An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Background The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. Methods 6–8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. Results We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone ( P < 0.001), as well as the levels of the myocardial injury markers CK-MB and ROS ( P < 0.001); it also significantly increased plasma NO levels. Pathological staining also showed that diabetic rats benefited significantly from the combination therapy. Further mechanistic studies confirmed this finding. The protein phosphorylation levels of PI3K/Akt signalling pathway in the heart tissue of diabetic I/R rats were significantly higher after the combination treatment than after one treatment alone (all P < 0.05). Conclusion I-Post combined with nicorandil treatment maintains effective cardioprotection against diabetic myocardial I/R injury by activating the PI3K/Akt signalling pathway.
<b><i>Background:</i></b> Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. <b><i>Summary:</i></b> Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. <b><i>Key Messages:</i></b> More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.
Objective
To explore the impact of gene methylation in Shh/Bmp4 signaling pathway on the enteric nervous system (ENS) in rectal end of fetal mice with anorectal malformations (ARM).
Methods
A total of 15 Sprague Dawley pregnant rats were randomly divided into 3 groups of ETU, ETU+ 5-azaC and normal.At gestational Day 10, ETU and ETU+ 5-azaC groups received 1% ETU via gavage while ETU+ 5-azaC group had an intraperitoneal injection of 5-azaC (3 mg/kg). At gestational Day 12, cesarean section was performed.The incidence of ARMs, the content of DNA methyltransferase (DNMT1, DNMT3a & DNMT3b), the methylation status of Shh gene promoter region and the expression of key components in Shh/Bmp4 signaling pathway in rectal end of fetal mice were detected by polymerase chain reaction (PCR), immunohistochemistry and Western blot.
Results
a) The incidence of ARMs was 98.3% and 64.9% in ETU and ETU+ 5-azaC groups respectively and there were statistical differences (P<0.0001); b) The expression of DNMTs (DNMT1, DNMT3a & DNMT3b) was significantly higher in rectal tissue of ETU/ETU+ 5-azaC group than that of control group (DNMT1: ETU vs normal, 3.63±0.26 vs 1.00±0.09, P<0.0001; ETU+ 5-azaC vs normal, 2.33±0.27 vs 1.00±0.09, P=0.0003; DNMT3a: ETU vs normal, 3.05±0.28 vs 1.00±0.29, P=0.0003; ETU+ 5-azaC vs normal, 2.20±0.07 vs 1.00±0.29, P<0.0001; DNMT3b: ETU vs normal, 2.62±0.49 vs 1.00±0.26, P=0.0005; ETU+ 5-azaC vs normal, 2.33±0.30 vs 1.00±0.26, P=0.0028). The expression of DNMT1/DNMT3a was significantly higher in rectal tissue of ETU group than that in ETU+ 5-azaC group (DNMT1: 3.63±0.26 vs 2.33±0.27, P=0.0025; DNMT3a: 3.05±0.28 vs 2.20±0.07, P=0.0033) while no significant inter-group difference existed in the expression level of DNMT3b; c) The methylation level of Shh gene promoter was significantly higher in rectal end of ETU group than that in ETU+ 5-azaC/control group (ETU vs ETU+ 5-azaC: 7.13±0.66 vs 5.20±1.21, P=0.0263; ETU vs normal: 7.13±0.66 vs 2.81±0.27, P<0.0001) and ETU+ 5-azaC group was obviously higher than control group (5.20±1.21 vs 2.81±0.27, P=0.0300); d) Shh/Bmp4 expression level was significantly lower in rectal end of ETU/ETU+ 5-azaC group than that of control group (Shh: ETU vs normal, 1.00±0.23 vs 3.81±0.25, P<0.0001; ETU+ 5-azaC vs normal, 2.19±0.60 vs 3.81±0.25, P=0.0121; Bmp4: ETU vs normal, 1.00±0.18 vs 4.91±0.36, P<0.0001; ETU+ 5-azaC vs normal, 2.16±0.23 vs 4.91±0.36, P<0.0001) and Shh/Bmp4 expression level in ETU group was also lower than that in ETU+ 5-azaC group (Shh: 1.00±0.23 vs 2.19±0.60, P=0.011; Bmp4: 1.00±0.18 vs 2.16±0.23, P=0.0019); e) S-100 labeled submucosa and intermuscular nerve plexus in rectal tissue of ETU group significantly decreased compared with that of normal group (P<0.0001) and ETU+ 5-azaC group was significantly different from that in ETU group (P<0.0001). The c-kit labeled Cajal stromal cells and NSE labeled ganglion cells were not obviously expressed in rectum of ETU/ETU+ 5-azaC group.
