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Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

The development of targeted drugs in the Eastern Asia region is going through a flourishing stage. With the continuous advancement of technology and medical research, biotechnology companies and research institutions in the region have made significant progress in cancer field. The Eastern Asian region not only actively participates in clinical trials, but is also committed to developing personalized medical plans to meet the diverse genotypes and phenotypes of patients. The governments and enterprises are increasingly valuing innovation, strengthening international cooperation, and promoting drug development. This paper summarizes the development of genetic testing technology, targeted drugs approval, ongoing promising clinical trials in the field of lung cancer and the important progress made by governments in the Eastern Asian region, and proposed key factors that will contribute to the promising future prospects in the region. The targeted drug market in the Eastern Asian region is expected to drive the medical field forward., Competing Interests: Prof. Yi-Long Wu reports grants and personal fees from AstraZeneca, BMS, Pfizer; and personal fees from Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, Roche, outside the submitted work. Prof. Hidehito Horinouchi reports grants from AstraZeneca, Roche/Chugai, MSD, Abbvie, BMS/Ono and Daiichi-Sankyo; and personal fees from AstraZeneca, Roche/Chugai, MSD, BMS/Ono and Abbvie. The other authors have no competing interests to declare., (© 2024 The Author(s).)

Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disease. Metal ion dyshomeostasis and Aβ aggregation have been proposed to contribute to AD progression. Metal ions can bind to Aβ and promote Aβ aggregation, and ultimately lead to neuronal death. Bifunctional (metal chelation and Aβ interaction) compounds are showing promise against AD. In this work, eleven new 3,3'-diamino-2,2'-bipyridine derivatives 4a-4k were synthesized, and evaluated as bifunctional agents for AD treatment. In vitro Aβ aggregation inhibition assay confirmed that most of the synthesized compounds exhibited significant self-induced Aβ 1-42 aggregation inhibition. Among them, compound 4d displayed the best inhibitory potency of self-induced Aβ 1-42 aggregation with IC 50 value of 9.4 µM, and it could selectively chelate with Cu 2+ and exhibited 66.2% inhibition of Cu 2+ -induced Aβ 1-42 aggregation. Meanwhile, compound 4d showed strong neuroprotective activity against Aβ 1-42 and Cu 2+ -treated Aβ 1-42 induced cell damage. Moreover, compound 4d in high dose significantly reversed Aβ-induced memory impairment in mice., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study compared the changes in chemical components during the processing of different types of Aconiti Lateralis Radix Praeparata(ALRP) in "Jianchang" faction, i.e., dried ginger-steamed ALRP pieces(Yin-FP), sand-fried ALRP pieces(Yang-FP), and rice swill water-bleached ALRP pieces(DFP), and provided a scientific basis for the mechanism in toxicity reduction and efficacy enhancement from a compositional perspective. Samples were collected during the processing of the three types of ALRP pieces, yielding raw ALRP pieces, water-bleached Yin-FP, ginger juice-moistened Yin-FP, steamed Yin-FP, water-bleached Yang-FP, sand-fried Yang-FP, water-bleached DFP, rice swill water-bleached DFP, and roasted DFP. Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, aconine, mesaconine, hypaconine, salsolinol, fuziline, and higenamine in the extracts were determined by UPLC-MS/MS, and then content analysis and cluster heatmap analysis were performed on 11 sets of samples. During the processing of the three types of ALRP pieces, bleaching significantly reduced the content of 12 alkaloids; steaming, stir-frying, and roasting significantly reduced the content of diester-type alkaloids(aconitine, mesaconitine, and hypaconitine) and significantly increased the content of monoester-type alkaloids(benzoylaconine, benzoylmesaconine, and benzoylhypaconine) and aminoalcohol-type alkaloids(aconine, mesaconine, and hypaconine). During the processing of Yin-FP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. During the processing of Yin-FP, Yang-FP, and DFP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. Steamed Yin-FP showed a higher increase in content than fried Yang-FP and roasted DFP. Comprehensive analysis of content differences in toxic and therapeutic components in three ALRP pieces suggests that the distinctive processing methods in "Jianchang" faction can indeed achieve detoxification and efficacy enhancement on ALRP. This study provides references for understanding the mechanisms of action of the three processing methods.

