The Effectiveness and Safety of Cupping Therapy on CV8 Shenque for Urticaria; a Protocol for Systematic Review and Meta-Analysis.

Purpose: Urticaria is a common mast-cell-driven disease that poses a great burden on patients and society. Suggested therapeutic methods include avoidance of triggers and the use of medications, such as H1-antihistamines; however, limitations remain regarding efficacy, dealing with comorbidities, and adverse events. Cupping therapy (CT) at CV8 Shenque has been used in traditional Chinese medicine for the treatment of various dermatological diseases, including urticaria. The efficacy of the treatment has been revealed by previous clinical trials and case reports. This study was performed to provide a protocol for a systematic review and meta-analysis to analyze the effectiveness and safety of CT at CV8 Shenque for urticaria patients. Patients and Methods: Searches of electronic databases using manual searches and contact with the corresponding authors will be performed using predefined criteria for all randomized controlled trials on CT at CV8 Shenque for urticaria patients. Every part of the process will be conducted by two independent researchers, with conflicts being solved by a third author. The primary outcomes will be symptom scores, quality of life, and effective rate. Secondary outcomes will be adverse events and diagnostic test results. RevMan 5.4 software will be used to perform the meta-analysis. The Cochrane Collaboration "Risk of bias" tool will be used for risk of bias judgments. Results: Our study will evaluate the effectiveness and safety of CT at CV8 Shenque as a treatment option for urticaria. Conclusion: This systematic review is the first to investigate the effect of CT at CV8 Shenque for urticaria patients. Our study will provide objective evidence of an alternative approach to urticaria for clinicians and patients. Study Registration: PROSPERO (Registration number: CRD42023434913).

Temsirolimus Enhances Anti-Cancer Immunity by Inducing Autophagy-Mediated Degradation of the Secretion of Small Extracellular Vesicle PD-L1.

Tumor-derived small extracellular vesicle (sEV) programmed death-ligand 1 (PD-L1) contributes to the low reactivity of cells to immune checkpoint blockade therapy (ICBT), because sEV PD-L1 binds to programmed death 1 (PD-1) in immune cells. However, there are no commercially available anti-cancer drugs that activate immune cells by inhibiting tumor-derived sEV PD-L1 secretion and cellular PD-L1. Here, we aimed to investigate if temsirolimus (TEM) inhibits both sEV PD-L1 and cellular PD-L1 levels in MDA-MB-231 cells. In cancer cell autophagy activated by TEM, multivesicular bodies (MVBs) associated with the secretion of sEV are degraded through colocalization with autophagosomes or lysosomes. TEM promotes CD8+ T cell-mediated anti-cancer immunity in co-cultures of CD8+ T cells and tumor cells. Furthermore, the combination therapy of TEM and anti-PD-L1 antibodies enhanced anti-cancer immunity by increasing both the number and activity of CD4+ and CD8+ T cells in the tumor and draining lymph nodes (DLNs) of breast cancer-bearing immunocompetent mice. In contrast, the anti-cancer effect of the combination therapy with TEM and anti-PD-L1 antibodies was reversed by the injection of exogenous sEV PD-L1. These findings suggest that TEM, previously known as a targeted anti-cancer drug, can overcome the low reactivity of ICBT by inhibiting sEV PD-L1 and cellular PD-L1 levels.

Atorvastatin Enhances the Efficacy of Immune Checkpoint Therapy and Suppresses the Cellular and Extracellular Vesicle PD-L1.

According to clinical studies, statins improve the efficacy of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade therapy for breast cancer; however, the underlying mechanisms are unclear. Herein, we showed that atorvastatin (ATO) decreased the content of PD-L1 in extracellular vesicles (EVs) by reducing cellular PD-L1 expression and inhibiting EV secretion in breast cancer cells, thereby enhancing the efficacy of anti-PD-L1 therapy. ATO reduced EV secretion by regulating the Rab proteins involved in EV biogenesis and secretion. ATO-mediated inhibition of the Ras-activated MAPK signaling pathway downregulated PD-L1 expression. In addition, ATO strongly promoted antitumor efficacy by inducing T cell-mediated tumor destruction when combined with an anti-PD-L1 antibody. Moreover, suppression of EV PD-L1 by ATO improved the reactivity of anti-PD-L1 therapy by enhancing T-cell activity in draining lymph nodes of EMT6-bearing immunocompetent mice. Therefore, ATO is a potential therapeutic drug that improves antitumor immunity by inhibiting EV PD-L1, particularly in response to immune escape during cancer.

