Advancing Natural Product Discovery: A Structure-Oriented Fractions Screening Platform for Compound Annotation and Isolation.

Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from Aspergillus sp. GE2-6, revealing 27 undescribed compounds. Compounds 7-22 were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (5). Compounds 23 and 24 were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A (1) and asperphenalenone E (28) exhibited potent anti-influenza (PR8) activities, with IC50 values of 21.9 ± 0.2 and 12.9 ± 0.1 µM, respectively. Meanwhile, asperphenalenone (26) and asperphenalenone P (27) treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC50 values of 6.1 ± 0.9 and 4.6 ± 1.1 µM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.

Perceived experts are prevalent and influential within an antivaccine community on Twitter.

Perceived experts (i.e. medical professionals and biomedical scientists) are trusted sources of medical information who are especially effective at encouraging vaccine uptake. The role of perceived experts acting as potential antivaccine influencers has not been characterized systematically. We describe the prevalence and importance of antivaccine perceived experts by constructing a coengagement network of 7,720 accounts based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the antivaccine community. Perceived experts had a sizable presence across the coengagement network, including within the antivaccine community where they were 9.8% of individual, English-language users. Perceived experts within the antivaccine community shared low-quality (misinformation) sources at similar rates and academic sources at higher rates compared to perceived nonexperts in that community. Perceived experts occupied important network positions as central antivaccine users and bridges between the antivaccine and provaccine communities. Using propensity score matching, we found that perceived expertise brought an influence boost, as perceived experts were significantly more likely to receive likes and retweets in both the antivaccine and provaccine communities. There was no significant difference in the magnitude of the influence boost for perceived experts between the two communities. Social media platforms, scientific communications, and biomedical organizations may focus on more systemic interventions to reduce the impact of perceived experts in spreading antivaccine misinformation.

Nondestructive estimation method of live chicken leg weight based on deep learning.

In the broiler-breeding industry, phenotype determination is critical. Leg weight is a fundamental indicator for breeding, and noninvasive testing technology can reduce damage to animals. This study proposes a broiler leg weight estimation system comprising a weight-estimation model and computed tomography (CT) acquisition equipment. The weight-estimation model can automatically process the scan results of live broiler chickens from the CT acquisition equipment. The weight-estimation model comprises an improved you-only-look-once (YOLOv5) segmentation algorithm and a random forest fitting network. The segmentation head was introduced into the YOLOv5 network, combined with a multiscale attention mechanism and an atrous spatial pyramid pooling architecture, and a new network model, YOLO- measuring chicken leg weight (YOLO-MCLW), was proposed to improve segmentation efficiency and accuracy. Morphological parameters were extracted from the obtained mask image, and a random forest network was used for fitting. The experiments show that the system exhibited an average absolute error of 7.27 g and an average percentage error of 4.82% in tests on 50 individual legs of 25 broiler chickens. The prediction R2 of broiler chicken legs can reaches 88.98%, the segmentation intersection over union result reaches 95.45%, and 37.04 images are processed per second. This system provides technical support for the part determination of broiler chickens in commercial breeding.

An algorithm for power transmission line fault detection based on improved YOLOv4 model.

In response to the escalating demand for real-time and accurate fault detection in power transmission lines, this paper undertook an optimization of the existing YOLOv4 network. This involved the substitution of the main feature extraction network within the original YOLOv4 model with a lighter EfficientNet network. Additionally, the inclusion of Grouped Convolution modules in the feature pyramid structure replaced conventional convolution operations. The resulting model not only reduced model parameters but also effectively ensured detection accuracy. Moreover, in enhancing the model's reliability, data augmentation techniques were employed to bolster the robustness of the power transmission line fault detection algorithm. This optimization further utilized the DIoU loss function to stabilize target box regression. Comparative experiments demonstrated the improved YOLOv4 model's superior performance in terms of loss function optimization while significantly enhancing detection speed under equivalent configurations. The parameter capacity was reduced by 81%, totaling merely 43.65 million, while the frame rate surged by 85% to achieve 24 frames per second. These experimental findings validate the effectiveness of the algorithm.

The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.

