The endoperoxide group of artemisinins is universally accepted an essential group for their anti‐cancer effects. In this study, a series of D‐ring‐contracted artemisinin derivatives were constructed ...by combining ring‐contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty‐six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H‐NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA‐MB‐436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 μM, and its activity was approximately 1/3 of the positive control Palbociclib.
Context.
Nanoflares are impulsive energy releases that occur due to magnetic reconnection in the braided coronal magnetic field, which is a potential mechanism for heating the corona. However, there ...are still sporadic observations of the interchange of braiding structure segments and footpoints inside coronal loops, which is predicted to be the morphological evolution of the reconnecting magnetic bundles in the nanoflare picture.
Aims.
This work aims to detect the evolutions of the pairs of braiding strands within the apparent single coronal loops observed in Atmospheric Imaging Assembly (AIA) images.
Methods.
The loop strands were detected on two kinds of upsampled AIA 193 Å images, which were obtained by upscaling the point spread function matched AIA images via bicubic interpolation and were generated using a super-resolution convolutional neural network. The architecture of the network is designed to map the AIA images to unprecedentedly high spatial resolution coronal images taken by the High-resolution Coronal Imager (Hi-C) during its brief flight.
Results.
At times, pairs of separate strands that appear braided together later evolved into pairs of almost parallel strands with completely exchanged parts. These evolutions offer morphological evidence that magnetic reconnections between the braiding strands have taken place, which is further supported by the appearance of transient hot emissions containing significant high-temperature components (
T
> 5 MK) at the footpoints of the braiding structures.
Conlusions.
The brief appearances of the two rearranging strands support the idea that magnetic reconnections have occurred within what appears to be a single AIA loop.
Escherichia fergusonii is a rare opportunistic pathogen in humans and animals, especially with biofilm.
In one case, E. fergusonii with biofilm was detected in the bile, and silver staining was used ...to prove it had biofilm. The clinical characteristics and drug susceptibility of eight cases of E. fergusonii retrieved from the literature were also summarized.
This is a case of E. fergusonii with biofilm, which has not been reported in China. The 8 cases retrieved from the literature did not specify whether they had biofilm, but we analyzed their clinical characteristics and drug susceptibility. All patients were treated with antimicrobial drugs. 8 cases showed sensitivity to piperacillin/tazobactam and imipenem in 6 cases (75%), but poor sensitivity to levofloxacin and ciprofloxacin.
The silver staining method proved biofilm in this case, which is the first case of E. fergusonii with biofilm in China.
Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish
Yin and invigorate the
kidney in traditional Chinese medicine (TCM) and ...has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on
Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that
Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of
Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development.
Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. 1 While it is still disputable whether adjuvant ...chemotherapy is necessary for stage I patients. 2 IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. 3 Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. 4-6 There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy.
We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3.
A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001).
IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.
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•Astragalin elicited a protective effect against STZ-induced diabetic spermatogenic dysfunction in male mice.•Astragalin treatment increased sperm parameters, the weight of ...reproductive organs, and organ coefficient.•Astragalin reversed the pathological changes of testicular tissue in diabetic mice.•Astragalin inhibited oxidative stress in diabetic mice.•Astragalin reduced the overexpression of inflammatory factors TNF-α and iNOS.
Spermatogenic dysfunction is a common complication in men with diabetes and is the most important manifestation of diabetes-related male reproduction damage. Astragalin (AG) is one of the main flavonoids from Cuscuta chinensis, which has rich pharmacological activities. This study aimed to establish whether AG may contribute to the recovery from spermatogenic dysfunction. AG (3.3, 10 and 30 mg/kg) and Clomiphene (5 mg/kg) were orally administered to streptozotocin-induced diabetic male mice for 8 weeks. After the experiments performed, reproductive organs, sperm parameters and histomorphological changes were analysed. Antioxidant and anti-inflammatory capacity were estimated in testicular tissues. The results revealed that AG significantly improved the reproductive organs, sperm parameters and testicular morphology to different degrees in diabetic mice. Nitric oxide (NO) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), markedly increased in the testicular tissue after AG was administered. Interestingly, AG also downregulated the protein expressions of tumour necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in testes. In conclusion, AG is a potential beneficial agent to protect diabetic-induced spermatogenic dysfunction in male mice by increasing antioxidant enzymes activities and inhibiting inflammation.