The effectiveness and safety of Simiao Xiaobi decoction on rheumatoid arthritis: A study protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disease that contributes to progressive disability, systemic complications, higher mortality, and societal burden. Typical symptoms of RA include symmetrical pain and swelling in multiple joints, morning stiffness, and elevated levels of erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor. The representative treatment for RA is medication, including disease-modifying antirheumatic drugs, glucocorticoids, and nonsteroidal anti-inflammatory drugs. However, these medications are not yet curative nor preventative and are associated with several adverse effects, leading to their discontinuation. Recent articles reported that Simiao Xiaobi decoction (SXD) could relieve the symptoms of RA by clinical trial and experimental study, but an evidence-based review on the effectiveness and safety of SXD on RA has not yet been provided. METHODS: Searching for randomized controlled trials on the use of SXD for RA will be performed by using multiple electronic databases, manual search, and contacting the authors by e-mail if needed. Studies will be selected according to the predefined criteria and the data collected on study participants, interventions, control groups, outcome measurements, their results, adverse events, and risk of bias will be summarized. The primary outcome will be the disease activity score (including effective rate, swollen joint count, tender joint count, and morning stiffness), and the secondary outcomes will be blood tests (including erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. We will use Review Manager software to perform a meta-analysis, the Cochrane Collaboration "risk of bias" tool for assessing the risk of bias, and grades of recommendation, assessment, development and evaluation for the determination of the quality of evidence. TRIAL REGISTRATION NUMBER: https://inplasy.com; INPLASY202230026. RESULTS: We are going to investigate the effectiveness and safety of SXD for RA. CONCLUSION: This study will provide reliable evidence on whether SXD is effective on RA.

Macitentan improves antitumor immune responses by inhibiting the secretion of tumor-derived extracellular vesicle PD-L1.

Extracellular vesicles (EVs) carrying tumor cell-derived programmed death-ligand 1 (PD-L1) interact with programmed death 1 (PD-1)-producing T cells, thus significantly lowering a patient's response to immune checkpoint blockade drugs. No drug that reinvigorates CD8+ T cells by suppressing EV PD-L1 has been approved for clinical usage. Here we have identified macitentan (MAC), an FDA-approved oral drug, as a robust booster of antitumor responses in CD8+ T cells by suppressing tumor cell-derived EV PD-L1. Methods: EV was analyzed by the data from nanoparticle tracking, immunoblotting analyses, and nano-flow cytometry. Antitumor immunity was evaluated by luciferase assay and immune phenotyping using flow cytometry. Clinical relevance was analyzed using the cancer genome atlas database. Results: MAC inhibited secretion of tumor-derived EV PD-L1 by targeting the endothelin receptor A (ETA) in breast cancer cells and xenograft models. MAC enhanced CD8+ T cell-mediated tumor killing by decreasing the binding of PD-1 to the EV PD-L1 and thus synergizing the effects of the anti-PD-L1 antibody. MAC also showed an anticancer effect in triple-negative breast cancer (TNBC)-bearing immunocompetent mice but not in nude mice. The combination therapy of MAC and anti-PD-L1 antibody significantly improved antitumor efficacy by increasing CD8+ T cell number and activity with decreasing Treg number in the tumors and draining lymph nodes in TNBC, colon, and lung syngeneic tumor models. The antitumor effect of MAC was reversed by injecting exogenous EV PD-L1. Notably, ETA level was strongly associated with the innate anti-PD-1 resistance gene signature and the low response to the PD-1/PD-L1 blockade. Conclusion: These findings strongly demonstrate that MAC, already approved for clinical applications, can be used to improve and/or overcome the inadequate response to PD-1/PD-L1 blockade therapy.

