Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1.

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.

Brain abscess from oral microbiota approached by metagenomic next-generation sequencing: A case report and review of literature.

BACKGROUND: Brain abscess is a serious and potentially fatal disease caused primarily by microbial infection. Although progress has been made in the diagnosis and treatment of brain abscesses, the diagnostic timeliness of pathogens needs to be improved. CASE SUMMARY: We report the case of a 54-year-old male with a brain abscess caused by oral bacteria. The patient recovered well after receiving a combination of metagenomic next-generation sequencing (mNGS)-assisted guided medication and surgery. CONCLUSION: Therefore, mNGS may be widely applied to identify the pathogenic microorganisms of brain abscesses and guide precision medicine.

GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

The stability of physicians' risk attitudes across time and domains.

Risk attitude is known to influence physicians' decision-making under uncertainty. Research on the risk attitudes of physicians is therefore important in facilitating a better understanding of physicians' decisions. However, little is known about the stability of physicians' risk attitudes across domains. Using five waves of data from a prospective panel study of Australian physicians from 2013 to 2017, we explored the stability of risk attitudes over a four-year period and examined the association between negative life events and risk attitudes among 4417 physicians. Further, we tested the stability of risk attitude across three domains most relevant to a physician's career and clinical decision-making (financial, career and clinical). The results showed that risk attitude was stable over time at both the mean and individual levels but the correlation between domains was modest. There were no significant associations between negative life events and risk attitude changes in all three domains. These findings suggest that risk attitude can be assumed to be constant but domain-specificity needs to be considered in analyses of physician decision-making.

MRI-based radiomics assessment of the imminent new vertebral fracture after vertebral augmentation.

BACKGROUND: Imminent new vertebral fracture (NVF) is highly prevalent after vertebral augmentation (VA). An accurate assessment of the imminent risk of NVF could help to develop prompt treatment strategies. PURPOSE: To develop and validate predictive models that integrated the radiomic features and clinical risk factors based on machine learning algorithms to evaluate the imminent risk of NVF. MATERIALS AND METHODS: In this retrospective study, a total of 168 patients with painful osteoporotic vertebral compression fractures treated with VA were evaluated. Radiomic features of L1 vertebrae based on lumbar T2-weighted images were obtained. Univariate and LASSO-regression analyses were applied to select the optimal features and construct radiomic signature. The radiomic signature and clinical signature were integrated to develop a predictive model by using machine learning algorithms including LR, RF, SVM, and XGBoost. Receiver operating characteristic curve and calibration curve analyses were used to evaluate the predictive performance of the models. RESULTS: The radiomic-XGBoost model with the highest AUC of 0.93 of the training cohort and 0.9 of the test cohort among the machine learning algorithms. The combined-XGBoost model with the best performance with an AUC of 0.9 in the training cohort and 0.9 in the test cohort. The radiomic-XGBoost model and combined-XGBoost model achieved better performance to assess the imminent risk of NVF than that of the clinical risk factors alone (p < 0.05). CONCLUSION: Radiomic and machine learning modeling based on T2W images of preoperative lumbar MRI had an excellent ability to evaluate the imminent risk of NVF after VA.

Extracellular matrix in synovium development, homeostasis and arthritis disease.

Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.

Immune-mediated necrotizing myopathy: Report of two cases.

BACKGROUND: Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase, with unique skeletal muscle pathology and magnetic resonance imaging features. CASE SUMMARY: In this paper, two patients are reported: One was positive for anti-signal recognition particle antibody, and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody. CONCLUSION: The clinical characteristics and treatment of the two patients were analysed, and the literature was reviewed to improve the recognition, diagnosis, and treatment of this disease.

Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats.

Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H2O2 to establish an apoptosis model. The control, H2O2 and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H2O2-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H2O2 group. Compared with the H2O2 group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.

Selenomethionine attenuates ochratoxin A-induced small intestinal injury in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation.

