TEMPO-Mediated Interrupted 6π-Photocyclization of ortho-Biaryl-Appended 1,3-Dicarbonyl Compounds toward 10-Phenanthrenols.

In this paper, we present an example of a photoinduced catalyst, halogen-, and base-free TEMPO-mediated interrupted 6π-photocyclization/dehydrogenative aromatization of ortho-biaryl-appended 1,3-dicarbonyl compounds for the preparation of 10-phenanthrenols. The reaction involves rapid photocycloaddition via a 1,2-biradical of 1,3-dicarbonyl compounds, followed by subsequent dehydrogenative aromatization of 1,4-biradical intermediates using TEMPO as the commercially available oxidant rather than trapped by TEMPO to form an alkoxyamine product.

Photoredox/Cobalt-Catalyzed Cascade Oxidative Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles under Oxidant-Free Conditions.

An efficient oxidant-free, photoredox-mediated cascade cyclization strategy for the synthesis of 1,3,4-oxadiazoles by using an organo acridinium photocatalyst and a cobaloxime catalyst has been developed. Various acylhydrazones have been transformed into the corresponding 1,3,4-oxadiazole products in up to 96% yield, and H2 is the only byproduct. Mechanistic experiments and density functional theory (DFT) calculation studies indicate carbon-centered radicals rather than oxygen-centered radicals as π-radicals produced by the oxidation of photoexcited Mes-Acr+* along with deprotonation, which is responsible for this transformation. The practical utility of this method is highlighted by the one-pot gram-scale synthesis starting directly from commercially available aldehydes and acylhydrazides.

Visible-Light-Promoted 6π Photocyclization of ortho-Biaryl-Appended ß-Ketoesters.

A photocatalyst- and additive-free visible-light-induced 6π-photocyclization of ortho-biaryl-appended ß-ketoesters has been developed. Upon irradiation with visible light, substrates undergo 6-endo-trig cyclization/1,5-H shift to 9,10-dihydrophenanthren-9-ols with high efficiency and selectivity. The reaction proceeds via conrotatory ring closure followed by a suprafacial 1,5-hydrogen shift leading to the observed single trans-fused products. Preliminary mechanistic studies reveal the feasibility of both 1,5-H shift and intersystem crossing of the diradical intermediate.

Synthesis of 10-Phenanthrenols via Photosensitized Triplet Energy Transfer, Photoinduced Electron Transfer, and Cobalt Catalysis.

Due to the inert redox activity and high triplet energy, radical chemistry of 1,3-dicarbonyl compounds usually requires prefunctionalization substrates, external oxidant, and high-energy UV light. Here, we report a visible-light-driven photocatalyst/cobaloxime system composed of a photosensitized energy transfer reaction (PEnT) and photoinduced electron transfer reaction (PET) and with an interrupted 6π-photocyclization/dehydrogenative aromatization in one pot to synthesize 10-phenanthrenols. Preliminary mechanistic studies revealed that fac-Ir(ppy)3 plays the dual roles of energy transfer catalysis for photocycloaddition via 1,2-biradical intermediates of 1,3-dicarbonyl compounds and photoredox/cobaloxime catalysis dehydrogenative aromatization of 1,4-biradical rather than the intermediates via 6π photocyclization in the tandem reaction. In contrast to previous well-established radical chemistry of 1,3-dicarbonyl compounds, we provide a new strategy for the activation of 1,3-dicarbonyl compounds under visible light catalysis, affording a novel cyclization strategy with extremely high atom economy for the synthesis of 10-phenanthrenols.

[Research Hotspots and Trends of Multimorbidity].