Sulfisoxazole Elicits Robust Antitumour Immune Response Along with Immune Checkpoint Therapy by Inhibiting Exosomal PD-L1.

Despite their potent antitumor activity, clinical application of immune checkpoint inhibitors has been significantly limited by their poor response rates (<30%) in cancer patients, primarily due to immunosuppressive tumor microenvironments. As a representative immune escape mechanism, cancer-derived exosomes have recently been demonstrated to exhaust CD8+ cytotoxic T cells. Here, it is reported that sulfisoxazole, a sulfonamide antibacterial, significantly decreases the exosomal PD-L1 level in blood when orally administered to the tumor-bearing mice. Consequently, sulfisoxazole effectively reinvigorates exhausted T cells, thereby eliciting robust antitumor effects in combination with anti-PD-1 antibody. Overall, sulfisoxazole regulates immunosuppression through the inhibition of exosomal PD-L1, implying its potential to improve the response rate of anti-PD-1 antibodies.

The complete chloroplast genome of Bupleurum euphorbioides, a traditional medicinal plant.

Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic tree indicated that B. euphorbioides was most closely related to B. latissimum.

The complete chloroplast genome of Bupleurum euphorbioides, a traditional medicinal plant.

Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree indicated that B. euphorbioides was the most closely related to B. latissimum.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Paeonia japonica (Paeoniaceae).

Paeonia japonica, distributed throughout Asia, is a traditional medicinal herb in Korea, with many potential beneficial effects including pain-relieving, anti-inflammatory, and anti-cancer activities. Despite its high pharmacological value, the genetic information on Paeonia japonica remains limited. In this study, the chloroplast genome of P. japonica was sequenced using next-generation sequencing (NGS) technology and genome and phylogeny were analyzed using multiple tools. The chloroplast genome of P. japonica was 152,731 bp in length with an inverted repeat region of 26,656 bp, including a large single-copy region of 84,389 bp and a small single copy region of 17,030 bp. The P. japonica chloroplast genome included 113 genes comprising 80 protein-coding genes, 27 tRNA, and 5 rRNA genes. Phylogenetic analysis indicated that P. japonica and P. obovata share a close evolutionary relationship.

Co-Administration of Gagam-Sipjeondaebo-Tang and Ibuprofen Alleviates the Inflammatory Response in MPTP-Induced Parkinson's Disease Mouse Model and RAW264.7 Macrophages.

Parkinson's disease (PD), a common neurodegenerative disease, is characterized by degeneration of dopaminergic neurons with neuroinflammation. Gagam-Sipjeondaebo-Tang (GST), a traditional herbal formula made of twelve medicinal herbs, is known to be effective in PD, and the use of ibuprofen has been associated with a lower risk of PD. The aim of this study was to evaluate whether the combined administration of GST and ibuprofen affects the inflammatory response of Parkinson's disease. MPTP-induced parkinsonian mouse models were treated with GST or ibuprofen using oral gavage once a day for 5 days. The effects of GST were examined by measuring the TH level and expression of CD68 in the mice brain in addition to behavioral tests. The anti-inflammatory effect of GST on the LPS-treated RAW264.7 murine macrophages was examined using the NO assay. Inflammatory cytokines were analyzed using quantitative-PCR and flow cytometry. In the results, GST significantly improved the loss of dopaminergic neurons and alleviated PD-induced behavioral deficits. GST also decreased macrophage activation in the MPTP-induced PD mouse model. Interestingly, co-administration of GST and ibuprofen showed a synergistic effect in improving the loss of dopaminergic neurons and decreasing the activation of macrophages. Moreover, the NO level decreased in LPS-stimulated macrophages with this combined treatment. GST reduced iNOS, COX-2, IL-1ß, and IL-6 levels, and co-administration with ibuprofen showed a synergistic effect. Furthermore, pretreatment of GST reduced the expression levels of MCP-1 and IL-12 p70 in LPS-stimulated RAW264.7 cells. These results can possibly suggest a future therapeutic approach for PD patients.