The aim of this study was to investigate whether selenomethionine (SeMet) could attenuate intestinal injury in rabbits induced by ochratoxin A (OTA). Sixty 35-day-old IRA rabbits with similar weights were randomly assigned to the control group, OTA group (0.2 mg OTA/kg b.w), OTA+ 0.2 mg/kg Se (0.2 mg OTA/kg b.w + 0.2 mg SeMet/kg feed), OTA+ 0.4 mg/kg Se (0.2 mg OTA/kg b.w + 0.4 mg SeMet/kg feed) and OTA+ 0.6 mg/kg Se (0.2 mg OTA/kg b.w + 0.6 mg SeMet/kg feed). The rabbits were examined after oral administration of different doses of SeMet for 21 days and were intragastrically administered OTA for 7 consecutive days. The results showed that pretreatment with different doses of SeMet protected against the changes in serum biochemical indicators and the decline in production performance caused by OTA exposure. In addition, the activities of SOD, GSH-PX and T-AOC were significantly increased, and the levels of MDA and ROS were decreased after SeMet pretreatment; thus, oxidative damage in rabbit jejunum tissue due to OTA exposure was inhibited. SeMet stimulates Nrf2 and inhibits the NF-κB signalling pathway; the anti-inflammatory response and antioxidative stress in rabbits were improved, and the intestinal barrier damage caused by OTA exposure was improved. In summary, SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement.

[Identifying Depressive Disorder With Sleep Electroencephalogram Data: A Study Based on Deep Learning].

Objective: To explore the effectiveness of using deep learning network combined Vision Transformer (ViT) and Transformer to identify patients with depressive disorder on the basis of their sleep electroencephalogram (EEG) signals. Methods: The sleep EEG signals of 28 patients with depressive disorder and 37 normal controls were preprocessed. Then, the signals were converted into image format and the feature information on frequency domain and spatial domain was retained. After that, the images were transmitted to the ViT-Transformer coding network for deep learning of the EEG signal characteristics of the rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with depressive disorder and those in normal controls, respectively, and to identify patients with depressive disorder. Results: Based on the ViT-Transformer network, after examining different EEG frequencies, we found that the combination of delta, theta, and beta waves produced better results in identifying depressive disorder. Among the different EEG frequencies, EEG signal features of delta-theta-beta combination waves in REM sleep achieved 92.8% accuracy and 93.8% precision for identifying depression, with the recall rate of patients with depression being 84.7%, and the F0.5 value being 0.917±0.074. When using the delta-theta-beta combination EEG signal features in NREM sleep to identify depressive disorder, the accuracy was 91.7%, the precision was 90.8%, the recall rate was 85.2%, and the F0.5 value was 0.914±0.062. In addition, through visualization of the sleep EEG of different sleep stages for the whole night, it was found that classification errors usually occurred during transition to a different sleep stage. Conclusion: Using the deep learning ViT-Transformer network, we found that the EEG signal features in REM sleep based on delta-theta-beta combination waves showed better effect in identifying depressive disorder.

Investigation of ß-caryophyllene as terpene penetration enhancer: Role of stratum corneum retention.

Terpenes are usually used as penetration enhancers (PE) for transdermal drug delivery (TDD) of various molecules. However, TDD of hydrophilic macromolecules is becoming an urgent challenge due to their potent activities. The aim of this study was to investigate the potential application of ß-caryophyllene (ß-CP), a sequiterpene, as PE for TDD of hydrophilic macromolecules for the first time. Commonly used PEs, namely azone and 1,8-cineole (1,8-CN), were applied as controls. Transepidermal water loss (TEWL) analysis revealed that the reduction of skin barrier function caused by ß-CP was reversible. Transdermal experiments showed that when skin was treated with ß-CP or azone, there was a significant permeation-enhancing effect on fluorescein isothiocyanate (FITC) and FITC-dextran with different molecular weight (MW) of 4k or 10k. CLSM analysis confirmed that ß-CP and azone can facilitate the penetration of FD-4k through epidermis and dermis. However, the cytotoxicity of azone against epidermal keratinocytes was significantly higher than ß-CP and 1,8-CN. Additionally, application of ß-CP and 1,8-CN didn't increase erythema index (EI) but the EI values of azone group increased significantly and irreversibly, indicating the high biocompatibility of the natural terpenes. ß-CP had better permeation-enhancing effect and higher stratum corneum (SC) retention than 1,8-CN due to its increased carbon chain length and lipophilicity, as further demonstrated by molecular dynamics (MD) simulation studies. Skin electrical resistance (SER) and attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) studies revealed a significant interfering effect of ß-CP on SC lipids. Taken together, ß-CP exhibited significant penetration enhancement of hydrophilic macromolecules due to its SC retention and SC lipid fluidization ability.

