A copper-catalyzed Friedel–Crafts propargylation/hydroamination/aromatization sequence is described. In the presence of a catalytic amount of CuI, this sequential reaction can convert ethynyl ...benzoxazinanones and indoles into a diverse set of 3,3′-biindoles with high efficiency and selectivity. Moreover, the synthesis of other indole–heteroaryl molecules and the catalytic asymmetric formation of axially chiral 3,3′-biindoles are demonstrated.
The emergence of clinically relevant β-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria ...acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of β-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu2+ and Zn2+) treatment group was 2–10 times higher than that in the control. Moreover, heavy metals (Cu2+ and Zn2+) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River.
Display omitted
•Ampicillin-resistant pathogenic bacteria were isolated and identified in the Xiangjiang River.•The pathogenic bacteria cover P. monteilii, A. hydrophila, A. baumannii, and S. epidermidis.•The selective pressure of heavy metals contributed to the bloom of the pathogenic bacteria.•Cu2+ and Zn2+ increased the horizontal transfer of plasmids in the pathogenic bacteria.•Heavy metals may ultimately cause the prevalence of multidrug-resistant pathogenic bacteria.
This study provided a reference for the effects of selective stress of heavy metal pollutants on the prevalence of ampicillin-resistant opportunistic pathogenic bacteria.
•Five stages of Mesozoic mineralisation have been identified.•190–165Ma events in the Erguna block occurred during the subduction of MOB.•140–120Ma events are associated with the closure of MOB and ...the subduction of PPO.
North-eastern China and surrounding regions host some of the best examples of Phanerozoic juvenile crust on the globe. However, the Mesozoic tectonic setting and geodynamic processes in this region remain debated. Here we attempt a systematic analysis of the spatio-temporal distribution patterns of ore deposits in NE China and surrounding regions to constrain the geodynamic milieu. From an evaluation of the available geochronological data, we identify five distinct stages of ore formation: 240–205Ma, 190–165Ma, 155–145Ma, 140–120Ma, and 115–100Ma. The Triassic (240–205Ma) magmatism and associated mineralisation occurred during in a post-collisional tectonic setting involving the closure of the Paleo-Asian Ocean. The Early-Mid Jurassic (190–165Ma) events are related to the subduction of the Paleo-Pacific Ocean in the eastern Asian continental margin, whereas in the Erguna block, these are associated with the subduction of the Mongol–Okhotsk Ocean. From 155 to 120Ma, large-scale continental extension occurred in NE China and surrounding regions. However, the Late Jurassic magmatism and mineralisation events in these areas evolved in a post-orogenic extensional environment of the Mongol–Okhotsk Ocean subduction system. The early stage of the Early Cretaceous events occurred under the combined effects of the closure of the Mongol–Okhotsk Ocean and the subduction of the Paleo-Pacific Ocean. The widespread extension ceased during the late phase of Early Cretaceous (115–100Ma), following the rapid tectonic changes resulting from the Paleo-Pacific Oceanic plate reconfiguration.
Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.
The present study aimed to investigate the influence of delayed or missed ...dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.
A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.
For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.
It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.
In this work, we report an ultrasensitive electrochemical biosensor for microRNA-21 (miRNA-21) detection by using a competitive RNA-RNA hybridization configuration. A biotinylated miRNA of the ...self-same sequence with the target miRNA is mixed with the samples, and allowed competition with the target miRNA for a thiolated RNA probe immobilized onto a tungsten diselenide (WSe
) nanosheet modified electrode. Thereafter the current response is obtained by forming the hybridized biotinylated miRNA with streptavidin-horseradish peroxidase (HRP) conjugates to catalyze the H
O
+ hydroquinone (HQ) system. Benefiting from the high specific surface area of WSe
nanosheets, the competitive hybridization configuration and the signal amplification of the H
O
+ HQ detection system, the proposed assay exhibits a wide linear range of 0.0001-100 pM towards target miRNA with a detection limit of 0.06 fM (S/N = 3), and shows excellent discrimination ability for base-mismatched miRNA sequences. Therefore, the designed platform has promising prospects for the detection of miRNA in biomedical research and early clinical diagnosis.
Transition metal-catalyzed cycloaddition has been established as a powerful tool for heterocycle synthesis. Despite impressive advances, the exploitation of new catalysis strategies and systems is ...still highly significant to enrich the heterocycle family. Herein, we disclosed a cooperative catalysis system merging an achiral Pd catalyst and a chiral Co catalyst for the asymmetric 4+2 cycloaddition between vinyl benzoxazinones and
-acylpyrazoles. Chiral tetrahydroquinolines bearing two contiguous, unusual
-configured stereocenters were produced in high yields and enantio- and diastereoselectivities. The pyrazole directing group can be easily converted into many other functional groups, thus demonstrating the flexibility of the present methodology.