Objective: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China., Methods: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database., Results: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs., Conclusion: The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes ( Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF- β 1/Smad pathway and downregulated α-smooth muscle actin ( α -SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Connexin43 (Cx43) is a major gap junction protein in glial cells. Mutations have been found in the gap-junction alpha 1 gene encoding Cx43 in glaucomatous human retinas, suggestive of the involvement of Cx43 in the pathogenesis of glaucoma. However, how Cx43 is involved in glaucoma is still unknown. We showed that increased intraocular pressure in a glaucoma mouse model of chronic ocular hypertension (COH) downregulated Cx43, which was mainly expressed in retinal astrocytes. Astrocytes in the optic nerve head where they gather and wrap the axons (optic nerve) of retinal ganglion cells (RGCs) were activated earlier than neurons in COH retinas and the alterations in astrocytes plasticity in the optic nerve caused a reduction in Cx43 expression. A time course showed that reductions of Cx43 expression were correlated with the activation of Rac1, a member of the Rho family. Co-immunoprecipitation assays showed that active Rac1, or the downstream signaling effector PAK1, negatively regulated Cx43 expression, Cx43 hemichannel opening and astrocyte activation. Pharmacological inhibition of Rac1 stimulated Cx43 hemichannel opening and ATP release, and astrocytes were identified to be one of the main sources of ATP. Furthermore, conditional knockout of Rac1 in astrocytes enhanced Cx43 expression and ATP release, and promoted RGC survival by upregulating the adenosine A3 receptor in RGCs. Our study provides new insight into the relationship between Cx43 and glaucoma, and suggests that regulating the interaction between astrocytes and RGCs via the Rac1/PAK1/Cx43/ATP pathway may be used as part of a therapeutic strategy for managing glaucoma., (© 2023 Wiley Periodicals LLC.)

In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.

Objective: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema., Methods: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up., Results: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides( Z =2.64, P < 0.01; Z =2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 ( P =0.59, P =0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side( Z =4.24, P < 0.01), while no significant difference was showed on the control side( Z =1.73, P =0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side ( Z =3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points ( P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment ( P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average., Conclusion: 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.

Alzheimer's disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer's disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of "drug-active ingredient-ingredient target." A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer's disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer's signal pathway, thus reducing the production of A β , inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor., Competing Interests: The authors have no conflicts of interest., (Copyright © 2021 Yi Kuan Du et al.)

Suicide,a major public health problem,is the death caused by injuring oneself with the intent to die.In this paper,we reviewed the genes encoding serotonin system,calcium voltage-gated channel subunit alpha1 C,γ-aminobutyric acid,and spindle and kinetochore associated complex subunit 2,as well as their related brain regions,from the perspective of imaging genetics,aiming to provide new ideas for the research and intervention on suicidal behavior.

Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.

Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity, is a key regulator of cytoskeletal reorganization in dendrites and spines. Here, we investigated whether and how Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA A receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO did not affect spine-like branch density in single dendrites, but significantly reduced the dendritic complexity, which resulted in a decrease in the total number of dendritic spine-like branches. These results suggest that Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

Objective: To study the regulatory effect of atorvastatin (ATV) on the extracellular signal-regulated kinase (ERK) 1/2 pathway and explore its effect on acute myocardial infarction (AMI) rats., Materials and Methods: The rat model of AMI was established, and the model rats were randomly divided into AMI group and ATV-AMI group, and Sham group was also set up. At 4 weeks after successful modeling, the cardiac function indexes of Sprague-Dawley (SD) rats were detected via magnetic resonance imaging (MRI) and echocardiography (ECG). After the rats were executed, the left ventricular weight index (LVWI) was measured, and the myocardial damage was detected via hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the messenger ribonucleic acid (mRNA) expressions of collagen I and collagen III in myocardial tissues were detected via Real Time-Polymerase Chain Reaction (PCR), and the expressions of ERK1/2 pathway-related proteins in myocardial tissues were detected via Western blotting., Results: After administration of ATV for AMI, the fractional shortening (FS%) and ejection fraction (EF%) were significantly restored. Compared with that in ATV-AMI group, LVWI was significantly increased in AMI group (p<0.05), indicating that ATV could improve the cardiac function after AMI. The results of HE staining and TUNEL staining showed that ATV-AMI group had slighter myocardial damage and significantly lower apoptosis rate than AMI group, indicating that ATV could reverse AMI through the ERK1/2 pathway. Besides, the mRNA expressions of collagen I and collagen III were higher in AMI group and ATV-AMI group than those in Sham group (p<0.05), while they were significantly lower in ATV-AMI group than those in AMI group (p<0.05). The expressions of ERK1/2 pathway-related proteins were also higher in AMI group and ATV-AMI group than those in Sham group (p<0.05)., Conclusions: ATV can significantly improve the cardiac function of SD rats after AMI, whose mechanism is related to the expression of the ERK1/2 pathway.