Herpes simplex virus type 2 encephalitis in a child with chronic progressive white matter lesions: A case report.

RATIONALE: This case is a rare manifestation of central nervous system infection of Herpes simplex virus (HSV)-2. Due to few studies in China, it provides a pathological basis for further diagnosis and treatment of HSV-2. PATIENT CONCERNS: We describe a patient with HSV-2 virus infection who was diagnosed with HSV-2 encephalitis in a Chinese patient. DIAGNOSIS: Based on brain biopsy and pathological findings, the patient was diagnosed with HSV-2 encephalitis. INTERVENTIONS: Hormone and antiviral therapy were given. OUTCOME: The patient eventually died. LESSONS: The diagnosis and differential diagnosis of the disease is very difficult. Its differential diagnosis include cerebrovascular disease, bacteria or fungi and other viral infection of the brain.

Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains.

While MRI contrast agents such as those based on Gadolinium are needed for high-resolution mapping of brain metabolism, these contrast agents require intravenous administration, and there are rising concerns over their safety and invasiveness. Furthermore, non-contrast MRI scans are more commonly performed than those with contrast agents and are readily available for analysis in public databases such as the Alzheimer's Disease Neuroimaging Initiative (ADNI). In this article, we hypothesize that a deep learning model, trained using quantitative steady-state contrast-enhanced structural MRI datasets, in mice and humans, can generate contrast-equivalent information from a single non-contrast MRI scan. The model was first trained, optimized, and validated in mice, and was then transferred and adapted to humans. We observe that the model can substitute for Gadolinium-based contrast agents in approximating cerebral blood volume, a quantitative representation of brain activity, at sub-millimeter granularity. Furthermore, we validate the use of our deep-learned prediction maps to identify functional abnormalities in the aging brain using locally obtained MRI scans, and in the brain of patients with Alzheimer's disease using publicly available MRI scans from ADNI. Since it is derived from a commonly-acquired MRI protocol, this framework has the potential for broad clinical utility and can also be applied retrospectively to research scans across a host of neurological/functional diseases.

Protective Effect of Selenomethionine on T-2 Toxin-Induced Rabbit Immunotoxicity.

T-2 toxin is a trichothecene mycotoxin produced by fusarium species, which is mainly prevalent in grain and livestock feed. One of the main effects of this toxin is immunodepression. Previous studies have shown that T-2 toxin can cause damage to immune organs and impaired immune function in animals. However, selenomethionine (SeMet) as an organic selenium source can not only promote the growth and development of the body but also effectively improve the body's immune function. In this study, rabbits were exposed to 0.4-mg/kg T-2 toxin, and abnormal blood routine indicators were found in the rabbits. HE staining also showed obvious lesions in the spleen and thymus tissue structures, accompanied by a large number of bleeding points. In addition, rabbits showed strong oxidative stress and inflammatory response after T-2 toxin action. 0.2 mg/kg, 0.4 mg/kg, and 0.6 mg/kg organic selenium were added to the feed. However, it was found that 0.2 mg/kg selenium can effectively improve the abnormal changes of blood routine and spleen and thymus tissue of rabbits. On the other hand, it can significantly increase the expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the spleen and thymus, and downregulate the expression of reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, inflammatory factors interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood were also significantly inhibited; the expression of proliferating cell nuclear antigen (PCNA) in the spleen and thymus was also significantly increased after low-dose selenium treatment. Surprisingly, 0.4 mg/kg and 0.6 mg/kg of selenium did not effectively alleviate the immunotoxic effects caused by T-2 toxin, and cause damage to a certain extent. In summary, our results show that 0.2 mg/kg of SeMet can effectively alleviate the immunotoxicity caused by T-2 toxin. Selenium may protect rabbits from T-2 toxin by improving its antioxidant and anti-inflammatory capabilities.

Comparative Proteome Analysis Indicates The Divergence between The Head and Tail Regeneration in Planarian.

