Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Historical context, process, and development trends of pediatric thyroid cancer research: a bibliometric analysis.

Objective: At present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends. Methods: We searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions. Results: The top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined. Conclusion: Extensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

Symmetry Breaking and Spin-Orbit Coupling for Individual Vacancy-Induced In-Gap States in MoS2 Monolayers.

Spins confined to point defects in atomically thin semiconductors constitute well-defined atomic-scale quantum systems that are being explored as single-photon emitters and spin qubits. Here, we investigate the in-gap electronic structure of individual sulfur vacancies in molybdenum disulfide (MoS2) monolayers using resonant tunneling scanning probe spectroscopy in the Coulomb blockade regime. Spectroscopic mapping of defect wave functions reveals an interplay of local symmetry breaking by a charge-state-dependent Jahn-Teller lattice distortion that, when combined with strong (≃100 meV) spin-orbit coupling, leads to a locking of an unpaired spin-1/2 magnetic moment to the lattice at low temperature, susceptible to lattice strain. Our results provide new insights into the spin and electronic structure of vacancy-induced in-gap states toward their application as electrically and optically addressable quantum systems.

Diastereomers of Steroidal Alkaloids with Cytotoxic Activities against Non-Small-Cell Lung Cancer from the Bulbs of Fritillaria sinica.

Eleven new steroidal alkaloids, along with nine known related compounds, were isolated from the bulbs of Fritillaria sinica. Seven pairs of diastereomers were identified, including six and four 20-deoxy cevanine-type steroidal alkaloid diastereomers with molecular weights of 413 and 415, respectively. Structures were elucidated based on spectroscopic data analysis, chemical derivatization, and single-crystal X-ray diffraction analysis. Compounds 5, 9, 11, 12, 16, and 20 exhibited significant in vitro cytotoxic activity against non-small-cell lung cancer with CC50 values from 6.8 ± 3.9 to 12 ± 5 µM.

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics.

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.

MATLAB language assisted data acquisition and processing in liquid chromatography Orbitrap mass spectrometry: Application to the identification and differentiation of Radix Bupleuri from its adulterants.

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.

Interactive Learning of Intrinsic and Extrinsic Properties for All-Day Semantic Segmentation.

Scene appearance changes drastically throughout the day. Existing semantic segmentation methods mainly focus on well-lit daytime scenarios and are not well designed to cope with such great appearance changes. Naively using domain adaption does not solve this problem because it usually learns a fixed mapping between the source and target domain and thus have limited generalization capability on all-day scenarios (i. e., from dawn to night). In this paper, in contrast to existing methods, we tackle this challenge from the perspective of image formulation itself, where the image appearance is determined by both intrinsic (e. g., semantic category, structure) and extrinsic (e. g., lighting) properties. To this end, we propose a novel intrinsic-extrinsic interactive learning strategy. The key idea is to interact between intrinsic and extrinsic representations during the learning process under spatial-wise guidance. In this way, the intrinsic representation becomes more stable and, at the same time, the extrinsic representation gets better at depicting the changes. Consequently, the refined image representation is more robust to generate pixel-wise predictions for all-day scenarios. To achieve this, we propose an All-in-One Segmentation Network (AO-SegNet) in an end-to-end manner. Large scale experiments are conducted on three real datasets (Mapillary, BDD100K and ACDC) and our proposed synthetic All-day CityScapes dataset. The proposed AO-SegNet shows a significant performance gain against the state-of-the-art under a variety of CNN and ViT backbones on all the datasets.

Need analysis of a dietary application among caregivers of patients with disorders of amino acid metabolism (AAMDs): A mixed-method approach.