Objective To clarify the hotspots and trends of multimorbidity research and to provide evidence for further research in China. Methods Papers on multimorbidity were retrieved from PubMed and Web of Science (from inception to August 11,2021).BICOMB and gCLUTO were used for bibliometric and clustering analysis,and CiteSpace was employed for analysis of authors and citations,and burst detection of keywords. Results The research on multimorbidity has been on the rise.Among the authors,Mercer SW published the most papers on this topic and Fortin M was the most cited author.Karolinska Institute topped the institutions in the number of published papers,and the paper published in Lancet by Barnett K in 2012 was the most cited.A total of 75 high-frequency keywords were extracted,on the basis of which seven research hotspots were summarized:epidemiology (including the prevalence and trend),medication (involving polypharmacy,medication compliance,etc.),medical expenditure (including cost and medical services),aging (such as elderly patients,frailty,and disability),psychology (involving mental health,social support,etc.),multimorbidity management (such as the treatment,primary health care,and integrated care),and comorbidity of cardiovascular and metabolic diseases (involving obesity,stroke,diabetes,etc.). Conclusions Multimorbidity is concerned as a major health threat and public health problem worldwide.The management of multimorbidity is more complex than that of one disease,which thus faces more challenges.Therefore,researchers,health care providers,and policy-makers should underscore it.

[Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index].

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.Mycobacterium tuberculosis(Mtb)standard strain H37Rv was injected via tail vein to infect the mice receiving moderate-dose iron to establish an iron-overloaded mouse model of active TB.HE staining and Mtb culture were employed to analyze tuberculous lesions and bacterial loads of lung, spleen and liver tissues. Results The weight gain percentages of mice in the negative control, low-, medium-, and high-dose iron groups were 25.47%, 25.22%, 24.74%, and 21.36%, respectively, which was significantly lower in the high-dose group than in the negative control(F=17.235, P=0.027), low-dose(F=15.206, P=0.031), and medium-dose(F=11.061, P=0.036)groups.Liver had the highest iron content, followed by spleen, kidney, and small intestine.The iron content in heart and lung tissues of the low-dose group had no significant difference compared with those of the negative control group(F=19.023, P=0.715;F=23.193, P=0.902).Serum iron and ferritin in the iron-overloaded mice increased in a dose-dependent manner, while transferrin and transferrin receptor had no significant changes.HE and Prussian blue staining showed that the iron-overloaded mice had different degrees of iron deposition in tissues and high-dose iron caused liver and kidney damage.The lung(F=23.227, P=0.017), spleen(F=19.023, P=0.021), and liver(F=17.392, P=0.009)of the iron-overloaded mice with TB had a significantly shorter time of bacterial culture than those of the TB-infected mice without iron overload.The lung(F=21.012, P=0.007), spleen(F=20.173, P=0.002), and liver(F=19.091, P=0.005)of the iron-overloaded mice with TB had significantly higher bacterial loads than those of the TB-infected mice without iron overload. Conclusions The exogenous iron-overloaded mouse model with similar symptoms to patients with clinical iron overload can be established by intraperitoneal injection of medium-dose(7.50 mg/dose, 3 times/week for 4 weeks)iron dextran.Mtb injection through the tail vein can help construct a mouse model of iron overload combined with active TB.

A Newly Designed Seed-Loading Device for Verifying the Safety of 125I Implants to the Canine Carotid Artery.

A seed-loading device was designed and modeled using the Monte Carlo method to verify the biological effect of iodine-125 (125I) particles on blood vessels through animal experiments. The dose distribution characteristics of irradiated vessels were established by adjusting the design variables and geometry. The deviation between the actual value and the theoretical value was verified in vitro by the thermoluminescence dosimetry (TLD) method. After verification, the device was used to examine the biological effect of 125I irradiation of canine carotid arteries in two dogs (and one control dog) for 180 days. The hollow cylinder seed-loading device was constructed with an inner diameter of 0.5 cm and a length of 3.3 cm. When six seeds were loaded into a single layer, the source strength ratio of the intermediate layer to the edge layer was 0.7:1. When six layers of seeds were arranged at 0.45-cm intervals, the deviations between the maximum, minimum and mean energy fluence within 2.25 cm of the vessel wall were 2.19% and -4.12%, respectively, and -9% and 4%, respectively, when verified in vitro using TLD. The carotid arteries showed good tolerance to 0.56 kGy (range of 0.51-0.58 kGy) after 180 days of irradiation. In conclusion, this 125I seed-loading device overcomes the random distribution of seeds and lays an accurate radiophysical foundation for subsequent biological experiments. The preliminary results showed that the carotid artery has good tolerance to 0.56 kGy irradiation.