Sex differences in the association between self-rated health and high-sensitivity C-reactive protein levels in Koreans: a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey.

BACKGROUND: No studies have investigated the association between self-rated health (SRH) and high-sensitivity C-reactive protein (hs-CRP) levels in South Koreans. We explored this association and analyzed differences between sexes. METHODS: Using cross-sectional data from the 2015-2017 Korea National Health and Nutrition Examination Survey, we analyzed the association between SRH and high hs-CRP levels (> 1.0 mg/L) in 14,544 Koreans aged ≥ 19 years who responded to the SRH survey and had available hs-CRP test results. Differences in sociodemographic factors were analyzed using the Pearson's chi-square test for categorical variables or the Mann-Whitney U test for continuous variables. Multiple logistic regression analysis was used to measure the association between hs-CRP levels and SRH according to sex while adjusting for other possible confounders. RESULTS: The percentage of very poor to poor SRH was higher in the high hs-CRP group (22.4%) than in the low hs-CRP group (17.66%). Among men, the risk of a high hs-CRP level increased with worse SRH (adjusted for confounders; P for trend < 0.001). After adjusting for all confounders, including chronic diseases, men with very poor SRH showed a higher odds ratio (OR) for high hs-CRP levels than those with very good SRH (fully adjusted OR, 1.74; 95% CI, 1.04-2.90). Significant correlations were absent among women. CONCLUSIONS: Poor SRH was correlated with low-grade inflammation (high hs-CRP levels) among Korean male adults. These findings could be useful for developing health improvement programs and in goal setting at a national scale.

Efficacy of Korean red ginseng (Panax ginseng) for middle-aged and moderate level of chronic fatigue patients: A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Chronic fatigue (CF) is unexplained fatigue lasting more than 6 months. Korean red ginseng (KRG) is known to have higher anti-fatigue substance than white ginseng. However, its efficacy and safety for CF is unknown. The purpose of this study was to investigate the effect of KRG on CF by various measurements and objective indicators. DESIGN: A randomized, double-blind, clinical trial was conducted on 50 patients with CF. INTERVENTION: Participants were allocated to KRG or placebo group (1:1 ratio) and visited hospital every 2 weeks during taking 3 g KRG or placebo for 6 weeks and followed up 4 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome measurement was fatigue VAS. Secondary outcome measurements included FSS, CFSQ, SRI, scales of various fields (Depression: BDI; Sleep: ISI; Quality of life: EQ-5D 5 L), biochemical test (Antioxidants: d-ROMs, TBARS, BAP, and SOD; Cortisol concentration: salivary cortisol), blinding assessment, and adverse events. RESULTS: The fatigue VAS declined significantly in each group, but there were no significant differences between the groups. The 2 groups also had no significant differences in the secondary outcome measurements and there were no adverse events. Sub-group analysis indicated that patients with initial fatigue VAS below 80 mm and older than 50 years had significantly greater reductions in the fatigue VAS if they used KRG rather than placebo. CONCLUSIONS: By our study, KRG did not show absolute anti-fatigue effect but provided the objective evidence of fatigue-related measurement and the therapeutic potential for middle-aged individuals with moderate fatigue.

Retrospective case series on Gwakhyangjeonggi-san prescribed to patients with chronic urticaria.