It was previously shown that EphB/ephrinB reverse signaling in retinal ganglion cells (RGCs) is activated and involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model. In the present work, we first show that ephrinB/EphB forward signaling was activated in COH retinas, and RGC apoptosis in COH retinas was reduced by PP2, an inhibitor of ephrinB/EphB forward signaling. We further demonstrate that treatment of cultured Müller cells with ephrinB1-Fc, an EphB1 activator, or intravitreal injection of ephrinB1-Fc in normal rats induced an increase in phosphorylated EphB levels in these cells, indicating the activation of ephrinB/EphB forward signaling, similar to those in COH retinas. The ephrinB1-Fc treatment did not induce Müller cell gliosis, as evidenced by unchanged GFAP expression, but significantly up-regulated mRNA and protein levels of tumor necrosis factor-α (TNF-α) in Müller cells, thereby promoting RGC apoptosis. Production of TNF-α induced by the activation of ephrinB/EphB forward signaling was mediated by the NR2B subunit of NMDA receptors, which was followed by a distinct PI3K/Akt/NF-κB signaling pathway, as pharmacological interference of each step of this pathway caused a reduction of TNF-α production, thus attenuating RGC apoptosis. Functional analysis of forward and reverse signaling in such a unique system, in which ephrin and Eph exist respectively in a glial element and a neuronal element, is of theoretical importance. Moreover, our results also raise a possibility that suppression of ephrinB/EphB forward signaling may be a new strategy for ameliorating RGC apoptosis in glaucoma.

Purpose: Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model., Methods: The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used., Results: Elevation of intraocular pressure induced a significant increase in ghrelin and GHSR-1a expression in retinal cells, including RGCs and Müller cells. Western blot confirmed that the protein levels of ghrelin exhibited a transient upregulation at week 2 after surgery (G2w), while the GHSR-1a protein levels were maintained at high levels from G2w to G4w. In COH retinas, the ratio of LC3-II/LC-I and beclin1, two autophagy-related proteins, were increased from G1w to G4w, and the cleavage product of caspase3, an apoptotic executioner, was detected from G2w to G4w. Intraperitoneal injection of ghrelin significantly increased the number of surviving RGCs; inhibited the changes of LC3-II/LC-I, beclin1, and the cleavage products of caspase3; and reduced the number of TUNEL-positive cells in COH retinas. Ghrelin treatment also reversed the decreased levels of p-Akt and p-mTOR, upregulated GHSR-1a protein levels, and attenuated glial fibrillary acidic protein levels in COH retinas., Conclusions: All these results suggest that ghrelin may provide neuroprotective effect in COH retinas through activating ghrelin/GHSR-1a system, which was mediated by inhibiting retinal autophagy, ganglion cell apoptosis, and Müller cell gliosis.