BACKGROUND: A dietary application can assist the caregivers of AAMDs children in auto-calculating the protein intake, hence improving dietary compliance. However, existing dietary application for patients with AAMDs only focus on delivering the nutritional content of food and monitoring the dietary intake but were lacking in other educational components. OBJECTIVE: To assess the uses, needs and preferences towards a dietary application among the caregivers of AAMDs patients. METHODS: We conducted a mixed-method study comprising focus group discussion (FGD) and a quantitative questionnaire survey among caregivers of patients aged between 6-month-old to 18-year-old with AAMDs who are receiving active treatment, both medical and dietetic treatment in the genetic clinic, Hospital Kuala Lumpur (HKL). RESULTS: A total of 76 and 20 caregivers participated in the survey and FGD respectively. All the caregivers (100%) possessed a smartphone and most of the caregivers (89.5%) had the experience of using smartphone or other technological devices to search for health or medical information. However, majority of the participants were not aware of the existence of any web-based or mobile application related to AAMDs (89.5%). While for the qualitative part, three themes emerged: (1) experience with current source of information; (2) needs for supporting self-management educational contents and needs for technological design application. Most of the caregivers used the nutritional booklet as sources of reference but some of them searched for web-based information. Features perceived by the caregivers included a digital food composition database, sharing diet recall with healthcare providers, self-monitoring diet intake as well as low protein recipes. Besides that, user-friendly and ease to use were also perceived as the important features by the caregivers. CONCLUSION: The identified features and needs by the caregivers should be integrated into the design of the apps to promote acceptance and usage.

Undescribed steroidal alkaloids from the bulbs of Fritillaria sinica.

Eight undescribed steroidal alkaloid derivatives, including three cevanine-type isosteroidal alkaloids (two N-oxide glycosides and one D-ring aromatization) (1-3), one verazine-type steroidal alkaloid derivative (4), three solanidine-type steroidal alkaloid glycosides (5-7), and one veratramine-type analogue (8), along with three known compounds (9-11) were isolated from the bulbs of Fritillaria sinica. Their structures were elucidated by comprehensive analysis of spectroscopic data, acidic hydrolysis, and X-ray crystal diffractions. In the in vitro bioassay, the anti-cancer effect, anti-oxidation and anti-inflammatory activities for the isolates were evaluated at a concentration of 10 µM.

Systematical characterization of gypenosides in Gynostemma pentaphyllum and the chemical composition variation of different origins.

Gynostemma pentaphyllum (Thunb.) Makino is an herbaceous plant of Cucurbitaceae family, which has been widely used as an herbal tea and traditional Chinese medicine. Since its saponins are similar to ginsenosides and have a wide range of activities, it has attracted wide interest. However, there are still a large number of unknown saponins that have not been isolated, especially some trace gypenosides. In the present study, a HILIC × RP offline two-dimensional liquid separation combined with a multimode data acquisition was developed for the systematical characterization of gypenosides. On top of the negative mode information, considering that saponins are prone to in-source fragmentations in positive ion mode, a precursor ion list data acquisition method was used for the targeted acquisition of multistage positive data. Reference herbal drug was taken as a golden sample to probe the chemical composition of G. pentaphyllum. The mixed sample of commercially available samples were also analyzed in parallel. Furthermore, the chemical compositions of commercially available samples from different sources were compared. In total, 1108 saponins were characterized, among which 588 were accurately characterized, with 574 identified in the reference herbal drug and 700 in the mixed commercially available samples. The commercially available samples showed great composition variation. These findings clarified the material basis and provided clues for quality control of G. pentaphyllum.

Effects of heat shock protein 90 on complement activation in myocardial ischemia/reperfusion injury after pioglitazone preconditioning.