INTRODUCTION: Chronic urticaria (CU) is characterized by repeated occurrence of wheals or itching for more than 6 weeks. When urticarial symptoms repeatedly occur despite taking western medicines such as antihistamines, herbal medicines have potential as an alternative for them. Among various herbal medications for CU, we mostly prescribe Gwakhyangjeonggi-san (GJS) made by Lee Je-ma, the founder of Sasang Constitutional Medicine (SCM) in Korea. The purpose of this study is to investigate whether GJS actually helps in treating CU. METHODS: We performed a retrospective review of the medical records of 30 patients to whom GJS was administered in order to compare the changes in urticaria activity scores (UAS) and in western medicines taken at the beginning of treatment of GJS and at 6 months after completion of the treatment. RESULTS: The UAS after 6 months from treatment (1.63 ± 2.06) with GJS for an average of 57.30 ± 35.88 days was significantly decreased compared to the score before treatment (5.10 ± 0.99), showing a statistically significant difference (p< 0.001). 46.67% of the patients (14/30 patients) reported that their symptoms were completely eliminated, and 66.67% of the patients taking anti-histamines (18/27 patients) were able to stop it completely. DISCUSSION: Based on the findings, GJS helps patients reduce taking western medicines such as anti-histamines, and we hypothesize that GJS improves symptoms of CU by the gastrointestinal protective activity and anti-oxidative/depressive effect. Further clinical study is warranted.

Elimination of alpha-gal xenoreactive epitope: alpha-galactosidase treatment of porcine heart valves.

BACKGROUND AND AIM OF THE STUDY: Porcine heart valves are among the most widely used tissue valves in clinical heart valve implantation. However, immunologic responses have been implicated as potential causes of the limited durability of xenograft heart valves. The study aim was to determine the effectiveness of alpha-galactosidase treatment used to degrade the major xenoreactive antigens found in xenograft heart valves. METHODS: Fresh porcine heart valves and pericardium treated with alpha-galactosidase were studied to evaluate the xenoreactive galactose (alpha1,3) galactose (alpha-gal) antigen. Removal of the alpha-gal epitope from the porcine heart valve was monitored via 3,3'-diaminobenzidine staining intensity, while the removal of alpha-gal from N-glycans on porcine heart valves treated with recombinant alpha-galactosidase was determined either qualitatively or quantitatively by mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The porcine pericardium was used for monitoring the change in mechanical properties after alpha-galactosidase treatment. In addition, the biomechanical modification property of collagen fiber rearrangement on tissue was assessed using transmission electron microscopy (TEM). RESULTS: Following a 24-h incubation at pH 7.2, 4 degrees C, employing 0.1 U/ml of Bacteroides thetaiotaomicron-derived recombinant alpha-galactosidase, the enzyme effectively removed the alpha-gal epitopes expressed on porcine heart valves. The identification type of alpha-gal N-glycan on fresh aortic valve, aortic wall, pulmonary valve, and pulmonary wall was 7.1%, 10.3%, 6% and 8%, respectively. In the presence of alpha-galactosidase treatment, alpha-gal-containing N-glycans were converted into alpha-gal-negative N-glycans. Likewise, alpha-gal-containing N-glycans were not detected when MALDI-TOF MS quantitative analysis was used. Furthermore, no significant difference was observed in the mechanical properties and findings from TEM in alpha-galactosidase-treated porcine pericardial tissue when compared to fresh porcine pericardium. CONCLUSION: Alpha-galactosidase can effectively remove the alpha-gal epitope from porcine heart valves and pericardium. This may possibly alleviate harmful xenoreactive immunologic responses by alpha-gal, without adversely affecting the biomechanical properties of the alpha-galactosidase-processed tissue.

Changes of the Structural and Biomechanical Properties of the Bovine Pericardium after the Removal of α-Gal Epitopes by Decellularization and α-Galactosidase Treatment.

