This study reports an oxytrifluoromethylation method for construction of oxazoles and furans motif and the concurrent incorporation of a 2,2,2‐trifluoroethyl group at the aromatic C5‐position. ...High‐valent copper(III) trifluoromethyl compounds are crucial to this reaction that induces oxy‐trifluoromethylation of alkynes with a pendant amide/enol group functioning as the oxygen‐nucleophile. A wide substrate scope is demonstrated with high efficiency and with broad functional group tolerance. Late‐stage functionalization of dehydrocholic acid, a complex drug compound, is accomplished to show the potential of this method for practical drug design.
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Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of ...cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80-90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified.
Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups.
The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plants take up a wide range of trace metals/metalloids (hereinafter referred to as trace metals) from the soil, some of which are essential but become toxic at high concentrations (e.g., Cu, Zn, Ni, ...Co), while others are non‐essential and toxic even at relatively low concentrations (e.g., As, Cd, Cr, Pb, and Hg). Soil contamination of trace metals is an increasing problem worldwide due to intensifying human activities. Trace metal contamination can cause toxicity and growth inhibition in plants, as well as accumulation in the edible parts to levels that threatens food safety and human health. Understanding the mechanisms of trace metal toxicity and how plants respond to trace metal stress is important for improving plant growth and food safety in contaminated soils. The accumulation of excess trace metals in plants can cause oxidative stress, genotoxicity, programmed cell death, and disturbance in multiple physiological processes. Plants have evolved various strategies to detoxify trace metals through cell‐wall binding, complexation, vacuolar sequestration, efflux, and translocation. Multiple signal transduction pathways and regulatory responses are involved in plants challenged with trace metal stresses. In this review, we discuss the recent progress in understanding the molecular mechanisms involved in trace metal toxicity, detoxification, and regulation, as well as strategies to enhance plant resistance to trace metal stresses and reduce toxic metal accumulation in food crops.
Contamination of soil with trace metals/metalloids can cause toxicity to plants and threaten food safety. This review presents recent progress in understanding the molecular mechanisms of trace metal/metalloid toxicity and detoxification, and strategies to enhance plant resistance to trace metal stresses and reduce toxic metal accumulation in food crops.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
LINKED CONTENT
This article is linked to Cardoso et al papers. To view these articles, visit
https://doi.org/10.1111/apt.17650
and
https://doi.org/10.1111/apt.17725
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The palladium‐catalyzed oxidation of alkenes, the Wacker–Tsuji reaction, is undoubtedly a classic in organic synthesis and provides reliable access to methyl ketones from terminal alkenes under mild ...reaction conditions. Methods that switch the selectivity of the reaction to provide the aldehyde product are desirable because of the access they provide to a valuable functional group, however such methods are elusive. Herein we survey both the methods which have been developed recently in achieving such selectivity and discuss common features and mechanistic insight which offers promise in achieving the goal of a general method for anti‐Markovnikov‐selective olefin oxidations.
Out of wack: The Wacker–Tsuji reaction provides reliable access to methyl ketones from terminal alkenes under mild reaction conditions. Methods leading to a switch in the selectively of the reaction to provide the aldehyde product are desirable. Recent developments and mechanistic insights which offer promise in achieving the goal of a general method for anti‐Markovnikov‐selective olefin oxidation are discussed.
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Background and aims Cereals are the main dietary source of cadmium (Cd). Rice grains often contain higher levels of Cd than other cereals, but the reasons are unknown. The aims of this study were to ...compare Cd uptake, translocation and influx kinetics between rice, wheat and maize and to investigate whether the expression and functionality of Nramp5 genes differ between the three crop species. Methods Two cultivars each of rice, wheat and maize were grown hydroponically and exposed to a range of Cd concentrations. Nramp5 genes were cloned from the three plants and their expression levels determined. The Cd transport activities of Nramp5 proteins were tested in yeast. Results Under hydroponic conditions, Cd uptake in rice was 2.5–8.1 and 1.1–3.6 times that of wheat and maize, respectively. The maximum Cd influx velocity of rice was 6.5 and 2.2 times that in wheat and maize, respectively. Wheat showed the lowest Cd uptake but the highest Cd root-to-shoot translocation. The absolute expression level of OsNramp5 in rice roots was 4–5 times that of TaNramp5A and TaNramp5D in wheat or ZmNramp5 in maize. All Nramp5 proteins were localized to the plasma membrane. When expressed in yeast, OsNramp5 showed a greater Cd transport activity than wheat or maize Nramp5. Conclusions Rice has a greater Cd uptake ability than wheat or maize, likely because OsNramp5 is more highly expressed and the protein has a higher Cd transport activity than wheat or maize Nramp5.
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BFBNIB, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Neurogenic detrusor overactivity (NDO) affects the quality of life (QoL) of millions of individuals worldwide. The purpose of this study was to assess the efficacy and safety of onabotulinumtoxinA in ...patients with NDO using a network meta-analytic approach, which can also quantify and compare the efficacy of onabotulinumtoxinA across different dosages.
