized as a risk factor for cardiovascular diseases (CVDs) mortality but few studies examine the utility of WHO's interim targets (2006) concerning PM control on CVD mortality. This review aimed to synthesize the long-term exposed to ambient PM exposures on overall CVD mortality according to WHO's interim targets; meanwhile, subgroup analysis by ethnicity, smoking status and PM assessment method were also conducted. We systematically searched studies published between January 1974 and Jul 2017 in PubMed and Embase. Quality of each study was assessed using Critical Appraisal Skill Programme (CASP) checklist. Fixed-effects or random-effects model of meta-analysis was determined by the test of heterogeneity. Subgroup analyses were conducted according to ethnicity, smoking status, PM assessment method and interim PM targets of WHO guidelines. Overall, 16 eligible studies were included, covering 15,511,997 participants and 542,991 CVD deaths. Five studies concerning PM2.5 were rated as good quality. The pooled hazard ratio (HR) of every 10µg/m3 increment of PM2.5 exposure for CVD mortality was 1.12 (95%CI = 1.08-1.16), but it was not significant for PM10 (HR = 1.02, 95%CI = 0.89-1.16). Compared with the annual PM2.5 exposure level within WHO's interim targets (1.11-1.16), significantly smaller HR was observed for subjects with an exposure level below WHO's air quality guideline (HR = 1.03, 95%CI = 1.02-1.04). The pooled HR was relatively higher for studies in Asian and with at least 11 years' follow-up and those adopting relatively poor methods (category 1) in assessing PM2.5, whilst the risk was similar regardless of smoking status. Egger and Begg's tests showed no evidence for publication bias. Long-term ambient PM2.5 exposure level was positively associated with the overall CVD mortality. Different interim targets above the WHO's Air Quality Guideline level exerted a similar scale of CVD risk, but there is no evidence for a threshold.

Highly efficient and selective enrichment of phosphopeptides using porous anodic alumina membrane for MALDI-TOF MS analysis.

Because of its good biocompatibility, high surface-to-volume ratio, and distinct surface electrical properties, porous anodic alumina (PAA) membrane has been used to selectively enrich phosphopeptides from a mixture of synthetic peptides and tryptic digest product of beta-casein by a direct MALDI-TOF MS analysis. As we reported previously, PAA membrane has strong incorporation ability to the phosphate anion. Herein, we describe the application of PAA membrane as a selective sampling absorbent for phosphopeptides. The PAA membrane could enrich phosphopeptides with high efficiency and selectivity; for example, the tryptic digest product of beta-casein at a concentration as low as 4 x 10(-9) M can be satisfactorily detected. Compared to that from the nonenriching peptide mixture, the MS signal of the phosphorylated peptides enriched by the PAA membrane is remarkably improved. In addition, acidic peptides have insignificant influence on the enriching process. Results show that the adsorption of phosphate anions on the PAA membrane plays a determining role in achieving highly selective enriching capacity toward phosphopeptides. The feasibility of PAA membranes as specific absorbents for phosphopeptides is also demonstrated.