Prevalence of mental health problems in frontline healthcare workers after the first outbreak of COVID-19 in China: a cross-sectional study.

BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.

Efficacy and Safety of Different Antiplatelet Strategies in Survivors of Myocardial Infarction With Acute Coronary Syndrome.

PURPOSE: Many patients with acute coronary syndrome may experience recurrent myocardial infarction although they are receiving optional therapy, but they are still associated with poor clincial outcomes. The goal of this study was to assess different antiplatelet strategies in these patients. METHODS: This retrospective trial compared ticagrelor (180-mg loading dose, 90-mg BID maintenance dose) and clopidogrel (300- to 600-mg loading dose, 150-mg daily maintenance dose) for the prevention of cardiovascular events in 1083 patients with acute coronary syndrome and recurrent myocardial infarction admitted to the hospital undergoing percutaneous coronary intervention. FINDINGS: At the 24-month follow-up, a major adverse cardiovascular and cerebrovascular event (MACCE) occurred in 10.5% of patients receiving ticagrelor compared with 13.2% in the clopidogrel group (P = 0.023). Meanwhile, ticagrelor caused a higher rate of minor bleeding (18.1% vs 15.3%; P = 0.008). A survival analysis showed that ticagrelor decreased the incidence of MACCE (log-rank test, P < 0.001) and all-cause death (log-rank test, P = 0.001). The advantage of ticagrelor was also presented according to analysis of Seattle Angina Questionnaire scores. IMPLICATIONS: In patients with recurrent myocardial infarction, the ticagrelor antiplatelet strategy significantly reduced the MACCE rate without increasing the risk of major bleeding, although patients did have a higher risk of minor bleeding.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Tight N-observable uncertainty relations and their experimental demonstrations.

The uncertainty relation, as one of the fundamental principles of quantum physics, captures the incompatibility of noncommuting observables in the preparation of quantum states. In this work, we derive two strong and universal uncertainty relations for N(N ≥ 2) observables with discrete and bounded spectra, one in multiplicative form and the other in additive form. To verify their validity, for illustration, we implement in the spin-1/2 system an experiment with single-photon measurement. The experimental results exhibit the validity and robustness of these uncertainty relations, and indicate the existence of stringent lower bounds.

Vitexin alleviates ER-stress-activated apoptosis and the related inflammation in chondrocytes and inhibits the degeneration of cartilage in rats.

Excessive extracellular matrix degradation and chondrocyte apoptosis are the pathological features of osteoarthritis (OA). The ability of flavonoid compounds isolated from Chinese hawthorn leaves to exert protective effects on several diseases, via inhibition of oxidative stress and inflammation, has been demonstrated in several studies. This study explored the effects of vitexin on chondrocytes, and the underlying mechanisms thereof. Vitexin, an active ingredient in hawthorn leaf extracts, was shown to exert protective effects on chondrocytes, by inhibiting the expression of GRP78 and PDI, and an apoptotic protein (CHOP) induced by interleukin-1ß. It also modulated thapsigargin-induced upregulation of GRP78 and PDI and subsequently an apoptotic protein (CHOP). Among rat chondrocytes, both the ER stress-activated nuclear factor kappa B (NF-κB) pathway and the induced expression of inflammatory cytokines (IL-6 and TNF-α) were significantly inhibited by vitexin. Finally, vitexin attenuated the progression of OA in vivo in rats. Taken together, all data demonstrate the relationship of ER stress and inflammation in the progression of OA, the ability of vitexin to protect chondrocytes and thus its therapeutic potential in patients with OA.

Real-Time Monitoring of Gross Beta Radioactivity in Tap Water and Committed Effective Dose.

To achieve real-time monitoring of gross beta radioactivity in drinking water, a scintillating fiber array system was developed. Using this system, the gross beta radioactivity in tap water at Tsinghua University campus in Beijing was monitored, and the same water samples were measured using the evaporation concentration method as a comparison experiment. Finally, the annual committed effective doses to children and adults who drank the tap water for a long time were estimated. The results showed that the gross beta radioactivity in tap water was 0.09 ± 0.03 Bq L using the scintillating fiber array system and 0.076 ± 0.009 Bq L using the evaporation concentration method. The annual committed effective dose values were less than the dose reference level of 0.1 mSv y, as suggested by the World Health Organization. The scintillating fiber array system can be used for measuring gross beta radioactivity in drinking water and protecting public health.