BACKGROUND: Heat shock protein 90 (HSP90) appears to have a pivotal function in ischemic preconditioning. Pioglitazone preconditioning (PioC) attenuates myocardial ischemia/reperfusion (I/R) injuries. OBJECTIVES: The current study aims to investigate the role of HSP90, complement C3 and C5a, and nuclear factor kappa-B (NF-κB) in PioC-induced cardioprotection. MATERIAL AND METHODS: A total of 80 rats were randomly categorized into 4 groups, as follows: sham, I/R, PioC, and PioC+HSP90 inhibitor geldanamycin (PioC+GA). The sham group rats had a thoracotomy, in which the ligature was passed by the heart with no ligation (150 min). The other 3 groups were exposed to ischemia (30 min) followed by reperfusion (2 h). In the PioC group, pioglitazone (3 mg/kg) was administered intravenously 24 h before ischemia. In the PioC+GA group, after being pretreated with pioglitazone, GA was administered (intraperitoneally, 1 mg/kg) 30 min before ischemia. Myocardial infarct sizes (ISs), apoptosis rates, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin I (cTnI) serum levels were determined. The HSP90, C3, NF-κB, C5a, B-cell lymphoma-2 (Bcl-2), and Bax expression levels, as well as interleukin (IL)-1ß, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), and tumor necrosis factor alpha (TNF-α) mRNA levels were measured. RESULTS: The myocardial ISs, serum CK-MB, cTnI and LDH levels, apoptosis rates, IL-1ß, IL-6, TNF-α, ICAM-1 release, as well as Bax, C5a, C3, and NF-κB protein expression were considerably lower in the PioC group than in the I/R group (p < 0.05). The Bcl-2 and HSP90 expression was higher in the PioC group than in the I/R group (p < 0.05). Geldanamycin inhibited the effects of PioC. These data strongly demonstrate that the PioC-induced is dependent upon HSP90 activity. CONCLUSIONS: The HSP90 is indispensable for PioC-mediated cardioprotection. The HSP90 attenuates I/R-induced ISs, apoptosis of cardiomyocytes and myocardial inflammation through C3, C5a and NF-κB activation inhibition.

[Chemical Composition of VOCs from Service Stations Vapor Processing Device and Associated Contributions to Secondary Pollution].

Vapor processing device is a device that can control the headspace pressure in the underground storage tanks and recover the vapor. By analyzing the chemical composition of volatile organic compounds (VOCs) at the inlet and outlet of the vapor processing device, the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAP) were estimated by maximum incremental reaction (MIR) and fractional aerosol coefficients (FAC), and the secondary pollution formation contribution of VOCs were quantitatively evaluated. The results showed that:① the ρ(total volatile organic compounds, TVOC) at the inlet and outlet of the vapor processing device were 436-706 g·m-3 and 4.98-10.04 g·m-3, respectively. Alkanes (72%±4%), oxygenated organics (14%±2%), and olefins (11%±5%) were the dominant components of VOCs emissions. There were little differences in VOCs emissions from the different vapor processing devices; the key species were i-pentane (approximately 25%), followed by n-butane, i-butane, and n-pentane. ② The ozone source reactivity (SR) of VOCs emissions from the outlet of the vapor processing device was 2.6-3.3 g·g-1, and the OFP was 3.5-25.6 g·m-3. Olefins contributed the most (43%-69%), followed by alkanes (20%-35%) and oxygenated organics (10%-22%). Butene, cis-2-butene, trans-2-butene, i-pentane, and propionaldehyde were the species that highly contributed to OFP. ③ Aromatics in VOCs emissions contributed the most to SOAP (80%-92%), and the main active species were toluene, 1, 2, 4-trimethylbenzene, 1, 3, 5-trimethylbenzene, and p-diethylbenzene. The research showed that different VOCs species emitted by the vapor processing device contributed obvious differences to the secondary atmospheric pollution, and butene species and aromatics such as toluene were the focus of VOCs emission control of vehicle gasoline and vapor processing device.

Exosomal HSP90 induced by remote ischemic preconditioning alleviates myocardial ischemia/reperfusion injury by inhibiting complement activation and inflammation.