A novel Cu–Zr nanoglass consisting of glassy nano-cells connected by oxide interfaces is proposed. Compared to conventional nanoglasses, the novel oxide-connected nanoglass presents ultrahigh tensile ...strength and superior tensile plasticity at ambient temperature. Subjected to tensile loading, the oxide interfaces are found to promote the nucleation of shear transformation zones (STZs) due to the existence of excess free volume. Meanwhile, the strong bonding between metallic and oxygen atoms in the oxide interface makes it difficult for STZs to propagate through. Thus, the STZs are effectively proliferated and confined inside the cell interior without any mature shear band (SB) formed. The results provide new ideas for toughening metallic glasses with a decent combination of plasticity and strength, thus making it possible to overcome the longstanding strength-ductility trade-off dilemma.
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•A novel NG consisting of glassy nano-cells connected by glassy oxide interfaces is proposed.•The novel NG exhibits a superior combination of ultrahigh strength and ductility.•Massive STZs are promoted to form in the vicinity of the oxide interface.•Shear transformation is strictly confined in the interior of glassy cells.
•This study first reported the protection effect of betaine on DM mice with BTB dysfunction and the possible mechanisms.•Betaine at different doses could increase the body weight and the weight of ...reproductive organs in DM mice.•Betaine reversed the pathological changes of testicular tissue in DM mice.•Betaine can prevent biotin from passing through BTB and has a protective effect on the integrity of BTB in DM mice.•Betaine inhibited oxidative stress in DM mice.
Blood-testis barrier (BTB) impairments is one of the major secondary complications of diabetes. Betaine (BET) is the important active ingredients isolated from Lycium barbarum, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. This study aimed to establish whether BET contributes to the recovery from BTB dysfunction in streptozotocin (STZ) induced diabetic mice.
BET (200, 400, 800 mg/kg) was orally administered to diabetic mice for 8 weeks. Testis tissues were collected for histopathological and biochemical analysis, the reproductive organ weight was estimated. Antioxidant enzyme activity and BTB associated protein expressions were determined with their corresponding assay kits and western blot analysis. The results revealed that BET significantly improved the weight of the reproductive organs and testicular morphology in diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked down-regulated the expressions of p38 MAPK phosphorylation and up-regulation the protein expressions of ZO-1, Occludin, Claudin-11, N-cadherin, and Connexin-43 after BET administration compared with the diabetic group. In conclusion, these results demonstrated that BET exerts protective effects on diabetes-induced BTB dysfunction, which may be through regulating oxidative stress-mediated p38 MAPK pathways.
Twin-field quantum key distribution (TF-QKD) has emerged as a promising solution for practical quantum communication over long-haul fiber. However, previous demonstrations on TF-QKD require the phase ...locking technique to coherently control the twin light fields, inevitably complicating the system with extra fiber channels and peripheral hardware. Here, we propose and demonstrate an approach to recover the single-photon interference pattern and realize TF-QKD without phase locking. Our approach separates the communication time into reference frames and quantum frames, where the reference frames serve as a flexible scheme for establishing the global phase reference. To do so, we develop a tailored algorithm based on fast Fourier transform to efficiently reconcile the phase reference via data postprocessing. We demonstrate no-phase-locking TF-QKD from short to long distances over standard optical fibers. At 50-km standard fiber, we produce a high secret key rate (SKR) of 1.27 Mbit/s, while at 504-km standard fiber, we obtain the repeaterlike key rate scaling with a SKR of 34 times higher than the repeaterless secret key capacity. Our work provides a scalable and practical solution to TF-QKD, thus representing an important step towards its wide applications.
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