NADPH oxidase, as a major source of intracellular reactive oxygen species (ROS), assumes an important role in the immune response and oxidative stress response of the body. NADPH 9 oxidase 2 (NOX2) is the first and most representative member of the NADPH oxidase family, and its effects on the development of tumor cells are gaining more and more attention. Our previous study suggested that NCF4 polymorphism in p40phox, a key subunit of NOX2, affected the outcome of diffuse large B-cell lymphoma patients treated with rituximab. It hypothesized that NOX2-mediated ROS could enhance the cytotoxic effects of some anti-tumor drugs in favor of patients with tumors. Several reviews have summarized the role of NOX2 and its congeners-mediated ROS in anti-tumor therapy, but few studies focused on the relationship between the expression of NOX2 and anti-tumor drug resistance. In this article, we systematically introduced the NOX family, represented by NOX2, and a classification of the latest inhibitors and agonists of NOX2. It will help researchers to have a more rational and objective understanding of the dual role of NOX2 in tumor drug resistance and is expected to provide new ideas for oncology treatment and overcoming drug resistance in cancer.

Kinematic analysis of countermovement jump performance in response to immediate neuromuscular electrical stimulation.

The purpose of this study was to examine the effect of neuromuscular electrical stimulation (NMES) immediate intervention training on the countermovement jump (CMJ) height and to explore kinematic differences in the CMJ at each instant. A total of 15 male students who had never received electrical stimulation were randomly selected as the research participants. In the first test, the CMJ performance was completed with an all-out effort. The second experiment was best performed immediately to complete the CMJ operation after NMES for 30 min. Both experiments used a high-speed camera optical capture system to collect kinematic data. The results of this experiment revealed that after im-mediate NMES training, neuromuscular activation causes post-activation potentiation, which increases the height of the center of gravity of the CMJ and affects the angular velocity of the hip joint, the velocity and acceleration of the thigh and the shank and the velocity of the soles of the feet. The use of NMES interventional training based on the improvement of technical movements and physical exercises is recommended in the future.

The role and influence of perceived experts in an anti-vaccine misinformation community.

The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts who spread anti-vaccine misinformation may be warranted.

Estimation and sensitivity analysis of a COVID-19 model considering the use of face mask and vaccination.

To model the COVID-19 infection and develop effective control measures, this paper proposes an SEIR-type epidemic model considering the impact of face-mask wearing and vaccination. Firstly, the effective reproduction number and the threshold conditions are obtained. Secondly, based on the data of South Korea from January 20, 2022 to March 21, 2022, the model parameters are estimated. Finally, a sensitivity analysis and the numerical study are conducted. The results show that the face-mask wearing is associated with [Formula: see text] and [Formula: see text] reductions in the numbers of cumulative cases and newly confirmed cases, respectively, after a period of 60 days, when the face mask wearing rate increases by [Formula: see text]. Furthermore, the vaccination rate is associated with [Formula: see text] and [Formula: see text] reductions in the numbers of cumulative cases and the newly confirmed cases, respectively, after the same period of 60 days when the vaccination rate is increased by [Formula: see text]. A combined measure involving face-mask wearing and vaccination may be more effective and reasonable in preventing and controlling this infection. It is also suggested that disease control departments should strongly recommended the wearing of face masks s as well as vaccination to prevent the unvaccinated people from becoming infected.

A Velocity Measurement Method Based on Charge Induction.

In this paper, based on the principle of charge induction, a new velocity measurement method is proposed. A moving target generates a low-frequency electric field, which can be induced with an electrode and detection frontend. Velocity measurements are achieved by placing two electrodes at a fixed distance to detect the characteristic times. Firstly, the electric field generated by the moving target is modeled, and the theoretical output of the detection frontend is obtained via a simulation of the target passing by a single electrode. Then, according to the theoretical output, the velocity measurement simulation results of double electrodes are given for various driving conditions, such as a single vehicle driving in a single lane, a single vehicle changing lanes, two vehicles driving close together, and a multiple-vehicle situation. Finally, the above driving conditions are experimentally verified in sunny weather, windy and rainy weather, and a night environment.

[Protective effect of total flavonoids of Rhododendron simsii on focal cerebral ischemia-reperfusion injury through SOCE pathway in rats].