BACKGROUND/AIMS: The activation of the complement system and subsequent inflammatory responses are important features of myocardial ischemia/reperfusion (I/R) injury. Exosomes are nanoscale extracellular vesicles that play a significant role in remote ischemic preconditioning (RIPC) cardioprotection. The present study aimed to test whether RIPC-induced plasma exosomes (RIPC-Exo) exert protective effects on myocardial I/R injury by inhibiting complement activation and inflammation and whether exosomal heat shock protein 90 (HSP90) mediates these effects. METHODS: Rat hearts underwent 30 min of coronary ligation followed by 2 h of reperfusion. Plasma exosomes were isolated from RIPC rats and injected into the infarcted myocardium immediately after ligation. Sixty rats were randomly divided into Sham, I/R, I/R + RIPC-Exo (50 µg/µl), and RIPC-Exo + GA (geldanamycin, 1 mg/kg, administration 30 min before ligation) groups. Cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB), infarct size, the expression of HSP90, complement component (C)3, C5a, c-Jun N-terminal kinase (JNK), interleukin (IL)-1ß, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule -1 (ICAM-1) were assessed. RESULTS: RIPC-Exo treatment significantly reduced I/R-induced cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB) and infarct size. These beneficial effects were accompanied by decreased C3 and C5a expression, decreased inflammatory factor levels (IL-1ß, TNF-α, and ICAM-1), decreased JNK and Bax, and increased Bcl-2 expression. Meanwhile, the expression of HSP90 in the exosomes from rat plasma increased significantly after RIPC. However, treatment with HSP90 inhibitor GA significantly reversed the cardioprotection of RIPC-Exo, as well as activated complement component, JNK signalling and inflammation, indicating that HSP90 in exosomes isolated from the RIPC was important in mediating the cardioprotective effects during I/R. CONCLUSION: Exosomal HSP90 induced by RIPC played a significant role in cardioprotection against I/R injury, and its function was in part linked to the inhibition of the complement system, JNK signalling and local and systemic inflammation, ultimately alleviating I/R-induced myocardial injury and apoptosis by the upregulation of Bcl-2 expression and the downregulation of proapoptotic Bax.

Letrozole + Ziwu Liuzhu Transcutaneous Electrical Acupoint Stimulation Improves Ovulation-Induced Pregnancy Rate in Obese Women with Polycystic Ovary Syndrome: A Prospective Cohort Study.

Objective: This study investigated the effect of letrozole with/without meridian-infusion percutaneous electrical stimulation on the rates of ovulation-induced pregnancy in patients with obese polycystic ovary syndrome (obPCOS). Materials and Methods: Patients with obPCOS, ages 20-40, each with a body mass index (BMI) ≥24 kg/m2, and/or waist circumference ≥80 cm, and at least 1 side tubal patency were enrolled at the Guangdong Women and Children Hospital, Guangzhou, China. They were divided into 2 groups: ZLT [Ziwu Liuzhu + transcutaneous electrical acupoint stimulation] and control. Baseline conditions and pregnancy status were collected for all patients. Multivariate Cox regression analysis and sensitivity analysis of propensity score matching (PSM) were performed for the groups after multiple interpolations. Results: From July 2021 to September 2022, 345 patients with obPCOS were recruited: 53 cases/69 cycles in the ZLT group and 292 cases/396 cycles in the control group. The 2 sets of baselines were flush. The anovulatory cycle rates were: ZLT, 2.89% (2/69); and control, 1.77% (7/396); P > 0.05. Multifollicle growth-cycle rates were: ZLT, 0% (0/69); and control, 0.76% (3/396); P > 0.05. Multivariate COX regression analysis showed adjusted hazard ratio (aHR) 95% confidence interval (CI): 2.11 (1.19, 3.73); P = 0.011. Multivariate Cox regression analysis with multiple imputation showed aHR 95% CI: 2.11 (1.19, 3.73); P = 0.013. In the overweight group (24-28 kg/m2), the pregnancy rate of the control and ZLT groups were 20.2% and 32.3%, respectively, aHR 95% CI: 1.76 (0.87,3.55); P = 0.113. In the obese cohort (≥ 28 kg/m2), the control and ZLT groups, pregnancy rates were 10.7% and 27.3%, respectively, aHR 95% CI: 3.46 (1.21, 9.92); P = 0.021; (Pfor interaction = 0.369). The caliper value was set as 0.2 for BMI and antral-follicle count, and PSM was performed at 1:1, aHR 95%CI: 2.45 (1.01, 5.96); P = 0.048. Conclusions: Letrazole + ZLT had a positive effect on ovulation-induced pregnancy rates in patients with obPCOS.