Previous studies have demonstrated that 5ɑ-androst-3β,5,6β-triol (Triol), a synthesized steroid compound, showed notable neuroprotective effect in cultured cortical neurons. In the present study, we explored whether and how Triol have neuroprotective effect on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model. COH model was produced by injecting superparamagnetic iron oxide micro-beads into the anterior chamber, and Triol was administrated (4.8μg/100g, i.p., once daily for 4 weeks). Immunohistochemistry experiments showed that in whole flat-mounted COH retinas, the number of CTB-labeled survival RGCs was progressively reduced, while TUNEL-positive signals were significantly increased from 1 to 4 weeks after the micro-bead injection. Triol administration significantly attenuated the reduction in the number of CTB-labeled RGCs, and partially reduced the increased number of TUNEL-positive signals in COH retinas. Furthermore, Triol administration partially reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and significantly rescued the activities of mitochondrial respiratory chain complex (MRCC) I/II/III in COH retinas. Our results suggest that Triol prevents RGCs from apoptotic death in COH retinas by reducing the lipid peroxidation and enhancing the activities of MRCCs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal cell apoptosis. The antisense RNA of brain-derived neurotrophic factor (BDNF-AS) is a natural antisense transcript that is transcribed opposite the gene that encodes BDNF. The aim of this study was to determine whether knockdown of BDNF-AS can suppress hypoxia/reoxygenation (H/R)-induced neuronal cell apoptosis and whether this is mediated by the BDNF-TrkB-PI3K/Akt pathway. We detected the expression of BDNF and BDNF-AS in brain tissue from 20 patients with cerebral infarction and five patients with other diseases (but no cerebral ischemia). We found that BDNF expression was significantly downregulated in patients with cerebral infarction, whereas the expression of BDNF-AS was significantly upregulated. In both human cortical neurons (HCN2) and human astrocytes, H/R significantly induced the expression of BDNF-AS, but significantly decreased BDNF expression. H/R also significantly induced apoptosis and reduced the mitochondrial membrane potential in these cells. Following downregulation of BDNF-AS by siRNA in human cortical neurons and human astrocyte cells, BDNF expression was significantly upregulated and the H/R-induced upregulation of BDNF-AS was significantly attenuated. BDNF-AS siRNA inhibited H/R-induced cell apoptosis and ameliorated the H/R-induced suppression of mitochondrial membrane potential. H/R inhibited the expression of BDNF, p-AKT/AKT, and TrKB, and this inhibition was recovered by BDNF-AS siRNA. In summary, this study indicates that BDNF-AS siRNA induces activation of the BDNF-TrkB-PI3K/Akt pathway following H/R-induced neurotoxicity. These findings will be useful toward the application of BDNF-AS siRNA for the treatment of neurodegenerative diseases.

Background: Depressive symptoms have been linked with insulin resistance in middle-aged and elderly populations. A strong relationship between peripheral insulin resistance and glucose homeostasis imbalance has been well established in previous studies. The role of serum fructosamine and fasting blood glucose (FBG) in elevating glucose homeostasis has been documented in the literature., Objectives: The aim of the study was to examine the association of serum fructosamine and FBG with major depressive disorder (MDD)., Material and Methods: The study analyzed the clinical characteristics and biochemical parameters of 305 patients with MDD and 312 healthy individuals., Results: Serum concentrations of lipoprotein-cholesterol (HDL-C), total protein (TP) and creatinine (Cr) were found to be significantly different between the two groups. Serum fructosamine and fasting blood glucose (FBG) concentrations were high in patients with MDD compared with healthy individuals (2.3 ± 0.26 vs. 2.1 ± 0.27, p = 0.018; 4.7 ± 0.45 vs. 4.5 ± 0.45, p < 0.001). The levels of serum fructosamine and FBG were also significantly higher in patients with MDD when all participants were stratified by gender. Age was found to be positively correlated with FBG, serum fructosamine and Cr (r = 0.203, p < 0.001; r = 0.129, p = 0.025; r = 0.129, p = 0.024), and negatively correlated with TP (r = -0.114, p = 0.047) in patients with MDD. However, there were no correlations between age and FBG, serum fructosamine or Cr in the healthy controls. In a multivariate logistic regression analysis, increased serum fructosamine and FBG concentrations were positively associated with MDD independently of age and gender, after adjustment for age and potential confounding factors (OR = 6.313, CI95 %:2.953-13.393, p < 0.001; OR = 2.251, CI95 %: 1.464-3.462, p < 0.001)., Conclusions: The study results suggest that increased serum fructosamine and FBG concentrations are associated with depressive conditions, which may influence glucose metabolism and impair glucose homeostasis in patients with MDD.

Objective: To investigate the relationship between atrial fibrillation (AF) and serum soluble CD163., Methods: A total of 336 patients with heart valve disease were included in this study, including 167 with AF and 169 with sinus rhythm. The clinical data were compared between the two grops, and Logistic regression analysis was used to identify the risk factors associated with AF., Results: The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor (TNF), interleukin-6 (IL - 6), high-sensitivity C-reactive protein (hs-CRP) and left atrial diameter (LAD) all differed significantly between the two groups (P<0.05). Serum soluble CD163 levels in AF patients were significantly higher than those in patients with sinus rhythm (P<0.05). Serum soluble CD163 was positively correlated with TNF (r=0.244, P=0.244), IL-6 (r=0.186, P=0.186), hs-CRP (r=0.183, P=0.183) and LAD (r=0.194, P=0.194) in patients with AF. Logistic regression analysis showed that LAD, IL-6, TNF, hs-CRP and CD163 were all associated with AF. ROC curve analysis showed that the area under curve of serum soluble CD163 was 0.861 in patients with AF (CI 95%: 0.820-0.901, P<0.01) with a sensitivity and a specificity of 80.8 and 76.9%, respectively., Conclusion: Serum soluble CD163 level may be a risk factor for AF, and an increased soluble CD163 level may indicate active inflammation in AF patients.