This paper explored the protective effect of total flavonoids of Rhododendron simsii(TFR) on focal cerebral ischemia-reperfusion injury(CIRI) in rats and its relationship with the store-operated calcium entry(SOCE) pathway regulated by stromal intera-ction molecule(STIM) and calcium release-activated calcium modulator(Orai).Rats were randomly assigned into the sham group, model(middle cerebral artery occlusion, MCAO) group, TFR(60 mg·kg~(-1)) group, TFR(60 mg·kg~(-1))+SOCE pathway inhibitor 2-aminoethoxydiphenyl borate(2-APB, 2.5 mg·kg~(-1)) group, and 2-APB(2.5 mg·kg~(-1)) group.The rats in the sham group and MCAO group were administrated with normal saline, and those in the TFR group and TFR+2-APB group were administrated with TFR(60 mg·kg~(-1)) by gavage for 14 days until sampling.The rats in the 2-APB group and TFR+2-APB group were intraperitoneally injected with 2-APB(2.5 mg·kg~(-1)) after operation.The levels of interleukin-1(IL-1), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) in serum were measured by ELISA.The cerebral infarction and the pathological status of ischemic brain tissue were detected via TTC staining and HE staining, respectively.The protein and mRNA levels of STIM1, STIM2, Orai1, cysteinyl aspartate specific proteinase 3(caspase-3), and protein kinase B(PKB) in brain tissue were respectively determined by Western blot and RT-qPCR.The growth of brain neurons in each group was observed via immunofluorescence method.The results showed that compared with the MCAO group, TFR lowered the levels of IL-1, IL-6 and TNF-α in serum and the score of neurological function, ameliorated the pathological injury of brain tissue, and decreased the infarct size.Moreover, TFR up-regulated the mRNA and protein levels of STIM1, STIM2, Orai1, and PKB, down-regulated those of caspase-3 in brain tissue, and increased the double-labeled positive cells under fluorescence microscope.However, the above effects were significantly weakened by the addition of 2-APB, a SOCE inhibitor.The results suggested that TFR may play a protective role against focal cerebral ischemia-reperfusion injury by up-regulating the expression of SOCE-related signal molecules, promoting neurogenesis around the ischemic area, improving the survival state of neurons, and redu-cing the activity of inflammatory mediators.

Efficient method for whole-breast irradiation therapy using Halcyon linear accelerators.

BACKGROUND: The Halcyon is a linear accelerator-based treatment machine designed for a high-throughput simplified workflow. The machine features a compact jawless design, dual-layer multileaf collimators, and a single 6-MV flattening filter-free (FFF) beam. However, the machine's 6-MV FFF beam may restrict its applicability to conventional techniques, such as field-in-field (FiF) radiotherapy, for breast cancer treatment. This study developed a practical and efficient hybrid method for imaging, planning, and irradiation procedures for whole-breast irradiation using Halcyon linear accelerators. MATERIALS AND METHODS: The proposed method involves five major steps: (1) field arrangement, (2) planning target volume (PTV) generation and evaluation, (3) basal plan generation, (4) inverse planning intensity-modulated radiation therapy plan generation, and (5) plan evaluation and irradiation. The PTV is generated using isodose curves plotted on the basis of tangential fields, which are applied to create a basal plan. Subsequently, a basal-dose-compensation approach is applied to further optimize the treatment plan. This efficient workflow necessitates executing only one onboard cone-beam computed tomography procedure. This study included 10 patients with early-stage breast cancer who were treated at our center. The performance of the proposed method was evaluated by comparing its corresponding irradiation time and dose statistics with those derived for a dynamically flattened beam-based FiF (DFB-FiF) method. RESULTS: All plans were normalized to ensure that 98% of the prescribed dose covered 95% of the PTV. On average, the global maximum doses in the proposed and DFB-FiF methods were lower than 106%. The homogeneity index for right-sided (left-sided) breast cancer was 0.053 (0.056) in the proposed method and 0.073 (0.076) in the DFB-FiF method. The dose statistics of normal tissues, including the contralateral breast, heart, and lungs, were comparable between the methods. However, the irradiation time per monitor unit in the proposed method was approximately five times faster than that in the DFB-FiF method, but the planning time and complexity were similar between the methods. CONCLUSIONS: This study developed and evaluated an efficient and practical hybrid method for whole-breast irradiation using the Halcyon. This method can significantly reduce the irradiation time, while providing comparable dose statistics to the DFB-FiF method.

Modeling for COVID-19 with the contacting distance.

COVID-19 is a public health emergency for human beings and brings some very harmful consequences in social and economic fields. In order to model COVID-19 and develop the effective control measures, this paper proposes an SEIR-type epidemic model with the contacting distance between the healthy individuals and the asymptomatic or symptomatic infected individuals, and the immigration rate of the healthy individuals since the contacting distance and the immigration rate are two critical factors which determine the transmission of COVID-19. Firstly, the threshold values of the contacting distance and the immigration rate are obtained to analyze the presented model. Secondly, based on the data from January 10, 2020, to March 18, 2020, for Wuhan city, all parameters are estimated. Finally, based on the estimated parameters, the sensitivity analysis and the numerical study are conducted. The results show that the contacting distance and the immigration rate play an important role in controlling COVID-19. Meanwhile, the extinct lag decreases as the contacting distance increases and/or the immigration rate decreases. Our study could give some reasonable suggestions for the health officials and the public and provide a theoretical issue for globally controlling the COVID-19 pandemic.