Conclusions
The methylation status of rectal end in ARM rat model may be changed by interventions.The low methylation level of Shh gene may promote the expression of key components in Shh/Bmp4 signaling pathway and the number of S-100 labeled nerve plexus significantly increases and promotes the development of rectal ENS.
Key words:
Anus, abnormalities; Rectum, abnormalities; DNA methylation; Shh/Bmp4 signaling pathway; Enteric nervous system
Two-color stimulated Raman scattering (SRS) microscopy with label-free mapping of lipid/protein distributions has shown promise in virtual histology. Despite previous demonstrations of SRS in tumor delineation and diagnosis, the speed and efficiency of the current technique requires further improvements for practical use. Here, we integrate parallel dual-phase SRS detection with strip mosaicing, which reduces the imaging time of a whole mouse brain section from 70 to 8 minutes. We further verified our method in imaging fresh human surgical tissues, showing its great potential for rapid SRS histology, especially for large scale, large quantity imaging tasks.
Rapid histology of brain tissues with sufficient diagnostic information has the great potential to aid neurosurgeons during operations. Stimulated Raman Scattering (SRS) microscopy is an emerging label-free imaging technique, with the intrinsic chemical resolutions to delineate brain tumors from normal tissues without the need of time-consuming tissue processing. Growing number of studies have shown SRS as a “virtual histology” tool for rapid diagnosis of various types of brain tumors. In this review, we focus on the basic principles and current developments of SRS microscopy, as well as its applications for brain tumor imaging.
Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organs and leading to diverse features. It is reported to be at a two to threefold higher risk of death in SLE than the general population.1 Common causes of death include infection, cardiovascular disease, and renal disease.2 The exact pathogenetic mechanisms of SLE are yet unclear. Since the clinical presentation is known to vary across geographical locations, genders, and ethnicity, researches from various sites covering different population groups can help gain valuable insight regarding clinical characteristics of the disease worldwide as well as in particular groups.3 Lupus takes a chronic course with remitting and relapsing patterns.4, 5 Furthermore, repeated flares can lead to chronic damage accrual, especially for lupus nephritis patients. Hence, instituting measures to ensure prompt diagnosis of flares will protect against damage development.6, 7 Therefore, it may help clinical management to further understand the unique characteristics associated with flares during the course of lupus. And a real-world study is useful in reflecting on the real situations in the clinical setting. SLE patients, who visited the inpatients department (IPD) and outpatient department (OPD) of the Department of Rheumatology and Immunology at First Affiliated Hospital of Kunming Medical University and fulfilled the inclusion criteria mentioned below, were enrolled for the study. Patients who were newly diagnosed and those already under treatment were both recruited in the study. Patients who did not show up for follow-up visits during the study period were defined as drop-outs. This study fulfills the recommendations put forth by the Institutional Review Board of Kunming Medical University. All patients underwent regular history taking and physical examinations (all clinical data collected are shown in Table 1). Patients who experienced at least one episode of flare were recorded as flare, and patients without any episode of flare during the observation period were recorded as censored. Features specific to SLE were noted and definitions were accepted and incorporated by SLICC in their 2012 classification criteria for SLE.8 ANA was examined with the indirect immunofluorescence method with Hep-2 cells as substrates. Anti-dsDNA antibody was also detected using indirect immunofluorescence method and anti-Smith antibody was detected by western blot. Hypocomplementemia was defined as the presence of either low C3 or C4 or both. According to the reference value of the test, low C3 was defined as a serum level less than 0.7 g/L as well as C4 below 0.1 g/L as low C4. Disease activity was measured by SLEDAI-2K scores.9 For research, a score of 3 or 4 has been used as an appropriate cutoff to differentiate active versus inactive disease.10, 11 For patients with active disease at baseline and improved SLEDAI-2K scores in subsequent visits, the minimum SLEDAI-2K score in follow-up was considered as the new baseline for re-evaluating flare. SLEDAI-2K scores ≥3 points increase in subsequent visits from new baseline scores was defined as flare, and the period from the new baseline to the flare was calculated as time to flare.12 Statistical software IBM SPSS version 26 was used for analysis. A p value of <.05 was taken to be statistically significant. Kaplan–Meier analysis was used to estimate the difference in time to flare between binary variables. Univariate analysis with log-rank test was done to seek potential factors affecting flare. Multivariate analysis with COX proportional hazards regression was carried out to identify adjusted predictors for the occurrence of flare. Data were collected from 199 patients with ages