The BDNF-TrkB-CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation.

Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF-TrkB-CREB (brain-derived neurotrophic factor-tropomyosin-related kinase B-CAMP response element-binding protein) signalling pathway in bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with sesame oil or 2, 20 and 200 mg/kg body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting. BDNF promoter IV methylation level was detected by bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of BDNF promoter IV; downregulated BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the BDNF-TrkB-CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation.

Deep chemical identification of phytoecdysteroids in Achyranthes bidentata Blume by UHPLC coupled with linear ion trap-Orbitrap mass spectrometry and targeted isolation.

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study.

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents' experiences related to the management of their child's daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.

HSP90-Mediates Liraglutide Preconditioning-Induced Cardioprotection by Inhibiting C5a and NF-κB.

OBJECTIVE: We previously showed that HSP90 is involved in postconditioning cardioprotection by inhibiting complement C5a. Here, we investigated whether HSP90-mediated C5a/NF-κB inhibition is responsible for the cardioprotection conferred by liraglutide. METHODS: Rat hearts underwent a 30 min occlusion of the anterior descending coronary artery, after which reperfusion was performed for 2 h. A total of 100 rats were randomly assigned to the following groups: ischemia/reperfusion (I/R), sham, liraglutide preconditioning (LP, liraglutide, 0.18 mg/kg, intravenously, 12 h before ischemia), HSP90 inhibitor geldanamycin (GA, 1 mg/kg, intraperitoneally, 30 min before ischemia) plus LP, and C5a receptor antagonist PMX53 (1 mg/kg, intravenously, 30 min before ischemia) plus LP. Cardiac injury, C5a/NF-κB activation, and inflammation were investigated. RESULTS: LP significantly attenuated I/R-induced cardiomyocyte apoptosis, infarct size, and secretion of creatine kinase-MB, lactate dehydrogenase and cardiac troponin I. These effects were complemented by decreased C5a levels, nuclear factor (NF)-κB signaling, inflammatory cytokine expression, and increased HSP90 levels. GA, an HSP90 inhibitor, promotes C5a activation, NF-κB signaling, and inflammation and suppresses cardioprotection by LP. By contrast, PMX53, a C5a inhibitor, suppressed C5a activation, NF-κB signaling, and inflammation, and enhanced cardioprotection by LP. CONCLUSION: HSP90 markedly contributes to LP cardioprotection by inhibiting inflammatory responsesand C5a/NF-κB signaling , ultimately attenuating I/R-induced cardiomyocyte apoptosis by suppressing the proapoptotic factor Bax, and inducing the anti-apoptotic factor Bcl2.

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB.

BACKGROUND: Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. METHODS: Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. RESULTS: MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1ß, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. CONCLUSION: HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

Local Semantic Enhanced ConvNet for Aerial Scene Recognition.

Aerial scene recognition is challenging due to the complicated object distribution and spatial arrangement in a large-scale aerial image. Recent studies attempt to explore the local semantic representation capability of deep learning models, but how to exactly perceive the key local regions remains to be handled. In this paper, we present a local semantic enhanced ConvNet (LSE-Net) for aerial scene recognition, which mimics the human visual perception of key local regions in aerial scenes, in the hope of building a discriminative local semantic representation. Our LSE-Net consists of a context enhanced convolutional feature extractor, a local semantic perception module and a classification layer. Firstly, we design a multi-scale dilated convolution operators to fuse multi-level and multi-scale convolutional features in a trainable manner in order to fully receive the local feature responses in an aerial scene. Then, these features are fed into our two-branch local semantic perception module. In this module, we design a context-aware class peak response (CACPR) measurement to precisely depict the visual impulse of key local regions and the corresponding context information. Also, a spatial attention weight matrix is extracted to describe the importance of each key local region for the aerial scene. Finally, the refined class confidence maps are fed into the classification layer. Exhaustive experiments on three aerial scene classification benchmarks indicate that our LSE-Net achieves the state-of-the-art performance, which validates the effectiveness of our local semantic perception module and CACPR measurement.