Knowledge Injected Prompt Based Fine-tuning for Multi-label Few-shot ICD Coding.

Automatic International Classification of Diseases (ICD) coding aims to assign multiple ICD codes to a medical note with average length of 3,000+ tokens. This task is challenging due to a high-dimensional space of multi-label assignment (tens of thousands of ICD codes) and the long-tail challenge: only a few codes (common diseases) are frequently assigned while most codes (rare diseases) are infrequently assigned. This study addresses the long-tail challenge by adapting a prompt-based fine-tuning technique with label semantics, which has been shown to be effective under few-shot setting. To further enhance the performance in medical domain, we propose a knowledge-enhanced longformer by injecting three domain-specific knowledge: hierarchy, synonym, and abbreviation with additional pretraining using contrastive learning. Experiments on MIMIC-III-full, a benchmark dataset of code assignment, show that our proposed method outperforms previous state-of-the-art method in 14.5% in marco F1 (from 10.3 to 11.8, P<0.001). To further test our model on few-shot setting, we created a new rare diseases coding dataset, MIMIC-III-rare50, on which our model improves marco F1 from 17.1 to 30.4 and micro F1 from 17.2 to 32.6 compared to previous method.

Ionothermal synthesis of octahedral lanthanoid coordination networks exhibiting slow magnetization relaxation and efficient photoluminescence.

An ionothermal reaction of lanthanoid salts with tetraethyl-p-xylenediphosphonate (tepxdp) in ionic liquids, such as choline chloride and malonic acid, resulted in the formation of three novel lanthanoid-organic coordination networks with the formula [Ln(H2pxdp)1.5]n {Ln = Tb (1), Dy (2) and Ho(3) and H4pxdp = p-xylenediphosphonic acid}. The structures, photoluminescence and magnetic properties of the three compounds were investigated in detail. Single crystal X-ray diffraction analysis revealed that the three compounds are isostructural and the Ln3+ ions show an unusual six-coordinate environment with the {LnO6} octahedron. In these compounds, each {PO3C} tetrahedron is corner-shared with two {LnO6} octahedra and each {LnO6} octahedron is corner-shared with six {PO3C} tetrahedra, thus forming an inorganic layer in the crystallographic ab plane. The inorganic layers are further connected by a phenyl group, leading to a three-dimensional framework. Compound 1 exhibits the strong and characteristic emission of TbIII with an impressive quantum yield of 46.2%. Detailed magnetic analysis demonstrated that compound 2 displays a slow magnetic relaxation of magnetization with multiple relaxation mechanisms. The anisotropic energy barrier and the pre-exponential factor τ0 are 51.2 K and 3.9 × 10-7 s, respectively, in the presence of a direct-current field of 500 Oe. This work demonstrates a successful strategy to isolate octahedrally coordinated lanthanoid complexes through ionothermal synthesis to exhibit the single-ion-magnet-like behaviour and photoluminescence properties.

Fetuin-A in Infants Born Small- or Large-for-Gestational-Age.

Fetuin-A is a multifunctional glycoprotein that has been implicated in insulin resistance and bone metabolism. We assessed whether fetuin-A is associated with poor or excessive fetal growth. In the Shanghai Birth Cohort, we conducted a nested case-control study of 60 trios of small-for-gestational-age (SGA, birth weight <10th percentile), optimal-for-gestational-age (OGA, 25-75th, the reference) and large-for-gestational-age (LGA, >90th percentile) infants matched by sex and gestational age. Cord plasma concentrations of fetuin-A and fetal growth factors [insulin, proinsulin, insulin-like growth factor (IGF)-I and IGF-II] were measured. Cord plasma fetuin-A concentrations were higher in SGA (809.4 ± 306.9 µg/ml, P = 0.026) and LGA (924.2 ± 375.9 µg/ml, P < 0.001) relative to OGA (680.7 ± 262.1 µg/ml) newborns, and were not correlated to insulin, proinsulin, IGF-I and IGF-II (all P > 0.2). Higher fetuin-A concentrations were associated with increased risks of SGA [OR = 1.67 (1.08-2.58) per SD increment, P = 0.024] and LGA [OR = 2.36 (1.53-3.66), P < 0.001]. Adjusting for maternal and neonatal characteristics and fetal growth factors, the elevated risk changed little for LGA [adjusted OR = 2.28 (1.29-4.01), P = 0.005], but became non-significant for SGA (P = 0.202). Our study is the first to demonstrate that fetuin-A may be involved in excessive fetal growth. This association is independent of fetal growth factors.