ranging from 18 to 59 years old (31.9 ± 9.5), out of which 94.97% (189) were female and 5.03%10 were male. A detailed description of the patient's clinical characteristics and treatments at baseline has been produced in Table 1. Among all 199, the flare was seen in 31.7% (63) patients, whereas 68.3% experienced no flare during the study period (585 patient-days), and the average follow-up duration was 159.5 days. The predicted percentage with the flare at 182 and 365 days was 21.4% and 56.5% (shown in Figure 1A). Gender (p = .016) and anti-dsDNA antibody (p = .042) were revealed to be potentially significant predictors of flare, and acute rash (p = .072) came close to being a potential predictor of flare. (Comparison of time to flare among factors is shown in Figure 1B–D). (Shown in Table S1). Potential predictors of time to flare identified by the Kaplan–Meier analysis. Acute rash, anti-dsDNA antibody, and gender associated with flare were plugged into the COX regression model as variation, time to flare/censor was set as time, and flare was set as status. Acute rash (p = .026) and anti-dsDNA antibody (p = .047) were found to be independent predictors of flare in lupus patients. On the other hand, the male gender (p = .042) was found to be more susceptible to flare (shown in Table S2). In this study, as time extension, the drop-out rate increased. A high drop-out rate could be the result of this being a real-world study in which patients were not strictly advised to follow-up at a fixed time. In natural clinical working in our IPD, patients with active or severe disease or suffer from new symptom(s) usually are asked to come back to the clinic every month after discharge, as well as patients with the mild disease come back every 3 months, and patients in remission visit every 6–12 months, or go to the local hospital to complete visit. Hence, the high drop-out rate in this study may result from that most patients in remission make less frequent visits during follow-up, or go to local hospitals. Even so, drop-outs due to non-adherence are concerning, in that non-compliant behavior may increase the risk for flares and morbidity in SLE.13 Physicians should devote more attention to counseling non-compliant patients to ensure better follow-up and management. In this study, acute rash conferred two times higher risk of developing flare. This was similar to a study done by Nikpour et al.14 And we found an anti-dsDNA antibody to be associated with a twofold higher risk of developing flare earlier in the course of the disease. Peng et a found the anti-dsDNA antibody to be a potential predictor of flare in univariate analysis.15 A prospective study conducted by Petri et al. found baseline anti-dsDNA antibodies to be associated with only hematological flares 1 year after the start of the study, but not with global flares.12 Similarly, Nickpour et al. found that antibodies were able to predict only hematological and renal flares, but not successive global flares in disease activity.15 Interestingly, the male gender was seen as more susceptible to flare. Male lupus patients faced 2.5 times the hazards of a female patient developing flare and had a shorter flare-free time. This study was limited by the small sample size as well as the short duration of follow-up. A study conducted for a longer duration of time as well as recruiting patients from both IPD and OPD may be more useful for detecting any flare, damage accrual, and survival of patients over time, which could identify predictors of SLE outcome with better precision. In conclusion, the increase in the onset of flare in lupus is gradual. Acute rash and anti-dsDNA antibody at baseline are recognized as factors predicting time to flare. And male gender is a risk factor for earlier flare. This work is supported by grants from the National Natural Science Foundation of China (32270947, 82060259 and 81760296), Yunnan Province High-level health technical talents (leading talents) (L-2019004, L2019011), Yunnan Province Special Project for Famous Medical Talents of the “Ten Thousand Talents Program” (YNWR-MY-2018-040, YNWR-MY-2018-041), and Yunnan Province Clinical Center for Skin Immune Diseases (ZX2019-03-02), the Funding of Ministry of Science and Technology of Yunnan Province (2018ZF016). XW, BU, and YY contributed equally to this work and were responsible for the management of the research and drafting of the article. XW and BU were responsible for recruiting and following up with patients. SL, RC, and YC provided invaluable research consultation. RB contributed to re-arrange the following up data used in revision. JX oversaw the entire research project and the writing of the manuscript. We thank all the study participants for their participation. None. The data that support the findings of this study are available from the corresponding author upon reasonable request. Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
There is a huge impact on the image quality of Micro‐OLED display in the production, which looks like a white ring or white dot under the microscope. This phenomenon is called Circular Mura in this paper. The root caucus locks in the common effect of residual sulfur hexafluoride (SF6) and the solution of ethyl ketocy clazocine (EKC) on the anode surface. Circular Mura was finally successfully solved through equipment modification and process optimization.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)