Recent advances in age-related metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 25% of the world's population and has become a leading cause of chronic liver disease. In recent years, an increasing amount of data suggests that MASLD is associated with aging. As the population ages, age-related MASLD will become a major global health problem. Targeting an aging will become a new approach to the treatment of MASLD. This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD, including: Oxidative stress, autophagy, mitochondrial homeostasis, bile acid metabolism homeostasis, and dysbiosis. The aim is to identify effective therapeutic targets for age-related MASLD and its progression.

Research progress on the mitochondrial mechanism of age-related non-alcoholic fatty liver.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Reduced activity and slower metabolism in the elderly affect the balance of lipid metabolism in the liver leading to the accumulation of lipids. This affects the mitochondrial respiratory chain and the efficiency of ß-oxidation and induces the overproduction of reactive oxygen species. In addition, the dynamic balance of the mitochondria is disrupted during the ageing process, which inhibits its phagocytic function and further aggravates liver injury, leading to a higher incidence of NAFLD in the elderly population. The present study reviewed the manifestations, role and mechanism of mitochondrial dysfunction in the progression of NAFLD in the elderly. Based on the understanding of mitochondrial dysfunction and abnormal lipid metabolism, this study discusses the treatment strategies and the potential therapeutic targets for NAFLD, including lipid accumulation, antioxidation, mitophagy and liver-protecting drugs. The purpose is to provide new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.

Development of a Supportive Parenting App to Improve Parent and Infant Outcomes in the Perinatal Period: Development Study.

BACKGROUND: The transition to parenthood can be challenging, and parents are vulnerable to psychological disorders during the perinatal period. This may have adverse long-term consequences on a child's development. Given the rise in technology and parents' preferences for mobile health apps, a supportive mobile health intervention is optimal. However, there is a lack of a theoretical framework and technology-based perinatal educational intervention for couples with healthy infants. OBJECTIVE: The aim of this study is to describe the Supportive Parenting App (SPA) development procedure and highlight the challenges and lessons learned. METHODS: The SPA development procedure was guided by the information systems research framework, which emphasizes a nonlinear, iterative, and user-centered process involving 3 research cycles-the relevance cycle, design cycle, and rigor cycle. Treatment fidelity was ensured, and team cohesiveness was maintained using strategies from the Tuckman model of team development. RESULTS: In the relevance cycle, end-user requirements were identified through focus groups and interviews. In the rigor cycle, the user engagement pyramid and well-established theories (social cognitive theory proposed by Bandura and attachment theory proposed by Bowlby) were used to inform and justify the features of the artifact. In the design cycle, the admin portal was developed using Microsoft Visual Studio 2017, whereas the SPA, which ran on both iOS and Android, was developed using hybrid development tools. The SPA featured knowledge-based content, informational videos and audio clips, a discussion forum, chat groups, and a frequently asked questions and expert advice section. The intervention underwent iterative testing by a small group of new parents and research team members. Qualitative feedback was obtained for further app enhancements before official implementation. Testing revealed user and technological issues, such as web browser and app incompatibility, a lack of notifications for both administrators and users, and limited search engine capability. CONCLUSIONS: The information systems research framework documented the technical details of the SPA but did not take into consideration the interpersonal and real-life challenges. Ineffective communication between the health care research team and the app developers, limited resources, and the COVID-19 pandemic were the main challenges faced during content development. Quick adaptability, team cohesion, and hindsight budgeting are crucial for intervention development. Although the effectiveness of the SPA in improving parental and infant outcomes is currently unknown, this detailed intervention development study highlights the key aspects that need to be considered for future app development.

Ventilatory response to exercise is preserved in patients with obesity hypoventilation syndrome.

STUDY OBJECTIVES: Blunted ventilatory responses to hypoxia and hypercapnia during resting conditions are common findings in patients with obesity hypoventilation syndrome (OHS). Exercise increases the work and oxygen cost of breathing and produces excessive carbon dioxide (CO2). The aim of this investigation was to study ventilatory responses to incremental exercise in patients with OHS. METHODS: Sixty-eight obese adults with OHS (n = 15), eucapnic obstructive sleep apnea (n = 26), or simple obesity (n = 27) participated in an incremental exercise test on a cycle ergometer and an in-laboratory sleep study. RESULTS: The peak oxygen uptake (peak VO2) and peak pulse oxygen was decreased in patients with OHS compared with patients with either obstructive sleep apnea or simple obesity. The ventilatory response to exertional metabolic demand (nadir VE/VCO2, ∆VE/∆VCO2 slope, and VE/VCO2 at peak exercise) did not significantly differ among the 3 groups. Minute ventilation, tidal volume, respiratory frequency, tidal volume/respiratory frequency, and inspiratory time/total time ratio at a given work rate were comparable among the 3 groups. Among the whole cohort, apnea-hypopnea index was not independently associated with peak VO2, and no association was found between the ∆VE/∆VCO2 slope and resting arterial partial pressure of CO2. CONCLUSIONS: The ventilatory response to incremental exercise is preserved in patients with OHS compared with patients with obstructive sleep apnea and simple obesity who were matched for age and body mass index. This result highlights the complexity of the respiratory control system during exercise for patients with OHS, which may be uncoupled with the ventilatory response during sleep and resting conditions.

Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs.

Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004-17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development.

Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels.

BACKGROUND: This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF). METHODS: One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA). RESULTS: BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment. CONCLUSIONS: wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores.

The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases.

Adipose tissue has been considered as a crucial source of certain pro-inflammatory cytokines; conversely, these pro-inflammatory cytokines are involved in regulating the proliferation and apoptosis of adipocytes, promoting lipolysis, inhibiting lipid synthesis and decreasing blood lipids, etc. In recent decades, extensive studies have indicated that pro-inflammatory cytokines play important roles in the development of lipid metabolism of metabolic diseases, including obesity, atherosclerosis, steatohepatitis and hyperlipoproteinemia. However, the involved pro-inflammatory cytokines types and the underlying mechanisms remain largely unknown. The "re-discovery" of cancer as a metabolic disorder largely occurred in the last five years. Although pro-inflammatory cytokines have been intensively investigated in cancer research, there are very few studies about the roles of pro-inflammatory cytokines in the lipid metabolism of cancer. In the current review, we provide an overview of the progress that has been made in the roles of different pro-inflammatory cytokines in lipid metabolism of metabolic diseases including cancer.

High Strength and Deformation Mechanisms of Al0.3CoCrFeNi High-Entropy Alloy Thin Films Fabricated by Magnetron Sputtering.

Recently, high-entropy alloy thin films (HEATFs) with nanocrystalline structures and high hardness were developed by magnetron sputtering technique and have exciting potential to make small structure devices and precision instruments with sizes ranging from nanometers to micrometers. However, the strength and deformation mechanisms are still unclear. In this work, nanocrystalline Al0.3CoCrFeNi HEATFs with a thickness of ~4 µm were prepared. The microstructures of the thin films were comprehensively characterized, and the mechanical properties were systematically studied. It was found that the thin film was smooth, with a roughness of less than 5 nm. The chemical composition of the high entropy alloy thin film was homogeneous with a main single face-centered cubic (FCC) structure. Furthermore, it was observed that the hardness and the yield strength of the high-entropy alloy thin film was about three times that of the bulk samples, and the plastic deformation was inhomogeneous. Our results could provide an in-depth understanding of the mechanics and deformation mechanism for future design of nanocrystalline HEATFs with desired properties.

Subtly Manipulated Expression of ZmmiR156 in Tobacco Improves Drought and Salt Tolerance Without Changing the Architecture of Transgenic Plants.

Plants in the juvenile state are more tolerant to adverse conditions. Constitutive expression of MicroRNA156 (miR156) prolonged the juvenile phase and increased resistance to abiotic stress, but also affected the architecture of transgenic plants. In this study, we investigated the possibility of subtle manipulation of miR156 expression in flowering plants, with the goal to increase tolerance to abiotic stress without altering the normal growth and development of transgenic plants. Transgenic tobacco plants expressing ZmmiR156 from maize were generated, driven either by the cauliflower mosaic virus (CaMV) 35S promoter or the stress-inducible ZmRab17 promoter. Expression of ZmmiR156 led to improved drought and salt tolerance in both 35S::MIR156 and Rab17::MIR156 transgenic plants, as shown by more vigorous growth, greater biomass production and higher antioxidant enzyme expression after a long period of drought or salt treatment, when compared to wild type and transgenic vector control plants. However, constitutive expression of ZmmiR156 also resulted in retarded growth, increased branching and delayed flowering of transgenic plants. These undesirable developmental changes could be mitigated by using the stress-inducible ZmRab17 promoter. Furthermore, under drought or salt stress conditions, expression of ZmmiR156 reduced the transcript level of NtSPL2 and NtSPL9, the genes potentially targeted by ZmmiR156, as well as that of CP1, CP2, and SAG12, the senescence-associated genes in tobacco. Collectively, our results indicate that ZmmiR156 can be temporally manipulated for the genetic improvement of plants resistant to various abiotic stresses.