BACKGROUND: Bovine pericardium is one of the most widely used materials in bioprosthetic heart valves. Immunologic responses have been implicated as potential causes of limited durability of xenogenic valves. This study aimed to determine the effectiveness of decellularization and α-galactosidase (α-gal) to remove major xenoreactive antigens from xenogenic tissues. MATERIALS AND METHODS: Recombinant Bacteroides thetaiotaomicron (B. thetaiotaomicron) α-gal or decellularization, or both were used to remove α-gal from bovine pericardium. It was confirmed by α-gal-bovine serum albumin-based enzyme-linked immunosorbent assay (ELISA), high-performance anion exchange chromatography, flow cytometry, 3,3'-diaminobenzidine-staining, and lectin-based ELISA. The mechanical properties of bovine pericardium after decellularization or α-gal treatment were investigated by tests of tensile-strength, permeability, and compliance. Collagen fiber rearrangement was also evaluated by a 20,000× transmission electron microscope (TEM). RESULTS: Recombinant B. thetaiotaomicron α-gal could effectively remove α-gal from bovine pericardium B. thetaiotaomicron (0.1 U/mL, pH 7.2) while recombinant human α-gal removed it recombinant human α-gal (10 U/mL, pH 5.0). There was no difference in the mechanical properties of fresh and recombinant α-gal-treated bovine pericardium. Furthermore, the TEM findings demonstrated that recombinant α-gal made no difference in the arrangement of collagen fiber bundles with decellularization. CONCLUSION: Recombinant B. thetaiotaomicron α-gal effectively removed α-gal from bovine pericardium with a small amount under physiological conditions compared to human recombinant α-gal, which may alleviate the harmful xenoreactive immunologic responses of α-gal. Recombinant α-gal treatment had no adverse effects on the mechanical properties of bovine pericardium.

Anti alpha-gal immune response following porcine bioprosthesis implantation in children.

BACKGROUND AND AIM OF THE STUDY: Porcine bioprostheses have been widely used in cardiac surgery in the treatment of valvular heart disease. However, in younger patients, their use has been limited by early failures known to be associated with an immune response and subsequent degeneration. The natural antibodies directed at Galalpha1, 3-Galbeta1-4GlcNAc-R(alpha-Gal), have been thought to initiate an immune response in humans transplanted with porcine organ xenografts. The study aim was to determine the anti alpha-Gal immune response following commercial porcine bioprosthesis implantation in children. METHODS: Between January 2008 and April 2008, 19 consecutive patients underwent pulmonary valve replacement (PVR) with a commercially available porcine bioprosthesis for an incompetent pulmonary valve with congenital heart diseases. The median age at surgery was 132 months (range: 14-330 months). Previous PVR with a porcine bioprosthesis had been performed in seven patients at a median of 44 months (range: 26-117 months) before surgery (re-PVR group). Sera were obtained sequentially five times: immediately before surgery, and at one day, one week, three weeks, and two months postoperatively. All serum samples were analyzed using an enzyme-linked immunosorbent assay to investigate the alpha-Gal immune response. RESULTS: There were no operative deaths or complications. There was no statistically significant difference between the titers of anti alpha-Gal antibodies of the PVR and re-PVR groups. The titer of anti alpha-Gal antibodies (IgM and IgG) was decreased on the first postoperative day, but increased in the first postoperative week, regardless of the isotype. Whilst the titer of the anti alpha-Gal IgM antibody began to decrease after three weeks postoperatively, the titer of anti alpha-Gal IgG antibody remained increased after two months. CONCLUSION: The implantation of a porcine bioprosthesis elicits the increased formation of anti alpha-Gal antibodies during the early postoperative period in children, with different patterns between the two isotypes. The IgM antibody response was rapid and transient, while the IgG antibody response was longer and more delayed.

Surface morphology and interdiffusion of LiF in Alq3-based organic light-emitting devices.

Highly efficient organic light-emitting devices (OLEDs) have been realized by insertion of a thin insulating lithium fluoride (LiF) layer between aluminum (Al) cathode and an electron transport layer, tris-(8-hydroxyquinoline) aluminum (Alq(3)). In this paper, we study the surface morphology of LiF on Alq(3) by synchrotron X-ray scattering and atomic force microscopy (AFM) as a function of thickness of LiF. We also study the interdiffusion of LiF into Al cathode as well as into Alq(3) layer as a function of temperature. Initially, LiF molecules are distributed randomly as clusters on the Alq(3) layer and then gradually form a layer as increasing LiF thickness. The interdiffusion of LiF into Al occurs more actively than into Alq(3) in annealing process. LiF on Alq(3) induces the ordering of Al to (111) direction strongly with increasing LiF thickness.