OBJECTIVE: Even a small fragment from the body of planarian can regenerate an entire animal, implying that the different fragments from this flatworm eventually reach the same solution. In this study, our aim was to reveal the differences and similarities in mechanisms between different regenerating fragments from this worm. MATERIALS AND METHODS: In this experimental study, we profiled the dynamic proteome of regenerating head and tail to reveal the differences and similarities between different regenerating fragments using 2-DE combined with MALDITOF/ TOF MS. RESULTS: Proteomic profiles of head and tail regeneration identified a total of 516 differential expressed proteins (DEPs) and showed a great difference in quantity and fold changes of proteome profiles between the two scenarios. Briefly, out of the 516 DEPs, 314 were identified to be specific for anterior regeneration, while 165 were specific for posterior regeneration. Bioinformatics analysis showed a wide discrepancy in biological activities between two regenerative processes; especially, differentiation and development and signal transduction in head regeneration were much more complex than that in tail regeneration. Protein functional analysis combined with protein-protein interaction (PPI) analysis showed a significant contribution of both Wnt and BMP signaling pathways to head regeneration not but tail regeneration. Additionally, several novel proteins showed completely opposite expression between head and tail regeneration. CONCLUSION: Proteomic profiles of head and tail regeneration identified a total of 516 differential expressed proteins (DEPs) and showed a great difference in quantity and fold changes of proteome profiles between the two scenarios. Briefly, out of the 516 DEPs, 314 were identified to be specific for anterior regeneration, while 165 were specific for posterior regeneration. Bioinformatics analysis showed a wide discrepancy in biological activities between two regenerative processes; especially, differentiation and development and signal transduction in head regeneration were much more complex than that in tail regeneration. Protein functional analysis combined with protein-protein interaction (PPI) analysis showed a significant contribution of both Wnt and BMP signaling pathways to head regeneration not but tail regeneration. Additionally, several novel proteins showed completely opposite expression between head and tail regeneration.

EMDS-5: Environmental Microorganism image dataset Fifth Version for multiple image analysis tasks.

Environmental Microorganism Data Set Fifth Version (EMDS-5) is a microscopic image dataset including original Environmental Microorganism (EM) images and two sets of Ground Truth (GT) images. The GT image sets include a single-object GT image set and a multi-object GT image set. EMDS-5 has 21 types of EMs, each of which contains 20 original EM images, 20 single-object GT images and 20 multi-object GT images. EMDS-5 can realize to evaluate image preprocessing, image segmentation, feature extraction, image classification and image retrieval functions. In order to prove the effectiveness of EMDS-5, for each function, we select the most representative algorithms and price indicators for testing and evaluation. The image preprocessing functions contain two parts: image denoising and image edge detection. Image denoising uses nine kinds of filters to denoise 13 kinds of noises, respectively. In the aspect of edge detection, six edge detection operators are used to detect the edges of the images, and two evaluation indicators, peak-signal to noise ratio and mean structural similarity, are used for evaluation. Image segmentation includes single-object image segmentation and multi-object image segmentation. Six methods are used for single-object image segmentation, while k-means and U-net are used for multi-object segmentation. We extract nine features from the images in EMDS-5 and use the Support Vector Machine (SVM) classifier for testing. In terms of image classification, we select the VGG16 feature to test SVM, k-Nearest Neighbors, Random Forests. We test two types of retrieval approaches: texture feature retrieval and deep learning feature retrieval. We select the last layer of features of VGG16 network and ResNet50 network as feature vectors. We use mean average precision as the evaluation index for retrieval. EMDS-5 is available at the URL:https://github.com/NEUZihan/EMDS-5.git.

[Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism].

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Acute Elevated Resistin Exacerbates Mitochondrial Damage and Aggravates Liver Steatosis Through AMPK/PGC-1α Signaling Pathway in Male NAFLD Mice.