Target-triggered configuration change of DNA tetrahedron for SERS assay of microRNA 122.

A surface-enhanced Raman scattering (SERS) method is proposed for the assay of microRNA 122 based on configuration change of DNA tetrahedron. Firstly, a DNA tetrahedron was self-assembled with one vertex labeled with toluidine blue (TB). Then, it was immobilized on the porous Ni/SiO2@PEI@Au as a SERS platform, which was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). At this time, the DNA tetrahedron was contracted; so, the TB is close to AuNPs and the Raman signal is high. When target microRNA 122 existed, with the nicking enzyme amplification strategy, a great deal of DNA signal chains (S5) was obtained, which can extend the contracted DNA tetrahedron and change it into a three-dimensional DNA tetrahedron. In this case, the TB was far from AuNPs, resulting in a lower Raman signal. Due to the configuration change of DNA tetrahedron, the Raman signal at 1624 cm-1 (with the excitation wavelength of 633 nm) has a linear relationship with the logarithm concentration of microRNA 122. This SERS assay has high sensitivity for microRNA 122 with a determination range from 0.01 aM to 10 fM and a detection limit of 0.009 aM. The recoveries from spiked samples were in the range 95 to 109%. This SERS strategy is designed based on the target-triggered configuration change of DNA tetrahedron, which can give new insight for DNA structures in bioanalysis. Graphical abstract A sensitive surface-enhanced Raman scattering (SERS) biosensor was developed to detect microRNA 122 using the configuration change of DNA tetrahedron to indirectly control the position of TB and hot spot.

Fetuin-A and fetal growth in gestational diabetes mellitus.

OBJECTIVE: Fetuin-A is a glycoprotein produced by hepatocytes and has been associated with insulin resistance and bone growth in postnatal life. Gestational diabetes mellitus (GDM) is a condition characterized by insulin resistance. It is unclear whether GDM may affect cord blood fetuin-A levels and whether fetuin-A is associated with fetal growth. RESEARCH DESIGN AND METHODS: In a nested case-control study of 153 matched pairs of neonates of mothers with GDM and euglycemic pregnancies in the Shanghai Birth Cohort, we evaluated cord blood fetuin-A in association with GDM and fetal growth. RESULTS: Comparing the newborns of GDM versus euglycemic mothers, cord blood fetuin-A concentrations were similar (mean±SD: 783.6±320.0 vs 754.8±281.9 µg/mL, p=0.53), while insulin-like growth factor (IGF)-I (76.6±27.8 ng/mL vs 68.1±25.1 ng/mL, p=0.008) and IGF-II (195.3±32.5 ng/mL vs 187.5±30.8 ng/mL, p=0.042) concentrations were higher. Cord blood fetuin-A was not correlated with insulin, IGF-I or IGF-II. Cord blood fetuin-A was negatively correlated with birth weight (r=-0.19, p=0.025) and birth length (r=-0.24, p=0.005) z scores in GDM pregnancies, while there were no significant correlations in euglycemic pregnancies (tests for interaction: p=0.014 for birth length, p=0.013 for birth length). Adjusting for maternal and neonatal characteristics, the differential associations remained. CONCLUSIONS: GDM was not associated with cord blood fetuin-A levels. Fetuin-A was negatively associated with fetal growth in GDM but not in euglycemic pregnancies. This novel observation suggests a GDM-conditional negative correlation of fetuin-A with fetal growth.

Adenosine triphosphate responsive metal-organic frameworks equipped with a DNA structure lock for construction of a ratiometric SERS biosensor.

A novel ratiometric surface-enhanced Raman scattering (SERS) biosensor was constructed based on stimuli-responsive DNA functionalized metal organic frameworks (MOFs) for detection of adenosine triphosphate (ATP). As a result, the detection range of ATP was 1 nM to 200 nM with a detection limit of 0.4 nM. The ratiometric SERS biosensor strategy offers a lower detection limit and exhibits a more enhanced performance than the typical SERS detection based on single signal response, which may have potential for detection of other biomolecules or metal ions.

[Protective effects of gliclazide on myocardium of diabetic rats and its mechanism].

