Cyano-tetrazole is the first reported compound that bears four nitrogen atoms in a single five-membered ring. This unique molecular scaffold has long been ignored after its discovery in 1885, mainly ...attributed to the scarcity of available synthetic methods. Indeed, the most popular approach to tetrazoles (that is the cycloaddition reaction between nitriles and azides) has inevitably excluded the possibility of introducing valuable cyano groups to decorate the final heterocyclic cores. Here, we describe a completely different disconnection strategy to the long time-pursued cyano-tetrazoles via a simple, direct, and practical cycloaddition transformation between readily accessible aryl diazonium salts and diazoacetonitrile. This method provides both regioisomers of disubstituted tetrazoles from the same set of starting materials in a metal cation controlled fashion.
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•A novel BODIPY-based molecular fluorescent probe was designed and synthesized.•The probe exhibited excellent selectivity and sensitivity toward nerve agent simulants.•Detection ...mechanism of base-assisted tunable PET process was clearly discussed.•In situ monitoring of DCNP in liquid and gas phase was realized by strips immobilized with probe.
A fluorescent BODIPY probe (SO-BOD) conjugated with a 2-salicylaldoxime group via an ethynyl spacer was designed and synthesized for highly sensitive and selective detection of DCNP (a simulant of Tabun). The probe exhibited significant fluorescent quenching in the presence of Et3N, and 30-fold fluorescence enhancement was achieved in the presence of DCNP. Integration of experimental and computational methods well illustrated that these fluorescence variations were attributed to the intramolecular photo-induced electron transfer (PET) process. Except for the low limit of detection (34 nM) to DCNP, SO-BOD also showed a rapid response (t1/2 = 175 s) and high selectivity. Furthermore, naked-eye detection of DCNP was carried out in both the liquid and vapor phases by test strips immobilized with the probe.
Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new ...treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.
This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.
A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.
Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.
ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Transgenic rice producing insecticidal proteins from Bacillus thuringiensis (Bt) could help protect the plants from damage by lepidopteran pests. However, one concern is the potential of Bt rice to ...harm non-target natural enemies, which play a vital role in pest control. In the present study, the potential effects of Cry1C rice and Cry2A rice on different life-table parameters and population dynamics of Pseudogonatopus flavifemur, a parasitoid of rice planthoppers, were evaluated under laboratory and field condition. The exposure of P. flavifemur to plant-produced Bt proteins was also analyzed. Results indicated that direct feeding on rice plants was the main exposure pathway of P. flavifemur to the Cry1C and Cry2A proteins. No significant difference on the development, survival, longevity, fecundity, and prey consumption of P. flavifemur was detected over two generations between the Bt and non-Bt rice treatments. Furthermore, the population dynamics of P. flavifemur were not affected by Cry1C rice and Cry2A rice. In conclusion, the tested Cry1C rice and Cry2A rice do not appear to harm the parasitoid P. flavifemur.
Fecal microbiota transplantation (FMT) has been used in a wide variety of diseases. In this article, we reported a 46-year-old female with diabetic neuropathy (DN) achieved remission by the treatment ...of FMT.
The patient with an 8-year history of diabetes and hypertension was admitted to hospital due to sensitive pain of her right thigh and poor blood glucose control. The traditional hypoglycemic and analgesic treatment were useless to her symptoms.
Diabetic-induced neuropathy was considered.
This patient received twice FMTs for 3 months.
After twice FMTs, the clinical response of patient was pleasant. The glycemic control was improved, with a remarkable relief of the symptoms of painful DN in particular. No obvious adverse effects were observed during the FMTs and follow-up observation-testing.
We proposed that FMT could be a promising treatment in patients with diabetes or diabetes-related complications like DN. FMT also appeared to be definitely safer and more tolerable than the pharmacologic treatment in patients with DN.
Mission planning of air strike operations is hard because it has to give instructions to a large number of units during a relatively long period of time in an uncertain environment. If some ...instruction parameters can be calculated by an intelligent agent, better strategies can be found more quickly. In a specific combat scenario of air strike operations against islands, an intelligent model is proposed to improve the performance and flexibility of mission planning. The proposed intelligent mission planning model is based on rule-based decision and uses a fully connected recurrent neural network to calculate some of the decision parameters. The proposed intelligent mission planning model shows better results as compared to rule-based decision making with randomized parameters, and it performs as good as experts in the test set of the specific combat scenario.