Clinical and genetic features of Mowat-Wilson syndrome: an analysis of 3 cases / 中国当代儿科杂志

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant genetic disease caused by zinc finger E-box-binding homeobox 2 (ZEB2) gene mutation and has various clinical manifestations including intellectual disability/global developmental delay, unusual facies and multiple congenital malformations. This article reports the clinical features and gene mutations of three children diagnosed with MWS by ZEB2 gene analysis. All three children had Hirschsprung disease and unusual facies. One child died of severe heart failure and pneumonia at the age of 4 months. Global developmental delay was not discovered by her parents due to her young age. The other two children had severe global developmental delay. All three children carried a de novo heterozygous nonsense mutation in the ZEB2 gene, among which c.756C>A (p.Y252X) had not been reported before. Such mutations produced truncated proteins and were highly pathogenic. MWS is presented with strong clinical and genetic heterogeneity. Clinicians should consider the possibility of MWS when a child has unusual facies of MWS, intellectual disability/global developmental delay and multiple congenital malformations. Gene detection helps to make a confirmed diagnosis.

Assessing the Performances of Protein Function Prediction Algorithms from the Perspectives of Identification Accuracy and False Discovery Rate.

The function of a protein is of great interest in the cutting-edge research of biological mechanisms, disease development and drug/target discovery. Besides experimental explorations, a variety of computational methods have been designed to predict protein function. Among these in silico methods, the prediction of BLAST is based on protein sequence similarity, while that of machine learning is also based on the sequence, but without the consideration of their similarity. This unique characteristic of machine learning makes it a good complement to BLAST and many other approaches in predicting the function of remotely relevant proteins and the homologous proteins of distinct function. However, the identification accuracies of these in silico methods and their false discovery rate have not yet been assessed so far, which greatly limits the usage of these algorithms. Herein, a comprehensive comparison of the performances among four popular prediction algorithms (BLAST, SVM, PNN and KNN) was conducted. In particular, the performance of these methods was systematically assessed by four standard statistical indexes based on the independent test datasets of 93 functional protein families defined by UniProtKB keywords. Moreover, the false discovery rates of these algorithms were evaluated by scanning the genomes of four representative model organisms (Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae and Mycobacterium tuberculosis). As a result, the substantially higher sensitivity of SVM and BLAST was observed compared with that of PNN and KNN. However, the machine learning algorithms (PNN, KNN and SVM) were found capable of substantially reducing the false discovery rate (SVM < PNN < KNN). In sum, this study comprehensively assessed the performance of four popular algorithms applied to protein function prediction, which could facilitate the selection of the most appropriate method in the related biomedical research.

Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics.

Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR. This update includes: (i) 2000 drug resistance mutations in 83 targets and 104 target/drug regulatory genes, which are resistant to 228 drugs targeting 63 diseases (49 targets of 61 drugs with patient prevalence data); (ii) differential expression profiles of 758 targets in the disease-relevant drug-targeted tissue of 12 615 patients of 70 diseases; (iii) expression profiles of 629 targets in the non-targeted tissues of 2565 healthy individuals; (iv) 1008 target combinations of 1764 drugs and the 1604 target combination of 664 multi-target drugs; (v) additional 48 successful, 398 clinical trial and 21 research targets, 473 approved, 812 clinical trial and 1120 experimental drugs, and (vi) ICD-10-CM and ICD-9-CM codes for additional 482 targets and 262 drugs against 98 disease conditions. This update makes TTD more useful for facilitating the patient focused research, discovery and clinical investigations of the targeted therapeutics. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp.

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic S1 in ovarian cancer cells.

The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl-2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy.

Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information.

Extensive drug discovery efforts have yielded many approved and candidate drugs targeting various targets in different biological pathways. Several freely accessible databases provide the drug, target and drug-targeted pathway information for facilitating drug discovery efforts, but there is an insufficient coverage of the clinical trial drugs and the drug-targeted pathways. Here, we describe an update of the Therapeutic Target Database (TTD) previously featured in NAR. The updated contents include: (i) significantly increased coverage of the clinical trial targets and drugs (1.6 and 2.3 times of the previous release, respectively), (ii) cross-links of most TTD target and drug entries to the corresponding pathway entries of KEGG, MetaCyc/BioCyc, NetPath, PANTHER pathway, Pathway Interaction Database (PID), PathWhiz, Reactome and WikiPathways, (iii) the convenient access of the multiple targets and drugs cross-linked to each of these pathway entries and (iv) the recently emerged approved and investigative drugs. This update makes TTD a more useful resource to complement other databases for facilitating the drug discovery efforts. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp.