•Residual capacity tests on SRCFST columns subjected to full-range fire were conducted.•The behaviour and residual resistance of SRCFST columns were analyzed.•FE models were developed and validated ...against the test results.•Residual strength of SRCFST columns subjected to three different paths were compared.•Current guidelines were extended to assess the residual strength of SRCFST columns.
Steel-reinforced concrete-filled thin-walled steel tube (SRCFST) is gaining popularity in construction, primarily due to its superior structural performance. However, there is still a scarcity of studies investigating the residual capacity of SRCFST columns subjected to a full-range fire. A comprehensive research was conducted in this, involving both experimental testing and numerical simulation, to investigate the residual capacity of SRCFST columns. Six SRCFST columns were tested under combined loading and temperature to achieve the temperature distribution, failure modes, residual strength, and structural response within the cross-section. The developed finite element (FE) model was used to validate the test results. Three different paths, including after exposure to fire and without initial load, the full-range fire, and the actual path in the current test, were considered toevaluate the influence of different time-load-temperature paths on the mechanical properties of SRCFST columns. Results reveal that the region comprised of profiled steel and surrounded concrete forms a composite constrained region, with little loss of strength and stiffness occurring in the core region. The initial load level and heating time ratio were found to have a significant negative influence on the residual load-carrying capacity and ductility of SRCFST columns. In contrast, circular SRCFST columns are more resistant to the effects of fire than square SRCFST columns. Finally, the existing design methods were used and extended to evaluate the residual load-carrying capacity of SRCFST columns subjected to a complete temperature-load-time process.
This paper aims to experimentally study the fire performance of steel-reinforced concrete-filled steel tubular (SRCFST) columns without fire protection. Eight SRCFST specimens with cruciform section ...profiled steel were tested under the ISO-834 standard fire. The various test parameters including cross-section type of steel tube (circular or square), the load ratio and load eccentricity were considered and discussed. The temperature distribution, failure modes, axial and lateral deformation, fire resistance of the specimens obtained by test were investigated in detail. The results show that the cruciform section profiled steel provided great confinement effect to core concrete, and can efficiently suppress the generation and development of cracks in concrete. The specimens with diverse load ratio or loading method present various tendency of axial deformation versus time curves, i.e. five stages for axially loading specimens with common load ratio (n = 0.4) and three stages for specimens with high load ratio (n > 0.4) or specimens under eccentric compression. The critical temperature of SRCFST specimens is much lower than that of steel structures and CFST columns at same parameters, and the fire resistance of SRCFST columns has significant improvement compared with CFST columns. Moreover, available design method for SRCFST columns and CFST columns were compared with test results to evaluate the applicability for SRCFST specimens.
Display omitted
•Fire performance of eight SRCFST columns was experimentally investigated.•Profiled steel provided restraint on concrete and improved the fire resistance of SRCFST columns.•Load ratio is a significant factor affecting the fire resistance and axial deformation.•Critical temperature of SRCFST columns is lower than that of CFST columns and steel structures.
Different fertilization regimes differentially impact the physicochemical properties, diversity, and ecosystem functioning of soil microbial communities. However, there is little research on the ...relationship between soil quality, microbial diversity, and crop production under different long-term fertilization regimes, especially on woody plants. Therefore, in this study, we investigated changes in the soil microbial communities of walnut orchards after nine years of continuous fertilization (no fertilizer, only chemical fertilizer, chemical + organic fertilizer, chemical + biofertilizer, and chemical + organic + biofertilizer), and analyzed the link between fertility improvement and yield increase from a microbial perspective. The results showed that the soil quality index was strongly correlated with organic fertilizers and biofertilizers addition, and exhibited a significant relationship with walnut yield. Furthermore, the addition of organic fertilizers or biofertilizers promoted the enrichment of microorganisms beneficial to soil fertility, crop growth (Bacillus spp.) and soil bioremediation (Solicoccozyma spp.) and decreased the amounts of Fusarium spp. in the walnut orchard soil. Moreover, structural equation modeling indicated strong and positive relationships between walnut yield and the diversity of the keystone microbial communities. Overall, the results confirm the feasibility of using multiple fertilizer blends to improve soil fertility and reveal the fundamental role of fungal diversity in maintaining economic forest tree production.
Display omitted
•Long-term fertilization dramatically altered soil microbial community composition.•SEM was used to evaluate the link between microbial diversity and walnut yield.•Biofertilizer boosts microbes beneficial to soil fertility and crop growth.•It is preferable to combine multiple fertilizers for walnut plantation management.•Fungal diversity plays a key role in maintaining economic forest tree production.
Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in ...microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE-xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu.
PDF