Resistin was identified as a link between obesity and insulin resistance and is associated with many diseases in mice. Deciphering the related development and molecular mechanism is necessary for the treatment of these diseases. Previous studies have revealed that increased resistin levels are correlated with lipid accumulation and play a role in non-alcoholic fatty liver disease (NAFLD) development. However, the exact mechanisms underlying these processes remain unclear. To further clarify whether acute elevated resistin level exacerbated liver steatosis, a high-fat diet-induced NAFLD animal model was used and treated with or without resistin for 6 days. We discovered that resistin altered mitochondrial morphology, decreased mitochondrial content, and increased lipid accumulation in HFD mice. qRT-PCR and western blot analysis showed that acute elevated resistin significantly altered the gene expression of mitochondrial biogenesis and liver lipid metabolism molecules in HFD mice. Consequently, in vitro experiments verified that resistin reduced the mitochondrial content, impaired the mitochondrial function and increased the lipid accumulation of palmitate-treated HepG2 cells. Additionally, we demonstrated that resistin upregulated proinflammatory factors, which confirmed that resistin promoted the development of inflammation in NAFLD mice and palmitate-treated HepG2 cells. Signaling-transduction analysis demonstrated that acute elevated resistin aggravated liver steatosis through AMPK/PGC-1α pathway in male mice. This reveals a novel pathway through which lipogenesis is induced by resistin and suggests that maintaining mitochondrial homeostasis may be key to treatments for preventing resistin-induced NAFLD aggravation.

Identification of COVID-19 samples from chest X-Ray images using deep learning: A comparison of transfer learning approaches.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) constitutes a public health emergency globally. The number of infected people and deaths are proliferating every day, which is putting tremendous pressure on our social and healthcare system. Rapid detection of COVID-19 cases is a significant step to fight against this virus as well as release pressure off the healthcare system. OBJECTIVE: One of the critical factors behind the rapid spread of COVID-19 pandemic is a lengthy clinical testing time. The imaging tool, such as Chest X-ray (CXR), can speed up the identification process. Therefore, our objective is to develop an automated CAD system for the detection of COVID-19 samples from healthy and pneumonia cases using CXR images. METHODS: Due to the scarcity of the COVID-19 benchmark dataset, we have employed deep transfer learning techniques, where we examined 15 different pre-trained CNN models to find the most suitable one for this task. RESULTS: A total of 860 images (260 COVID-19 cases, 300 healthy and 300 pneumonia cases) have been employed to investigate the performance of the proposed algorithm, where 70% images of each class are accepted for training, 15% is used for validation, and rest is for testing. It is observed that the VGG19 obtains the highest classification accuracy of 89.3% with an average precision, recall, and F1 score of 0.90, 0.89, 0.90, respectively. CONCLUSION: This study demonstrates the effectiveness of deep transfer learning techniques for the identification of COVID-19 cases using CXR images.

Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole.

Flurbiprofen (FP) is one of the most potent nonsteroidal anti-inflammatory drugs with very low bioavailability of approximately 12% following transdermal administration, compared to that after oral administration. This study aimed to deliver FP as a microemulsion (ME) gel by transdermal administration. Galangal essential oil (GEO) was extracted from Rhizoma Alpiniae Officinarum and identified by GC-MS. The most abundant constituent was determined to be 1,8-cineole (52.06%). Compared to azone, GEO was proved to exert significantly higher (p < .01) penetration enhancement effect and significantly (p < .001) lower skin cell toxicity. The formulation (FP-GEO-ME gel) was prepared using GEO as an oil phase and a penetration enhancer. Compared to that of FP solution, the enhancement ratio (ER) of FP-GEO-ME gel was 4.06. In addition, more than 25% 1,8-cineole permeated through the rat skin. In vivo pharmacokinetic studies revealed that the AUC0-t of FP after transdermal administration of FP-GEO-ME gel was higher by approximately 4.56-fold than that of marketed FP cataplasms. The relative bioavailability of FP and 1,8-cineole after transdermal administration compared to oral administration of FP-GEO-ME were determined to be 96.58% and 85.49%, respectively. FP-GEO-ME gel significantly inhibited carrageenan-induced hind-paw edema and decreased PGE2 levels in rat serum. GEO-ME gel also exhibited significant anti-inflammatory effects at 2 h after the therapy (p < .05). The synergistic effects of FP and GEO were expected for the application of FP-GEO-ME gel. In conclusion, GEO-ME gel may be a promising formulation for transdermal administration of anti-inflammatory hydrophobic drugs, such as FP.