The problem of high power consumption in data centers is becoming more and more prominent. In order to improve the energy efficiency of data centers, cooperatively optimizing the energy of IT systems ...and cooling systems has become an effective way. In this paper, a model-free deep reinforcement learning (DRL)-based joint optimization method MAD3C is developed to overcome the high-dimensional state and action space problems of the data center energy optimization. A hybrid AC-DDPG cooperative multi-agent framework is devised for the improvement of the cooperation between the IT and cooling systems for further energy efficiency improvement. In the framework, a scheduling baseline comparison method is presented to enhance the stability of the framework. Meanwhile, an adaptive score is designed for the architecture in consideration of multi-dimensional resources and resource utilization improvement. Experiments show that our proposed approach can effectively reduce energy for data centers through the cooperative optimization while guaranteeing training stability and improving resource utilization.
Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltration in the tumor microenvironment. Osteopontin is related to tumor metastasis and proliferation. Osteopontin is ...expressed not only by tumor cells but also by TAMs. The purpose of the current study was to assess the prognostic significance of osteopontin expressed by TAMs (TOPN) in patients with non-small cell lung cancer.
Tissue microarray was used to detect the expression of TOPN, TAMs, and microvascular density in 159 patients with non-small cell lung cancer undergoing complete pulmonary resection in our hospital between 2003 and 2006. The correlations between TOPN, TAMs, and clinicopathologic data were analyzed with χ(2) tests. Quantitation of TAMs or TOPN and microvascular density analyses was performed using Bonferroni correction and the Student's t test. The prognostic value of TOPN was evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis.
In the recurrence and metastasis group, microvascular density was higher than that in the control group (14.4 ± 1.06 versus 8.9 ± 1.02; p = 0.0002). In the TOPN-positive group, microvascular density was increased compared with that in the TOPN-negative group (14.3 ± 1.37 versus 10.7 ± 0.91; p = 0.0273). Osteopontin expressed by TAMs was an independent predictor for overall survival (p = 0.017) and disease-free survival (p < 0.001), especially for stage I non-small cell lung cancer. The 6-year overall and disease-free survival rates in TOPN-positive patients were 22.64% and 16.98%, respectively, which were significantly lower than those of TOPN-negative patients (50.00% and 39.62%, respectively).
Osteopontin expressed by TAMs is a valuable independent predictor of tumor recurrence and survival in patients with non-small cell lung cancer.
To understand the friction and wear of working mediums in iron ore ball mills, experiments were conducted using the ball cratering method under dry and wet milling conditions, which mimic the ...operating conditions in ball mills. The liner sample is made of Mn16 steel, the ball had a diameter of 25 mm and was made of GCr15 steel, and the iron ore powder was screened from the magnetite particles with mesh number of 20. The results indicate that a different wear condition makes the COF change in a converse way and causes a different wear pattern in wear craters, followed by the corresponding temperature rise.
•The effect of ore powder and slurry on friction behavior was discussed through contrast.•The friction heating-up was detected by thermal infrared imager.•Wear behavior under increasing contact load was analyzed.•The wear mechanism under different wear environments was investigated by industrial microscope.
In this study, an effective method was developed to extract the polysaccharide from
(PFSV) by destroying the cell wall. Box-Behnken design was employed to determine the optimal processing conditions ...as follows: processing temperature (80°C), processing time (0.81 h) and amount of HCl (1.5 ml). Under these conditions, the yield of PFSV reached 5.94 ± 0.16%. The purified polysaccharide (PFSV-2) was found to be a hetero-polysaccharide with an average molecular weight of 20.377 kDa. The backbone of PFSV-2 was composed of an →6)-
-Gal
-(1→ and →2,6)-
-Man
-(1→ and →2)-
-Fuc
-(1→ and was branched of t-
-Man
-(1→ at position 2 of residue B. PFSV-2 showed hypolipidemic activity by decreasing lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Furthermore, PFSV-2 downregulated the
, and
genes and upregulated the
and
genes. These findings suggested PFSV-2 may be a promising candidate in lipid regulation therapy.
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