PubMed, EMBASE, and the Controlled Trials Register were searched to identify randomized controlled trials comparing onabotulinumtoxinA to a control for NDO in adult patients. The primary outcome was the mean number of urinary incontinence (UI) episodes per week. Urodynamic parameters included the maximum cystometric capacity (MCC) and the maximum detrusor pressure (MDP). The safety of onabotulinumtoxinA was determined by the incidence of various frequent adverse events (AEs). Two authors extracted data independently, and the statistical analyses were performed using RevMan 5.1.0 software.
A total of 1,915 patients from six randomized controlled trials were included in this meta-analysis. The onabotulinumtoxinA-treated groups had a significantly decreased mean number of urinary incontinence episodes per week (at week 6) (onabotulinumtoxinA200U: MD: -10.72, 95% CI: -13.4 to -8.04, P<0.00001; 300 U: MD: -11.42, 95% CI: -13.91 to -8.93, P<0.00001), MDP (200 U: MD: -33.46, 95% CI: -39.74 to -27.18, P<0.00001; 300 U: MD: -31.72, 95% CI: -37.69 to -25.75, P<0.00001), and greater increased MCC (200 U: MD: 141.30, 95% CI: 121.28 to 161.32, P<0.00001; 300 U: MD: 151.39, 95% CI: 130.43 to 172.34, P<0.00001) compared to the placebo-treated groups. However, there were no significant differences between the onabotulinumtoxinA-treated groups for the number of weekly UI episodes at 6 weeks (MD: 0.08, 95% CI: -2.57 to 2.73, P = 0.95). Similarly, we also observed that there were no significant differences in MCC (MD: -9.97, 95% CI: -33.15 to 13.20, P = 0.40) and MDP (MD: -1.86, 95% CI: -8.09 to 4.37, P = 0.56). Considering the AEs, the onabotulinumtoxinA-treated groups were often associated with more complications, including urinary tract infections (UTIs) (RR: 1.47, 95% CI: 1.29 to 1.67, P<0.00001), urinary retention (RR: 5.58, 95% CI: 3.53 to 8.83, P<0.00001), hematuria (RR: 1.70, 95% CI: 1.01 to 2.85, P = 0.05), and muscle weakness (RR: 2.59, 95% CI: 1.36 to 4.91, P = 0.004).
OnabotulinumtoxinA can significantly reduce the frequency of urge urinary incontinence and improve urodynamic parameters (MCC and MDP) in patients with NDO at 6 weeks after treatment. This meta-analysis indicates that onabotulinumtoxinA is effective and safe for treating patients with NDO compared to placebo. Additionally, we did not observe any statistical or clinical differences in efficacy between 300 and 200 U dosages.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels ...are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross‐linked nanocomposite hydrogel, the click reaction improves drug‐release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.
Cross‐linked hydrophilic polymer chains that can form gels are widely utilized for biomedical applications, such as drug delivery. Various studies have also demonstrated the effects of particle size and surface morphology on drug release from particles in liver cancer therapy. Mechanistic understandings of responsive hydrogels in responsive stimuli are provided, by which better clinical choices may be approached.
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Traffic is very important to route planning and people's daily lives. Traffic prediction is still very challenging as it is affected by many complex factors including dynamic spatio-temporal ...dependencies and external factors (e.g., road types and nearby points of interest) in the road network. Dynamic spatio-temporal dependencies simultaneously contain spatial and temporal dependencies. Existing models for predicting traffic of links only consider the spatial dependencies from the perspective of links or the whole road network by ignoring the spatial dependencies among regions. To this end, this paper proposes a new Spatio-Temporal Neural Network (STNN) with the encoder-decoder architecture to improve the accuracy of traffic predictions by additionally taking into account the region-based spatial dependencies and external factors. Specifically, STNN learns dynamic spatio-temporal dependencies from historical traffic time series via an encoder in the perspective of the road network, with two spatial models, i.e., region-based spatial model and link-based spatial attention model in the perspectives of regions and links, respectively. Further, STNN decodes the output from the encoder via a decoder with a temporal attention model for recording long-term dependencies and fuses external factors in the road network, to improve network-wide traffic predictions. We conduct extensive experiments to evaluate the performance of STNN on three real-world traffic datasets, which shows that STNN is significantly better than the state-of-the-art models.
Tungsten ditelluride (WTe2) is a semimetal with orthorhombic Td phase that possesses some unique properties such as Weyl semimetal states, pressure‐induced superconductivity, and giant ...magnetoresistance. Here, the high‐pressure properties of WTe2 single crystals are investigated by Raman microspectroscopy and ab initio calculations. WTe2 shows strong plane‐parallel/plane‐vertical vibrational anisotropy, stemming from its intrinsic Raman tensor. Under pressure, the Raman peaks at ≈120 cm−1 exhibit redshift, indicating structural instability of the orthorhombic Td phase. WTe2 undergoes a phase transition to a monoclinic T′ phase at 8 GPa, where the Weyl states vanish in the new T′ phase due to the presence of inversion symmetry. Such Td to T′ phase transition provides a feasible method to achieve Weyl state switching in a single material without doping. The new T′ phase also coincides with the appearance of superconductivity reported in the literature.
The plane‐parallel/plane‐vertical vibrational anisotropies of WTe2 single crystal under high pressure are investigated by Raman spectroscopy and ab initio calculations. WTe2 undergoes a phase transition from orthorhombic Td to monoclinic T′ phase at 8 GPa, where the Weyl states vanish in the new T′ phase due to the presence of inversion symmetry.
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