The aim of the present study was to evaluate the efficacy and safety of lignin peroxidase (LIP) as a skin-lightening agent in patients with melasma. A self-controlled clinical study was performed in 31 women who had melasma on both sides of the face. This study involved 8 weeks of a full-face product treatment. The skin color was measured at days 0, 7, 28 and 56 using a chromameter on the forehead and cheeks. Standardized digital photographic images of each side of the face of all subjects were captured by a complexion analysis system. Clinical scores of the pigmentation were determined by two dermatologists. After using the LIP whitening lotion for 7 days, the luminance (L*) values of the melasma and the normal skin were significantly increased from baseline. The L* values continued to increase at days 28 and 56. The melasma area severity index (MASI) score was statistically decreased after 28 days of treatment. No treatment-related adverse events were observed. LIP whitening lotion was able to eliminate the skin pigmentation after 7 days of treatment, and provides a completely innovative approach to rapid skin lightening. The LIP whitening lotion exhibited good compatibility and was well tolerated.

A series of novel oxoisoaporphine-based inhibitors (10-aminoalkylamino-1-azabenzanthrone Ar-NH(CH(2))(n)NR(1)R(2)) of acetylcholinesterase (AChE) has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE) and AChE-induced β-amyloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the submicromolar range in most cases. Non-competitive binding mode was found for these derivatives by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibit significant inhibitory activity on AChE-induced Aβ aggregation with inhibitory potency from 54.5% to 93.5%. Finally, six out of twelve synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To study the changes in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus metabolites in first-episode patients with positive symptoms of schizophrenia., Methods: Twenty first-episode patients with positive symptoms of schizophrenia underwent diffusion tensor imaging (DTI) and proton multi-voxel spectroscopy (1H-MRS) examination. 1H-MRS images were obtained from two sides of the frontal white matter, the head of the hippocampus and the anterior cingulate fasciculus regions. The metabolites detected included N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and the ratios of NAA/Cr, Cho/Cr and NAA/Cho were determined. The fractional anisotropy (FA) values were measured in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus., Results: The Cho/Cr ratio was significantly reduced in the left frontal white matter (1.18 ± 0.21) of the patients as compared to the right side (1.44 ± 0.34, P<0.05). In the left head of the hippocampus, NAA/Cr (1.34 ± 0.45) and Cho/Cr (1.41 ± 0.39) were significantly reduced compared to those of the right side (1.75 ± 0.15 and 1.76 ± 0.36, respectively, P<0.05). No significant differences in the metabolite levels were found between the left and right anterior cingulate fasciculus (P>0.05). DTI showed similar FA values between the left and right sides of the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus (P>0.05)., Conclusions: Patients with positive symptoms of schizophrenia have diminished neuronal integrity and/or function in the left frontal white matter and head of the hippocampus, but not in the anterior cingulate fasciculus.

In optical frequency, surface plasmons of metal provide us a prominent way to build compact photonic devices or circuits with non-diffraction limit. It is attributed by their extraordinary electromagnetic confining effect. But in the counterpart of lower frequencies, plasmonics behavior of metal is screened by eddy current induced in a certain skin depth. To amend this, spoof plasmons engineered by artificial structures have been introduced to mimic surface plasmons in these frequencies. But it is less useful for practical application due to their weak field confinement as manifested by large field decaying length in the upper dielectric space. Recently, a new type of engineered plasmons, domino plasmon was theoretically proposed to produce unusual field confinement and waveguiding capabilities that make them very attractive for ultra-compact device applications [Opt. Exp. 18, 754-764 (2010)]. In this work, we implemented these ideas and built three waveguiding devices based on domino plasmons. Their strong capabilities to produce versatile and ultra-compact devices with multiple electromagnetic functions have been experimentally verified in microwaves. And that can be extended to THz regime to pave the way for a new class of integrated wave circuits., (© 2011 Optical Society of America)