Simultaneous degradation of toxic refractory organic pesticide and bioelectricity generation using a soil microbial fuel cell.

In this study, the soil microbial fuel cells (MFCs) were constructed in the topsoil contaminated with toxic refractory organic pesticide, hexachlorobenzene (HCB). The performance of electricity generation and HCB degradation in the soil-MFCs were investigated. The HCB degradation pathway was analyzed based on the determination of degradation products and intermediates. Experimental results showed that the HCB removal efficiencies in the three groups (soil MFCs group, open circuit control group and no adding anaerobic sludge blank group) were 71.15%, 52.49% and 38.92%, respectively. The highest detected power density was 77.5 mW/m(2) at the external resistance of 1000 Ω. HCB was degraded via the reductive dechlorination pathway in the soil MFC under anaerobic condition. The existence of the anode promoted electrogenic bacteria to provide more electrons to increase the metabolic reactions rates of anaerobic bacteria was the main way which could promote the removal efficiencies of HCB in soil MFC.

Schisandrin B protects PC12 cells against oxidative stress of neurodegenerative diseases.

Increasing evidence places Schisandrin B (Sch B) at an important position in nerve protection, indicating that Sch B might play a positive role in the therapy of neurodegenerative diseases. However, there is little information on it. Our studies showed that pretreatment with Sch B could reduce lactate dehydrogenase, malondialdehyde, and reactive oxygen species release and significantly increase the cell viability and the superoxide dismutase level. Sch B (10 µM) markedly inhibited cell apoptosis, whereas LY294002 (20 µM), a phosphatidylinositol-3 kinase inhibitor, blocked the antiapoptotic effect. More importantly, Sch B (10 µM) increased the phosphoprotein kinase B/protein kinase B (Akt) and B-cell lymphoma-2/Bcl-2 associated X protein ratios on preincubation with cells for 2 h, which was then inhibited by LY294002 (20 µM). Results indicate that Sch B can protect PC12 cells from apoptosis by activating the phosphatidylinositol-3 kinase/Akt signaling pathway and may emerge as a potential drug for neurodegenerative diseases.

[Effect of Schisandra chinensis lignans on neuronal apoptosis and p-AKT expression of rats in cerebral ischemia injury model].

OBJECTIVE: To observe the effect of Schisandra chinensis lignans (SCL) on neuronal apoptosis and PI3K/AKT signaling pathway of rats in the cerebral ischemia injury model, and study its possible mechanism. METHOD: Rats were orally administered SCL high, middle and low dose groups (100, 50, 25 mg x kg(-1)) for 14 days. The cerebral ischemia injury model was established by using the suture-occluded method to rate the neurological functions. The cerebral infarction area was observed by TTC staining. The pathological changes in brain tissues were determined by HE staining. Bcl-2 and Bax expressions were detected by immunohistochemical assay. The protein expressions of p-AKT and AKT were assayed by Western blotting. RESULT: Compared with the model group, SCL high, middle and low dose groups showed reduction in the cerebral infarction area to varying degrees, improve the pathological changes in brain tissues, promote the expression of apoptin Bcl-2 and p-AKT, and inhibit the expression of apoptin Bax. CONCLUSION: SCL shows a protective effect on rats with cerebral ischemia injury. Its mechanism may be related to the increase in p-AKT ability and antiischemic brain injury capacity and the inhibition of nerve cells.

[Photochemical reaction types of the azole fungicide fluconazole under UV-vis irradiation].

This study selected the azole fungicide fluconazole as a model compound, and investigated its photodegradation kinetics and photoreaction types in pure water. It was found that under UV-vis irradiation (lambda > 200 nm), the fluconazole photodegraded fast and followed the pseudo-first-order kinetics, whereas under simulated sunlight (lambda > 290 nm), photodegradation did not occur. The ROS scavenging experiments and competition kinetic examination indicated that the compound underwent both direct photolysis and self-sensitized photooxidation via *OH other than 1O2. The bimolecular rate constant for the reaction between fluconazole and *OH was (5.95 +/- 0.58) x 10(9) L x (mol x s)(-1), and the corresponding environmental half-life was calculated to be (32.41 +/- 3.16) h in surface waters. Furthermore, it was deduced from the photodegradation product identification that the UV-vis degradation pathways involved photoinduced defluorination, hydrolysis and photooxidation.