Objective: To investigate the protective effects of gliclazide on myocardium of diabetic rats and its possible mechanisms. Methods: Sixty healthy SD rats were randomly divided into two groups: normal group (NC, n=10) and model group (n=50). Rats in model group were fed with high glucose and high fat diet for 4 weeks and then intraperitoneally injected with STZ (45 mg/kg) to establish a diabetic model and randomly selected FBG ≥ 16.7 mmol / L as a successful diabetes model. Thirty-eight diabetic rats were randomly divided into model group (MC, n=9), gliclazide group (Glic, 80 mg/kg, n=10), glibenclamide group (Glib, 2.5 mg/kg, n=10) and fasudil group (Fas, 10 mg/kg, n=9). NC group and MC group were given equal volume distilled water by gavage, Glic group and Glib group were treated with gliclazide or glibenclamide by gavage, and the Fas group was treated with fasudil by intraperitoneal injection. Rats in each group were given once a day and recorded body mass and fasting blood glucose (FBG) weekly for 8 weeks. At the end of the experiment, the heart weight was measured, and the heart weight index (HWI) was calculated; the contents of glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), the level of serum malondialdehyde MDA) and the activity of superoxide dismutase (SOD) were measured; the pathological changes of myocardial tissue were observed by HE and Masson staining. The expressions of RhoA, ROCK1, eNOS, Bcl-2 and Bax protein were detected by Western blot. Results: Compared with NC group, in MC group, the levels of FBG, HWI, HbA1c, TC, TG, LDL-C, MDA, myocardial collagen deposition and cardiomyocyte apoptosis rate and RhoA, ROCK1, Bax protein in myocardial tissue were increased significantly, while the SOD activity, the levels of HDL-C, eNOS, Bcl-2 and body weight were decreased significantly (P＜0.01). Compared with MC group, Glic treatment decreased the levels of FBG, HWI, HbA1c, LDL-C, TG, TC and MDA, increased the levels of SOD activity and HDL-C (P＜0.01 or P＜0.05); decreased myocardial collagen deposition, inhibited cardiomyocyte apoptosis (P ＜ 0.01); decreased the expression levels of RhoA, ROCK1 and Bax protein; increased the levels of eNOS and Bcl-2 protein (P＜0.01 or P＜0.05). Compared with Glic group, in Glib group, the levels of blood lipids, BM, FBG, HWI, MDA, myocardial fibrosis and cardiomyocyte apoptosis rate were increased, the levels of SOD and Bcl-2 were decreased, and the expressions of RhoA, ROCK1 and Bax in myocardial tissue were upregulated (P＜0.01 or P＜0.05). Conclusion: Gliclazide significantly alleviates myocardial injury and reduces myocardial apoptosis in diabetic rats, and its mechanism may be related to lowering blood glucose, improving oxidative stress and regulating RhoA / ROCK1 / eNOS signaling pathway.

Combining Porous Magnetic Ni@C Nanospheres and CaCO3 Microcapsule as Surface-Enhanced Raman Spectroscopy Sensing Platform for Hypersensitive C-Reactive Protein Detection.

In this work, we have designed an efficient and rapid surface-enhanced Raman spectroscopy (SERS) immunosensor for a supersensitive analysis of hypersensitive C-reactive protein (hs-CRP) with a label-free method by combining porous magnetic Ni@C nanospheres to aggregate together for simplifying the experiment operation and CaCO3 microcapsule to encapsulate rhodamine B as the Raman signal. The final solution containing the signal molecule was dropped on the Ag nanoparticle substrate, and the signal could be enhanced by Ag particles. First, rhodamine B was encapsulated in the CaCO3 microcapsule when it precipitated to form microcubes. Subsequently, the porous CaCO3 microcapsule was assembled layer by layer with poly(ether imide) (PEI) and a second antibody to obtain rhodamine B@CaCO3@PEI@Ab2. Then, the functionalized magnetic Ni@C nanospheres were prepared to immobilize the primary antibody (Ab1). Finally, the immunosensor was fabricated by the sandwiched antibody-antigen interactions. Compared to the DNA hydrogel, the low-cost CaCO3 microcapsule would be rapidly dissolved by ethylene diamine tetraacetic acid, releasing rhodamine B to produce a strong Raman signal for a rapid and efficient detection of hs-CRP. With the hs-CRP concentration ranging from 0.1 pg mL-1 to 1 µg mL-1, the SERS intensity of the platform has a linear relationship with the logarithm of hs-CRP concentration, and the detection limit was 0.01 pg mL-1. By this smart design, this work can give a direction for a rapid label-free SERS analysis.