A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced β-amyloid (Aβ) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tacrine or its congener, connected through an oligomethylene linker containing an amine group at variable position. These hybrids exhibit high AChE inhibitory activity with IC(50) values in the nanomolar range in most cases. Moreover, five out of the 12 hybrids of this series, particularly those bearing a tetrahydroacridine moiety, exhibit a significant in vitro inhibitory activity toward the AChE-induced and self-induced Aβ aggregation, which makes them promising anti-Alzheimer drug candidates., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Two new compounds, cinnamic aldehyde cyclic d-galactitol 3'R,4'S-acetal (1) and cinnamomumolide (2), along with six known compounds, syringaresinol (3), lyoniresinol (4), 5,7,3'-trimethoxyl-( - )-epicatechin (5), 5,7-dimethoxyl-3',4'-di-O-methylene-( +/- )-epicatechin (6), 2-methoxyl-4-hydroxy cinnamyl aldehyde (7), and glucosyringic acid (8), have been isolated from the dried tender stems of Cinnamomum cassia. Their structures were elucidated based on spectroscopic data. Compound 2 was elucidated as 8-methoxyl-9-hydroxy-3',4'-methylenedioxy-3S,4R-diphenyl butyrolactone, named cinnamomumolide, which exhibited activity in protecting against the injury caused by hydrogen peroxide oxidation on human umbilical vein endothelial cells, with an EC(50) value of 10.7 microM. Compounds 3-8 were isolated from the title plant for the first time.

Aim: To explain the effect of daurisoline (DS) on delayed afterdepolarization (DAD)., Methods: Ca(2+)-sensitive microelectrode technic was used to record intracellular Ca2+ activity (alpha Cai) and triggered activity (TA) arising from DAD in myocardium., Results: Strophantin G 3 mumol.L-1 yielded an increase in resting myocardial alpha Cai by 0.19 +/- 0.11 mumol.L-1 and transient elevations of alpha Cai by 1.48 +/- 0.55 and 4.96 +/- 1.81 mumol.L-1, respectively during the development of DAD and TA. By pretreatment with DS or verapamil, strophantin G-caused elevations of the alpha Cai in resting and provoked myocardia were eliminated and TA disappeared. DS 50 mumol.L-1 reduced Na(+)-free medium-induced elevation of dog Purkinje fibrous alpha Cai and abolished caffeine-induced increase of dog myocardial alpha Cai., Conclusions: DS inhibited DAD and TA by preventing an increase of alpha Cai via transmembrane Ca2+ entry and Ca2+ release from the reticulum.

The improved neutral ligand ETH1001 Ca(2+)-sensitive microelectrodes (Ca-ISE, tip diameter 0.4-0.8 mumol.L-1) are highly ion selective and sensitive and therefore can be reliably used to measure cytoplasmic Ca2+ activity (alpha iCa) in myocardia. The resting alpha iCa in guinea-pig ventricular trabecula, canine ventricular myocardia and Purkinje fibers were respectively 0.19 +/- 0.01, 0.20 +/- 0.02 and 0.46 +/- 0.07 mumol.L-1. Three mumol.L-1 strophantin G increased the resting and dynamic myocardial alpha iCa by 0.18 +/- 0.02 and 6.69 +/- 2.09 mumol.L-1 respectively, as well as engendered triggered activity (TA). When pretreated with 100 mumol.L-1 dauricine (Dau), strophantin G could no longer increase alpha iCa and TA disappeared. It is suggested thus the applicability of Ca-ISE for measurement of myocardia alpha iCa and TA is obvious.

A calcium ion-selective PVC membrane electrode based on neutral carrier n,n,n',n'-tetracyclohexyl-3-oxapetanediamide, using di-(2-ethylhexyl)phthalate as the plasticizer and potassium tetrakis (4-chlorophenyl) borate as the additive is reported in this paper. The ion selective membrane consists of 1 wt% of the Ca2+ selective ligand, 65 wt% of the plasticizer, 1 wt% of the additive and 33 wt% of poly (vinyl chloride) powder. The electrode has the linear response range of 2.0 x 10(-7)-10(-1) mol/L with the Nernstian slope of 28 mV/decade at 25 degrees C and the detection limit of 2.0 x 10(-8) mol/L. The response time of the calcium ion-selective electrode is as the concentration of calcium ion is rapidly shifted from 10(-5) to 10(-4) mol/L. The potential stability and reproducibility are good. The free calcium in blood serum was determined by the calcium ion-selective electrode with satisfactory results.