Corrigendum: A Stronger Multi-observable Uncertainty Relation.

This corrects the article DOI: 10.1038/srep44764.

Gross beta determination in drinking water using scintillating fiber array detector.

A scintillating fiber array detector for measuring gross beta counting is developed to monitor the real-time radioactivity in drinking water. The detector, placed in a stainless-steel tank, consists of 1096 scintillating fibers, both sides of which are connected to a photomultiplier tube. The detector parameters, including working voltage, background counting rate and stability, are tested, and the detection efficiency is calibrated using standard potassium chloride solution. Water samples are measured with the detector and the results are compared with those by evaporation method. The results show consistency with those by evaporation method. The background counting rate of the detector is 38.131 ±â€¯0.005 cps, and the detection efficiency for ß particles is 0.37 ±â€¯0.01 cps/(Bq/l). The MDAC of this system can be less than 1.0 Bq/l for ß particles in 120 min without pre-concentration.

A Necessary and Sufficient Criterion for the Separability of Quantum State.

Quantum entanglement has been regarded as one of the key physical resources in quantum information sciences. However, the determination of whether a mixed state is entangled or not is generally a hard issue, even for the bipartite system. In this work we propose an operational necessary and sufficient criterion for the separability of an arbitrary bipartite mixed state, by virtue of the multiplicative Horn's problem. The work follows the work initiated by Horodecki et al. and uses the Bloch vector representation introduced to the separability problem by J. De Vicente. In our criterion, a complete and finite set of inequalities to determine the separability of compound system is obtained, which may be viewed as trade-off relations between the quantumness of subsystems. We apply the obtained result to explicit examples, e.g. the separable decomposition of arbitrary dimension Werner state and isotropic state.

Ensembling Variable Selectors by Stability Selection for the Cox Model.

As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs) have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010), a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR) and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region Λ in lasso and the parameter λmin properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify Λ and λmin. Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

Expression of KGF-1 and KGF-2 in Skin Wounds and Its Application in Forensic Pathology.

The expression of keratinocyte growth factor-1 (KGF-1) and keratinocyte growth factor-2 (KGF-2) in skin wounds in mice was studied using multiple methods. The dynamic expression of KGF-1 and KGF-2 for antemortem and postmortem injuries as well as the examination of antemortem injuries after death under different temperature and over varying time periods was studied. It demonstrates that skin KGF-1 resulting from an antemortem injury starts to rise at 6 hours, reaches its peak at 1 day, and starts to drop at 5 days. The expression of skin KGF-2 resulting from an antemortem injury starts to rise at 12 hours, reaches its peak at 7 days, and begins to drop at 10 days. Skin KGF-1 and skin KGF-2 after death stabilize within 7 days at 4°C and -20°C, within 5 days at 20°C, and within 1 day at 30°C. The application of KGF-1 and KGF-2 indicators in skin wound age determination is both feasible and reliable.

A Stronger Multi-observable Uncertainty Relation.

Uncertainty relation lies at the heart of quantum mechanics, characterizing the incompatibility of non-commuting observables in the preparation of quantum states. An important question is how to improve the lower bound of uncertainty relation. Here we present a variance-based sum uncertainty relation for N incompatible observables stronger than the simple generalization of an existing uncertainty relation for two observables. Further comparisons of our uncertainty relation with other related ones for spin- and spin-1 particles indicate that the obtained uncertainty relation gives a better lower bound.

Compton suppression in BEGe detectors by digital pulse shape analysis.

A new method of pulse shape discrimination (PSD) for BEGe detectors is developed to suppress Compton-continuum by digital pulse shape analysis (PSA), which helps reduce the Compton background level in gamma ray spectrometry. A decision parameter related to the rise time of a pulse shape was presented. The method was verified by experiments using 60Co and 137Cs sources. The result indicated that the 60Co Peak to Compton ratio and the Cs-Peak to Co-Compton ratio could be improved by more than two and three times, respectively.